Gums, Resins and Latexes of Plant Origin: Chemistry, Biological Activities and Uses (Reference Series in Phytochemistry) 3030913775, 9783030913779

Citation preview

Reference Series in Phytochemistry Series Editors: J.-M. Mérillon · K. G. Ramawat

Hosakatte Niranjana Murthy Editor

Gums, Resins and Latexes of Plant Origin Chemistry, Biological Activities and Uses

Reference Series in Phytochemistry Series Editors Jean-Michel Mérillon, Faculty of Pharmaceutical Sciences, Institute of Vine and Wine Sciences, University of Bordeaux, Villenave d’Ornon, France Kishan Gopal Ramawat, Department of Botany, University College of Science, M. L. Sukhadia University, Udaipur, Rajasthan, India

This series provides a platform for essential information on plant metabolites and phytochemicals, their chemistry, properties, applications, and methods. By the strictest definition, phytochemicals are chemicals derived from plants. However, the term is often also used to describe the large number of secondary metabolic compounds found in and derived from plants. These metabolites exhibit a number of nutritional and protective functions for human wellbeing and are used e.g. as colorants, fragrances and flavorings, amino acids, pharmaceuticals, hormones, vitamins and agrochemicals. The series offers extensive information on various topics and aspects of phytochemicals, including their potential use in natural medicine, their ecological role, role as chemo-preventers and, in the context of plant defense, their importance for pathogen adaptation and disease resistance. The respective volumes also provide information on methods, e.g. for metabolomics, genetic engineering of pathways, molecular farming, and obtaining metabolites from lower organisms and marine organisms besides higher plants. Accordingly, they will be of great interest to readers in various fields, from chemistry, biology and biotechnology, to pharmacognosy, pharmacology, botany and medicine. The Reference Series in Phytochemistry is indexed in Scopus.

Hosakatte Niranjana Murthy Editor

Gums, Resins and Latexes of Plant Origin Chemistry, Biological Activities and Uses

With 235 Figures and 92 Tables

Editor Hosakatte Niranjana Murthy Department of Botany Karnatak University Dharwad, Karnataka, India

ISSN 2511-834X ISSN 2511-8358 (electronic) Reference Series in Phytochemistry ISBN 978-3-030-91377-9 ISBN 978-3-030-91378-6 (eBook) https://doi.org/10.1007/978-3-030-91378-6 © Springer Nature Switzerland AG 2022 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG. The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Preface

Natural gums and mucilage are plant secretions, exuding naturally or on incision or infection, which usually harden on drying and are soluble in water. Gums are polysaccharides, which are complex carbohydrates. Gums are an important ingredient in pharmaceutical preparations owing to their biodegradability, abundant availability, non-toxicity, and low cost. Gums are also known for their multifarious uses in food industries like baking, meat, fruit, and vegetables. Resins are non-volatile products of plants from which they exude naturally (surface resins) or can be obtained by incision or infection (internal resins). They are insoluble in water but soluble in an organic solvent. They are lipid-soluble mixtures of volatile and non-volatile terpenoids, alkaloids, and phenolic compounds. Plant resins are valued for the production of varnishes, adhesives, and glazing agents. They are also used as incense and perfumes. Latexes are colloidal suspensions or emulations of water-insoluble substances suspended in an aqueous phase, which may be released on cutting a plant. They are produced in specialized internal secretary structures called laticifers. The suspensions may consist of terpenoids, phenolics, alkaloids, proteins, essential oils, and other compounds. Plant latex is a source of natural rubber that is used in the preparation of products such as gloves, condoms, and latex clothing. With this backdrop, this book encompasses research work on bioactive compounds in natural gums, resins, and latexes across the globe to present the latest research for the enhanced appreciation of this topic. The chapters presented in this volume focus on several research subjects that have provided critical information on the natural plant-based gums, resins, and latexes, as well as their chemical composition, properties, and bioactive principles. There is a wealth of useful references that should prove to be an invaluable source for the reader. Self-explanatory illustrations and tables have been incorporated into each chapter, complementary to the main text. I would like to thank and express my deepest gratitude to all the contributors who helped me to complete this book. I also thank Professor Jean-Michel Merillon and Professor Kishan Gopal Ramawat, Series Editors, for their constant encouragement. I thank Dr. Sylvia Blago and Johanna Klute for their support. Finally, I am thankful to the Springer team for completing this assignment successfully. Dharwad, India July 2022

Hosakatte Niranjana Murthy v

Contents

Part I 1

2

3

4

5

Introduction to Gums, Resins, and Latexes

..............

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of Plant Origin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Hosakatte Niranjana Murthy

3

Pharmaceutical Applications of Various Natural Gums and Mucilages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vipul Prajapati, Sonal Desai, Shivani Gandhi, and Salona Roy

25

Tree Gum-Based Renewable Materials and Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vinod V. T. Padil and Miroslav Černík

59

Natural Gums for Fruits and Vegetables Preservation: A Review . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nishant Kumar, Pratibha, Anka Trajkovska Petkoska, and Mohit Singla Application of Guar Gum and Its Derivatives in Agriculture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Manar El-Sayed Abdel-raouf, Asmaa Sayed, and Mai Mostafa

81

117

6

Exudate Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Deepak Mudgil and Sheweta Barak

133

7

Gums as Pharmaceutical Excipients: An Overview . . . . . . . . . . . . Selvakumar Muruganantham, Venkateshwaran Krishnaswami, D. AnithaManikandan, Nirmal Aravindaraj, Jeseeta Suresh, Mohanraj Murugesan, and Ruckmani Kandasamy

145

Part II 8

Plant Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Chemistry, Biological Activities, and Uses of Moi Gum . . . . . . . . . Sumit Mishra, Ch. Jamkhokai Mate, and Nandkishore Thombare

191 193

vii

viii

9

10

Contents

Chemistry, Biological Activities, and Uses of Locust Bean Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Neha Duhan, Sheweta Barak, and Deepak Mudgil Chemistry, Biological Activities, and Uses of Moringa Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Leena Kumari, Madhuri Baghel, Subhamay Panda, Kalyani Sakure, Tapan Kumar Giri, and Hemant Badwaik ........

11

Chemistry, Biological Activities, and Uses of Tara Gum Sonal Desai, Vipul Prajapati, and Chandni Chandarana

12

Chemistry, Biological Activities, and Uses of Cashew Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Daiany Priscilla Bueno da Silva, Lorrane Kelle da Silva Moreira, Iara Barbosa Cabral, Cassio Nazareno Silva da Silva, Karla de Aleluia Batista, James Oluwagbamigbe Fajemiroye, and Elson Alves Costa

225

241

265

291

13

Chemistry and Food Applications of Persian Gum . . . . . . . . . . . . Rassoul Kadkhodaee and Maryam Mahfouzi

307

14

Chañar Gum (Geoffrea decorticans) . . . . . . . . . . . . . . . . . . . . . . . . Lismet Lazo, Romina Colla, Marina Ciancia, Cristina Matulewicz, María L. Auad, Camilo J. Orrabalis, Mauricio Filippa, and Martin Masuelli

333

15

Chemistry, Biological Activities, and Uses of Basil Seed Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Abinash Chand Bharati, Prashant Kumar Yadav, Shailendra Pandey, Pranay Wal, Manoj Kumar Sagar, and Ajay Kumar

Part III 16

17

Plant Resins and Oleoresins . . . . . . . . . . . . . . . . . . . . . . . . .

Chemistry, Biological Activities, and Uses of Copaiba Oil Resins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Milena Campelo Freitas de Lima, Rayssa Ribeiro, Josiane Elizabeth Almeida e Silva, Sthephanie Silva dos Santos Tavares, Yuri Campello Dias de Araujo, and Valdir F. da Veiga-Junior Chemistry, Biological Activities, and Uses of Balsams . . . . . . . . . . Ana Tayná Chaves Aguiar, Ian-Gardel Carvalho Barcellos-Silva, Nathalia Rodrigues de Oliveira Habib-Pereira, Ananda Silva Antonio, and Valdir F. da Veiga-Junior

357

375

377

399

Contents

18

19

ix

Chemistry, Biological Activities, and Uses of Copal Resin (Bursera spp.) in Mexico . . . . . . . . . . . . . . . . . . . . . . . . . . . . José Blancas, Itzel Abad-Fitz, Leonardo Beltrán-Rodríguez, Sol Cristians, Selene Rangel-Landa, Alejandro Casas, Ignacio Torres-García, and José Antonio Sierra-Huelsz Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of Commiphora wightii . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Prerna Sarup, Sonia Pahuja, and Jai Malik

433

447

20

Chemistry and Biological Activities of Garcinia Resin . . . . . . . . . . Hosakatte Niranjana Murthy and Guggalada Govardhana Yadav

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia serrata Roxb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Tanveer Alam, Shah Alam Khan, and Lubna Najam

517

Chemistry, Biological Activities, and Uses of Benzoin Resin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Mohammad Sohail Akhtar and Tanveer Alam

559

Ethnobotany, Chemistry, and Biological Activities of Some Commiphora Species Resins . . . . . . . . . . . . . . . . . . . . . . . . . Aman Dekebo, Seifu Juniedi, Xuebo Hu, and Chuleui Jung

581

22

23

24

Chemistry, Biological Activities, and Uses of Araucaria Resin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Ajay Kumar, Swati Singh, Munmun Kumar Singh, Atul Gupta, Sudeep Tandon, and Ram Swaroop Verma

479

609

25

Chemistry, Biological Activities, and Uses of Asafetida . . . . . . . . . Sonia Singh, Neetu Agrawal, and Prabhat Kumar Upadhyay

629

26

Chemistry and Applications of Propolis . . . . . . . . . . . . . . . . . . . . . Milena Popova, Boryana Trusheva, and Vassya Bankova

657

27

Propolis: A Multifaceted Approach for Wound Healing . . . . . . . . Gregorio Bonsignore, Simona Martinotti, and Elia Ranzato

689

Part IV

Plant Latexes

....................................

28

Chemistry, Biological Activity, and Uses of Clusia Latex . . . . . . . . Claudio Augusto Gomes da Camara, Anita Jocelyne Marsaioli, Volker Bittrich, and Marcilio Martins de Moraes

29

Chemistry, Biological Activities, and Uses of Calotropis Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Anifat Adenike Bankole and Thies Thiemann

699 701

769

x

30

31

32

Contents

Chemistry, Biological Activities, and Uses of Ficus carica Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . María Victoria Castelli and Silvia Noelí López Chemistry, Biological Activities, and Uses of Jatropha Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . R. Vijayalakshmi, A. Vetriselvi, Eli José Miranda Ribeiro Junior, and Patrícia de Araújo Rodrigues Chemistry, Biological Activities, and Uses of Latex from Selected Species of Apocynaceae . . . . . . . . . . . . . . . . . . . . . . . . . . . Clarissa Marcelle Naidoo, Ashlin Munsamy, Yougasphree Naidoo, and Yaser Hassan Dewir

Part V 33

Plant Waxes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Chemistry, Biological Activities, and Uses of Carnauba Wax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Eli José Miranda Ribeiro Junior, Joy Ruby Violet Stephen, Murugan Muthuvel, Amitava Roy, Patrícia de Araújo Rodrigues, Marajá João Alves de Mendonça Filho, Renato Araújo Teixeira, Antony de Paula Barbosa, and Stephen Rathinaraj Benjamin

Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

801

823

845

869

871

895

About the Editor

Hosakatte Niranjana Murthy, Professor at PostGraduate Department of Botany, Karnatak University, Dharwad, India, has obtained his Ph.D. from Karnatak University, India. He has a tremendous passion for research and academics. Since 1986, he has served in various positions at the Post-Graduate Department of Botany, Karnatak University, Dharwad, India. Apart from his teaching experience of 35 years, he possesses extensive research experience in the area of plant biotechnology. He has postdoctoral and collaborative research experience in many foreign research institutes. Prof. Murthy carried out research at Biotechnology Division, Tata Energy Research Institute, New Delhi, India (1992); Crop Science Department, University of Guelph, Guelph, Canada (1993); Research Centre for the Development of Horticultural Technology, Chungbuk National University, Cheongju, South Korea (2000-2001, 2002, 2004, 2006-2007, 20132014); and in the Department of Biological Sciences, University of Nottingham, Nottingham, United Kingdom (2005-2006) as a postdoctoral fellow/visiting scientist. He is the recipient of various prestigious fellowships including Biotechnology National Associate, Biotechnology Overseas Associate (awarded by the Department of Biotechnology, Ministry of Science and Technology, Government of India), Brain Pool Fellowship (awarded by the Korean Society of Science and Technology, South Korea), Visiting Fellowship (awarded by the Korea Science and Engineering Foundation, South Korea), and Commonwealth Post-doctoral Fellowship (awarded by the Association of Commonwealth Universities, UK). He has completed more than 15 research projects funded by various agencies and xi

xii

About the Editor

guided several Ph.D. students. He has published more than 225 research articles in international peer-reviewed journals with high impact factors. His research work has been cited more than 4800 times by fellow researchers and has an H-index (Hirsch index) of 38 as recorded by Scopus. Professor Hosakatte Niranjana Murthy, along with South Korean collaborators, has developed biotechnological methods for the production of pharmaceutically important secondary metabolites from cell and organ cultures of Ginseng, Siberian ginseng, Echinacea, and St. John’s wort using large-scale bioreactors. His experimental investigations on the use of adventitious root cultures and bioreactor technologies for the production of biomass and secondary metabolites have paved the way for the commercialization of plant secondary metabolites. Various ginseng-based commercial products have been released and are currently available in the market.

Contributors

Itzel Abad-Fitz Centro de Investigación en Biodiversidad y Conservación (CIByC) – Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico Manar El-Sayed Abdel-raouf Petroleum Application Department, Egyptian Petroleum Research Institute, Cairo, Egypt Neetu Agrawal Institute of Pharmaceutical Research, GLA University, Mathura, UP, India Ana Tayná Chaves Aguiar Department of Chemical Engineering, Military Institute of Engineering – IME, Rio de Janeiro, Brazil Tanveer Alam Natural & Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman Josiane Elizabeth Almeida e Silva Departamento de Ciências Biológicas, Instituto de Ciências Biológicas, Universidade Federal do Amazonas, Manaus, AM, Brazil D. Anitha Manikandan Centre for Excellence in Nanobio Translational Research (CENTRE), Department of Pharmaceutical Technology, University College of Engineering, Anna University BIT Campus, Tiruchirappalli, Tamil Nadu, India Ananda Silva Antonio Federal University of Rio de Janeiro, Chemistry Institute, Núcleo de Análises Forenses (NAF – LADETEC/IQ – UFRJ), Rio de Janeiro, Brazil Renato Araújo Teixeira Department of Geography, Federal Institute of Goiás, Inhumas, Goiás, Brazil Nirmal Aravindaraj Centre for Excellence in Nanobio Translational Research (CENTRE), Department of Pharmaceutical Technology, University College of Engineering, Anna University BIT Campus, Tiruchirappalli, Tamil Nadu, India María L. Auad Center for Polymers and Advanced Composites, Department of Chemical Engineering, Auburn University, Auburn, AL, USA Hemant Badwaik Rungta College of Pharmaceutical Sciences and Research, Kohka, Bhilai, India xiii

xiv

Contributors

Madhuri Baghel Rungta College of Pharmaceutical Sciences and Research, Kohka, Bhilai, India Anifat Adenike Bankole Department of Chemistry, Faculty of Science, United Arab Emirates University, Al Ain, Abu Dhabi, UAE Vassya Bankova Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria Sheweta Barak Mansinhbhai Institute of Dairy & Food Technology (MIDFT), Mehsana, Gujarat, India Antony de Paula Barbosa Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil Ian-Gardel Carvalho Barcellos-Silva Department of Chemical Engineering, Military Institute of Engineering – IME, Rio de Janeiro, Brazil Leonardo Beltrán-Rodríguez Jardín Botánico – Instituto de Biología. Universidad Nacional Autónoma de México, Ciudad de México, Mexico Stephen Rathinaraj Benjamin Post-Graduate Programme in Medical Sciences, Department of Medicine, Faculty of Medicine, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Ceará, Brazil Abinash Chand Bharati Department of Pharmacy, Indira Gandhi National Tribal University, Amarkantak, India Volker Bittrich Campinas, Brazil José Blancas Centro de Investigación en Biodiversidad y Conservación (CIByC) – Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico Gregorio Bonsignore DiSIT- Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Alessandria, Italy Iara Barbosa Cabral Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil Alejandro Casas Instituto de Investigaciones en Ecosistemas y Sustentabilidad, Universidad Nacional Autónoma de México, Morelia, Michoacán, Mexico María Victoria Castelli Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario – CONICET, Rosario, Argentina Miroslav Černík Institute for Nanomaterials, Advanced Technologies and Innovation (CXI), Technical University of Liberec (TUL), Liberec, Czech Republic Chandni Chandarana Department of Pharmaceutical Quality Assurance, SSR College of Pharmacy, Silvassa, Union Territory of Dadra Nagar Haveli & Daman Diu, India

Contributors

xv

Marina Ciancia Facultad de Agronomía, Departamento de Biología Aplicada y Alimentos, Cátedra de Química de Biomoléculas (CIHIDECAR,CONICET-UBA), Universidad de Buenos Aires, Buenos Aires, Argentina Romina Colla Instituto de Física Aplicada-CONICET-Universidad Nacional de San Luis, San Luis, Argentina Elson Alves Costa Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil Sol Cristians Jardín Botánico – Instituto de Biología. Universidad Nacional Autónoma de México, Ciudad de México, Mexico Claudio Augusto Gomes da Camara Departamento de Química, Universidade Federal Rural de Pernambuco, Recife, PE, Brazil Cassio Nazareno Silva da Silva Laboratory of Polymer Chemistry, Institute of Biological Sciences, Campus Samambaia, Universidade Federal de Goiás, Goiânia, GO, Brazil Daiany Priscilla Bueno da Silva Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil Lorrane Kelle da Silva Moreira Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil Valdir F. da Veiga-Junior Departamento de Química, Instituto de Ciências Exatas, Universidade Federal do Amazonas, Manaus, AM, Brazil Departamento de Engenharia Química, Instituto Militar de Engenharia, Rio de Janeiro, RJ, Brazil Karla de Aleluia Batista Department of Academic Areas, Goias Federal Institute of Education, Science, and Technology Campus Goiânia Oeste, Goiânia, GO, Brazil Patrícia de Araújo Rodrigues Post-Graduate Programme in Medical Sciences, Department of Medicine, Faculty of Medicine, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Ceará, Brazil Yuri Campello Dias de Araujo Departamento de Engenharia Química, Instituto Militar de Engenharia, Rio de Janeiro, RJ, Brazil Milena Campelo Freitas de Lima Departamento de Química, Instituto de Ciências Exatas, Universidade Federal do Amazonas, Manaus, AM, Brazil Marcilio Martins de Moraes Departamento de Química, Universidade Federal Rural de Pernambuco, Recife, PE, Brazil Nathalia Rodrigues de Oliveira Habib-Pereira Department of Chemical Engineering, Military Institute of Engineering – IME, Rio de Janeiro, Brazil

xvi

Contributors

Aman Dekebo Department of Applied Chemistry, Adama Science and Technology University, Adama, Ethiopia Sonal Desai Department of Pharmaceutical Quality Assurance, SSR College of Pharmacy, Silvassa, Union Territory of Dadra Nagar Haveli & Daman Diu, India Yaser Hassan Dewir Plant Production Department, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia Department of Horticulture, Faculty of Agriculture, Kafrelsheikh University, Kafr El-Sheikh, Egypt Sthephanie Silva dos Santos Tavares Departamento de Engenharia Química, Instituto Militar de Engenharia, Rio de Janeiro, RJ, Brazil Neha Duhan Centre for Rural Development and Technology, Indian Institute of Technology Delhi, New Delhi, India James Oluwagbamigbe Fajemiroye Laboratory of Pharmacology of Natural and Synthetic Products, Institute of Biological Sciences, Federal University of Goiás, Goiânia, Brazil Mauricio Filippa Área de Química Física, Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Laboratorio de Investigación y Servicios de Química Física (LISeQF-UNSL), Laboratorio de Química Física, Facultad de Química, Bioquímica y Farmacia-Universidad Nacional de San Luis, San Luis, Argentina Shivani Gandhi Department of Pharmaceutics, SSR College of Pharmacy, Silvassa, Union Territory of Dadra Nagar Haveli & Daman Diu, India Tapan Kumar Giri Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India Atul Gupta Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, India Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India Xuebo Hu Lab of Drug Discovery and Molecular Engineering, College of Plant Science and Technology, Huazhong (Central China) Agricultural University, Wuhan, China Chuleui Jung Agricultural Science and Technology Research Institute Andong National University, Andong, Republic of Korea Department of Plant Medicals, Andong National University, Andong, Republic of Korea Seifu Juniedi Department of Applied Biology, Adama Science and Technology University, Adama, Ethiopia Rassoul Kadkhodaee Department of Food Nanotechnology, Research Institute of Food Science and Technology, Mashhad, Iran

Contributors

xvii

Ruckmani Kandasamy Centre for Excellence in Nanobio Translational Research (CENTRE), Department of Pharmaceutical Technology, University College of Engineering, Anna University BIT Campus, Tiruchirappalli, Tamil Nadu, India Shah Alam Khan National University of Science and Technology, Muscat, Sultanate of Oman Venkateshwaran Krishnaswami Centre for Excellence in Nanobio Translational Research (CENTRE), Department of Pharmaceutical Technology, University College of Engineering, Anna University BIT Campus, Tiruchirappalli, Tamil Nadu, India Ajay Kumar Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, India Government Pharmacy College, BRD Medical College Campus, Gorakhpur, India Nishant Kumar National Institute of Food Technology Entrepreneurship and Management, Sonipat, Haryana, India Leena Kumari Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India Lismet Lazo Instituto de Física Aplicada-CONICET-Universidad Nacional de San Luis, San Luis, Argentina Silvia Noelí López Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario – CONICET, Rosario, Argentina Maryam Mahfouzi Department of Food Nanotechnology, Research Institute of Food Science and Technology, Mashhad, Iran Jai Malik University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India Anita Jocelyne Marsaioli Instituto de Química, Universidade Estadual de Campinas, Campinas, SP, Brazil Simona Martinotti DiSIT- Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Alessandria, Italy Martin Masuelli Instituto de Física Aplicada-CONICET-Universidad Nacional de San Luis, San Luis, Argentina Área de Química Física, Departamento de Química, Facultad de Química, Bioquímica y Farmacia, Laboratorio de Investigación y Servicios de Química Física (LISeQF-UNSL), Laboratorio de Química Física, Facultad de Química, Bioquímica y Farmacia-Universidad Nacional de San Luis, San Luis, Argentina Ch. Jamkhokai Mate Department of Chemistry, Birla Institute of Technology, Mesra, Ranchi, India

xviii

Contributors

Cristina Matulewicz Universidad de Buenos Aires – Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Centro de Investigación de Hidratos de Carbono (CIHIDECAR), Buenos Aires, Argentina Facultad de Ciencias Exactas y Naturales, Departamento de Química Orgánica, Universidad de Buenos Aires, Buenos Aires, Argentina Marajá João Alves de Mendonça Filho Network Teaching and Learning Center, Department of Geography, State University of Goiás, Anapolis, Goiás, Brazil Eli José Miranda Ribeiro Junior Faculty of Inhumas, FacMais, Goiás, Brazil Sumit Mishra Department of Chemistry, Birla Institute of Technology, Mesra, Ranchi, India Mai Mostafa Polymer Chemistry Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt Deepak Mudgil Mansinhbhai Institute of Dairy & Food Technology (MIDFT), Mehsana, Gujarat, India Ashlin Munsamy School of Life Sciences, Westville Campus, University of KwaZuluNatal, Durban, South Africa Hosakatte Niranjana Murthy Department of Botany, Karnatak University, Dharwad, Karnataka, India Selvakumar Muruganantham Centre for Excellence in Nanobio Translational Research (CENTRE), Department of Pharmaceutical Technology, University College of Engineering, Anna University BIT Campus, Tiruchirappalli, Tamil Nadu, India Mohanraj Murugesan Centre for Excellence in Nanobio Translational Research (CENTRE), Department of Pharmaceutical Technology, University College of Engineering, Anna University BIT Campus, Tiruchirappalli, Tamil Nadu, India Murugan Muthuvel Department of Pharmaceutical Chemistry, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India Clarissa Marcelle Naidoo School of Life Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South Africa Yougasphree Naidoo School of Life Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South Africa Lubna Najam DAV(PG) College Muzaffarnagar, CCS University, Meerut, India Camilo J. Orrabalis Laboratorio. De Ingeniería de Materiales y Nanotecnología, Universidad Nacional de Formosa, Formosa, Argentina Vinod V. T. Padil Institute for Nanomaterials, Advanced Technologies and Innovation (CXI), Technical University of Liberec (TUL), Liberec, Czech Republic

Contributors

xix

Sonia Pahuja Swami Vivekanand College of Pharmacy, Patiala, Punjab, India Subhamay Panda Post-Graduate Department of Zoology, Banwarilal Bhalotia College, Asansol, India Shailendra Pandey Department of Pharmacy, SN Medical College, Agra, India Anka Trajkovska Petkoska Faculty of Technology and Technical Sciences, St. Kliment Ohridski University – Bitola, Veles, North Macedonia Milena Popova Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria Vipul Prajapati Department of Pharmaceutics, SSR College of Pharmacy, Silvassa, Union Territory of Dadra Nagar Haveli & Daman Diu, India Pratibha National Institute of Technology, Kurukshetra, Haryana, India Selene Rangel-Landa Instituto de Investigaciones en Ecosistemas y Sustentabilidad, Universidad Nacional Autónoma de México, Morelia, Michoacán, Mexico Elia Ranzato DiSIT- Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Alessandria, Italy Rayssa Ribeiro Departamento de Engenharia Química, Instituto Militar de Engenharia, Rio de Janeiro, RJ, Brazil Amitava Roy Department of Pharmaceutical Technology, University of North Bengal, Siliguri, India Salona Roy Department of Pharmaceutics, SSR College of Pharmacy, Silvassa, Union Territory of Dadra Nagar Haveli & Daman Diu, India Manoj Kumar Sagar Government Pharmacy College, BRD Medical College Campus, Gorakhpur, India Kalyani Sakure Rungta College of Pharmaceutical Sciences and Research, Kohka, Bhilai, India Prerna Sarup Swami Vivekanand College of Pharmacy, Patiala, Punjab, India Asmaa Sayed Polymer Chemistry Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt José Antonio Sierra-Huelsz People and Plants International, Bristol, VT, USA Munmun Kumar Singh Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, India Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India Sonia Singh Institute of Pharmaceutical Research, GLA University, Mathura, UP, India

xx

Contributors

Swati Singh Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, India Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India Mohit Singla Tezpur University, Tezpur, Assam, India Mohammad Sohail Akhtar School of Pharmacy, College of Pharmacy & Nursing, University of Nizwa, Nizwa, Oman Joy Ruby Violet Stephen Department of Geography, Queen Mary’s College (A), Chennai, India Jeseeta Suresh Centre for Excellence in Nanobio Translational Research (CENTRE), Department of Pharmaceutical Technology, University College of Engineering, Anna University BIT Campus, Tiruchirappalli, Tamil Nadu, India Sudeep Tandon Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, India Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India Thies Thiemann Department of Chemistry, Faculty of Science, United Arab Emirates University, Al Ain, Abu Dhabi, UAE Nandkishore Thombare Department of Chemistry, Birla Institute of Technology, Mesra, Ranchi, India Ignacio Torres-García Escuela Nacional de Estudios Superiores, Unidad Morelia, Universidad Nacional Autónoma de México, Morelia, Michoacán, Mexico Boryana Trusheva Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria Prabhat Kumar Upadhyay Institute of Pharmaceutical Research, GLA University, Mathura, UP, India Ram Swaroop Verma Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, India Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India A. Vetriselvi Department of Botany, Queen Mary’s College, Chennai, India R. Vijayalakshmi Department of Botany, Queen Mary’s College, Chennai, India Pranay Wal Department of Pharmacy, Pranveer Singh Institute of Technology, Kanpur, India Prashant Kumar Yadav Mission College of Pharmacy, Varanasi, India Guggalada Govardhana Yadav Department of Botany, Karnatak University, Dharwad, Karnataka, India

Part I Introduction to Gums, Resins, and Latexes

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of Plant Origin Hosakatte Niranjana Murthy

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Gums: Chemical Compositions, Properties, and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Chemical Compositions of Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Properties of Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Applications of Plant-Based Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Resins: Chemical Compositions and Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Oleoresins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Balsams . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Varnish and Lacquer Resins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Latex: Chemical Compositions and Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Chemical Constituents of Plant Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4 6 6 7 9 12 12 13 15 16 16 18 19

Abstract

Plant gums are natural polysaccharide polymers which are freely available in nature, eco-friendly, and nontoxic substances. They are superior compared to synthetic polymers because of their biocompatibility and biodegradability. Plant gums have food, cosmetic, pharmaceutical, biomedical, and industrial applications. Resins of plant origin have got several therapeutic uses and have been used in varied systems of medicine. Besides medicinal application plant resins have been used as industrial materials such as varnishes, printing inks, coloring materials, disinfectants, and perfumery materials. Plant latexes are natural biomaterials that contain a variety of phytochemicals such as alkaloids, terpenoids, phenolics, proteins, and enzymes. Antibacterial, antifungal, anthelmintic, cytotoxic, and insect-repellent properties are all present in these compounds. Latex is a natural rubber source as well as a source of industrial enzymes like proteases. H. N. Murthy (*) Department of Botany, Karnatak University, Dharwad, Karnataka, India © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_1

3

4

H. N. Murthy

The present review provides an overview of different sources, compositions, properties, and applications of plant gums, resins, and latexes. Keywords

Biomedical applications · Latexes · Oleoresins · Plant gums · Polysaccharides · Resins · Secondary metabolites

1

Introduction

Gums, resins, and latexes are natural plant products which are used since time immemorial by humans as medicine and industrial raw materials especially in food, cosmetics, pharmaceutical, textile, and paint industries. Gums, resins, and latexes are generally referred to as sap or exudates of plants [1]. In the past plant exudates such as gums and resins are used wrongly as synonymous words [2]. It was Langenheim [1] who has given better dimensions and definitions to gums, resins, latexes, and waxes in her book Plant Resins: Chemistry, Evolution, Ecology, and Ethnobotany. Gums are a complicated chain of hydrophilic polysaccharides made up of galactose, arabinose, and rhamnose that are generated during the gummosis process. Gum synthesis is aided by celluloses and hemicelluloses in the plant cell wall, and starch is also a source of gum synthesis. Gums are frequently generated traumatically, as a result of microbial infection, insect attack, or mechanical injury, according to plant anatomists [3]. However, according to the opinion of some other researchers gummosis is a natural process. In some plants, gum is created by a special set of cells known as undifferentiated parenchyma cells, whereas in other plants, cell wall breakdown leads to the formation of a cavity, which contribute to the formation of gum [1]. Gum, generated only from the lamella of secondary cell walls, can fill xylem channels; gums can also form in the bark tissues, as seen in the Acacia species (gum arabic). To avoid confusion, it is critical to know the difference between gums and mucilages. Galactose, arabinose, xylose, rhamnose, and galacturonic acid are water-soluble complex acidic or neutral polysaccharide polymers with a high molecular weight that make up plant mucilages. Mucilages are chemically identical to gums and can be found in solitary secretary cells, canals, cavities, epidermal cells, and trichomes (Table 1). Gums are made by a variety of plant species, both natural and cultivated for gum extraction. Acacia gum, Indian tragacanth gum, tragacanth gum, and ghatti gum are some of the exudate gums (Table 2). Guar gum, locust bean gum, tara gum, and other seeds produce seed gums, which are extracted from the endosperm region of many seeds (Table 3). Malabar spinach mucilage and okra mucilage are examples of mucilage polysaccharides (Table 4). Plant resins are lipid-soluble mixtures of volatile and nonvolatile terpenoid and/or phenolic secondary compounds released in specialized structures within or on the surface of plants that can influence ecological interactions [1]. Oils are used to describe a variety of resin components. Essential oils are made up of mono- and

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of. . .

5

Table 1 Characteristics of resins, gums, oils, waxes, and latex [1] Resins

Primary components Terpenoids and phenolic compounds

Solubility Lipid soluble

Gums

Polysaccharides

Mucilages

Polysaccharides

Water soluble Water soluble

Oil (fats)

Fatty acids and glycerol

Waxes

Fatty acids esterified with long-chain alcohols The complex mixture may include terpenoids, phenolic compounds, proteins, carbohydrates, etc.

Latex

Lipid soluble Lipid soluble Lipid soluble

Secretory tissue Canals, pockets, cavities, trichomes, and epidermal cells Cavities Idioblasts, epidermal cells, trichomes, ducts, and cavities None Unspecialized epidermal cells Laticifers

Table 2 List of some natural exudate gums Gum Acacia gum Acacia gum Indian tragacanth gum Tragacanth gum

Ghatti gum

Source Acacia senegal (L.) Wild Acacia seyal Delile [syn.Vachellia seyal (Delille) P.J.H. Herter] Sterculia urens Roxb.

Family Fabaceae Fabaceae

Commercial name Gum arabic Talha gum

Malvaceae

Gum karaya

Astragalus gummifer Labill. Astragalus microcephalus Willd. Astragalus kurdicus (Boiss.) Podlech Astragalus gossypium Fisch. Anogeissus latifolia Wall. Anogeissus acuminata (Roxb. ex DC.) Wall. ex Guill. & Perr. Anogeissus bentii Baker Anogeissus dhofarica A.J. Scott

Fabaceae

Gum tragacanth

Combretaceae

Ghatti gum

Table 3 List of some seed-based gums Gum Guar gum Locust bean gum Tara gum

Source Cyamopsis tetragonoloba (L.) Taub. Ceratonia siliqua L.

Family Fabaceae Fabaceae

Commercial name Guar gum Carab gum

Tara spinosa(Feuillee ex Molina) Britton & Rose (synonym: Caesalpinia spinosa L.)

Fabaceae

Tara gum

6

H. N. Murthy

Table 4 List of some mucilage polysaccharides Gum Malabar spinach mucilage Okra mucilage

Source Basella alba Linn. Abelmoschus esculentus (L.) Moench

Family and parts used Basellaceae, aerial parts Malvaceae, fruits

sesquiterpenes; cedarwood oil is made up of resins from the Cupressaceae family with a lot of sesquiterpenes, and copaiba oil is made up of resins from the Leguminosae family. Conifers, dicotyledonous, and monocotyledonous angiosperms all generate resins [1]. Resinous oils should be distinguished from oils, fats, and waxes. The synthesis of fatty acids from carbohydrates is followed by the coupling of these fatty acids with glycerol via enzymatic action to generate triglycerides/esters, which are natural oils and fats. Waxes are a lipid-soluble mixture of fatty acid alcoholic esters, straight-chain alkanes, long-chain ketones, and aldehydes. The cuticle of leaves, stems, and fruits is made up of waxes, which are a component of epidermal cells. Latexes are thick, creamy white, a milky emulsion in a certain group of plants belonging to Euphorbiaceae, Convolvulaceae, and others which are produced in specialized cells called laticifers. Latexes are composed of terpenoids, proteins, fatty acids, carbohydrates, tannins, alkaloids, and minerals. There are plants belonging to 40 families, and more than 20,000 species are reported to produce latexes [4].

2

Gums: Chemical Compositions, Properties, and Applications

2.1

Chemical Compositions of Gums

Gums are polysaccharides that have glycosidic connections that connect various monosaccharide units [5]. Cassia, locust bean, and tara gums, for example, have only two monosaccharide units, as shown in Table 5. These are termed as galactomannans because their molecular backbone has a larger proportion of mannopyranosyl and galactopyranosyl units [6]. The degree of solubility and thickening ability of galactomannans are regulated by their structure, degree of branching, and mannose/galactose ratio [7]. –OH, -C¼O, -C-O, -C-H, and -CH2, -COO, -C-C-O, and –C-O-C are the functional groups found in gum polysaccharides, according to several research [8–11]. Carbohydrates made up 43.52–98.46% of the principal chemical components of natural plant gums. It has been noted that powdered gums have a high moisture content (0.71–17.50%). Significant variations in fat content (0–23.4%) have been documented, with both saturated and unsaturated fatty acids being present. The concentration of gum protein has been shown to range from 0.30–22.75% [11]. Gums’ emulsifying properties are due to the nature of proteins and fatty acids. At various quantities, Vinod et al. [12] found alanine, proline, glycine, leucine, methionine, threonine, tyrosine, tryptophan, aspartic acid, and glutamic acid in kondagogu gum (between 3.8 and 64.2%). Gum ash percentage

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of. . .

7

Table 5 Properties of some natural exudate gums Properties Moisture (%) Carbohydrate (%) Protein (%) Fat (%) Ash (%) Main carbohydrate type Molecular weight (kDa) Monosaccharide composition

Tragacanth gum 8.8–12.9 84.0–84.8

Acacia gum 6.49 87.88

Karaya gum 10.12–16.5 77.98

Ghatti gum 8.08–13.42 78.36–89.67

2.25 0 1.81 Galactan type

1.2–1.63 1.0–2.0 5.2–5.7 Galactan type

0.3–3.8 0 0 Galactan type

4.18–4.34 0 1.14–2.35 Galactan type

250–600

9500

840

12,000

Glactorse, arabinose, rhamnose, glucuronic acid, 4-Omethylglucuronic acid

D-galactose, L-rhamnose, D-galacturonic acid

D-galactose, L-fucose, D-xylose, L-arabinose, L-rhamnose

L-arabinose, D-galactose, D-mannose, D-xylose, D-glucuronic acid

has been observed to range from 0.18–8.46%. Minerals such as calcium, magnesium, manganese, zinc, and lead have been discovered in plant gums such as acacia and guar gum [13, 14].

2.2

Properties of Gums

Gums’ powder properties, shape, and color, as well as their physicochemical qualities, interfacial characteristics, viscosity and pH, and rheological characteristics are all crucial in the food and pharmaceutical industries. Powder factors such as bulk density, tapped density, angle of response, compressibility index, and Hausner’s ratio influence the flow behavior of milled material [15]. Natural gums have bulk and actual density values ranging from 0.16–0.84 g/cm3 and 0.20–1.67 g/cm3, respectively, suggesting particle packing and composition behavior. The angle of response is another important statistic to consider when designing equipment. It has something to do with the interparticulate friction of the ground material. When designing hoppers, the angle of inclination must be greater than the angle of repose to ensure gravity flow of particles. Natural gums’ angle responses ranged from 22.35–37.20 . The compressibility index and Hausner’s ratio are calculated using the bulk and tapped densities. These are intertwined elements influenced by the size, shape, surface area, moisture content, and cohesiveness of the material. Natural gums’ compressibility index and Hausner’s ratio ranged from 16.33–28.42 and 0.15– 1.39, respectively [11].

8

H. N. Murthy

Powdered natural gums are used in a variety of sectors due to their morphology and color. Although there are significant variances between gums from different sources, irregular granular features are recognized in all of them. Guar gum is distinguished by its irregular shape, which is discrete, smooth, elongated, and free of defects [11]. Almond and albizia exudate gums, for example, have smooth surfaces with or without pores, but Dalbergia sissoo exudate gum has a rough surface [17]. Locust bean and grewia gum particles, on the other hand, are mostly fibrous, with a variety of forms and sizes [16, 18]. A few studies have documented the color of various exudate gums, with lightness values ranging from 81.0–85.05 in most purified gums [19–21]. However, the lightness levels of various plant gums may be more or lower than the average figure provided above. Water absorption and swelling are two essential physicochemical features of plant gums. Because of their hydrophilic locations, plant gums’ water absorption capability is researched in environments where water is scarce [22]. Using these parameters, plant gums can be employed as thickeners and stabilizers in a variety of food and nonfood formulations. Cissus, fenugreek, acacia, flax, and malva gums have water absorption capacities ranging from 1.80–81.08 g/g dry weight [23–25]. Plant gums grow by swallowing and entangling a large number of water molecules in their chains and branches [26]. The ratio of the increase in weight or volume following water absorption to the original dry matter weight or volume is used to compute the swelling index of gums. The swelling indexes of corn, bael, cashew, and arabic gums were determined to be 1.51, 4.2, 3.19, and 5.68 respectively. The pH of the medium, according to research, has a considerable impact on the swelling index of gums. Corn gum, for example, swells the most at an acidic pH of 1.2, then rapidly shrinks when the pH is raised to neutral (7.4). Plant gums’ interfacial properties describe how they behave at the oil-water or air-water contact. Because gums are hydrophilic, they are not expected to have interfacial properties. However, they are commonly thought to have surface activity and play a significant role in the creation and stability of emulsions and foams. Plant gums improve the viscosity of the aqueous continuous phase, slowing the mobility of the dispersed media and preventing coalescence [27, 28]. Exudate gums, in particular, are emulsifiers and stabilizers [29, 30]. The amount of oil that a gum can maintain at a given concentration in an aqueous medium for 2 weeks without phase separation is known as its emulsion capacity [31]. Plant gums like acacia, apricot, and karaya have been demonstrated to have oil binding capabilities ranging from 0.58–1.21 g/g dry matter [22, 23, 25]. Plant gums froth and reduce interfacial tension, indicating that they are active on the surface. The presence of multiple gums has been discovered to lessen the surface tension at the interface of two immiscible phases. This decrease normally ranges between 60 and 42 mN m1 [32–34]. Apricot and karaya gums have a 35.33% foaming capacity, guar gum has a 30.67% foaming capacity, and locust bean gum has a 42.67% foaming capacity [16, 20]. The solubility of plant gums effects food applications such as emulsification, foaming, stability, thickening, and intrinsic viscosity [35]. The structure, molecular weight, and solvent type of plant gums determine their solubility [35]. Gums with a lower molecular weight and a higher galactose substitution within the chain dissolve

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of. . .

9

in water more easily. Plant gums dissolve in water and increase in viscosity, allowing them to thicken liquids to incredible depths. On the other hand, all gums do not significantly enhance the viscosity of water. It is worth noting that higher viscosity gums are known to be of greater quality than lower viscosity gums [36]. Inherent viscosity values for gum dispersions of fenugreek, guar, locust bean, apricot, and others range from 0.10–16.94 dL/g, according to various research findings [11]. Rheology is the study of how a material flows (liquid) and/or deforms (solid) in response to an external force. Natural gums have been extensively studied and recorded due to their importance in determining the consistency, mouthfeel, and ease of industrial handling of the product [37]. Differences in storage modulus and loss modulus, which are typically related with complicated viscosity, have been determined for rheological characterization of plant gums. Plant gums have different rheological properties due to differences in chemical structure.

2.3

Applications of Plant-Based Gums

2.3.1 Applications of Gums in the Food Industry Nontoxic, biodegradable, and cost-effective plant-based gums including gum acacia, gum ghatti, and gum tragacanth are “generally recognised as safe” by the US Food and Drug Administration. As a result, plant-based gums are used as a food additive in the food industry at concentrations of 0.3–1.3% (Fig. 1). For example, tragacanth gum is used as a fat substitute in nonfat yoghurt, white cheese, and reduced-fat sausage, as a stabilizer in fermented milk drinks and ice cream mixes, and as a binding enhancer in restructured mutton chops [38]. Plant-based gums are also used in the food sector as a polysaccharide food coating. When used as a food coating, tragacanth gum, for example, inhibits respiration, dehydration, and enzymatic browning. Tragacanth gum is also used as a thickening agent to improve viscosity and facilitate food emulsification [39]. Foods have also been preserved by using natural edible and biodegradable films made from natural gums [39]. 2.3.2 Pharmaceutical and Cosmetic Applications of Gums Gums from acacia, karaya, tragacanth, and gatti have been used as emulsifiers and suspending agents in a variety of medicinal formulations, including creams, emulsions, and tablet formulations (Table 6, Fig. 1) [40–47]. Gum arabic and tragacanth gums are used in cosmetics such as creams and lotions because of their emulsifying and stabilizing qualities [41, 42, 46, 48]. 2.3.3 Applications of Gums in Overcoming Environmental Pollution Toxic colors and heavy metals infiltrate sewage water, posing a serious environmental concern. Textile dyes and heavy metals have been removed from sewage water and aqueous media using a variety of adsorbents, including biobased polymers [38]. Masoumi and Ghaemy [49] developed a gum-g-polyamidoxime nanogel based on tragacanth gum for the removal of cadmium, zinc, cobalt, and chromium ions from aqueous solution. Saharaei et al. [50] developed a nanocomposite method

10

H. N. Murthy

Fig. 1 Applications of plant gums

Table 6 Pharmaceutical applications of some natural exudate gums Gum Acacia gum Karaya gum Tragacanth gum Ghatti gum

Applications Binder in tablets, emulsifying agent, emollient in cosmetics, and suspending agent Bulk laxative, dental adhesive, emulsifying agent, mucoadhesive, suspending agent, and sustaining agent in tablets Emollient in cosmetics, emulsifying agent, suspending agent, and sustained-release agent Binder, emulsifier, and suspending agent

Reference [41, 42] [43, 44] [45, 46] [47]

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of. . .

11

for removing crystal violet and congo-red dyes from polluted water, as well as heavy metals like lead and copper. As a result, plant gum–based hydrogels are useful chemicals for purifying water and removing heavy metal contamination (Fig. 1).

2.3.4 Synthesis of Gum-Based Nanofibers and Their Utilization Electrospinning is a process for making nanofibers with high surface area-to-volume ratios in the micrometre to nanometer size range [51]. Plant-based gums like tragacanth and acacia have been used to make nanofibers in pure form or by combining them with synthetic materials like polyvinyl alcohol, polylactic glycolic acid, and poly L-lactic acid to make homogenous nanofibers [52, 53]. These nanofibers have been used in wound dressing applications (Fig. 1). Nanofibers made from curcumin (3% w/v) are good for mending hyperplastic scars, carcinomas, and burn wounds, for example. Similarly, aloe vera extract–loaded scaffolds made of tragacanth gum and poly-e-caprolactone showed excellent wound healing and antiinflammatory activities [54]. The application of tragacanth gum for nanoencapsulation of different compounds on cotton fabrics increases textile washability and rubbing resistance [55]. Antibiotic and antimicrobial chemicals are loaded into tragacanth-based polymers as an alternate approach for delivering antimicrobial action. For example, peppermint oil–loaded tragacanth nanofibers shown antibacterial action against Staphylococcus aureus and Escherichia coli [56].

2.3.5

Biomedical Applications of Plant-Based Gums

Drug Delivery In the delivery of medicines, biopolymers are significantly more effective than synthetic compounds (Fig. 1). Regulated release is a way of distributing pharmaceuticals over a longer length of time, spanning from hours to days, in a regulated manner. A pH-responsive amphiphilic co-network hydrogel was created by combining tragacanth gum and a synthetic copolymer, poly(methyl methacrylate-alt-maleic anhydride)-g-polycaprolactone. In vitro drug release testing was performed on this hydrogel. The release of quercetin (a plant flavonol) as a model drug was influenced by the network topology of the hydrogel and ranged from 40–80% after 7 h [57].

Wound Healing For wound healing, tragacanth gum has been used to make hydrogels and composites in the form of creams/gels. For wound healing in rabbits, creams made from tragacanth gum (6–9%) and a mixture of water and glycerine (4:1%) were used as the carrier. The cream containing 6% tragacanth gum was shown to have the optimum healing effect [58]. Similarly, nanofibers made from curcumin-loaded tragacanth gum improved wound healing [59]. When compared to control wounds at the same time points, tragacanth gum-based films, hydrogels, and nanofibers, as well as other polymers, displayed improved wound healing ability [60, 61].

12

H. N. Murthy

Bone Tissue Engineering Adipose-derived mesenchymal stem cells were grown on uncoated tissue culture plates, plates coated with collagen-based hydrogels, and plates coated with tragacanth-based hydrogels [62]. Those cultivated on tragacanth gum hydrogels showed the highest alkaline phosphatize activity and extracellular mineralization when compared to stem cells cultured on collagen hydrogels or uncoated tissue culture plates. These findings indicate that tragacanth gum hydrogel could be used in orthopaedic applications to increase cell adhesion, proliferation, and oestrogenic differentiation.

3

Resins: Chemical Compositions and Uses

Plant resins are a lipid-soluble mixture of volatile and nonvolatile terpenoid and/or phenolic chemicals that are secreted in specialized structures within or on the surface of the plant and have possible ecological relevance. Terpenoid resins make up the majority of commercially utilized internally generated resins, though phenolic resins are also important. Components of phenolic resin found on the surface of plant organs have been employed in medicine [1]. Conifers, dicots, and monocots are examples of seed-bearing plants that produce resin. Endogenous canals (e.g., Agathis and Anacardium), endogenous cells, or pockets/cysts (Abies, Commiphora, and Cupressus), endogenous laticifers (Calophyllum and Convolvulus), or exogenous glandular trichomes or epidermal cells (Mimulus and Populus) generate resins [1].

3.1

Oleoresins

Oil resins, often called oleoresins, are terpenoid resins with a fluid consistency. They have a higher ratio of volatile to nonvolatile terpenes. The volatile fraction is made up of mono- and/or sesquiterpenes, also known as essential oils. Diterpenes are the principal elements of nonvolatile fractions in conifers and most angiosperms. Longleaf pine and slash pine were the two pine species used to make turpentine and rosin. Loblolly pine, short-leaf pine, pond or pitch pine, ponderosa pine, pinyon pine, sugar pine, and lodgepole pine are all used to create turpentine and rosin in the USA. Steam distillation in a copper still evaporates crude oleoresin obtained from injured trees. After the turpentine has been distilled off, molten resin remains in the still bottoms. Turpentine is used to thin oil-based paints, make varnishes, and serve as a raw material in the chemical industry. Rosin is a solid form of resin made by vaporizing the volatile liquid terpene components of fresh liquid resin. It is semitransparent and comes in a variety of colors ranging from yellow to black. Rosin is brittle at normal temperature, but it melts at a higher temperature. It is mostly made up of rosin acids, particularly abietic acid. Rosin is used in a variety of products, including printing inks, varnishes, adhesives, soaps, paper sizing, and sealing wax. Rosin is also used in pharmaceuticals and chewing gum as a glazing agent. Rosin is

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of. . .

13

used in a variety of plasters and ointments (Fig. 2) [1]. Cedrus, Juniperus, and Cupressus produce cedarwood oil, which is made up of volatile heartwood sesquiterpenes such as ß-cedrene, thujopsene, cuparene, cedrol, and widdrol. In fragrance compounding, cedarwood oil is used to smell soaps, room sprays, and disinfectants [63]. Wood oil is a fluid resin derived from a variety of Dipterocarpus and Anisoptera species found in Southeast Asia. Copaiba is a Copaifera species–derived oleoresin (Fabaceae). ß-caryophyllene, copaene, ß-selinene ß-bisabolene, -bergamotene, and -cadinene are sesquiterpene hydrocarbons found in this oleoresin. Copaiba resin is utilized in the manufacture of medical cosmetics (Fig. 2) [64].

3.2

Balsams

Balsam is a mixture of plant-specific resins and essential oils, which may contain resin acids, esters, or alcohols. Balsams are not as fluid as oleoresins, although they are soft and flexible at first. True balsams, according to some experts, are limited to phenolic resins containing principally cinnamic and benzoic acids [65]. Balsams have long been used as wound salves, as well as in fragrance, cosmetics, and incense [1]. Balsam fir (Abies balsamae, Pinaceae), a widely dispersed conifer in North America, is used to make Canada balsam. When dried, Canada balsam contains 20%

Fig. 2 Applications of plant resins

14

H. N. Murthy

volatile mono- and sesquiterpenes and 80% nonvolatile diterpenes, resulting in a hard, translucent layer. This film has a high refractive index that is comparable to glass, making it ideal for microscopic operations. It is used as an antiseptic salve for wounds, cuts, and burns, as well as treating colds, consumption, and as a laxative [66]. The leguminous tree Myroxylon balsamum, which grows naturally in South America, is used to make tolu balsam. This resin, which contains phellandrene as well as alcohols like guaiacol and cresol, is utilized in the perfumery business, as well as in medicine as cough syrup and topical applications. Myroxylon balsamum var. pereirae (syn. M. pereirae) grows primarily in Central America and is used to make Peru balsam. Cinnamyl cinnamate (or styracin), benzyl cinnamate (or cinnamein), and benzyl benzoate are some of the volatiles found in it [67]. Numerous mono-, sesqui-, and triterpenoid compounds, as well as major phenolic compounds, were reported by Wahlbert et al. [68]. In the fragrance industry, this resin is employed (Fig. 2). Asthma, catarrh, rheumatism, diarrhoea, and hemorrhoidal discomfort are all treated with it [69]. Storax is a resin derived from numerous Liquidambar species found across Turkey. It is made up of styrene, monoterpenes, and ß-pinene, phenolic compounds including cinnamyl alcohol and cinnamon acid, and isomers of 2,3-butanediol and 3-pheylproponol, as well as isomers of 2,3-butanediol and 3-pheylproponol [70]. American storax, sometimes known as sweet gum, is a copal resin that comes from the Liquidambar styraciflua tree. Cinnamic acid is free and esterified as cinnamyl cinnamate (styracin) and phenylpropyl cinnamate in this resin. Vanillin, borneol, and bornyl acetate, as well as various levels of styrene, are also present. In the chemical production of rubber and plastics, styrene is used. This resin is also utilized in the tobacco business as a flavoring agent in cigarettes [67]. Asian styrax, commonly known as styrax, benzoin, and gum benzoin, is a resin derived from Styrax species (Styrax benzoin, S. paralleloneurus, and S. tonkinensis). Styrax benzoin (Sumatra benzoin) is an evergreen tree native to Sumatra, the Malay Peninsula, and western Java. Sumatra benzoin is made up of coniferyl cinnamate, cinnamyl cinnamate (styracin), coniferyl benzoate, free cinnamic acid, and benzoic acids. Styrene, vanillin, and benzaldehyde are also present. Benzoin has long been used as an antiseptic, parasiticide, and expectorant stimulant [71]. In the flavor and fragrance sectors, it is also employed. Elemis are oleoresins found in Canarium, Dacryodes, Protium, Bursera (Burseraceae), Calophyllum and Symphonia (Clusiaceae), and Amyris (Rutaceae) species. Sesquiterpenes and a significant number of triterpenes make up these resins, which are more viscous than oleoresins, semisolid, and extremely aromatic. ß-amyrins, as well as elemi acids, were discovered in Manila elemi, (Canarium luzonicum) (which is also called old world elemi). Hard elemi, also known as Brazilian elemi, is a resin produced from Protium icicariba and P. heptaphyllum species. These resins have a strong scent and are used to make incense, caulk, and varnishes (Fig. 2, Table 7) [72]. Frankincense (archaic meaning “choice incense”), also known as gum or olibanum oil, is a resin derived from the Boswellia species (Burseraceae). The resin contains more than 20 monoterpenes and 28 sesquiterpenes [73], making it a complex blend of volatile chemicals. Frankincense is classified as gum resin because it contains a small amount of polysaccharides generated from

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of. . .

15

Table 7 List of some natural resins Resin Frankincense Indian frankincense Dammar White dammar Black dammar

Source Boswellia sacra Flueck. Boswellia serrata Triana & Planch. Dipterocarpus kerrii King Vateria indica L. Canarium strictum Roxb.

Family Burseraceae Burseraceae

Commercial name Oblibanum Indianolibanum

Dipterocarpaceae Dipterocarpaceae Burseraceae

Keruing oil White dammar Black dammar

epithelial cells of secretory structures. The therapeutic qualities of Indian frankincense (salai guggal), which is derived from Boswellia serrata (salai guggal), are well known. It is used to treat inflammatory disorders including rheumatoid arthritis and gout in the old Ayurvedic medical system. There have been reports of mono-, di-, and triterpenes, with various triterpenoid boswellic acids being identified as the biological active principle [74]. Another resin derived from Commiphora species found in Southern Arabia (e.g., Yemen and Oman) and Northeastern Africa is myrrh (Somalia, Ethiopia, and Sudan). Myrrh is made up of numerous terpenoids and is used to make incense and perfume. Antipyretic, antibacterial, stimulant, mouthwash, and stomach disorders are all common uses for this resin in Arabian medicine [67, 75]. Commiphora wightii is a drought- and salinity-resistant little tree native to arid regions of Arabia, Pakistan, India, and Bangladesh; the resin is known in India as guggal and is widely used as incense, a fixative in perfumery, and has been extensively explored for medical purposes [76]. Bursera is a resin derived from a variety of Bursera plants found in Central America. Mono-, sesqui-, and diterpenes, as well as a minor amount of phenylpropanoids, make up Bursera [77]. Bursera is used to make incense, as well as glueing, binding pigment, chewing for tooth difficulties, and filling dental cavities (Fig. 2) [78].

3.3

Varnish and Lacquer Resins

Dammar, sandarac, mastic, acaroids, and hard copal are all used as fragrances. Copal resins are the strongest and most durable of these varnishes, whereas dammar is a more clear varnish. Acaroids are used for metal and leather coatings, while sandarac is utilized for metal and paper coatings (Fig. 2). Dammar is a resin derived from various Dipterocarpaceae and Burseraceae genera [79]. Dammars derived from Shorea and Hopea species primarily contain tetracyclic dammarane series chemicals, as well as pentacyclic ursolic acids and related aldehydes [80]. Dammar is made up of sesquiterpene hydrocarbons such as copaenes, ß-caryophyllene, and ß-element, as well as the triterpene shoreic acid, according to Bisset et al. [81]. Dammars are employed as varnishes and in paintings, and experimental data suggests that dammar hydrocarbons could be employed in the petroleum sector [82]. Sandarac is a resin derived from several Cupressus species. African sandarac is made from

16

H. N. Murthy

Tetraclinis articulata (syn. Callitris quadrivalvis), whereas Australian sandarac is made from several species of Callitris. Polymerizable communic acid, sandaracopimaric acid, and a minor fraction of labdanoid diterpenoids are found in African sandarac. Metal, leather, and paper are all varnished with sandarac resin. It is also utilized to fill teeth (Fig. 2) [83]. Mastic is a resin produced by the Pistacia lentiscus and other Pistacia species found in Portugal, Spain, Greece, Syria, Israel, Morocco, and Tunisia. Mastic is a tepenoid resin made up of the acids moronic, oleanonic, masticadienoic, masticadienonic, and oleanolic [84]. Mastic is used to make varnishes, paints, surgical adhesives, and plastic surgery (Fig. 2) [85]. Acaroid is a resin derived from the endemic Australian grass tree Xanthorrhoea species (Xanthorrhoeaceae). Grass tree gum, black boy gum, and yackha gum are some of the other names for it. Benzoic and cinnamic acids are abundant in resin. Hydroxyland methoxyflavonone derivatives, as well as cinnamyl alcohol and para-coumaric acid, were found by Birch and Dahl [86]. In varnish, acaroid resin is utilized. Leguminous copals are resins from the West African plants Daniellia, Gossweilerodendron, Guibourtia, Oxystigma, and Tessmannia, as well as Colophospermum in southern Africa, Hymenaea in East Africa and the Americas, and Copaifera in West Africa and the Americas. Varnishes contain these resins. The resins obtained from Agathis species (Araucariaceae), the conifer with the most tropical distribution, are known as araucarian copals. Varnishes made from araucarian copals are very popular. Lacquers are natural varnishes made from liquid resins that are applied directly to the varnished surface without the need of a solvent or drying agent. Toxicodendron vernicifluum (syns. Rhus verniciflua, R. vernicifera, and T. verniciferum) belongs to the Anacardiaceae family and is used to make Chinese and Japanese lacquers. Urushiol gum is a resin made up of pentadecylcatecols and phenolics.

4

Latex: Chemical Compositions and Applications

Latexes are exudates produced by the a leticifer canal structure, which is made up of highly elongated cells that expand along with the plant. Latex was accumulated in the vacuoles of laticifer cells [87]. Leticifers can be found in the stems, petioles, leaves, and roots of plants. Latex is often a nontransparent white sap with a distinguishing hue in some situations.

4.1

Chemical Constituents of Plant Latex

Latex contains alkaloids, terpenoids, cardenolides, rubber, phenolics, furanocoumarins, and starch, in addition to proteases, oxidases, lectins, chitinbinding proteins, chitinases, glucosidases, and phosphatases [87]. Chemical components found in latexes (Fig. 3) have been linked to pharmacological activities such as anticancer, antibacterial, analgesic, antioxidant, and antidiabetic effects [88, 93].

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of. . .

17

Fig. 3 Biological activites of latexes

4.1.1 Alkaloids Alkaloids are significant secondary metabolites found in the latex of Apocynaceae, Campanulaceae, Moraceae, and Papaveraceae plants, among others. Alkaloids are nitrogen-containing alkaline chemicals with a ring structure that are made from amino acids including tyrosine, tryptophan, ornithine, and phenylalanine. Alkaloids are poisonous chemicals that play a crucial part in the immune system’s defense against microorganisms and herbivores. They have also been shown to have anticancer, antihypertensive, antimalarial, and neuroprotective properties [89]. The latex of the opium poppy contains up to 5% alkaloids. Morphine, papaverine, and codeine are opium alkaloids with substantial pharmacological activity [90]. Morphine, for example, is used as an analgesic, papaverine is used as an antispasmodic, and codeine is used as a sedative and cough suppressant [91]. 4.1.2 Terpenoids Hemiterpenes (C5), monoterpenes (C10), sesquiterpenes (C15), diterpenes (C20), sesterterpenes (C25), triterpenes (C30), and tetraterpenes (C40) are isoprenoids generated from isoprene units (C5). Monoterpenes, sesquiterpenes, and triterpenes are found in the latex fig (Ficus carica) [61]. Jeivad et al. [62] extracted lupeol esters (triterpenoid compounds) from the latex of the fig, notably lupeol acetate and lupeol palmitate, which were cytotoxic against hepatocellular cancer. The latex of the fig contains a variety of volatile chemicals [92] which could be employed as flavoring agents in the perfumery and cosmetic industries. Rubber is a terpenoid molecule made up of a cis-1,4-siprene polymer found in the latex of many plant species. Some of the most important rubber-producing plants include Hevea brasiliensis (44.3%), Ficus species (15–30%), Alstonia boonei (15.5%), and Parthenium argentatum

18

H. N. Murthy

(8%). Natural rubber is used in almost 40,000 products, including tires, medical equipment, surgical gloves, and a variety of engineering and consumer goods [94].

4.1.3 Phenolics The phenolic compounds are a large group of secondary metabolites found in latexes that are involved in the defense mechanism. Simple phenols, phenolic acids, flavonoids, xanthones, stilbenes, and lignans are the most common types of phenols [95]. Several phenolics were found in the latex of fig [92], including caffeic acid, 3,4-dihydroxybenzoic acid, ß-coumaric acid, luteolin, and ferulic acid. Aref et al. [96] revealed in vitro cytotoxic and antiviral effects of latex isolated from figs, and these activities were attributed to phenolics contained in the latex. Traditionally, the latex of the cluster fig (Ficus racemosa) has been used to make aphrodisiac medications to promote fertility and to treat cholera and mumps [97], and the qualities are attributed to many phenolic chemicals found in the latex. 4.1.4 Latex Proteins Proteases, protease inhibitors, oxidases, lectins, and chitinases are among the proteins found in plant latex, and they play an important part in defensive mechanisms [87]. Cysteine proteases have been found in Caricaceae, Moraceae, and Apocynaceae latex [98], as well as serine proteases in Moraceae, Apocynaceae, and Convolvulaceae latex [87]. Many proteases derived from the latex of various plants have been shown to be effective in the treatment of bleeding and wounds [99].

5

Conclusions

Plant-based gums are natural polysaccharide polymers that excel in terms of simplicity of use, environmental friendliness, and toxicity. Plant resins, on the other hand, are a mixture of volatile and nonvolatile terpenoid and/or phenolic compounds produced by specific structural elements. Secondary metabolites found in plant latex include alkaloids, terpenoids, cardenolides, rubber, phenolics, furanocoumarins, and starch, as well as proteases, oxidases, lectins, chitin-binding proteins, chitinases, glucosidases, and phosphatases. Plant gums are used to make suspending, emulsifying, gelling, and stabilizing agents. Gums can be found in a variety of industries, including food, textiles, cosmetics, and pharmaceuticals. Plant-based resins are used in medicine as well as industry. Bioactive compounds found in plant latex are essential in the pharmaceutical business. They also provide vital industrial resources such as enzymes and natural rubber. More research is needed in the realms of natural gums, resins, and latexes, particularly in the areas of exploration, collection, characterization, and application. Natural gum-based biomaterials have a lot of potential in the domains of tissue engineering and regenerative medicine. Future research could focus on molecular and structural factors, as well as the ecological implications of plant latexes. Product development based on plant-based natural gums, resins, and latexes is also crucial, given the increased demand for natural components.

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of. . .

19

References 1. Langenheim JH (2003) Plant resins: chemistry, evolution, ecology and ethnobotany. Timber Press, Portland 2. Hills WE (1987) Heartwood and tree exudates. Springer, New York 3. Fahn A, Werker E, Ben-Tzur P (1979) Seasonal effects of wounding and growth substances on development of traumatic resin ducts in Cedrus libani. New Phytol 82:537–544 4. Lewinsohn TM (1991) The geographical distribution of plant latex. Chem Aust 2:64–68 5. Mirhosseni H, Amid BT (2012) A review study on chemical compositions and molecular structure of newly plant gum exudates and seed gums. Food Res Int 46:387–398 6. Lazaridou A, Biliaderies CG, Izdorczyk MS (2000) Structural characterization and rheological properties of locust bean galactomannans: a comparison of samples from different carob tree plantations. J Sci Food Agric 81:68–75 7. Singthong J, Ningsnond S, Cui SW (2009) Extraction and physicochemical characterization of polysaccharide gum from Yanang (Tiliacora triandra) leaves. Food Chem 114:1301–1307 8. Jindal M, Rana V, Kumar V, Singh RS, Kennedy JF, Tiwary AK (2013) Sulfation of Aegle marmelos gum synthesis, physico-chemical and functional characterization. Carbohydr Polym 92:1660–1668 9. Singh AK, Selvam RP, Sivakumar T (2010) Isolation, characterization and formulation properties of a new plant gum obtained from Mangifera indica. Int J Pharmaceut Biomed Res 1:35–41 10. Petrea P, Amarioarei G, Apostolescu N, Puitel AC, Ciovica S (2013) Some aspects of the characterization of vegetable gums: Prunus persica (plum) and Prunus dometica (cherry). Cellul Chem Technol 47:369–375 11. Hamdani AM, Wani IA, Bhat NA (2019) Source, structure, properties and health benefits of plant gums: a review. Int J Biol Macromol 135:46–61 12. Vinond VTP, Sashidhar RB, Sarma VUM, Raju SS (2010) Comparative amino acid and fatty acid compositions of edible gums kondagogu (Cochlospermum gossypium) and karaya (Sterculia urens). Food Chem 123:57–62 13. Lelon JK, Jumba IO, Keter JK, Chemili W, Pdipr FDO (2010) Assessment of physical properties of gum Arabic from Acacia senegal verities in Baringo District, Kenya. African J Plant Sci 4:95–98 14. Cui W, Mazza G (1996) Physicochemical characteristics of flaxseed gum. Food Res Int 29:387– 402 15. Hamdani A, Rather SA, Shah A, Gani SM, Wani SM, Masoodi FA, Gani A (2014) Physical properties of barley and oats cultivars grown in high altitude Himalayan regions of India. Food Measure 8:296–304 16. Hamdani AM, Wani IA, Gani A, Bhat NA (2018) Effect of gamma irradiation on the physicochemical and structural properties of plant seed gums. Int J Biol Macromol 106:507–515 17. Munir H, Shahid M, Anjum F, Mudgil D (2016) Structural, thermal and rheological characterization of modified Dalbargia sissoo gum – a medicinal gum. Int J Biol Macromol 84:236–245 18. Nep EI, Conway BR (2010) Characterization of grewia gum, a potential pharmaceutical excipient. J Excipients Food Chem 1:30–40 19. Bashir M, Haripriya S (2016) Assessment of physical and structural characteristics of almond gum. Int J Biol Macromol 93:476–482 20. Hamdani AM, Wani IA, Gani A, Bhat NA, Masoodi FA (2017) Effect of gamma irradiation on physicochemical, structural and rheological properties of plant exudate gums. Innov Food Sci Emerg Technol 44:74–82 21. Sibaja-Hernandez R, Roman-Guerrero A, Sepulveda-Jimenez G, Rodriguez-Monroy M (2015) Physicochemical, shear flow behaviour and emulsifying properties of Acacia cochliacantha and Acacia farnesiana gums. J Food Sci Technol 38:191–199 22. Singh U (2001) Functional properties of grain legume flours. J Food Sci Technol 38:191–199 23. Bhushette PR, Annapure US (2017) Comparative study of Acacia nilotica exudate gum and Acacia gum. Int J Biol Macromol 102:266–271

20

H. N. Murthy

24. Koocheki A, Taherian AR, Bostan A (2013) Studies on the steady shear flow behaviour and functional properties of Lepidium perfoliatum seed gum. Food Res Int 50:446–456 25. Chung YH, Cui SW, Roberts KT, Ng PKW, Wang Q (2011) Evaluation of extrusion-modified fenugreek gum. Food Hydrocoll 25:1296–1301 26. Rana V, Rai P, Tiwary AK, Singh RS, Kennedy JF, Knill CJ (2011) Modified gums: approaches and applications in drug delivery. Cabrohydr Polym 83:1031–1047 27. Naji-Tabasi S, Razavi SMA (2016) New studies on basil (Ocimum bacilicum L.) seed gum: part II-emulsifying and foaming characteristics. Carbohydr Polym 149:140–150 28. Dikinson E (2009) Hydrocolloids as emulsifiers and emulsion stabilizers. Food Hydrocoll 23: 1473–1482 29. Perez-Mosqueda LM, Ramirez P, Alfaro MC, Rincon F, Munoz J (2013) Surface properties and bulk rheology of Sterculia apetala gum exudate dispersions. Food Hydrocoll 32:440–446 30. Alftren J, Penarrieta JM, Bergenstahl B, Nelson L (2012) Comparison of molecular and emulsifying properties of gum Arabic and mesquite gum using asymmetrical flow field flow fractionation. Food Hydrocoll 26:54–62 31. Mohamadi S, Abbasi S, Scanlon MG (2016) Development of emulsifying property in Persian gum using octenyl succinic anhydride (OSA). Int J Biol Macromol 89:396–405 32. Garti N, Leser ME (2001) Emulsification properties of hydrocolloids. Polym Adv Technol 12: 123–135 33. Garti N, Slavin Y, Aserin A (1999) Surface and emulsification properties of a new gum extracted from Portulaca oleracea L. Food Hydrocoll 13:145–155 34. Garti N, Madar Z, Aserin A, Stenheim B (1997) Fenugreek galactomannans as food emulsifiers. LWT-Food Sci Technol 30:305–311 35. Crequeira MA, Pinherio AC, Souza BW, Lima AM, Ribeiro C, Miranda C, Teixeira JA, Moreira RA, Coimbra MA, Goncalves MP, Vicente AA (2009) Extraction, purification and characterization of galactomannan from non – traditional source. Carbohydr Polym 75:408–414 36. Ofori-Kwakye K, Asantewaa Y, Kipo SL (2010) Physicochemical and binding properties of cashew tree gum in metronidazole tablet formations. Int J Pharm Sci 2:105–109 37. Ricon F, Munoz J, Ramirez P, Galan H, Alfaro MC (2014) Physicochemical and rheological characterization of Prosopis juliflora seed gum aqueous dispersions. Food Hydrocoll 35:348–357 38. Zare EN, Makvandi P, Tay FR (2019) Recent progress in the industrial and biomedical applications of tragacanth gum: a review. Carbohydr Polym 212:450–467 39. Tonyali B, Cikrikci S, Oztop MH (2018) Physicochemical and microstructural characterization of gum tragacanth added whey protein based films. Food Res Int 105:1–9 40. Samavati V, Emam-Dojomeh Z, Mehdinia A (2014) Effect of salts on pasting, thermal, and rheological properties of rich starch in the presence of non-ionic and ionic hydrocolloids. Corbohydr Polym 87:1559–1568 41. Beneke CE, Viljoen AM, Hamman JH (2009) Polymeric plant derived excipients in drug delivery. Molecules 14:2602–2620 42. Lu EX, Jiang ZQ, Zhang QZ (2003) A water-insoluble drug monolithic osmotic tablet system utilizing gum Arabic as an osmotic, suspending and expanding agent. J Contrl Release 92: 375–382 43. Jain NK, Dixit VK (1988) Studies on gums and their derivatives as bind agent. Indian J Pham Sci 50:113–114 44. Owen SC (2003) Gum tragacanth. In: Raymod CR, Paul JS, Paul JW (eds) Handbook of pharmaceutical excipients. The Pharmaceutical Press and the American Pharmaceutical Association, Washington, DC, pp 654–656 45. Munday DL, Philip JC (2000) Compressed xanthan and karaya gum matrices: hydration, erosion and drug release mechanism. Int J Pharm 203:179–192 46. Singh B, Sharma V (2014) Influence of polymer network parameters of tragacanth gum based pH responsive hydrogels on drug delivery. Carbohydr Polym 101:928–940 47. Park CR, Munday DL (2004) Evaluation of selected polysaccharide excipients in buccoadhesive tablets for sustained release of nicotine. Drug Dev Ind Pharm 30:609–617

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of. . .

21

48. Barak S, Mudgil D, Taneja S (2020) Exudate gums: chemistry, properties and food applications – a review. J Sci Food Agric 100:2828–2835 49. Masoumi A, Ghaemy M (2014) Removal of metal ions from water using nonohydrogel tragacanth gum-g-polyamindoxime: isotherm and kinetic study. Carbohydr Polym 108:206–215 50. Sahraei R, Pour ZS, Ghaemy M (2017) Novel magnetic bio-sorbent hydrogel beads based on modified gum tragancanth/graphene oxide: removal of heavy metals and dyes from water. J Clever Prod 142:2973–2984 51. Haider A, Haider S, Kang I (2018) A comprehensive review summarizing the effect of electrospinning parameters and potential applications of nanofibers in biomedical and biotechnology. Arab J Chem 11:1165–1188 52. Arora SK, Patel AA, Kumar N, Chuhan OP (2016) Determination of relationship between sensory viscosity rating instrumental flow behaviour of soluble dietary fibres. J Food Sci Technol 53:2067–2076 53. Ghayempour S, Montazer M (2018) A modified microemulsion method for fabrication of hydrogel tragacanth nanofibers. Int J Biol Macromol 115:317–323 54. Ghayempour S, Montazer M, Rad MM (2016) Encapsulation of Aloe vera extract into natural tragacanth gum as a novel green wound healing product. Int J Biol Macromol 93:344–349 55. Ghayempour S, Montazer M (2017) Ultrasound irradiation based in-situ synthesis of star like tragacanth gum/zinc oxide nonoparticles on cotton fabric. Ultrasonics Sonochem J 34:458–465 56. Ghayempour S, Montazer M (2019) A novel controlled release system based on tragacnth nanofibers loaded peppermint oil. Carbohydr Polym 205:589–595 57. Hemmati K, Masoumi A, Ghaemy M (2016) pH response tragacanth gum and poly(methyl methacrylate-co-maleic) anhydride-g-poly (caprolacotne) conetwork microgel for in vitro quercetin release. Polymer 59:49–56 58. Moghbel A, Hemmati AA, Agheli H, Rashidi I, Amraee (2005) The effect of tragacanth mucilage on the healing of full-thickness wound in rabbit. Arch Iranian Med 8:257–262 59. Ranjbar-Mohammadi M, Bahrami SH (2016) Electrospun curcumin loaded poly (e-caprolacotne)/gum tragacanth nanofibers for biomedical application. Int J Biol Macromol 84:448–456 60. Singh B, Sharma V (2017) Crosslinking of poly(vinylpyrrolidone)/acrylic acid with tragacanth gum for hydrogel formation for use in drug delivery applications. Carbohydr Polym 157:185–195 61. Zarekhalili Z, Bahrami SH, Ranjbar-Mohammadi M, Milan PB (2017) Fabrication and characterization of PVA/gum tragacanth/PCL hybrid nanofibrous scaffolds for skin substitutes. Int J Biol Macromol 94:679–690 62. Haeri SMJ, Sadeghi Y, Salehi M, Farahani RM, Mohsen N (2016) Osteogenic differentiation of human adipose-derived mesenchymal stem cells on gum tragacanth hydrogel. Biologicals 44: 123–128 63. Adams RP (1991) Cedarwood oil-analyses and properties. In: Linskens H, Jackson JF (eds) Modern methods in plant analysis. Springer, New York, pp 159–173 64. Cascon V, Gilbert B (2000) Characterization of chemical composition of oleoresins of Copaifera guianensis Desf., Copaifera duckei Dwyer and Copaifera multijuga Hayne. Phytochemistry 55:773–778 65. Leung AY, Foster S (1996) Encyclopaedia of common natural ingredients used in food, drugs and cosmetics, 2nd edn. Wiley, New York 66. Moreman DE (1998) Native American ethnobotany. Timber Press, Portland 67. Tyler VE, Brady LR, Robbins JE (1988) Pharmacognosy, 9th edn. Lea and Febrger, Philadelphia 68. Walberg I, Hjelte MB, Karlsson K, Enzell CR (1971) Constituents of commercial Tolu balsam. Acta Chem Scand 25:3285 69. Duke JA (1985) CRC handbook of medicinal herbs. CRC Press, Boca Raton 70. Hafizoglue H, Reunane M, Istek A (1996) Chemical constituents of balsam from Liquidambar orientale. Holzforschung 50:116–117 71. Pratt R, Youngken HW (1951) Pharmacognosy. J.B. Lippincott, London

22

H. N. Murthy

72. Mors WB, Rizzini CI (1966) Useful plants of Brazil. Holden Day, San Francisco 73. Rees A (1995) Frankincense and myrrh. New Plantsman 2:55–59 74. Mahajan B, Taneja SC, Sethi VK, Dhar KL (1995) Two triterpenoids from Boswellia serrata gum resin. Phytochemistry 39:453–455 75. Ageel AM, Mossa JS, Tariq M, Al-Yahya MA, Al-Said MS (1987) Plant used in Saudi folk medicine. King Saud University Press, Riyadh 76. Dev S (1988) Ayurveda and modern drug development. Proc Indian Natl Sci Acad A 54:12–42 77. Becerra JX, Venable DL, Evans PH, Bowers WS (2001) Interactions between chemical and mechanical defences in the plant genus Bursera and their implications for herbivores. Am Zool 41:856–876 78. Breedlove DE, Laughlin RM (1993) The flowering of man: a Tzotzil botany of Zincantan, Smithsonian contributions to anthropology, vol 35. Smithsonian Institution Press, Washington 79. Gianno R (1993) Semelai culture and resin technology. Connecticut Academy of Arts and Sciences, New Haven 80. Mills JS, White R (1994) Natural resins and lacquers. In: The organic chemistry of museum objects, 2nd edn. Butterworth Heinemann, London, pp 95–128 81. Bisset NG, Chavanel V, Lanz JP, Wolff RE (1971) Constituants sesquiterpeniqus et triterpeniques des resins du genre Shorea. Phytochemistry 10:2451–2463 82. Stout SA (1995) Resin-derived hydrocarbons in fresh and fossil dammar resins and Miocene rocks and oils in the Mahakam Delta Indonesia. In: Anderson KB, Crelling JC (eds) Amber, resinite and fossil resins, symposium series 617. American Chemical Society, Washington, DC, pp 43–75 83. Howes FN (1949) Vegetable gums and resins. Chronica Botanica, Waltham 84. Papageorgiou VP, Bakola-Christianopoulou MN, Apazidou KK, Psarros EE (1996) Gas chromatographic-mass spectroscopic analysis of acidic triterpenic fractions of mastic gum. J Chromatography A 769:263–273 85. Jost T, Sell Y, Foussereau J (1989) Contact allergy to Manila resin. Nomenclature and physicochemistry of Manila kauri, damar and copal resins. Contact Dermatitis 21:228–238 86. Birch AJ, Dahl CJ (1974) Some constituents of the resin of Xanthorrhoea preissii, australis and hastile. Australian J Chem 27:331–344 87. Konno K (2011) Plant latex and other exudates as plant defense systems: roles of various defense chemicals and proteins contained therein. Phytochemistry 72:1510–1530 88. Warowicak A, Nawrot R, Gozdzicka-Jozefiak A (2020) Pharmacologically active compounds from latex-bearing plants. Adv Bot Res 93:119–150 89. Matsuura HN, Fett-neto AG (2015) Plant alkaloids: main features, toxicology and mechanisms of action. Plant Toxins:1–15 90. Beaudoin GA, Facchini PJ (2014) Benzylisoqunoline alkaloid biosynthesis in opium poppy. Plant 240:19–32 91. Gu R, Wang Y, Long B, Kennelly E, Wu S, Liu B, Li P, Long C (2014) Prospecting for bioactive constituents from traditional medicinal plants through ethnobotanical approaches. Biol Pharm Bull 37:903–915 92. Oliveira AP, Silva LR, Andrade PB, Valentao P, Silva BM, Goncalves RF, Pereira JA, de Pinho PG (2010) Further insight into the latex metabolite profile of Ficus carica. J Agric Food Chem 58:10855–10863 93. Jevid F, Yassa N, Ostad SN, Hassannejad Z, Gheshlaghi GH, Sabzevari O (2020) Ficus carica L. Latex: possible chemo-preventive, appptotic activity and safety assessment. Iranian J Pharmaceut Res 19:231–240 94. Mooibroek H, Cornish K (2000) Alternative sources of natural rubber. Appl Microbiol Biotechnol 53:355–365 95. Abbas M, Saeed F, Anjum FM, Afzaal M, Tufail T, Bashir MS, Ishtiaq A, Hussain IS, Suleria HAR (2017) Natural polyphenols: an overview. Int J Food Prop 20:1689–1699

1

Chemical Constituents and Applications of Gums, Resins, and Latexes of. . .

23

96. Aref HL, Gaaliche B, Fekih A, Mars M, Aouni M, Chaumon P, Said K (2011) In vitro cytotoxic and antiviral activities of Ficus carica latex extracts. Nat Prod Res 25:310–319 97. Chaware GK, Kumar V, Kumar S, Kumar P (2020) Bioactive compounds, pharmaceutical activity and food application of Ficus racemosa: a critical reviw. Int J Fruit Sci 20:S969–S986 98. Ramos MV, Demarco D, da Costa Souza IC, de Freitas CDT (2019) Laticifers, latex and their roel in plant defense. Trends Plant Sci 24:553–567 99. Urs AP, Manjuprasanna VN, Rudresha GV, Yariswamy M, Vishwanath BS (2017) Plant latex proteases: natural wound healers. In: Chakarborti S, Dhalla NS (eds) Proteases in physiology and pathology. Springer Nature Singapore, Singapore, pp 297–323

2

Pharmaceutical Applications of Various Natural Gums and Mucilages Vipul Prajapati, Sonal Desai, Shivani Gandhi, and Salona Roy

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Applications of Naturally Available Gums in Pharmaceuticals . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Applications of Naturally Available Gums in Liquid Dosage Forms . . . . . . . . . . . . . . . . . 2.2 Applications of Naturally Available Gums in Solid Dosage Forms . . . . . . . . . . . . . . . . . . 2.3 Applications of Naturally Available Gums in Semisolid Dosage Forms . . . . . . . . . . . . . 3 Applications of Naturally Available Mucilages in Pharmaceutical Formulations . . . . . . . . . . 3.1 Application of Naturally Available Mucilages in Various Liquid Dosage Forms . . . . 3.2 Application of Naturally Available Mucilages in Solid Formulations . . . . . . . . . . . . . . . . 3.3 Applications of the Naturally Available Mucilages in Semisolid Dosage Forms . . . . . 4 Regularity Status of Naturally Available Gums for Pharmaceutical Applications . . . . . . . . . . 5 Future Perspectives of Naturally Available Gums and Mucilages . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

26 29 38 38 38 39 39 40 41 41 41 41 50

Abstract

Naturally available gums and mucilage of different origins are widely utilized as excipients in conventional, traditional, and novel pharmaceutical formulations. In recent years, there has been a tremendous evolution in naturally available polymers from varieties of sources for different functionalities in various fields but mostly now in pharmaceuticals. These natural polymers are preferred over synthetic polymers due to their flexible intrinsic characteristics, and their merits over synthetic polymers such as their abundant production, economical availability, nontoxic, biodegradable, and biocompatibility. Through comprehensive V. Prajapati (*) · S. Gandhi · S. Roy Department of Pharmaceutics, SSR College of Pharmacy, Silvassa, Union Territory of Dadra Nagar Haveli & Daman Diu, India S. Desai Department of Pharmaceutical Quality Assurance, SSR College of Pharmacy, Silvassa, Union Territory of Dadra Nagar Haveli & Daman Diu, India © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_2

25

26

V. Prajapati et al.

references, this chapter is compiled to make it attentive to one and all for future applications of various naturally available gums and mucilages for suitable pharmaceutical formulations, cosmetics, food products, and dairy products. Keywords

Emulsifier · Natural gums · Natural mucilages · Pharmaceutical applications · Release retardants · Stabilizer Abbreviations

CLNAI FAA FDA FG FSA GG GMP GRAS LBG M/G ratio TG UK USA USFDA

1

Canadian List of Acceptable Non-medical Ingredients Food Additives Amendment Food Drug Administration Fenugreek gum Food Standards Agency Guar gum Good Manufacturing Practices Generally Regarded As Safe Locust bean gum Mannose to galactose ratio Tara gum The United Kingdom The United States of America The United States of Food and Drug Administration

Introduction

In the last few decades, natural polymers have gained tremendous attention from researchers as they are biodegradable, biocompatible, nontoxic, readily available, and economical. These natural polymers have distinct roles in pharmaceuticals, foods, and other fields [1, 2]. Natural polymers are abundant and can be derived from various sources such as plants/plant parts, animals, marine, organisms, etc. [3]. Gums and mucilages are natural polymers and have a similar constitution. The gums and mucilages are either neutral or acidic. The presence of uronic acid or sulfate ester residues makes them acidic. On hydrolysis, they yield a mixture of sugars and uronic acid. Gums are pathological products resulting from pathological conditions brought about either by mechanical injury/incision, invasion, or by unfavorable conditions of growth, and are usually formed by changes in actual cell walls. Gums are mostly produced by the process of gummosis [4]. The natural gums are amorphous, translucent solids, soluble in water, insoluble in alcohol as well as in most organic solvents. Gums form viscous solutions in water or form jelly-like mass by absorbing water. The gums are obtained from trees and shrubs that belong to

2

Pharmaceutical Applications of Various Natural Gums and Mucilages

27

a number of families, especially Leguminosae, Rosaceous, Rutaceae, Anacardiaceae, Combretaceae, and Sterculiaceae [5]. Mucilages are physiological products produced by metabolic activities in plants. They are produced without injury to the plant. Mucilages can be produced either from seed coat which covers the families such as Plantaginaceae, Acanthaceae, Linaceae, and Brassicaceae, or fruit which covers families such as Poaceae, Asteraceae, and Lamiaceae [6]. Mucilages are found in the epidermal cell of leaves, in seed coats, roots, and barks. Mucilages are not exudates and swells when they come in contact with water [7]. Table 1 represents the salient differences between naturally available gums of various origins and mucilages with respect to their basic characteristics, occurrence, chemistry, and solubility. There are some similarities between the gums and mucilages. Both naturally available gums and mucilages are hydrocolloids, monosaccharide biodegradable biocompatible polymers bonded to uronic acid [13]. They can be obtained as the purified powder (additive) using suitable methods of extraction following purification for suitable functionalities or applications in different fields including various pharmaceutical formulations. Their gel forming characteristics is due to their structural hydrophilic moieties [13]. On contact with water, both forms high viscous aqueous solution in case of branched form as compared to that of the linear form of the same molecular weight [129]. Natural gums and mucilages can be obtained from varieties of natural sources such as a plant (herb), animal, seaweeds, fungi, and microbes. Gums and mucilages can be classified based on their origin, charge, nature, shape, and presence of monomeric units. The detailed classification of gums and mucilages in various ways along with few examples is illustrated in Fig. 1. Natural gums and mucilages are preferred due to a number of advantages over synthetic polymers. Various advantages and disadvantages of naturally obtained gums and mucilages are summarized in Table 2. In nature, gums and mucilages are located in suitable parts of their sources. Few examples are exhibited in Fig. 2 as a schematic illustration. Various conventional, as well as modern techniques, are utilized for the isolation and purification of plant-derived gums and mucilages. In general, the extraction of gums as well as mucilage is carried out by soaking or boiling dried plant material with water to form an aqueous solution. Chlorophyll is removed from the plant material before treating it with water. The aqueous solution thus generated is treated with either acetone or alcohol to precipitate gum or mucilage. The precipitated gum/mucilage is then filtered and dried at low temperatures. The dried gum/mucilage is stored in an airtight container to prevent moisture uptake [6, 7]. Natural gums and mucilages are used as binders, diluents, disintegrants, gelling agents, film formers, stabilizers, release retardants, thickeners, viscosity modifiers in various pharmaceutical preparations. As natural gums and mucilages are known to have wide applications, this chapter focuses on an in-depth review of applications of naturally available gums and mucilages with respect to various pharmaceutical formulations to extend their further use in existing and newly developed molecules/dosage forms/delivery systems in the field of pharmaceuticals.

28

V. Prajapati et al.

Table 1 Differences between naturally available gums and mucilages of various sources [8–10] Particulars Definition

Type of component Type of products with respect to plant metabolism Occurrence [6, 7, 13]

Naturally available gums The plant-originated gums are pathological products formed by exudations, mechanical injury, incision, or invasion of plant or plant parts [6, 7], or during an unfavorable condition. They are innumerable colloidal biodegradable natural polysaccharides generally gelatinous when wetted and harden during drying [13] Pathological or extracellular [6, 7, 26] Gums are not normal products of plant metabolism but are produced as a result in unfavorable conditions Plant gums are commonly found in barks, stems, roots, fruits, seeds of trees, and shrubs. They are also obtained through various processing from animals, sea weeds (marine source), and nonpathogenic microorganisms

Chemistry

Gums are polysaccharides and known to contain the salts of potassium, calcium, and magnesium referred to as “polyuronides”

Solubility

Gums readily dissolve in water to form a viscous solution

Hydrolysis

They mostly occur as salts of complex organic acids. Hence, on hydrolysis they resulting in to usually either D-glucuronic acid or D-galacturonic acid and several molecules of one or more sugars Limited use as dietary fiber as they are soluble in water

As dietary fiber

Naturally available mucilages The plant-originated mucilages are physiological translucent amorphous polymeric, a heterogeneous polysaccharide, product formed as a membrane thickening material (known as “membrane mucilages”) or within cells (known as “cell content mucilages”) by monosaccharide units [11] Physiological [6, 7, 26] Mucilages are normal products of plant metabolism and are produced without injury to the plant [6, 7] Plant mucilages are often found in epidermal leaf cells, seed coats, barks, roots, and middle lamella. They are also exuded by some microorganisms [149]. They are considered to support seed germination [140], water storage, act as a food reserve [129], and membrane thickener [149] Mucilages are polysaccharides with sulfuric acid esters. They contain hydrophilic groups to form viscous solutions, gels in presence of water, or act as emulsifiers [12]. Branched mucilages form more easily stable gels than linear mucilages of the same molecular mass [7] Mucilages do not dissolve readily in water and form sticky, spongy, or slimy masses [6, 7, 13] Its hydrolysis resulting in a mixture of sugars (L-arabinose, D-galactose, L-rhamnose, D-xylose, among others) and uronic acids (D-galacturonic acid) [7, 11] Due to their capacity for high-water absorption as well as gel formation, they are used as a dietary fiber to reduce cholesterol levels in the blood resulting in regulation of intestinal transit, constipation, and glucose in diabetics [14] (continued)

2

Pharmaceutical Applications of Various Natural Gums and Mucilages

29

Table 1 (continued) Particulars Identification test [7]

Formation characteristic Example

2

Naturally available gums Enzyme test: Dissolve 100 mg of gum powder in 20 ml distilled water; add 0.5 ml of benzidine in alcohol (90%). Shake and allow to stand for few minutes. The development of blue color confirms the presence of gum The process of formation is termed gummosis which takes place extracellularly to the plant Depending on the sources [6, 7] as: (a). Plant gums: Acacia gum, Tragacanth gum, Neem gum (b). Marine originated gums: Agar, alginates, carrageenans (c). Microbial originated gums: Chitin and chitosan from yeast, fungi; gellan gum (from Pseudomonas elodea), Xanthan gum (from Xanthomonas campestris) (d). Animal originated gums: Chitin and chitosan from the exoskeleton of insects and the shells of crustaceans (e). Other sources: E.g., pectin (extracted from the plant cell wall (Fig. 2), also secreted by “Sclerotinum rolfsii”), Mesquite gum from Prosopis juliflora

Naturally available mucilages Ruthenium red: Take a small quantity of dried mucilage powder, mount it on a slide with ruthenium red solution and observe under the microscope. The development of pink color confirming the presence of mucilages The process of formation is termed mucilage formation which takes place intracellularly to the plant Aloe mucilage (leaf mucilage), Asario mucilage (seed mucilage), Cassia tora mucilage, Cocculus mucilage, Cordia mucilage, Ocimum mucilage, fenugreek seed mucilage, Hibiscus mucilage, Isapgol mucilage, Mimosa mucilage, Ocimum seed mucilage, Shatavari mucilage, etc.

Applications of Naturally Available Gums in Pharmaceuticals

Plant-derived gums are hydrophilic having high molecular weights and made up of monosaccharide units. Various plant-originated naturally available gums have been identified (Table 3). Mostly they can be utilized as the GRAS excipient in varieties of conventional to novel pharmaceutical formulations for suitable functionalities due to their physicochemical characteristics. Several natural gums have been produced from marine (sea weeds) sources, animal and microbial sources (Table 3). Xanthan gum, the most widely utilized nonionic bacterial biodegradable high molecular weight polymer, was discovered in the 1950s at the National Center for Agricultural Utilization. In 1969, it has been approved by the United States Food Drug Administration (Fed. Reg. 345376) for safe use as a stabilizer and thickener in various food products. Its commercial production is started in the early 1960s by CP Kelco for various

30

V. Prajapati et al.

Fig. 1 A flowchart showing the detailed classification of natural gums and mucilages of various sources in different ways with their examples

Table 2 Advantages and disadvantages of naturally available gums and mucilages for suitable purposes in various pharmaceutical formulations Advantages of natural gums and mucilages for pharmaceutical formulation purpose Nontoxic, biodegradable, economic, and independent of fossil sources [16]

Safe for oral consumption [7] Economical and offers eco-friendly production [17]

Hydrophilic nature and having desired appearance and stability hence can be used in various pharmaceutical formulations [18, 19] Useful in gene therapy [8], biopharmaceutical [20], packaging field [21], food products [8], in food grade aerosols [22], as emulsifiers [23]. Also plays a major role in environmental sustainability [24]

Disadvantages of natural gums and mucilages for pharmaceutical formulation purpose Uncontrolled rate of hydration due to hydrophilic nature [7]. Hence, a moisture-proof package is required if any natural gums or mucilages are used for solid pharmaceutical formulations pH-dependent solubility and batch to batch variation [7] Susceptible for microbial contamination in case of liquid and semisolid pharmaceutical formulations, if used for suitable function at any concentration [7]. Hence, the addition of suitable compatible preservatives is required to minimize or eliminate the microbial bioburden in pharmaceutical formulations Sticky and muggy nature, hence difficult to handle, and the manufacturing process becomes tedious On storage, viscosity decreases [25]

2

Pharmaceutical Applications of Various Natural Gums and Mucilages

31

Fig. 2 A schematic illustration shows the location or source of a few gums and mucilages with respect to their sources

purposes. Its use in the various pharmaceutical formulation is started after 1973. It solubilizes completely in cold water, exhibits pseudoplastic behavior, and is preferred as a thickener [27]. Fenugreek gum, guar gum, tara gum, and locust bean gum are nonionic seed gums also known as galactomannans. The functionalities of these gums depend on the mannose to galactose ratio [28]. Karaya gum is chemically branched anionic polysaccharides. It has strong water-binding ability, acts as a good thickener, and is stable at low pH. Due to having a vinegary odor, its application is being restricted. Carrageenans, the major components of red algae cell walls, are the sea weed originated natural polysaccharides. They can be classified into kappa, iota, and lambda based on the number of sulfate groups attached to the galactose molecule. All three carrageenans are soluble in hot water whereas sodium salts of kappa and iota exhibit solubility in cold water. Kappa and iota are affected by the presence of salts in foods while lambda carrageenan is independent of salts concentration [29]. Gum arabic has a protein fraction which leads to its special functional properties. It is soluble in cold water and is stable in acidic solutions; its aqueous solution is acidic and displays Newtonian behavior. This gum offers high viscosity at high concentrations only [30]. The synergistic interaction between gums has added advantages as the concentration of gums used can be decreased and possibilities of obtaining novel functionalities. For example, synergistic interaction between gums that is k-carrageenan/locust bean gum is useful in producing hard capsules by refining barrier properties of the edible films [31]. Increased tensile strength of hydrogel films and improvement in transparency can be achieved by k-carrageenan/xanthan gum/gellan gum. Stable oil in water emulsion can be obtained by xanthan gum/locust bean gum [32].

Bhara gum

Carrageenan

5.

6.

Albizia gum

Badam gum

Seeds

Naturally available gums Source Common (type) name Extruded Acacia gum from tree (Anionic) Several Agar algae

4.

3.

2.

S no. 1.

–

Terminalia bellirica (Combretaceae) Chondrus crispus (Gigartinaceae)

3-linked b-D-galactopyranose and 4-linked a-D-galactopyranose or 4-linked 3,6-anhydro-a-Dgalactopyranose

Arabinose, galactose, uronic acid, with traces of rhamnose

L-arabinose, D-galactose, D-glucuronic acid, D-mannose, 4-O-methyl-D-glucuronic acid, L-rhamnose; all contents are in a specific ratio based on cultivation and varieties of Albizia.

The linear polysaccharide “agarose” and “agaropectin”

Main chemical constituents 1,3-linked β-d-galactopyranosyl

Terminalia catappa (Combretaceae)

Botanical name (family) Acacia arabica Acacia senegal (Leguminosae) Mainly “Gelidium amansii” Others such as, Gelidium robustum, Gelidium pristoides, etc. (Gelidiaceae) Albizia zygia (Leguminosae)

Gelling agent, stabilizer in emulsion and suspension, demulcent and laxative

Binder in a tablet formulation, stabilizer and good thickener in pharmaceutical liquids, and semisolid formulations. The hydrophilic film formed for the preparation of oral dissolving films of diclofenac sodium. Binder in tablet, release retardant in gastric floating matrix tablets Bucco-adhesive and mucoadhesive release retardant in tablets. Release retardant

Key applications in various pharmaceutical formulations as Suspending agent, emulsifier, binder in tablets, demulcent and emollient in cosmetic preparation. Suspending agent, emulsifier, gelling agent, surgical lubricant, disintegrant in tablets, laxative.

Table 3 The summary showing different applications of naturally available gums with sources in various pharmaceutical formulations

[47, 48]

[46]

[45]

[44]

[43, 58]

References [19, 41, 42]

32 V. Prajapati et al.

Copal gum

Cordia gum

Caesalpinia pulcherrima gum Cissus populnea gum Delonix gum

Dammar gum

Grewia gum

Guar gum

Ghatti gum

8.

9.

10.

13.

14.

15.

16.

12.

11.

Cashew gum

7.

Anogeissus latifolia (Combretaceae)

Cyamopsis tetragonoloba (Leguminosae)

Delonix regia (Fabaceae) Shorea wiesneri (Dipterocarpaceae) Grewia mollis (Malvaceae)

Caesalpinia pulcherrima (Fabaceae) Cissus populnea (Amplidaceae)

Cordia obliqua (Boraginaceae)

Anacardium occidentale (Anacardiaceae) Bursera bipinnata (Burseraceae)

β-1-3-linked D-galactose units with some ß1-6- linked D-galactose unit

Galactomannan nonionic natural biodegradable gum with mannose to galactose (M/G) ratio of 2:1

Water-resistant coating material, sustained release material Binder in solid formulations, suspending agent in liquid formulations. Generally regarded as safe for human oral consumption, binder, emulsifier, suspending agent, stabilizer, thickener, and gelling agent. Binder, emulsifier, suspending agent

Binder in tablets, suspending agent

– Alpha resin, beta resin, dammarol acid Glucose, rhamnose, galacturonic acid

Binder

Mucoadhesive agent.

Enteric resistant, sustained-release material.

Film former, Coating material for sustained release, and colon targeted drug delivery.

Suspending agent

–

Agathalic acid, agatholic acid, agathic acid with ciscommunic acid, transcommunic acid, polycommunic acid Galactose, rhamnose, mannose, xylose, glucose, arabinose, uronic acids Galactomannan with mannose to galactose (M/G) ratio of 3.6:1

Galactose, arabinose, rhamnose, glucose, glucuronic acid

Pharmaceutical Applications of Various Natural Gums and Mucilages (continued)

[58, 59]

[58]

[57]

[50]

[55, 56]

[54]

[52, 53]

[51]

[50]

[49]

2 33

Naturally available gums Source Common (type) name Fenugreek gum

Hakea gum

Hupu gum

Karaya gum

Katira gum

Khaya gum

Leucaena seed gum

Locust bean gum

S no. 17.

18.

19.

20.

21.

22.

23.

24.

Table 3 (continued)

Cochlospermum religiosum (Bixaceae) Khaya grandifoliola (Meliaceae) Leucaena leucocephala (Fabaceae) Ceratonia siliqua (Fabaceae)

Sterculia urens (Sterculiaceae)

Cochlospermum gossypium (Cochlospermaceae)

Botanical name (family) Trigonella foenumgraecum Linn (Fabaceae) Hakea gibbose (Proteaceae)

Galactomannan nonionic natural biodegradable gum with mannose to galactose (M/G) ratio of 4:1

l-rhamnose, d-galactose, and d-galacturonic acid in molar ratio 3: 2:1 Protein, sugar, galactose, arabinose, rhamnose, glucose, glucuronic acid Galactose, mannose

Main chemical constituents Galactomannan nonionic natural biodegradable gum with mannose to galactose (M/G) ratio of 1:1 Glucuronic acid:galactose: arabinose: mannose:xylose in ratio of 12: 43: 32: 5: 8 Rhamnose, glucuronic acid, β-D galactopyranose, α-D-glucose, β-Dglucose, galactose, arabinose, mannose, fructose α-d-galacturonic acid, α-l-rhamnose

GRAS status of US FDA for use in food and pharmaceutical industries as an excipient such as a binder, super-disintegrant and release retardant in tablets, and gelling

Emulsifier, suspending agent, binder, disintegrant

Binder

Suspending agent, emulsifier, dental adhesive, sustaining agent, bulk laxative. Carrier for colon targeting.

Sustaining agent.

Key applications in various pharmaceutical formulations as Binder, disintegrant, fast-dissolving matrix, and release retardant in tablets. Mucoadhesive agent.

[67–70, 117]

[66]

[65]

[64]

[62, 63]

[50]

[61]

References [28, 60, 117]

34 V. Prajapati et al.

Moi gum

Moringa oleifera gum Mucuna gum

Myrrh oleo gum Mimosa gum

Neem gum

Okra gum

Qodume shirazi seed gum

27.

28.

30.

32.

33.

34.

31.

29.

26.

Leucaena leucocephala gum Malva nut gum

25.

Alyssum homolocarpum (Brassicaceae)

Hibiscus esculentus (Malvaceae)

Commiphora myrrha (Burseraceae) Mimosa scabrella Mimosa pudica (Mimosaceae) Azadirachta indica (Meliaceae)

Leucaena leucocephala (Fabaceae) Scaphium scaphigerum (Sterculiaceae) Lannea coromandelica (Anacardiaceae) Moringa oleifera (Moringaceae) Mucuna flagillepes (Papilionaceae)

L-arabinose, fructose, D-galactose, D-glucuronic acid, glucose, allose, xylose Galactose, galacturonic acid, rhamnose, glucose, mannose, arabinose, xylose Mannose, galactose (M/G ratio 0.04), rhamnose, arabinose, xylose, glucose

Mannose, galactose

Sugars, protein

Arabinose, galactose, glucuronic acid, rhamnose D-galactose, D-mannose, D-glucose

–

Arabinose, galactose, glucuronic acid, 4-O-methylglucuronic acid, rhamnose –

Pharmaceutical Applications of Various Natural Gums and Mucilages (continued)

[79, 80]

[78]

Binder and hydrophilic matrix for controlled release drug delivery. Thickener.

[74–77]

[50]

[44]

[73]

[72]

[50]

[60]

[53, 71]

Binder, nanocarrier, suspending agent.

Microencapsulating agent, release retardant in non-sterile solid formulations. Mucoadhesive agent, binder, disintegrant. Release retardant, suspending agent, stabilizer in suspensions and emulsions. Release retardant, mucoadhesive agent, binder Release controlling agent, sustained-release agent.

Stabilizer, thickener.

agent, stabilizer in other formulations. Binder, emulsifier, mucoadhesive agent.

2 35

Sodium alginate

Sesbania gum

Sterculia foetida gum

Tamarind gum

Tara gum

Welan gum

37.

38.

39.

40.

41.

Naturally available gums Source Common (type) name Quince seed gum

36.

S no. 35.

Table 3 (continued)

Alcaligenes species (Alcaligenaceae)

Caesalpinia spinosa (Fabaceae)

Tamarindus indica (Leguminosae)

Sesbania grandiflora (Leguminosae) Sterculia foetida (Malvaceae)

Macrocystis pyrifera (Lessoniaceae)

Botanical name (family) Cydonia oblonga (Rosaceae)

Galactomannan nonionic natural biodegradable gum with mannose to galactose (M/G) ratio of 3:1 –

Acetylated glycanorhamnogalactouran units of D-galacturonic acid, D-glucuronic acid, D-galactose, and L-rhamnose Glucose:xylose:Galactose in ratio of 3:2:1

Galactose and mannose

Main chemical constituents L-arabinose, D-xylose, D-galactose, D-glucose, and D-mannose, uronic acid, protein, ash, and fat 1,4-β-d mannuronic and α-1glucuronic acid

Thickener

Binder, emulsifier, suspending agent, sustaining agent, mucoadhesive agent Stabilizer, thickener

Controlled release agent

Suspending agent, gelling agent, stabilizer, sustained-release agent, mucoadhesive agent. Gelling agent

Key applications in various pharmaceutical formulations as Shear-thinning agent, emulsifier.

[86]

[50]

[85]

[50, 84]

[83]

[82]

References [60, 81]

36 V. Prajapati et al.

44.

Xanthan gum

Gellan gum

43.

Microbial

Zedo gum

42.

Amygdalus scoparia (Rosaceae) Pseudomonas Elodea (Proteobacteria) Xanthomonas campestris Heteropolysaccharide composed by units of β-d-glucose linked by link 1–4, containing branching formed by β-d-mannose – 1,4-β-dglucuronic acid – 1,2-α-d-mannose, pyruvic acid, acetic acid

D-glucuronic acid, D-glucose, L-rhamnose

– Stabilizing agent, shear-thinning agent Temperature-dependent gelling agent, release retardant, ophthalmic drug delivery, nasal drug delivery Encapsulating agent for various molecules and cells, binder, release retardant, viscosity modifier, stabilizer, emulsifier, gelling agent [7, 32, 35]

[118]

[60]

2 Pharmaceutical Applications of Various Natural Gums and Mucilages 37

38

V. Prajapati et al.

In general, pharmaceutical formulations are broadly classified into sterile and non-sterile products. Both these products are subclassified into liquids, solids, and semisolids based on the state of matter. Liquid formulations are either monophasic or biphasic and include syrups, suspensions, and emulsions. Tablets and capsules are solid oral dosage forms while gels, lotions, and ointments are part of semisolid dosage forms. Applications of various naturally derived gums in different pharmaceutical dosage forms are discussed below.

2.1

Applications of Naturally Available Gums in Liquid Dosage Forms

Gums stabilizes both emulsion and suspension by preventing phase separation and by increasing viscosity, respectively [33]. Natural gums such as alginates, carrageenan, gum acacia, guar gum, locust bean gum, microcrystalline cellulose, tragacanth, and xanthan gum increase the viscosity of the solution and hence can be used as suspending agents in suspensions [34]. Xanthan gum has mucoadhesive property and hence can be used for ophthalmic solution [35]. Emulsification of flavor oils can be achieved by gum arabic [36]. Gum arabic can form stable oil-in-water emulsions [37]. Tragacanth forms high viscosity solutions among all gums but its rate of hydration is slow. It is used as a stabilizer in emulsion [36].

2.2

Applications of Naturally Available Gums in Solid Dosage Forms

Natural gums as a binder have adhesive properties, and they have the ability to form cohesive mass/granules [38]. Gelatin, gum acacia, tragacanth, starch, and guar gum have been conventionally used as a binder for wet granulation of tablet manufacturing processes. Acacia gum is used either in dry form or solution form, and forms very hard granules. Acacia gum is not widely used, because it is not compatible with other tablet excipients [36]. Guar gum, locust bean gum, and their derivatives are widely used as a disintegrant, binder, coating agent, and release retardant in solid dosage forms like tablets, capsules, and films [39]. Pectin has been utilized in various non-sterile pharmaceutical solid formulations as the release retardant either alone due to its acyl contents and cross-linking with polyvalent cations [153] or in suitable proportion in combination with sodium alginate due to its interpenetrating polymeric network formation [154].

2.3

Applications of Naturally Available Gums in Semisolid Dosage Forms

Gums have wide applications in semisolid dosage forms namely mucoadhesive and in situ gels. Chitosan and sodium alginate are gums of choice for

2

Pharmaceutical Applications of Various Natural Gums and Mucilages

39

mucoadhesive gels for various delivery systems due to their excellent gelling property, ability to adhere to the mucus membrane, and providing drug release for a longer period of time. Pectin and gellan gum are used for oral in situ gel; gellan gum and alginic acid are used for ocular in situ gel; and chitosan is used in the injectable in situ gel. Gellan gum and xanthan gum are suitable candidates for nasal in situ gel [40].

3

Applications of Naturally Available Mucilages in Pharmaceutical Formulations

Natural mucilages are obtained from the cell walls of different parts of plants [80]. Plant mucilage is either obtained from seed coat (myxospermy) or fruit epicarp (myxocarpy). Several species of plant mucilages have been used in various traditional medical systems throughout the world [8]. Plant mucilages are chemically high molecular weight polysaccharides consisting of sugars (namely L-arabinose, D-xylose, D-galactose, L-rhamnose) and uronic acids attached by glycosidic linkage. They are also said to contain glycoproteins, tannins, alkaloids, and steroids [24, 88]. Water-soluble mucilages form viscous solutions while others absorb water and swell to form jelly-like structures [89]. The solubility of mucilage in water depends on the hydrophilic interaction of functional groups of mucilage and solvent [43]. Based on their origin, chemical structure, and properties, the mucilages have multiple applications in the field of pharmaceuticals, cosmetics, agriculture, and textile industry [45]. Apart from pharmaceuticals and cosmeceuticals, the use of seeds mucilage in the form of edible films or as biodegradable film is increasing in the food industry for coating of fruits, vegetables, meat products, and dairy products to extend their shelf life [26, 90–92]. The plant-originated mucilage can also be used as gelling agent [94], stabilizer [95], for preparation of bioaerogels [96] for food products, and encapsulation of natural food dye [97, 98]. Mucilage offers stability to dairy products by decreasing syneresis [99, 100]. Formulation of nanoemulsion using mucilage for the preservation of food flavor is also reported [101]. Fabrication of mucilage-based bio-nanocomposite film [145] and biodegradable films [102] for food packaging are also described. Applications of various naturally derived mucilages in different pharmaceutical dosage forms are discussed in the following section.

3.1

Application of Naturally Available Mucilages in Various Liquid Dosage Forms

Mucilage forms a film around oil globules and prevents their agglomeration to stabilize the emulsion. It also increases the viscosity of the continuous phase of suspension to prevent the agglomeration of solid particles of suspension. Therefore, mucilage can be used as an emulsifying agent and a suspending agent [96]. Adansonia digitata leaves mucilage can be used as a suspending agent and

40

V. Prajapati et al.

results are comparable to those obtained with sodium carboxymethyl cellulose [103]. Spinacia oleracea leaves mucilage proven to be a better suspending agent as compared to tragacanth and bentonite [104]. The mucilage obtained from Lepidium sativum can be used as a suspending agent [105, 106]. Alyssum homolocarpum seed mucilage is used as a thickening agent and exhibits non-Newtonian and pseudoplastic behavior [79]. Okra mucilage (Abelmoschus esculentus) is said to exhibit emulsifying properties [108]. A study conducted by a group of scientists from Brazil revealed that cactus mucilages extracted from some cactus species possess good emulsifying properties, water holding capacity, oil holding capacity, and foaming property [109]. Grewia ferruginea bark mucilage produces viscous solution and possesses pseudoplastic behavior hence can be used as suspending agent [110]. Colocasia esculenta mucilage which is also known as “Taro mucilage,” is weakly acidic, acts as an emulsifier [111], and can also be utilized as suspending agent [112]. Basil seeds mucilage [113], Pereskia aculeata fruit mucilage [114], and mutamba seeds mucilage [115] exhibit pseudoplastic behavior and is said to possess emulsifying properties.

3.2

Application of Naturally Available Mucilages in Solid Formulations

Mucilages are widely used as a disintegrant, binding agent, or release retardant in tablet formulation because of their swelling and water holding ability [6–9, 48, 49, 118]. At low concentrations, mucilage acts as a binding agent. The function of mucilage as a release retardant can be attributed to its ability to form a sticky film on the tablet surface leading to the controlled release of drug from the tablet matrix. Lepidium sativum mucilage acts as a super disintegrant and releases retardant [105, 106]. Okra mucilage can be used as a binder at low concentrations and as a release retardant at high concentrations. Hibiscus mucilage can also be utilized as a release retardant [119]. Grewia ferruginea bark mucilage is a promising excipient for modified release dosage forms [110]. Colocasia esculenta mucilage has good flow properties and can be used as a binder in tablets [112]. This mucilage with alginate was used to prepare sustained-release microspheres of oxcarbazepine [112] and pregabalin [120] because of its swelling ability. Ocimum americanum (American Basil) seeds mucilage can be used as a disintegrant in the tablet formulation [121]. Basil seeds mucilage was also used to prepare gold nanoparticles/mucilage nanocomposite [122]. Natural mucilages have also been explored for microencapsulation of various oils. The use of tamarind seed mucilage to form microcapsules of sesame oil to prevents its rancidity by oxidation is demonstrated [123]. Sustained released beads of metformin using basil seeds mucilage along with sodium alginate [124] and of lamotrigine using okra mucilage along with pectin [125] were formulated. Hydrogels films based on basil seed mucilage loaded with tetracycline hydrochloride were optimized as biocompatible and biodegradable wound dressings [126].

2

Pharmaceutical Applications of Various Natural Gums and Mucilages

3.3

41

Applications of the Naturally Available Mucilages in Semisolid Dosage Forms

Plant-based mucilages have wider application as a gelling agent and as a thickening agent. Cocculus hirsutus leaves mucilage exhibits gelling property and can be used for the preparation of gel [127]. Grewia ferruginea bark mucilage can be used as mucoadhesive due to its good swelling property [110]. The mucilage obtained from Basella alba stem produces a viscous solution in water which is slightly acidic and is a promising natural polymer for formulations of topical gels [128]. A summary of various applications of naturally available mucilages with sources in the pharmaceutical formulations is described in Table 4.

4

Regularity Status of Naturally Available Gums for Pharmaceutical Applications

Various countries of the world have approved naturally available gums with their standards for the purpose of safe use in human beings. Table 5 shows the detail of the regularity status of few commonly used naturally available gums for food and pharmaceutical formulation purposes.

5

Future Perspectives of Naturally Available Gums and Mucilages

Ever since the first use of natural gums and mucilages in pharmaceutical dosage forms, their potential as formulation excipients has gradually been recognized and growing. This also resulted in a tremendous increase in the production and cultivation of naturally derived gums and mucilages. However, the interspecies variation in gums and mucilage with respect to chemical composition, rheological behavior, and functionality have not been investigated fully. Additionally, some gums/mucilages producing natural resources have not been explored completely, and such resources should be identified. The relationship between structure, functionality, and biological activity of some natural gums and mucilage is still to be investigated. Gene responsible for molecular structure, chemical composition, and functionality of gums and mucilages should be identified. Gene modification of naturally derived gums and mucilage to get customized functionality can be explored to formulate tailor-made dosage from.

6

Conclusion

Wide varieties of naturally available gums and mucilages have been used in various pharmaceutical formulations due to their fundamental physicochemical properties. These natural substances are known to have diversified functionalities due to their

7.

6.

Seeds

Senna sophera Chia

Cassia golden or Indian laburnum Cassia red or Ceylon cassia

4.

5.

Basil

Cassia sophera (Fabaceae) Salvia hispanica L. (Leguminosae)

C. roxburghii (Fabaceae)

Cassia fistula Linn. (Caesalpiniaceae)

Ocimum basilicum L. Ocimum americanum L. (Lamiaceae)

The plant-originated natural mucilages Common Source name Botanical name (family) Seeds Balangu or Lallemantia iberica Dragon’s (Lamiaceae) head Lallemantia royleana (Labiatae) Barhang Plantago major or great (Lesan-olplantain (Plantaginaceae) haml or Ribwart)

3.

2.

S no. 1.

Galactomannan

Galactomannan

Galactomannan

Main constituent Arabinogalactan; arabinose (37.88%, galactose (33.54%), glucose (4.11%), rhamnose (18.44%) Galactomannan polysaccharide, arabinose, galacturonic acid, glucuronic acid, rhamnose, galactose, xylose, sucrose, fructose, planteose, and glucose Glucomannan (43%), arabinose, rhamnose, galacturonic acid, xylan (24.29%), xylose, glucan (2.31%) Galactomannan

Stabilizer and thickener in pharmaceutical suspension, disintegrant in tablets (better than starch paste). Binder (better than starch of other sources). A potential encapsulator of a natural beet dye, probiotics, microorganisms, and green cardamomum essential oils.

Film former and disintegrant in tablet formulation; emulsifier and suspending agent in biphasic liquid formulation. Binder (12% w/v mucilage is equivalent to the same proportion of xanthan gum)

Edible coating for the preservation of essential oils, film former

Key applications in various pharmaceutical formulations as Film former, binder, release retardant

Table 4 The summary showing different applications of naturally available mucilages in various pharmaceutical formulations

[97, 133, 134]

[132]

[131]

[130]

[26, 116, 129]

[26, 91]

References [26, 107]

42 V. Prajapati et al.

Cress (asario)

Ivy gourd

Fenugreek

Indian jujube

Flaxseed or linseed

Mesquite

Mutamba

Moldavian dragonhead

8.

9.

10.

11.

12.

13.

14.

15.

Dracocephalum moldavica

Prosopis flexuosa, Prosopis juliflora (Leguminosae) Guazuma ulmifolia Lam. (Sterculiaceae)

Linum usitatissimum L. (Linaceae)

Ziziphus mauritiana (Rhamnaceae)

Coccinia indica (Cucurbitaceae) Trigonella foenum-graecum L. (Fabaceae)

Lepidium sativum (Brassicaceae)

The ratio of galactose: rhamnose: galacturonic acid: glucuronic acid: Glc (33: 21: 19: 19: 8) –

Arabinose (9.2–13.5%), galactose (20–28.4%), fructose (5–7.1%), rhamnose (21.2–27.2%), xylose (21.1–37.4%) Galactomannan; M/G ratio 1: 2.78

–

Galactomannan containing mannose, galactose, xylose

–

Galactomannan

Film former

Binder, disintegrant, film former, release retardant in tablets Emulsifier, stabilizer, suspending agent

Film former, hydrogel formation, disintegrant (2%w/ w for granulation and 4%w/ w for direct compression in tablets), release retardant in beads, tablets, and microparticles type solid formulation. Suspending agent (usually at 2% w/v) Film former, binder, disintegrant, better release retardant in the solid formulation. Binder in tablets (10–30%w/ w proportion exhibited 4–5.45 min disintegration time) Film former, binder, release retardant, gelling agent

Pharmaceutical Applications of Various Natural Gums and Mucilages (continued)

[8]

[115]

[26, 137]

[3, 26]

[136]

[26]

[105, 106, 135]

2 43

Quince

Qodume Shirazi or alyssum plant

Sage

Shame plant

19.

20.

21.

Mimosa pudica L. (Fabaceae, Mimosaceae)

Salvia macrosiphon (Lamiaceae)

Alyssum homolocarpum (Brassicaceae)

Cydonia oblonga Miller (Rosaceae)

The plant-originated natural mucilages Common Source name Botanical name (family) Pepper weed Lepidium perfoliatum or Qodume (Cruciferae) Shahri Psyllium, Plantago ovata, Plantago isabgol psyllium (Plantain)

18.

17.

S no. 16.

Table 4 (continued)

Galactomannan (93.95–95.35%); mannose (60.19–62.8%), rhamnose (0.77–1.57%), arabinose (1.34–1.48%), galactose (32.55–33.76%), glucose (2.55–3.02%) Glucoxylan, D-xylose, and D-glucuronic acid.

Glucose (45.6%), galactose (3.2%, fructose (7.4%), xylose (10.7%) Galactan, galactose (65.7%), rhamnose (18.3%)

Main constituent Arabinose (31.99%), galactose (12.77%), glucose (7.15%), rhamnose (3.40%) Arabinoxylan; arabinose (23%), xylose (75%)

Film former, matrix-forming agent in tablets and drug release retardant.

Binder, thickener (3.0–3.5%w/ w range), film former, viscosity modifier with the addition of calcium and magnesium ions Film former

Film former, lubricant, disintegrant, release retardant in tablets, beads, microparticles, coating agent, suspending agent, emulsifier Film former, binder

Key applications in various pharmaceutical formulations as Film former

[15, 48, 140]

[26, 93]

[26, 79, 87]

[26, 139]

[87, 138]

References [87, 89]

44 V. Prajapati et al.

Okra or lady’s finger

Pickle grass

Spleen warts

27.

28.

29.

30.

Aloe vera

Jake fruit

26.

31.

Bengal quince, golden apple Cordia

25.

Leaves

Barbados gooseberry

24.

Cashew nut

Baobab

Fruits

23.

22.

A. barbadensis and A. arborescens (Xanthorrhoeaceae)

Asplenium australasicum Fronds (Aspleniaceae)

Salicornia fruticose

Artocarpus heterophyllus (Moraceae) Abelmoschus esculentus

C. myxa and C. obliqua (Boraginaceae)

Aegle marmelos L. (Rutaceae)

Pereskia aculeata

Adansonia digitata L.

Anacardium occidentale

Arabinan, arabinorhamnogalactan, galactan, glucogalactomannan,

Gal: Man: Glc: Ara: Xyl: Fuc: Rha: GlcA: GalA (24: 8: 7: 12: 13: 23: 2: 10: 3)

–

Rhamnogalacturonan-I, homogalacturonan

–

–

–

Arabinogalactan

Xylogalacturonan

–

Release retardant in tablets, film former, suspending agent, mucoadhesive release retardant in microspheres. Disintegrant at low concentration (less than 5%w/ w) in fast dissolving tablets Film former, film coating agent in tablets, and release retardant in various solid, semisolid formulations Film former, Film coating agent in tablets, and release retardant

Binder (2.0–4.0%w/w range), granulating agent, release retardant in tablets Film former, matrix-forming agent in tablets, and drug release retardant. Film former, matrix forming agent in tablets and drug release retardant. Binder (range 6–8%w/w in tablets), prolonged or sustained release agent Film former, and binder in solid dosage form, emulsifier in liquid formulation. Binder (due to starch, 4%w/w)

Pharmaceutical Applications of Various Natural Gums and Mucilages (continued)

[6, 60]

[6, 60]

[143]

[142]

[141]

[103]

[136]

[15, 48, 140]

[15, 48, 140]

[132]

2 45

Baobab

Barbados gooseberry

Lacebark

Hibiscus rosa-sinensis

Okra

Spinach

Broom creeper or patalgarudi or Sisi leaves

33.

34.

35.

36.

37.

38.

Abelmoschus esculentus (Malvaceae) Basella alba (Amaranthaceae) Cocculus hirsutus L. (Menispermaceae)

Hibiscus rosa-sinensis Linn. (Malvaceae)

Hoheria populnea A. Cunn. (Malvaceae)

Pereskia aculeata Miller (Cactaceae)

Adansonia digitata L. (Malvaceae)

The plant-originated natural mucilages Common Source name Botanical name (family)

32.

S no.

Table 4 (continued)

Gal: Glc: Ara: Rha: GalA (39: 15: 36: 6: 4) Polysaccharides

Rhamnogalacturonan, rhamnose, galactose, galacturonic acid, and glucuronic acid (ratio 2:1:2:1, respectively) D-galactose, D-galacturonic acid, D-glucuronic acid, L-rhamnose Rhamnogalacturonan-I

Arabinogalactan

glucuronic acid, rhamnogalacturonan homogalacturonan, rhamnogalacturonans

Main constituent

Gelling agent due to gelatinous type polysaccharide in a topical formulation.

Binder, sustained release, release retardant in solid formulations. Suspending agent, natural mucoadhesive in microspheres Thickener in formulation

in various solid, semisolid formulations The hydrophilic matrix in tablet formulation of drugs, suspending agent, emulsifier, stabilizer, binder Film former, binder, release retardant, suspending agent, stabilizer Emollient, soothing agent, demulcent in cough medicines, and stabilizer, viscosity modifier in liquid formulation

Key applications in various pharmaceutical formulations as

[127]

[6, 7]

[142]

[1]

[159]

[8, 158]

[46, 156, 157]

References

46 V. Prajapati et al.

Yam

Taro

Shatavari

44.

45.

Orchis

43.

Root, tuber, and rhizome

41.

Spinach

Safed musli

Stem

40.

Cactus

42.

Cladodes (leaf-like stem)

39.

Asparagus racemosus (Asparagaceae)

Colocasia esculenta (Araceae)

Dioscorea opposita (Dioscoreaceae)

Chlorophytum borivilianum (Liliaceae)

Opuntia dillenii, Opuntia robusta, Opuntia monacantha, Opuntia spinulifera, Opuntia ficusindica Basella alba (Amaranthaceae) Palmate-tuber salep (Orchidaceae)

Polysaccharides containing arabinose, galactose, rhamnose, glucose, glucuronic acid, and other sugar residues

Arabinogalactan

Glc:Mannose:Gal:Xyl (50:33:11:5)

–

Gal: Glc: Ara: Rha: GalA (39: 16: 28: 4:12) Glucomannan

Arabinogalactan, rhamnogalacturonan

Binder, thickener, stabilizer, release retardant in gastroretentive drug delivery system Excellent thicker, binder, disintegrant, emulsifying (similar to gelatin), suspending (1–3%w/w level), stabilizing, and gelling agents, release retardant in tablet formulation. Binder in tablet formulation, antibacterial, antioxidant in pharmaceutical formulation Film former, binder, stabilizer, emulsifier, suspending agent, release retardant, microencapsulator for various molecules Matrix former for controlled release tablets

Thickener in formulation

Binder, film former, gelling agent, stabilizer

[111]

[23, 120]

[151, 152]

[144]

[155]

[6, 7]

[6, 7]

2 Pharmaceutical Applications of Various Natural Gums and Mucilages 47

Cassia gum Carrageenan

Cellulose gum Gellan gum Guar gum

Gum ghatti

Gum karaya

4 5

6

9

10

7 8

Algin

Name of gum Acacia (Gum arabic) Alginic acid

3

2

S. no. 1

GRAS/ FS REG GRAS/ FS GRAS/ FS GRAS/ FS

GRAS/ FS – REG/FS

GRAS

Status by FDA, USA [146] GRAS/ FS

Buccal drug delivery system

Ophthalmic solutions Oral suspension, syrup, buccal tablets, topical products, vaginal tablets –

– Dental paste, capsules, granules, topical lotions, transdermal products, inhalation products, nasal powder, controlled release films –

Ophthalmic inserts, tablets, capsules, and chewable tablets –

Included in FDA Inactive Ingredient Database for following dosage forms Oral preparations, buccal and sublingual tablets, intramuscular suspensions

No

Yes

– E416

Yes Yes

–

– E418 E412

Yes Yes

No

– E427 E407

Yes

Whether part of CLNAI, Canada [148] Yes

E400

Approval with their E numbers by FSA, UK [147] E414

–

–

– GRAS

–

– GRAS

–

GRAS

According to Handbook of Pharmaceutical Excipients [150] GRAS

Table 5 Regularity status of the naturally available gums of various sources for suitable application in pharmaceutical formulations

48 V. Prajapati et al.

Pectin

Tara gum Xanthan gum

12

14

15 16

– REG

GRAS, GMP –

GRAS/ FS –

Dental paste, topical powder, topical paste – Oral suspensions, tablets, rectal and topical products

Buccal, sublingual tablets, oral powders, suspensions, syrup, tablets Oral tablets, extended-release oral formulations –

E417 E415

Yes Yes

Yes

No

– E440

Yes

Yes

E410

E413

– GRAS

GRAS

–

–

GRAS

Note: Meaning of utilized abbreviations, GRAS: Generally recognized as safe; GRAS/FS: Substances generally recognized as safe in foods but limited in standardized foods where the standard provides for its use; GMP: In accordance with good manufacturing practices, or sufficient for the purpose, or quantity not greater than required; REG/FS: Food additives regulated under the Food Additives Amendment (FAA) and included in a specific food standard; REG: Food additives for which a petition has been filed and a regulation issued

13

Gum tragacanth Locust bean gum Oat gum

11

2 Pharmaceutical Applications of Various Natural Gums and Mucilages 49

50

V. Prajapati et al.

unique characteristics. They are used as binding agents, emulsifying agents, suspending agents, gelling agents, stabilizers, thickening agents, film formers, viscosity modifying agents, and release retardants in different conventional to a novel pharmaceutical formulation of suitable core materials. These nontoxic and biodegradable polymers have also been used in the form of edible films or biocompatible packaging for food products to increase their self-life. Natural gums and mucilages serve as renewable resources for sustainable supply of the pharmaceutical and food industry as excipients. Through this chapter, it can be concluded that the reader can get the attentive direction in the development of suitable drug delivery systems of various core materials using the naturally available gums and mucilages for the benefit of society. Their applications in the pharmaceutical fields can be increased in definite proportion using various compatible polymers. In the future, their function can be modified in the various pharmaceutical formulations as per the need of patients, pharmacists, and physicians.

References 1. Choudhary PD, Pawar HA (2014) Recently investigated natural gums and mucilages as pharmaceutical excipients: an overview. J Pharm 2014: Article ID 204849:1–9 2. Alonso-Sande M, Teijeiro-Osorio D, Remunán-López C, Alonso MJ (2009) Glucomannan, a promising polysaccharide for biopharmaceutical purposes. Eur J Pharm Biopharm 72(2): 453–462 3. Mirhosseini H, Amid BT (2012) A review study on chemical composition and molecular structure of newly plant gum exudates and seed gums. Food Res Int 46(1):387–398 4. Sharma DR, Sharma A, Kaundal A, Rai PK (2016) Herbal gums and mucilage as excipients for pharmaceutical products. Res J Pharmacogn Phytochem 8(3):145–152 5. Bahadur S, Sahu UK, Sahu D, Sahu G, Roy A (2017) Review on natural gums and mucilage and their application as excipient. J Appl Pharm Res 5(4):13–21 6. Prajapati VD, Jani GK, Moradiya NG, Randeria NP (2013) Pharmaceutical applications of various natural gums, mucilages and their modified form. Carbohydr Polym 92(2):1685–1699 7. Jani GK, Shah DP, Prajapati VD, Jain VC (2009) Gums and mucilages: versatile excipients for pharmaceutical formulations. Asian J Pharm Sci 4(5):309–323 8. Amiri MS, Mohammadzadeh V, Yazdi MET, Barani M, Rahdar A, Kyzas GZ (2021) Plantbased gums and mucilages applications in pharmacology and nanomedicine: a review. Molecules 26(6):1770 9. Jones JKN, Smith F (1949) Plant gums and mucilages. Adv Carbohydr Chem 243–291 10. Bhosale RR, Osmani RAM, Moin A (2014) Natural gums and mucilages: a review on multifaceted excipients in pharmaceutical science and research. Int J Pharmacogn Phytochem Res 15(4):901–912 11. de Oliveira Filho JG, Lira MM, de Sousa TL, Campos SB, Lemes AC, Egea MB (2021) Plantbased mucilage with healing and anti-inflammatory actions for topical application: a review. Food Hydrocoll Health 1:100012 12. Cevoli C, Balestra F, Ragni L, Fabbri A (2013) Rheological characterisation of selected food hydrocolloids by traditional and simplified techniques. Food Hydrocoll 33(1):142–150 13. George B, Suchithra TV (2019) Plant-derived bioadhesives for wound dressing and drug delivery system. Fitoterapia 137:104241 14. Thakur G, Mitra A, Pal K, Rousseau D (2009) Effect of flaxseed gum on reduction of blood glucose and cholesterol in type 2 diabetic patients. Int J Food Sci Nutr 60(sup:6):126–136

2

Pharmaceutical Applications of Various Natural Gums and Mucilages

51

15. Joseph B, George J, Mohan J (2013) Pharmacology and traditional uses of Mimosa pudica. Int J Pharm Sci Drug Res 5:41–44 16. Chang PR, Zhou Z, Xu P, Chen Y, Zhou S, Huang J (2009) Thermoforming starch-graftpolycaprolactone biocomposites via one-pot microwave assisted ring opening polymerization. J Appl Polym Sci 113(5):2973–2979 17. Rana V, Rai P, Tiwary AK, Singh RS, Kennedy JF, Knill CJ (2011) Modified gums: approaches and applications in drug delivery. Carbohydr Polym 83(3):1031–1047 18. Huanbutta K, Sittikijyothin W (2018) Use of seed gums from Tamarindus indica and Cassia fistula as controlled-release agents. Asian J Pharm Sci 13(5):398–408 19. Hezerlou A, Zolfaghari H, Banihashemi SA, Forghani S, Ehsani A (2021) Plant gums as the functional compounds for edible films and coatings in the food industry: a review. Polym Adv Technol 32:2306–2326 20. Salarbashi D, Tafaghodi M (2018) An update on physicochemical and functional properties of newly seed gums. Int J Biol Macromol 119:1240–1247 21. Jouki M, Yazdi FT, Mortazavi SA, Koocheki A (2013) Physical barrier and antioxidant properties of a novel plasticized edible film quince seed mucilage. Int J Biol Macromol 62: 500–507 22. Selvasekaran P, Chidambaram R (2021) Food-grade aerogels obtained from polysaccharides, proteins, and seed mucilages: role as a carrier matrix of functional food ingredients. Trends Food Sci Technol 112:455–470 23. Andrade LA, de Oliveira Silva DA, Nunes CA, Pereira J (2020) Experimental techniques for the extraction of taro mucilage with enhanced emulsifier properties using chemical characterization. Food Chem 327:127095 24. Nazari M (2021) Plant mucilage components and their functions in the rhizosphere. Rhizosphere 18:100344 25. Alam AS, Parrott EL (1971) Effect of aging on some physical properties of hydrochlorothiazide tablet. J Pharm Sci 60(2):263–266 26. Beikzadeh S, Khezerlou A, Jafari SM, Pilevar Z, Mortazavian AM (2020) Seed mucilages as the functional ingredients for biodegradable films and edible coatings in the food industry. Adv Colloid Interface Sci 280:102164 27. Sworn G (2000) Xanthan gum. In: Handbook of hydrocolloids, edited by Phillips GO and Williams PA, in Woodhead Publishing Series in Food Science, Technology and Nutrition, Woodhead Publishing, Published in North and South America by CRC Press LLC, England, pp 103–116 28. Mair H, Anderson M, Karl C, Magnuson K, Whstler RL (1993) Guar, Locust Bean, Tara, and Fenugreek Gums. In: Industrial gums, pp 181–226 29. Pegg AM (2012) The application of natural hydrocolloids to foods and beverages in natural food additives, ingredients and flavourings. Woodhead Publishing, Cambridge, pp 175–196 30. Anderson DMW, Stoddart JF (1966) Studies on uronic acid materials: part XV. The use of molecular-sieve chromatography in studies on Acacia senegal gum (gum Arabic). Carbohydr Res 2(2):104–114 31. Martins JT, Cerqueira MA, Bourbon AI, Pinheiro AC, Souza BW, Vicente AA (2012) Synergistic effects between κ-carrageenan and locust bean gum on physicochemical properties of edible films made thereof. Food Hydrocoll 29:280–289 32. Khouryieh H, Puli G, Williams K, Aramouni F (2015) Effects of xanthan–locust bean gum mixtures on the physicochemical properties and oxidative stability of whey protein stabilised oil-in-water emulsions. Food Chem 167:340–348 33. Deshmukh AS, Aminabhavi TM (2015) Pharmaceutical applications of various natural gums. In: Polysaccharides Bioactivity and Biotechnology edited by Ramawat KG, Mérillon JM, Springer International Publishing Switzerland, pp 1933–1967 34. Deb PK, Kokaz SF, Abed SN, Paradkar A, Tekade RK (2019) Pharmaceutical and biomedical applications of polymers. In: Basic fundamentals of drug delivery. Academic, New York, pp 203–267

52

V. Prajapati et al.

35. Ceulemans J, Vinckier I, Ludwig A (2002) The use of xanthan gum in an ophthalmic liquid dosage form: rheological characterization of the interaction with mucin. J Pharm Sci 91(4): 1117–1127 36. Durig T, Karan K (2019) Binders in wet granulation. In: The handbook of pharmaceutical wet granulation. Academic, pp 317–349 37. Whistler RL (1993) Exudate gums. In: Industrial gums. Academic, New York, pp 309–339 38. Bala R, Rana R, Madaan R (2019) Natural gums and mucilage as matrix formers in sustained released dosage forms. Res J Pharm Tech 12(10):5119–5125 39. Silveira JLM, Bresolin TMB (2011) Pharmaceutical use of galactomannans. Química Nova 34:292–299 40. Bora A, Deshmukh S, Swain K (2014) Recent advances in semisolid dosage form. Int J Pharm Sci Res 5(9):3596–3609 41. Lu EX, Jiang ZQ, Zhang QZ (2003) A water-insoluble drug monolithic osmotic tablet system utilizing gum arabic as an osmotic, suspending and expanding agent. J Control Release 92: 375–382 42. Beneke CE, Viljoen AM, Hamman JH (2009) Polymeric plant-derived excipients in drug delivery. Molecules 14:2602–2262 43. Kamel R, Afifi SM, Kassem IA, Elkasabgy NA, Farag MA (2020) Arabinoxylan and rhamnogalacturonan mucilage: outgoing and potential trends of pharmaceutical, environmental, and medicinal merits. Int J Biol Macromol 165:2550–2564 44. Gurpreet A, Karan M, Inderbir S, Sandeep A (2011) Formulation and evaluation of controlled release mucoadhesive matrix tablets: as oleo gum resin as a natural pharmaceutical excipient. Int J Pharm Sci Drug Res 3(2):84–88 45. Ciudad-Mulero M, Fernández-Ruiz V, Matallana-Gonzalez MC, Morales P (2019) Dietary fiber sources and human benefits: the case study of cereal and pseudocereals. In: Advances in food and nutrition research. Academic, New York, pp 83–134 46. Deshmukh SS, Katare YS, Shyale SS, Bhujbal SS, Kadam SD, Landge DA, Shah DV, Pawar JB (2013) Isolation and evaluation of mucilage of Adansonia digitata Linn as a suspending agent. J Pharm 1–4 47. Nayak AK, Pal D, Pany DR, Mohanty B (2010) Evaluation of Spinacia oleracea L. leaves mucilage as an innovative suspending agent. J Adv Pharm Tech Res 1(3):338 48. Ahuja M, Kumar A, Yadav P, Singh K (2013) Mimosa pudica seed mucilage: isolation; characterization and evaluation as tablet disintegrant and binder. Int J Biol Macromol 57: 105–110 49. Kaleemullah M, Jiyauddin K, Thiban E, Rasha S, Al-Dhalli S, Budiasih S, Gamal OE, Fadli A, Eddy Y (2017) Development and evaluation of Ketoprofen sustained release matrix tablet using Hibiscus rosa-sinensis leaves mucilage. Saudi Pharm J 25:770–779 50. Amelia MA, Rakesh RD, Shilpa NS (2011) Recent investigations of plant based natural gums, mucilages and resins in novel drug delivery systems. Indian J Pharm Educ Res 45(1): 86–99 51. Mukherjee B, Dinda SC, Barik BB (2008) Gum cordia: a novel matrix forming material for enteric resistant and sustained drug delivery – a technical note. AAPS PharmSciTech 9(1): 330–333 52. Braga RC, Teixeira-Sá DMA, Ribeiro AF, Miranda RL, Almeida LMD, Horta ACG, Moreira RDA (2011) Evaluation of Caesalpinia pulcherrima endospermic gum as affinity matrices for galactose-binding lectins interaction. Braz Arch Biol Technol 54:283–292 53. Sudarshan S, Sangeeta S, Bothra SB, Roshan P (2010) Pharmaceutical characterization of some natural excipient as potential mucoadhesive agent. Pharm Res J 4:91–104 54. Eichie FE, Amalime AE (2001) Evaluation of the binder effects of the gum mucilages of Cissus populnea and Acassia senegal on the mechanical properties of paracetamol tablets. Afr J Biotechnol 6(19):2208–2211 55. Adetogun GE, Alebiowu G (2009) Properties of Delonix regia seed gum as a novel tablet binder. Acta Pol Pharm 66(4):433–438

2

Pharmaceutical Applications of Various Natural Gums and Mucilages

53

56. Barhate AN, Virkar AR, Beldar GB, Shinde S (2014) Evaluation of Delonix regia seed gum as suspending agent in paracetamol suspensions. Int J PharmTech Res 6(2):530–536 57. Chaudhary A, Kulkarnı GT, Awasthı R, Kumar P (2016) Investigation on binding properties of Grewia asiatica mucilage in tablet formulations. Marmara Pharm J 20:353–367 58. Taheri A, Jafari SM (2019) Gum-based nanocarriers for the protection and delivery of food bioactive compounds. Adv Colloid Interf Sci 269:277–295 59. Jain NK, Dixit VK (1988) Studies on gums and their derivatives as binding agent. Indian J Pharm Sci 50:113–114 60. Pawar HA, Kamat SR, Choudhary PD (2015) An overview of natural polysaccharides as biological macromolecules: their chemical modifications and pharmaceutical applications. Biol Med 7:1 61. Alur HH, Pather SI, Mitra AK (1999) Evaluation of the gum from Hakea gibbosa as a sustained-release and mucoadhesive component in buccal tablets. Pharm Dev Technol 4: 347–358 62. Sreenivasa B, Prasanna RY, Mary S (2000) Design and studies of gum karaya matrix tablet. Int J Pharm Excip:239–242 63. Munday DL, Philip JC (2000) Compressed xanthan and karaya gum matrices: hydration, erosion and drug release mechanisms. Int J Pharm 203(1–2):179–192 64. Bharaniraja B, Jayaram KK, Prasada CM, Sen AK (2011) Different approaches of katira gum formulations for colon targeting. Int J Biol Macromol 49(3):305–310 65. Odeku OA, Itiola OA (2003) Evaluation of the effect of khaya gum on the mechanical and release properties of paracetamol tablets. Drug Dev Ind Pharm 29(3):311–320 66. Verma PRP, Razdan B (2003) Evaluation of Leucaena leucocephala seed gum as suspending agent in sulphadimidine suspensions. Indian J Pharm Sci 65:665–668 67. Deshmukh VN, Sakarkar DM, Wakade RB (2009) Formulation and evaluation of controlled release alginate microspheres using locust bean gum. J Pharm Res 2(3):458–461 68. Prajapati VD, Jani GK, Moradiya NG, Randeria NP, Nagar BJ (2013) Locust bean gum: a versatile biopolymer. Carbohydr Polym 94(2):814–821 69. Prajapati VD, Jani GK, Moradiya NG, Randeria NP, Maheriya PM, Nagar BJ (2014) Locust bean gum in the development of sustained release mucoadhesive macromolecules of aceclofenac. Carbohydr Polym 113:138–148 70. Prajapati VD, Maheriya PM, Roy SD (2021) Chapter 7 – Locust bean gum-derived hydrogels. In: Giri TK, Ghosh B (eds) Plant and algal hydrogels for drug delivery and regenerative medicine. Woodhead publishing series in biomaterials. Woodhead Publishing, pp 217–260 71. Anderson DM, Douglas DMB (1988) The composition of the proteinaceous gums exuded by some Leucaena species, subspecies and hybrids. Food Hydrocoll 2(3):247–253 72. Mitul TP, Jitendra KP, Umesh MU (2012) Assessment of various pharmaceutical excipients properties of natural Moringa oleifera gum. Int J Pharm Life Sci 3(7):1833–1847 73. Anthony AA, Obichukwu JN (2007) Mucuna gum microspheres for oral delivery of glibenclamide: in vitro evaluation. Acta Pharma 57:161–171 74. Mukherjee S, Srivastava HC (1955) The structure of neem gum. J Am Chem Soc 77(2): 422–423 75. Samrot AV, Angalene JLA, Roshini SM, Stefi SM, Preethi R, Raji P (2020) Purification, characterization and exploitation of Azadirachta indica gum for the production of drug loaded nanocarrier. Mater Res Express 7(5):055007 76. Ogunjimi AT, Alebiowu G (2014) Neem gum as a binder in a formulated paracetamol tablet with reference to Acacia gum BP. AAPS PharmSciTech 15(2):500–510 77. Kalaskar MG, Mutha RE, Tatiya AU, Firke SD, Surana SJ, Dhoka KA, Heda K (2021) Purification and modification of neem gum for enhancement of its suspending property. Future J Pharm Sci 7(1):1–8 78. Kalu VD, Odeniyi MD, Jaiyeoba KT (2007) Matrix properties of a new plant gum in controlled drug delivery. Arch Pharm Res 30(7):884–889

54

V. Prajapati et al.

79. Koocheki A, Mortazavi SA, Shahidi F, Razavi SMA Taherian AR (2009) Rheological properties of mucilage extracted from Alyssum homolocarpum seed as a new source of thickening agent. J Food Eng 91(3): 490–496 80. Hesarinejad MA, Razavi SMA, Koocheki A (2015) Alyssum homolocarpum seed gum: dilute solution and some physicochemical properties. Int J Biol Macromol 81:418–426 81. Rezagholi F, Hashemi SMB, Gholamhosseinpour A, Sherahi MH, Hesarinejad MA, Ale MT (2019) Characterizations and rheological study of the purified polysaccharide extracted from quince seeds. J Sci Food Agric 99(1):143–151 82. Alison CH, John RM, Martyn CD (1995) Structure and behavior in hydrophilic matrix sustained release dosage forms: the influence of pH on the sustained release performance and internal gel structure of sodium alginate matrices. J Control Release 33(1):143–152 83. Gayatri CP, Madhabhai MP (2009) Preliminary evaluation of sesbania seed gum mucilage as gelling agent. Int J PharmTech Res 1(3):840–843 84. Sharma N, Sinderpal T (2019) Sterculia gum: chemical structure, composition and physicochemical properties. Asian J Chem 32(1):1–8 85. Datta R, Bandyopadhyay AK (2006) A new nasal drug delivery system for diazepam using natural mucoadhesive polysaccharide obtained from tamarind seeds. Saudi Pharma J 14: 115–119 86. Li H, Hong SL, Xiaohai F, Pingkai O (2012) Optimization of exopolysaccharide welan gum production by Alcaligenes sp. CGMCC2428 with Tween-40 using response surface methodology. Carbohydr Polym 87(2):1363–1368 87. Anvari M, Tabarsa M, Cao R, You S, Joyner HS, Behnam S et al (2016) Compositional characterization and theological properties of anionic gum from Alyssum homolocarpum seeds. Food Hydrocoll 52:766–773 88. Tosif MM, Najda A, Bains A, Kaushik R, Dhull SB, Chawla P, Walasek-Janusz M (2021) A comprehensive review on plant-derived mucilage: characterization, functional properties, applications, and its utilization for nanocarrier fabrication. Polymers 13(7):1066 89. Koocheki A, Hesarinejad MA (2019) Qodume Shahri (Lepidium perfoliatum) seed gum. Emerg Nat Hydrocol 251–272 90. Jouki M, Yazdi FT, Mortazavi SA, Koocheki A (2013) Physical, barrier and antioxidant properties of a novel plasticized edible film from quince seed mucilage. Int J Biol Macromol 62:500–507 91. Behbahani BA, Shahidi F, Yazdi FT, Mortazavi SA, Mohebbi M (2017) Use of Plantago major seed mucilage as a novel edible coating incorporated with Anethum graveolens essential oil on shelf-life extension of beef in refrigerated storage. Int J Biol Macromol 94:515–526 92. Niknam R, Ghanbarzadeh B, Hamishehkar H (2019) Plantago major seed gum based biodegradable films: effects of various plant oils on microstructure and physicochemical properties of emulsified films. Polym Test 77:105868 93. Beikzadeh S, Peyghambardoust S, Homayouni RA, Beikzadeh M (2017) Effects of psyllium and marve seed mucilages on physical sensory and staling properties of sponge cake. J Agric Sci Technol 19:1079–1089 94. Ma F, Li X, Ren Z, Sarkka-Tirkkonen M, Zhang Y, Zhao D, Liu X (2021) Effects of concentrations, temperature, pH and co-solutes on the rheological properties of mucilage from Dioscorea opposita Thunb. and its antioxidant activity. Food Chem 360:130022 95. Feizi R, Goh KK, Mutukumira AN (2021) Effect of chia seed mucilage as stabiliser in ice cream. Int Dairy J 120:105087 96. Ubeyitogullari A, Ciftci ON (2020) Fabrication of bioaerogels from camelina seed mucilage for food applications. Food Hydrocoll 102:105597 97. Antigo JLD, Stafussa AP, de Cassia BR, Madrona GS (2020) Chia seed mucilage as a potential encapsulating agent of a natural food dye. J Food Eng 285:110101 98. Neto AA, Tomazini LF, Mizuta AG, Corrêa RC, Madrona GS, de Moraes FF, Peralta RM (2021) Direct microencapsulation of an annatto extract by precipitation of psyllium husk mucilage polysaccharides. Food Hydrocoll 112:106333

2

Pharmaceutical Applications of Various Natural Gums and Mucilages

55

99. Basiri S, Haidary N, Shekarforoush SS, Niakousari M (2018) Flaxseed mucilage: a natural stabilizer in stirred yogurt. Carbohydr Polym 187:59–65 100. Gürbüz Z, Erkaya-Kotan T, Şengül M (2021) Evaluation of physicochemical, microbiological, texture and microstructure characteristics of set-style yoghurt supplemented with quince seed mucilage powder as a novel natural stabiliser. Int Dairy J 114:104938 101. Geetanjali R, Sreejit V, Sandip P, Preetha R (2021) Preparation of Aloe vera mucilage-ethyl vanillin Nano-emulsion and its characterization. Mater Today Proc 43:3766–3773 102. Wang R, Li X, Ren Z, Xie S, Wu Y, Chen W, Ma F, Liu X (2020) Characterization and antibacterial properties of biodegradable films based on CMC, mucilage from Dioscorea opposita Thunb. and Ag nanoparticles. Int J Biol Macromol 163:2189–2198 103. Keshani-Dokht S, Emam-Djomeh Z, Yarmand MS, Fathi M (2018) Extraction, chemical composition, rheological behavior, antioxidant activity and functional properties of Cordia myxa mucilage. Int J Biol Macromol 118:485–493 104. Nayak AK, Pal D, Pany DR, Mohanty B (2010) Evaluation of Spinacia oleracea L. leaves mucilage as an innovative suspending agent. J Adv Pharm Technol Res 1(3):338 105. Prajapati VD, Maheriya PM, Jani GK, Patil PD, Patel BN (2014) Lepidium sativum Linn.: a current addition to the family of mucilage and its applications. Int J Biol Macromol 65:72–80 106. Ramadan MF, Oraby HF (2020) Lepidium sativum Seeds: Therapeutic Significance and Health-Promoting Potential, In: Nuts and Seeds in Health and Disease Prevention, Preedy VR, Watson RR, Academic Press Inc, United Kingdom, pp 273–289 107. Razavi SMA, Cui SW, Ding H (2016) Structural and physicochemical characteristics of a novel water-soluble gum Lallemantia royleana seed. Int J Biol Macromol 83:142–151 108. Gemede HF, Haki GD, Beyene F, Rakshit SK, Woldegiorgis AZ (2018) Indigenous Ethiopian okra (Abelmoschus esculentus) mucilage: a novel ingredient with functional and antioxidant properties. Food Sci Nutr 6(3):563–571 109. de Andrade VE, Alcântara MA, Dos Santos NA, Gondim AD, Iacomini M, Mellinger C, de Magalhaes Cordeiro AM (2021) Mucilages of cacti from Brazilian biodiversity: extraction, physicochemical and technological properties. Food Chem 346:128892 110. Haile TG, Sibhat GG, Molla F (2020) Physicochemical characterization of Grewia ferruginea hochst. A rich mucilage for potential use as a pharmaceutical excipient. Biomed Res Int 2020: 4094350 111. Alok S, Jain S, Verma A, Kumar M, Mahor A, Sabharwal M (2013) Plant profile, phytochemistry and pharmacology of Asparagus racemosus (Shatavari): a review. Asian Pac J Trop Dis 3 (3):242–251 112. Ghumman SA, Bashir S, Ahmad J, Hameed H, Khan IU (2017) Colocasia esculenta corms mucilage-alginate microspheres of oxcarbazepine: design, optimization and evaluation. Acta Pol Pharm 74(2):505–517 113. Hosseini-Parvar SH, Osano JP, Matia-Merino L (2016) Emulsifying properties of basil seed gum: effect of pH and ionic strength. Food Hydrocoll 52:838–847 114. Silva SH, Neves IC, Oliveira NL, de Oliveira AC, Lago AM, de Oliveira Giarola TM, de Resende JV (2019) Extraction processes and characterization of the mucilage obtained from green fruits of Pereskia aculeata Miller. Ind Crop Prod 140:111716 115. Pereira GA, Silva EK, Araujo NM, Arruda HS, Meireles MA, Pastore GM (2019) Mutamba seed mucilage as a novel emulsifier: stabilization mechanisms, kinetic stability and volatile compounds retention. Food Hydrocoll 97:105190 116. Haruna S, Aliyu BS, Bala A (2016) Plant gum exudates (Karau) and mucilages, their biological sources, properties, uses and potential applications: a review. Bayero J Pure Appl Sci 9:159–165 117. Prajapati VD, Jani GK, Moradiya NG, Randeria NP, Nagar BJ, Naikwadi NN, Variya BC (2013) Galactomannan: a versatile biodegradable seed polysaccharide. Int J Biol Macromol 60:83–92 118. Prajapati VD, Jani GK, Zala BS, Khutliwala TA (2013) An insight into the emerging exopolysaccharide gellan gum as a novel polymer. Carbohydr Polym 93(2):670–678

56

V. Prajapati et al.

119. Ameena K, Dilip C, Saraswathi R, Krishnan PN, Sankar C, Simi SP (2010) Isolation of the mucilages from Hibiscus rosasinensis Linn. and Okra (Abelmoschus esculentus Linn.) and studies of the binding effects of the mucilages. Asian Pac. J Trop Med 3(7):539–543 120. Ghumman SA, Bashir S, Noreen S, Khan AM, Malik MZ (2019) Taro-corms mucilagealginate microspheres for the sustained release of pregabalin: in vitro and in vivo evaluation. Int J Biol Macromol 139:1191–1202 121. Patel DM, Prajapati DG, Patel NM (2007) Seed mucilage from Ocimum americanum Linn. As disintegrant in tablets: separation and evaluation. Indian J Pharm Sci 69(3):431–435 122. Maqsood H, Uroos M, Muazzam R, Naz S, Muhammad N (2020) Extraction of basil seed mucilage using ionic liquid and preparation of AuNps/mucilage nanocomposite for catalytic degradation of dye. Int J Biol Macromol 164:1847–1857 123. Alpizar-Reyes E, Varela-Guerrero V, Cruz-Olivares J, Carrillo-Navas H, Alvarez-Ramirez J, Pérez-Alonso C (2020) Microencapsulation of sesame seed oil by tamarind seed mucilage. Int J Biol Macromol 145:207–215 124. Yari K, Akbari I, Yazdi SA (2020) Development and evaluation of sodium alginate-basil seeds mucilage beads as a suitable carrier for controlled release of metformin. Int J Biol Macromol 159:1–10 125. Das S, Ghosh A, Changder A, Nandi G, Ghosh LK (2020) Quality-by-design approach for development of sustained-release multiple-unit beads of lamotrigine based on ion-crosslinked composite of pectin and okra mucilage: an in vitro appraisal. Int J Biol Macromol 163: 842–853 126. Hosseini MS, Nabid MR (2020) Synthesis of chemically cross-linked hydrogel films based on basil seed (Ocimum basilicum L.) mucilage for wound dressing drug delivery applications. Int J Biol Macromol 163:336–347 127. Rao KM, Gnanaprakash K, Badarinath AV, Chetty CM, Alagusundaram M (2010) Preparation and evaluation of flurbiprofen gel; mucilage of Cocculus hirsutus leaf powder as gel base. Int J PharmTech Res 2(2):1578–1583 128. Chatchawal C, Nualkaew N, Preeprame S, Porasuphatana S, Priprame A (2010) Physical and biological properties of mucilage from Basella alba L. stem and its gel formulations. Int J Plant Sci 6(3):104–112 129. Chowdhury M, Sengupta A, Datta L, Chatterjee S (2017) Role of mucilage as pharmaceutical additives and cytoprotective agent. J Innov Pharm Biol Sci 4:46–52 130. Singh SK, Singh S (2010) Evaluation of Cassia fistula Linn. Seed mucilage in tablet formulations. Int J PharmTech Res 2:1839–1846 131. KSG AK, Palanisamy S, Rajasekaran A (2009) Evaluation of Cassia roxburghii Seed Gum as binder in tablet formulations of selected drugs. Int J Pharm Sci Nanotech 2(4): 726–732 132. Kumar A (2012) Cashew gum a versatile hydrophyllic polymer: a review. Curr Drug Ther 7: 2–12 133. Dehghani S, Noshad M, Rastegarzadeh S, Hojjati M, Fazlara A (2020) Electrospun chia seed mucilage/PVA encapsulated with green cardamonmum essential oils: antioxidant and antibacterial property. Int J Biol Macromol 161:1–9 134. da Silva SF, de Campo C, Paese K, Guterres SS, Costa TMH, Flores SH (2019) Nanoencapsulation of linseed oil with chia mucilage as structuring material: characterization, stability and enrichment of orange juice. Food Res Int 120:872–879 135. Bramhe NN, Kilor V (2014) Evaluation and optimization of Lepidium sativum seed mucilage as binder in tablet formulation. Int J Pharm Pharm Sci 6:285–291 136. Kolhe S, Kasar T, Dhole SN, Upadhye M (2014) Extraction of mucilage and its comparative evaluation as a binder. Am J Adv Drug Deliv 2(3):330–343 137. Selvi RS, Gopalakrishanan S, Ramajayam M, Soman R (2010) Evaluation of mucilage of Prosopis juliflora as tablet binder. Int J Pharm Pharm Sci 2:157–160 138. Nayak AK, Pal D, Santra K (2013) Plantago ovata F. mucilage-alginate mucoadhesive beads for controlled release of glibenclamide: development, optimization, and in vitro-in vivo evaluation. J Pharm 2013: Article ID: 151035:1–11

2

Pharmaceutical Applications of Various Natural Gums and Mucilages

57

139. Hakala TJ, Saikko V, Arola S, Ahlroos T, Helle A, uosmanen P et al. (2014) Structural characterization and tribological evaluation of quince seed mucilage. Tribol Int 77:24–31 140. Singh K, Kumar A, Langyan N, Ahuja M (2009) Evaluation of Mimosa pudica seed mucilage as sustained-release excipient. AAPS PharmSciTech 10:1121–1127 141. Narkhede SB, Bendale AR, Patel K, Vidyasagar G (2011) Isolation and evaluation of starch of Artocarpus heterophyllus as a tablet binder. Int J PharmTech Res 3:836–840 142. Sharma N, Kulkarni GT, Sharma A, Bhatnagar A, Kumar N (2013) Natural mucoadhesive microspheres of Abelmoschus esculentus polysaccharide as a new carrier for nasal drug delivery. J Microencapsul 30:589–598 143. Kumar R, Patil MB, Patil SR, Paschapur MS (2015) Isolation and evaluation of disintegrating properties of Salicornia fruticosa (L.) mucilage. Int J Pharm Tech Res 1:537–543 144. Deore SL, Khadabadi SS (2008) Standardisation and pharmaceutical evaluation of Chlorophytum borivilianum mucilage. Rasayan J Chem 1:887–892 145. Rohini B, Ishwarya SP, Rajasekharan R, VijayaKumar AK (2020) Ocimum basilicum seed mucilage reinforced with montmorillonite for preparation of bionanocomposite film for food packaging applications. Polym Test 87:106465 146. US Food and Drug Administration. Food additive status list. Revised as of April.;1 147. Food Standards Agency, Government of United Kingdom 148. Drugs and Health Products, Government of Canada 149. Naqvi SA, Khan MM, Shahid M, Jaskani MJ, Khan IA, Zuber M et al (2011) Biochemical profiling of mucilage extracted from seeds of different citrus rootstocks. Carbohydr Polym 83: 623–628 150. Sheskey PJ, Cook W, Cable CG (2019) Handbook of pharmaceutical excipients. Medicines Complete (Series Ed.), Last updated 12th November 151. Begum AT, Anbazhakan S (2013) Evaluation of antibacterial activity of the mucilage of Dioscorea esculenta (Lour.) Burkill. Int J Mod Biol Med 4:140–146 152. Okunlola A, Odeku OA (2011) Evaluation of starches obtained from four Dioscorea species as binding agent in chloroquine phosphate tablet formulations. Saudi Pharm J 19(2):95–105 153. Moslemi M (2021) Reviewing the recent advances in application of pectin for technical and health promotion purposes: from laboratory to market. Carbohydr Polym 254:117324 154. Prajapati VD, Mashru KH, Solanki HK, Jani GK (2013) Development of modified release gliclazide biological macromolecules using natural biodegradable polymers. Int J Biol Macromol 55:6–14 155. Razavi M, Nyamathulla S, Karimian H, Noordin MI (2014) Novel swellable polymer of orchidaceae family for gastroretentive drug delivery of famotidine. Drug Des Devel Ther 8: 1315–1329 156. Kamatou GPP, Vermaak I, Viljoen AM (2011) An updated review of Adansonia digitata: a commercially important African tree. S Afr J Bot 77(4):908–919 157. Arama E, Michaud P, Rauffiac R, Rodriguez F (1988) A new excipient in pharmaceutical formulation of theophylline tablets of the hydrophilic matrix type: the pulp of the baobab fruit (Adansonia digitata L.). Farmaco Prat 43(10):303–315 158. Pinto Nde C, Duque AP, Pacheco NR, Mendes Rde F, Motta EV, Bellozi PM, Ribeiro A, Salvador MJ, Scio E (2015) Pereskia aculeata: a plant food with antinociceptive activity. Pharm Biol 53(12):1780–1785 159. Sims IM, Smith AM, Morris GA, Ghori MU, Carnachan SM (2018) Structural and rheological studies of a polysaccharide mucilage from lacebark leaves (Hoheria populnea A. Cunn.). Int J Biol Macromol 111:839–847

3

Tree Gum-Based Renewable Materials and Nanoparticles Vinod V. T. Padil and Miroslav Černík

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 “Green” and Sustainable Products Based on Tree Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Tree Gum-Derived Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Tree Gum-Based Nanofibers . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Tree Gum-Based Carbon Nanostructures for Energy and Environmental Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Films Based on Tree Gums and Their Composites . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Tree Gum Sponges . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6 Greener Corrosion Inhibitors Based on Tree Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

60 62 62 65 67 68 71 73 74 75

Abstract

Carbohydrate gums based on trees are an important food additive as well as frameworks for potential nonfood applications. The current chapter exemplified the future development of nanoparticles, nanofibers, sponges, films, and composites based on tree gums for “green” and sustainable applications. Recent developments of tree gums explored to prepare and stabilize metal, nonmetal, bimetallic, and carbon nanostructures have been critically surveyed. Further, the development of renewable and recyclable products based on tree gums via varieties of techniques such as electrospinning, solution casting, self-assemblylyophilization, etc., is exemplified with suitable examples. The improvement of physicochemical, mechanical, and barrier properties of incorporating the gum-based material with other inorganic, organic, or nanoparticles as additives have been discussed. The sustainable gum-based products and their morphological, structural, and mechanical attributes were embodied by scanning electron V. V. T. Padil (*) · M. Černík Institute for Nanomaterials, Advanced Technologies and Innovation (CXI), Technical University of Liberec (TUL), Liberec, Czech Republic e-mail: [email protected]; [email protected] © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_3

59

V. V. T. Padil and M. Černík

60

microscopy (SEM), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Raman spectroscopy, X-ray diffraction techniques (XRD), and UV-vis spectroscopy, etc. The ensued gum-based polymeric products for environmental remediation, water purification, food packaging materials, carrier bags, lithium-ion batteries, energy harvesters, tissue engineering, regenerative medicine, and corrosion inhibitors have been elaborately discussed with the current and upcoming potential development of low-cost green products for a sustainable future. Keywords

Biodegradation · Corrosion inhibitors · Electrospun fibers · Films · Food packaging · Li-ion battery · Nanoparticles · Sponge · Tree gums · Water purification

1

Introduction

Tree gum carbohydrate polymers are versatile, natural, nontoxic, biodegradable, and sustainable “green” produce. Gums represent food additives, and the collection, processing, and trading also serve most of the society of particular sections of people as a commodity for their lives in many counties of the world. Most of the gums are used as food additives, but the nonfood applications of these renowned materials have not been researched thoroughly to exploit them in many potential applications. Even though gums belong to many cradles and are diversified into varieties of species and families, the present chapter focuses on tree gums sourced gums, commercially available, and ensuring food and nonfood grade gums are used for many impending applications. Tree gums are high-molecular-weight polysaccharides exuded from plants/trees as a defense mechanism against mechanical injury, chemical injury, microbial/insect attacks, and water stress. This process is called gummosis, and the obtained exudates form gels or viscous solutions in their respective solvents. Hydrocolloids, or watersoluble gums, have found applications in food, pharmaceutical, biomedical, and cosmetic industries owing to their abundance, low cost, biocompatibility, nontoxicity, gelling ability, chemical inertness, water binding potential, and emulsion stabilization ability [1–9]. The principal tree gums are gum arabic (GA) [Acacia seyal and Acacia senegal trees (Fabaceae)], gum tragacanth (GT), gum karaya (GK), and gum kondagogu (KG). The habitation, sources, extraction, purification, structural assignment, rheological attributes, morphological analysis, and food and nonfood applications have been extensively deliberated in literature [10–14]. Briefly, the chemical composition and availability of significant tree exudate are described. The gum arabic consists of high-molecular-weight (350–850 kDa) polysaccharides [galactose (44%), rhamnose (13%), glucuronic acid (16%), and arabinose (27%) residues], glycoproteins, and minerals (calcium, potassium, and magnesium), giving it the properties of a glue and

3

Tree Gum-Based Renewable Materials and Nanoparticles

61

binder that are edible by humans. Gum arabic is abundant in central Sudan, West Africa, and tropical/semitropical areas such as India and Pakistan. Sudan is the leading producer of Acacia gum worldwide, followed by Nigeria, Chad, Mali, and Senegal. However, the largest Acacia gum markets are found in Europe and the USA, and the largest gum consumer is Japan in East Asia. Gum karaya (Sterculia urens) is a partially acetylated gum that consists of neutral sugars (galactose, arabinose, rhamnose, etc.) and acidic sugars (galacturonic and glucuronic acid) with 8% acetyl groups [15]. The significant use of karaya gum has been extensively for it’s thickening, gelling, stabilizing, and emulsification functionalities with other food and nonfood system. The structural assignment for gum karaya consists of α-D-galacturonic acid α-L-rhamnose backbone with β-D-galactose and β-D glucuronic acid side chains [9]. Gum karaya has been exposed as an industrial gum with potential pharmaceutical, environmental, and food uses. Its modified forms have been explored in the biomedical (drug delivery, tissue engineering, and nanocarriers) industry, food packaging materials, and environmental remediation of pollutants [3, 16–21]. Tragacanth gum (TG) (Astragalus gummifer) is an exudate gum that belong to the family Fabaceae and consists of structural linkages such as α-L-arabinofuranose, 1,4-β-D-galalactopyranose, and poly 1,4-α-D-galalacturonate [13]. The major constituents of TG consist of protein (0.31–3.82% w/w) and carbohydrate (83.81–86.52% w/w) apart from mineral elements. There are two main fractions of TG, such as tragacanthin (a water-soluble fraction) and SFGT (bassorin), a water-insoluble portion [22]. Tragacanthin swells and forms a high-viscose gel-like structure in water. TG is predominantly used as a thickening, viscosity enhancer, stabilizing, emulsifying in food and nonfood applications, including NPs preparation and coating of food surface and edible films, and encapsulation of food ingredients [23, 24]. A detailed investigation on the structural and functional properties of TG showed that their solution properties depend on the concentration of gum in the water and the sugar (galactose, rhamnose) or protein contents in their structure. The major influencing factors such as electrostatic repulsion, apparent viscosity, and interfacial tension impact TG’s emulsification and emulsion instability [23]. Gum kondagogu (Cochlospermum gossypium) is an Indian tree gum exudates with potential food, pharmaceutical, and other nonfood applications [25, 26]. Gum Kondagogu has a high acidic sugar content, with glucuronic and galacturonic acids accounting for 52% of total carbohydrates and neutral sugars, including glucose, rhamnose, galactose, and arabinose [25]. The essential areas of nonfood applications of tree gums and their superior family can be diversified schematically represented in this chapter. The chapter exemplified the use of tree gums in nanoparticle synthesis and stabilization, nanofibers production, the development of sponges and bioplastic films, corrosion inhibitor, and materials for energy storage and harvesting. This chapter reviews the updated aspects of the manufacture, chemical structure, functional properties, primary applications, and regulatory issues for three well-established hydrocolloids, namely, gum tragacanth, gum karaya, and Larchwood arabinogalactan along with those of mesquite gum, whose full potential utilization is still to be exploited in several fields of application (Fig. 1).

V. V. T. Padil and M. Černík

62

Fig. 1 The overview of the tree gum reinforced green and sustainable produces

2

“Green” and Sustainable Products Based on Tree Gums

Green and sustainable chemistry entrusted the quality research and their products with reducing or eliminating the environmental impact of chemical toxicity by promoting sustainable technologies that are fundamentally nontoxic to living organisms and the environment. Polysaccharides and their family functions an innumerous number of sustainable and environmentally friendly organic biopolymers for many potential applications [27]. Among natural-based polymers, tree polymers have a significant place as they are nontoxic, biodegradable, and follow green chemistry principles.

2.1

Tree Gum-Derived Nanoparticles

Nanoparticles (NPs) derived from green synthesis protocols have tremendous potential in nanotechnology, and their applications in catalysis, pharmaceuticals, environmental bioremediation and biotechnology, food, and energy have been reflected [28, 29]. However, the advantages of green synthesis over chemical and physical approaches and ensuing NPs shape, size, and morphology have been critically deliberated extensively [30, 31]. Tree gums such as arabic, karaya, tragacanth, and kondagogu have been extensively used for metal, metal oxide, bimetallic NPs synthesis, and their insightful applications in various fields of sciences such as energy, water purification, catalysis, environmental remediation, and biomedical (tissue engineering, drug delivery, pharmaceutical, and disease treatment) [9, 13, 32–38]. Table 1 exemplified the recent advances of tree gum complexed NPs in multifarious fields.

3

Tree Gum-Based Renewable Materials and Nanoparticles

63

Table 1 Tree gums-based NPs: synthesis, properties, and applications Tree gums GA

Synthesis method Autoclaving the mixture of AgNO3 (0.5% (w/v), GA (0.1–0.5% (w/v) at 15 psi pressure at 120
C for 50 min Reverse micellization and in-situ reduction

NPs Ag; 26.2 nm

GA

Template method

Ag; 20 nm

GA

Green synthesis

Ag; 8.4 nm/spherical/ oval/quasi-spherical

GA

Nano-precipitation

Zein/GA; 80–170 nm

GA

Green synthesis

Pd; 5.3 nm

GA

Precipitation and complexation

Chitosan/GA; 100 nm

GA

Co-precipitation

Fe3O4: 70–90 nm

GA

Ag and Co; >40 nm

Application Antibacterial activity against fish pathogens Aeromonas hydrophila and Pseudomonas aeruginosa Biomedical appliances; potential antibacterial (Fusarium oxysporum and Aspergillus niger) and antidiabetic and excellent antioxidant properties Antimicrobial efficacy against human pathogens (Mycobacterium smegmatis and Candida albicans) - Antibacterial action against the oral pathogen (Streptococcus mutans) - Development of novel dental care products and endorse NPs appliances in COVID-19 pandemic inhibition - Encapsulation efficiency of the Ruta chalepensis (Rutin extract) - Delivery of bioactive compounds - Catalytic discoloration of Azo dyes - Encapsulation of curcumin by CS/GA nanoparticlestabilized Pickering emulsion - Delivery of bioactive components

References [39]

[40]

[41]

[42]

[43]

[44]

[45]

[46] (continued)

V. V. T. Padil and M. Černík

64 Table 1 (continued) Tree gums

Synthesis method

NPs

GA

Green and biological method

Selenium nanorods; 20 nm

GA

Seed-mediated method using template and stabilizer Heating and agitation at room temperature

Au nanorods; 24.5  6.1– 48.3  6.6 nm

GA

Green synthesis via precipitating assisted with microwave heating

ZnO nanofluids; 200–350 nm

TG

Solution casting

ZnO; 10–30 nm

TG

Green synthesis and redox polymerization

Ag; ~25 nm

TG

Green synthesis

Titania; mean pore 5– 8 nm

TG

Green sol gel process

GK

Green synthesis

Mg0.5Zn0. 5FeMnO4 magnetic NPs; 25–35 nm ZnO; 19 nm; flowerlike morphology

GK

Green synthesis

GA

ZnO; flower-like morphology; 20 nm

Au (7.8  1.8 nm); Ag (12.5  2.5 nm); Pt (5.0  1.2 nm); CuO (10.5  2.4 nm); and Fe3O4 (18.5  3.5 nm)

Application - Nanocarrier-based oral delivery of antioxidants (Dunaliella salina) - Photocatalysis degradation of rhodamine B Therapeutic application for melanoma tumors Photocatalysis degradation of MB dye under visible light - Antibacterial activities against Staphylococcus aureus and Escherichia coli - Antibacterial nanocomposite films against Staphylococcus aureus and Escherichia coli - Food packaging and biomedical arena - Anticancer drug delivery and antimicrobial agents Photocatalytic degradation of crystal violet Photocatalytic of reactive blue 21 under visible light Discoloration of methylene blue (MB) dye under visible light Adsorptive removal of NPs

References

[47]

[48]

[49]

[50]

[51]

[52]

[53]

[54]

[49]

[55]

(continued)

3

Tree Gum-Based Renewable Materials and Nanoparticles

65

Table 1 (continued) Tree gums GK

Synthesis method Green synthesis

NPs Au; 20–25 nm

KG

Green synthesis

Au; 12  2 nm

KG

Green synthesis

TiO2; 8–13 nm

KG

Green synthesis

Pd; 6.7  3.4 nm

KG

Green synthesis

Ag; 3 nm; spherical

KG

Green synthesis

KG

Green synthesis

Ag (5.5  2.5 nm); Au (7.8  2.3 nm); Pt (2.4  0.7 nm) Au; 15–30 nm

KG

Green synthesis

Au; 4–12.7  0.7 nm

KG

Green synthesis

Ag; 5.0  2.8 nm

Application Biocompatible system for anticancer drugs (gemcitabine hydrochloride) Environmental catalysis and antibacterial (E. coli and B. subtilis) activity Photocatalytic degradation of methylene blue in solar light Detection of glucose in human serum Antibacterial against S. aureus, E. coli, and P. aeruginosa Biomedical fields

References [17]

Fluorescently labeled NPs for drug delivery and cellular imaging Effective antiproliferative efficacy against the B16F10 cell line and for biomedical appliances Sensing and quantitative estimation of Hg ions in water samples

[60]

[56]

[57]

[58] [59]

[33]

[61]

[62]

Abbreviations: GA gum arabic, GK gum karaya, KG kondagogu gum, TG tragacanth gum

2.2

Tree Gum-Based Nanofibers

Recently, carbohydrate gums and their electrospinning garnered significant advances in many potential areas such as food, energy, ware purification, and biomedical (tissue engineering, nanomedicine, and drug delivery) [5, 63–66]. In this section, the electrospinning parameters of gum with the additives, solution properties, fibers’ characteristics, and potential appliances are deliberated. Many of the tree gums have not been done electrospinning alone, without the help of blending with other polymers or additives (nanoparticles or organic materials, etc.). Padil et al. [67] illustrated the system and process parameters of electrospinning of arabic, kondagogu, and

66

V. V. T. Padil and M. Černík

karaya gums with PVA as a blending polymer to generate smooth and defect-free nanofibers. The combination of GA, PVA, and graphene oxide (GO) blend mixtures were successfully electrospun into fibers [68]. The resulted fibers had a fiber diameter of 100 nm in sizes, and the smooth and uniform fibers were produced with the blend consists of GA (10 wt. % solutions) with GO (1 wt. %) and PVA (polyvinyl alcohol; 10 wt. %). The morphology of the fibers was visualized by SEM and found that GO addition interacted with the polymer blend to reduce the overall fiber diameter in addition to slight unsmooth and roughed. The ensued fiber was effectively removed methylene blue dye from water by chemisorption and monitored by pseudo-secondorder kinetics. In another research, a composition of TG, PVA, GO, and tetracycline (an antibiotic) resulted in nanofibers for transdermal drug delivery [69]. The succeeded fiber composite showed antibacterial, biocompatible, and low cytotoxicity would be advanced for drug delivery appliances. Many tree-based electrospun fibers were effectively employed for wound healing applications. Recently an electrospun fiber based on TG, ethylcellulose, and a natural antioxidant and antibacterial such as honey were incorporated into the membrane was developed [70]. The ensued fiber membrane was used as antibiotic-free material for wound healing purposes. The amount of honey incorporated (from 5% to 20%) into the electrospinning mixture and their produced nanofibers were assessed for swelling, degradation, cell proliferation assay, antioxidant, and antibacterial activity. The result highlighted that the 20% honey incorporated TG/ethylcellulose nanofibers had much improved antioxidant activity, antibacterial against S. aureus and E. coli bacteria, mechanical properties, proper cell growth, attachment, and proliferation. A composite nanofiber membrane comprises TG, PVA, and MoS2 (molybdenum disulfide) fabricated via electrospinning [71]. The composite membrane (uniform, smooth surface, round-shaped, and bead-free structure with a diameter between 50 and 100 nm) showed cytocompatible and antimicrobial action against Staphylococcus epidermidis, Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa, respectively. The introduction of MoS2, a 2D material, enhanced the tensile strength and further inhibited bacterial growth in the electrospinning medium. The composite TG/PVA/MoS2 nanofibers are efficiently used to release tetracycline hydrochloride (antibiotic) and others can advance the delivery of an assortment of antibiotics as well as for wound healing strategy. Tree gum-based electrospun nanofibers have tremendous potential for biomedical including tissue engineering, but their poor mechanical and thermal properties influenced the final product. However, mostly tree gum is blended with biodegradable synthetic polymers to improve the overall mechanical properties. The blend of poly(lactic acid) (PLA) and TG to generate electrospun fibers for the inclusion of zein and tetracycline hydrochloride (TCH) were fabricated [72]. In this research, zein enhanced the electrospinnability of the solution, whereas the PLA improved the mechanical property of the ensued fiber mat. The blending ratio of zein/TG directly depends on the fiber diameter as zein/TG (80/20 and 90/10) produced nanofibers ranged from 253  15 to 547  56 nm, and mechanical stress from 3.7 to 4.8 MPa,

3

Tree Gum-Based Renewable Materials and Nanoparticles

67

respectively. Further incorporation of TCH improved the tensile strength, swelling degree, and porosity of the composite mat. Thus developed scaffold fibers offered antibacterial, biodegradability, good cell growth, attachment, and proliferation characteristics, and can be advanced for tissue engineering and wound dressing material.

2.3

Tree Gum-Based Carbon Nanostructures for Energy and Environmental Applications

Tree gums obtained from low grades such as grade II and grade III types are not valuable for food applications due to their inherent acidic nature and high-level metal composition. In this context, these biowaste gums have been converted into carbon nano/microstructures and advanced for energy harvesting, electrode fabrication for batteries, and environmental applications [73, 74]. The development of tree-gum biowastes from gum arabic, guar gum, gum karaya were converted into micro/mesoporous carbon structures via carbonization and exfoliation have been reported [75]. The fabricated carbon nanostructures had a high surface area with enormous nano/microspores that could drive fast water evaporation by capillary action. The ensued carbon structures developed as energy harvester to generate electricity with an output voltage of ~0.4 V and a current of ~3 μA in an area of 1.0 cm  2.5 cm. This “green” electricity enabled to turn on a commercial blue light-emitting diode (LED) (2.5 V and 20 mA). Such an attempt would be an important milestone in strengthening a green and sustainable approach to overcome the energy deficiency by utilizing tree gum biowastes, which are costeffective, renewable, and practical. Gums with GO reinforced composites have potential uses in food, energy, and catalytic field. A sensor was designed for the combination of GA with GO [76]. GO-supported Pt NPs were fabricated using gum kondagogu as a template for catalysis of 4-nitrophenol to 4-aminophenol [58]. The electrode for the electrochemical detection of Pb2+ ions in plastic toys was modified by a carbon paste contrived using GA templated TiO2 (particle size ¼ 8.9  1.5 nm with a spherical shape) NPs [77]. The green synthesized TiO2 NPs were characterized by X-ray diffraction (XRD), Fourier transforms infrared, Raman spectroscopy, scanning electron microscopy–dispersive energy X-ray, transmission electron microscopy (TEM), high resolution-TEM, and UV–visible spectroscopy. The research provided simple processing, less expensive, and sensitive electrodes based on gum-based nanoparticles that would benefit the sensing of environmental metal ions. GK gum waste transformed into high porous carbon and developed an electrode for Li-ion batteries was studied. The supervened electrode showed a high volumetric capacity of 175.4 mAh cm3 at a current density of 3000 mA g1 for 5000 cycles and is appropriate for practical application [78]. The GK grades of type III gum obtained for Sterculia urens trees are converted into highly permeable carbon via carbonization and activation to produce highly porous electrodes for easy ion transport. Among the various other gum wastes such as arabic and guar

68

V. V. T. Padil and M. Černík

micro-carbon structures, the karaya gum-based microstructures had high tap density. The work exposed to a more competitive and opportunity for the development of biowastes reinforced electrodes for LiBs (Li-ion batteries).

2.4

Films Based on Tree Gums and Their Composites

The bio-based packaging films in food and other related industrial applications are booming this century. Many synthetic polymer types such as polyethylene, polypropylene, and polystyrene are notable food packaging films due to their excellent barrier properties, flexibility, and availability. However, the toxicity, non-biodegradability, and migration into food make them more critical for their uses as packaging materials. In this context, biopolymers and their composites films would provide an upcoming edible, coating, and active food packaging to replace petroleum-based synthetic polymers. Additionally, the antioxidant, antibacterial, and carriers for bioactive components contributed to their safety, barrier, and shelf life. There is a growing demand for food packaging films and edible films from polysaccharides, including gums [79–81]. Many tree gums such as GA, GK, KG, and TG have been explored to develop films and fibers for food packaging to incorporate additives and other molecules. This section elaborately discussed the potential tree gum-based films for packaging, coatings, and delivered bioactive ingredients for biomedical fields. TG is exposed as an essential tree gum to prepare food packaging films, coatings, and stabilizing of food and related products. Due to their poor mechanical, thermal, and barrier properties, TG blending with other biopolymer and additives (inorganic or NPs) favored improving their properties, supporting many potential applications. The blending of gums to improve the physicochemical, mechanical, and mechanical properties of the ensued films was showed for TG-locust bean gum (LBG) composites [82]. Both the gums (TG and LBG; each 1.0% (w/w%) in the ratio of TG/LBG;100/0, 75/25, 50/50, 25/75, and 0/100) to get appropriate film by solution casting. The ensued films fabricated based on various gum mixtures (TG/LBG) were thoroughly characterized by Fourier transform infrared (FTIR) spectroscopy, surface tension, barrier properties, and mechanical testing to assess their performance. The FTIR spectra showed a synergy effect via the formation of intermolecular hydrogen bonds between the TG and LBG and reduced surface tension observed, which favored coating using the blended mixture of TG/LBG rather than the individual gum. The developed films had homogenous, smooth surface morphology, high transparency, enhanced barrier properties (oxygen and water vapor), and mechanical attributes that would help to increase their shelf life. In another research, TG was used to combine whey protein isolate (WPI) to prepare mixed edible films. The ensued films had greater optical transparency and improved mechanical, barrier, and thermal properties [83]. TG has also been used as coating materials for fruits and vegetables to prevent moisture, microbial growth, and texture deterioration by dipping, spraying, and spreading techniques.

3

Tree Gum-Based Renewable Materials and Nanoparticles

69

Remarkable progress has been shown in the areas of food materials coatings using TG. The TG gum (07% w/w) coating over the banana slices and their performance declines in the browning index and enhanced rehydration were documented [84]. Also, coating with TG (1%) significantly decreased total mesophilic aerobic bacteria growth in Cheddar cheese compared with the control (polyvinyl acetate) after storing for 90 days [85]. The other benefits included the fat reduction and protection of vitamins in foods are also well documented. For instance, the TG with additives (CaCl2 (0.5%) and ascorbic acid (2%)) coating over the apples has improved their efficiency of vitamin C compared to soybean coating for 12 days storage [86]. Bio-based polysaccharide films and blends have unique requirements in tissue engineering and medical fields compared to synthetic or petroleum-based polymers because of their non-toxicity and environmentally friendly. A green and nontoxic film based on chitosan (CS) and TG was developed for bone tissue engineering [87]. Further, enhancing the properties of the conjugated film (chitosan/TG), nanoparticles such as TiO2 or silver (Ag)-doped TiO2 NPs were supplemented as additives. The bio-composite film based on two formulations was fabricated via ultrasonication and solution casting. Among the two variants of films tested, CS/TG with Ag-doped TiO2 film had better bioactivity and antibacterial efficiency. Widespread application of food packaging based on renewable, biodegradable, and natural materials (proteins, polysaccharides, lipids, etc.) is popular among society [88]. A composite film based on gum arabic reinforced nanocellulose film was fabricated via solution casting [89]. The addition of nanocellulose crystals (4% (w/w)) into the GA enhanced the mechanical attributes such as tensile strength (2.2 MPa) and elongation at break (62.8%), thermal and ultraviolet light barrier properties of the resultant films. Further, significant improvement in barrier properties such as water vapor (7.58  1010 g Pa1s1m1) and oxygen (40.12%) of the ensued film could benefit food packaging application. Biopolymers such as chitosan, GA, and another biodegradable synthetic polymer (PVA) incorporated into essential oils (black pepper and ginger) formulated film was prepared by solvent casting method [90]. The film with essential oils interaction was characterized with SEM, XRD, DSC, and FTIR techniques. Further, the film inhibited the growth of microorganisms such as Bacillus cereus, Staphylococcus aureus, Escherichia coli, and Salmonella typhimurium. The overall requirement of the developed film can be a potential appliance in wound dressing and packaging. Addition of oils such as Schisandra chinensis oil improves the quality of generated edible GK films such as water barrier properties and reduces hygroscopicity and surface roughness [91]. The GK film composition consists of 30% glycerol as plasticizer and oleogel (2.5–7.5%), and the resultant films were screened for the mechanical, thermal, barrier, and morphological analysis. The resultant GK/S. chinensis oil or oleogel possess biodegradability and can be used for potential applications. In another investigation, GK was used as a stabilizing agent to develop biodegradable film consisting of oregano essential oil (OE)/loquat seed starch (LSS) [92]. The influence of GK on the physicochemical, optical, barrier, mechanical,

70

V. V. T. Padil and M. Černík

antibacterial, and antioxidant activities was demonstrated. A comparative test for all the film analyses was carried out with Tween 80 as a stabilizing agent in the absence of GK to prove the efficiency of GK to contribute the same or better properties than Tween 80. The result highlighted the tensile strength, hydrophobicity, opacity, and homogeneity of the resultant films with GK incorporation. The advantages of using tree gum as food packaging films are it’s abundant availability, biodegradability, economical, and simple processing. GK with clay materials (cloisite Na+) and cinnamaldehyde bio-composite film were fabricated via solution casting to improve the mechanical and barrier properties [93]. The addition of glycerol (55% of gum, w/w) in the casting solution improved the filmforming performance. The clay nanoparticles interacted with GK biopolymer into a layered structure, as evidenced by XRD analysis. Further, hydrophilicity and water vapor permeability was reduced and improved the mechanical properties (tensile and elongation at break) by adding clay (0.25%, 0.50%) into the GK nanocomposite mixture. The developed GK/clay nanocomposite film showed antibacterial efficiency and was projected to be an active food packaging material. To improve the films’ physical, chemical, structural, mechanical, and barrier properties, blending biopolymers to generate composite films can improve the overall properties for prospective purposes. The kondagogu gum (KG) and sodium alginate (SA) mixed with appropriate proportions with glycerol constitute packaging films with improved functionalities (Fig. 2) [94]. The interaction between KG and SA via hydrogen bonding was confirmed by the attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) analysis. The addition of glycerol improved the smoothness and flexibility of the film, as indicated by SEM analysis. The blending ratio of biopolymers such as KG:SA (40:60%) was established to generate optimum films such as high water contact angle, hydrophobicity, mechanical strength, permeability, transparency, and biodegradability. Recently, research has developed a suitable chemical modification of tree gums and their utilization for film fabrication and applied for food packaging. This approach foresees overcoming the pristine gum’s brittleness, hygroscopic nature, and feeble mechanical properties. In this direction, KG (kondagogu gum) is chemically modified with dodecenyl succinic anhydride (DDSA), an esterifying agent, to form a DDSA-KG structure. The formation of the complex (DDSA-GK) was confirmed with 1H NMR and FTIR. The film based on DDSA-KG fabricated with nanocellulose showed enhanced mechanical, morphological, optical, barrier, antibacterial, and biodegradable properties [95]. The advantages for the esterification gums could suggest the plasticizing effect and steric hindrance to resist the hydrogen bond formation and thereby arrest the polymer chain aggregation. This behavior supported the significant improvement of the elongation of the films while reducing their tensile strength. Additionally, nanocellulose could improve the film’s mechanical attributes and barrier properties (both oxygen and water vapor barrier). Furthermore, the films showed antibacterial efficacy towards Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The significant impact of this work highlighted

3

Tree Gum-Based Renewable Materials and Nanoparticles

71

Fig. 2 The various steps involved in fabricating bio-composite films based on gum kondagogu and sodium alginate. Reproduced with permission from Ref. [94]

that the high biodegradation (98.2  1.7% for 28 days) of the films even after chemical modification as parallel to pristine GK samples. The research outcome envisages tree gum kondagogu-based films for advanced application in food packaging and tissue engineering.

2.5

Tree Gum Sponges

Sponges derived from synthetic and natural materials are conquering great prominence due to their brilliant physicochemical, structural, mechanical, and varieties of applications [96, 97]. The underlying properties rely on their structural association (2D or 3D configuration), high porosity, surface area, exceptionally high aspect ratio, excellent mechanical properties (tensile strength, elasticity, and flexibility), ultralightweight, high thermal stability, and conductivity [97].

72

V. V. T. Padil and M. Černík

Karaya gum (GK) and chitosan (CH) conjugated sponge (GK/CH) was prepared via the self-assembly lyophilization method [98]. The resultant sponge had lightweight (density ¼ 8 mg/cm3) with high porosity (98%) and showed excellent organic dyes’ adsorption. Dyes such as methylene blue (MB) and methyl orange (MO) were used for the adsorption-desorption and regeneration experiment (Fig. 3). The result of the study suggested that the adsorption of both anionic and cationic dyes by the sponge depends on pH and ionizable function group interaction with dyes. The adsorption isotherm and kinetics were evaluated. The adsorption isotherm of the anionic dye MO was found to correlate with the Langmuir model (R2 ¼ 0.99), while the adsorption of the cationic MB onto the sponge was better described by the Freundlich model (R2 ¼ 0.99) and adsorption kinetics for both dyes followed the pseudo-second-order model. The adsorption capacity of MO and MB was found to be 32.81 mg/g and 32.62 mg/g, respectively. The principal mechanism involved in the adsorption of both dyes onto the GK/CH sponge was investigated to be hydrogen bonding and electrostatic attraction. Further, the adsorption-desorption cycles of dyes onto the GK/CH sponge were successfully done six times without losing the adsorption capacity. In another research, gum kondagogu and sodium alginate composite (KG/SA) sponges were prepared via the self-assembly freeze-drying technique [99]. For a practical application of oil/water absorption, KG/SA sponge was silylated. KG/SA sponge showed low density (18 mg/cm3), high porosity (≈75.6%), enhanced water contact angle (133
), hydrophobic and oleophilic properties (Fig. 4). The prepared KG/SA sponge is endowed with excellent absorption capacity for oils and organic solvents up to 19–43 times its weight from water. The absorbed oil could quickly be recovered employing simple mechanical squeezing. Meanwhile, good reusability was also observed up to 10 absorption-squeezing cycles. The novel composite aerogels prepared in a cost-effective and straightforward freeze-drying method in this study are expected to have great potential for treating oil and chemical spills.

Fig. 3 Organic dyes adsorption onto karaya gum (GK) and chitosan (CH) conjugated sponge. Reproduced with permission from Ref. [98]

3

Tree Gum-Based Renewable Materials and Nanoparticles

73

Fig. 4 Preparation of gum kondagogu and sodium alginate composite sponges and modified form (silylated) for their practical oil/water separation. Reproduced with permission from Ref. [99]

2.6

Greener Corrosion Inhibitors Based on Tree Gums

Natural carbohydrate polymers and their derivatives are potential corrosion inhibitors apart from their food, pharmaceutical, and nonfood applications. Many introducing factors such as macromolecular weights, chemical composition, gelling properties, rheological attributes, and their unique molecular and electronic structures are the primary reason for their ability for corrosion inhibitors [100]. Green corrosion inhibitors based on tree gums are the alternative to organic or inorganic substances corrosion inhibitors for metal and alloys, as they possess severe environmental issues. The development of gum constituent corrosion inhibitors is safe and environmentally friendly, nontoxic, biodegradable, biocompatible, and less expensive. The mechanism of gum structures and their compositional ingredients influence the metal or alloy via synergic effect or other possible interactions to be established for the corrosion inhibition on broader perspectives and research [101]. The following section deals with the research carried out by prominent researchers on the developed natural gum corrosion inhibitors and their chemistry with detailed platforms. The development of gums as corrosion inhibitors for many reasons. The versatile, functional groups (-OH, -COOH, -C¼O, -COOCH3, etc.) in various gums can form complexes with metal ions or metal surfaces, the large surface area of the gum–metal complexes, and insoluble in most of the organic compounds are the primary key functions of gums [102, 103]. GA acted as a corrosion inhibitor for aluminum in alkaline environments, and their structural assignments, such as various carbohydrate moiety and protein

V. V. T. Padil and M. Černík

74

functionality, are responsible for the protection of corrosion [104]. Further, exploration of corrosion inhibition on mild steel and aluminum, the adsorption mechanism on GA on these materials were described based on thermodynamic. In another investigation, GA performed an excellent corrosion inhibitor in acidic conditions (HCl and H2SO4 solution) for mild steel and found that a high concentration of GA improved the corrosion inhibition and another method for monitoring the corrosion inhibition by weight loss and hydrogen gas evolution [105]. Some of the inorganic ions, such as iodide, were also contributed to improving the corrosion inhibition of GA on aluminum, and chemisorption and adsorption of GA onto aluminum was also proposed by Langmuir and Freundlich adsorption isotherms. Many methods of monitoring corrosion inhibition by GA are GCMS (determination of the chemical composition of the gum exudate), weight loss, hydrogen evolution, thermometric, X-ray photoelectron spectroscopy, Fourier transform infrared spectroscopy, and scanning electron microscopy techniques [106]. The NPs carrying GA are also potentially implemented for anticorrosion properties in aqueous electrolytes. The designated GA-Ag NPs were tested for their anticorrosion property against St37 steel in an acidic environment (15% HCl and 15% H2SO4 solutions) via weight loss, electrochemical, and surface methods [106]. The research underlined that GA-based Ag NPs complex performed as interface-type corrosion inhibitors via charge transfer resistances, as evidenced by electrochemical impedance spectroscopy. Further exploration of the evidence of obstructing metal oxidation via charge transfer by GA-AgNPs, thereby protecting the St37 steel, was also confirmed by Nyquist curves. The surface morphology of the protected St37 steel surface by the action of GA-AG NPs was further investigated using AFM, SEM, and EXDA analyses.

3

Conclusions

Tree gums are innovative natural carbohydrate polymers available in the universe for multidimensional appliances. The green synthesis of nanoparticles, nanofibers, sponges, films, and composites based on various tree gums has been extensively described in this chapter. The NPs synthesis, morphology, sizes, and applications have been shown since the last 3 years report with their essential features. Methods for producing tree gum-based films and electrospun membranes and strategies to incorporate bioactive agents to improve their performance in food packaging, wound healing, and edible films are presented. Further, the developed tree gum products for green and sustainable applications in innovative technologies such as energy, biomedical, food packaging, therapeutic, industrial, anticorrosive material, environmental remediation, etc., have been established. Acknowledgments This work was funded by the project “Tree Gum Polymers and their Modified Bioplastics for Food Packaging Application” granted by Bavarian-Czech-Academic-Agency (BTHA) (registration number LTAB19007 and BTHA-JC-2019-26) and SFB 1357/C02 funded by Deutsche Forschungsgemeinschaft (DFG). The authors would like to acknowledge the

3

Tree Gum-Based Renewable Materials and Nanoparticles

75

assistance provided by the Research Infrastructure NanoEnviCz (Project No. LM2018124) and the “Inter Excellence Action Programme” within the framework of the project “Bio-based Porous 2D Membranes and 3D Sponges Based on Functionalized Tree Gum Polysaccharides and their Environmental Application” (registration number LTAUSA19091) – TUL internal No.: 18309/ 136, supported by the Ministry of Education, Youth and Sports of the Czech Republic. The Ministry of Education also supported this work, Youth and Sports of the Czech Republic and the European Union – European Structural and Investment Funds in the Operational Programme Research, Development and Education – Project Hybrid Materials for Hierarchical Structures (HyHi, Reg. No. CZ.02.1.01/0.0/0.0/16_019/0000843).

References 1. Barak S, Mudgil D, Taneja S (2020) Exudate gums: chemistry, properties and food applications – a review. J Sci Food Agric 100:2828–2835 2. Padil VVT, Zare EN, Makvandi P, Černík M (2021) Nanoparticles and nanofibres based on tree gums: biosynthesis and applications. Compr Anal Chem 94:223–265 3. Raj V, Lee JH, Shim JJ, Lee J (2021) Recent findings and future directions of grafted gum karaya polysaccharides and their various applications: a review. Carbohydr Polym 258:117687 4. Williams PA, Phillips GO (2021) Gum arabic. In: Handb. Hydrocoll. Elsevier, pp 627–652 5. Koyyada A, Orsu P (2021) Natural gum polysaccharides as efficient tissue engineering and drug delivery biopolymers. J Drug Deliv Sci Technol 63:102431 6. Hamdani AM, Wani IA, Bhat NA (2019) Sources, structure, properties and health benefits of plant gums: a review. Int J Biol Macromol 135:46–61 7. Makvandi P, Baghbantaraghdari Z, Zhou W, Zhang Y, Manchanda R, Agarwal T, Wu A, Maiti TK, Varma RS, Smith BR (2021) Gum polysaccharide/nanometal hybrid biocomposites in cancer diagnosis and therapy. Biotechnol Adv 48:107711 8. Taheri A, Jafari SM (2019) Gum-based nanocarriers for the protection and delivery of food bioactive compounds. Adv Colloid Interf Sci 269:277–295 9. Padil VVT, Wacławek S, Černík M, Varma RS (2018) Tree gum-based renewable materials: sustainable applications in nanotechnology, biomedical and environmental fields. Biotechnol Adv 36:1984–2016 10. Vinod VTP, Sashidhar RB, Sarma VUM, Vijaya Saradhi UVR (2008) Compositional analysis and rheological properties of gum Kondagogu (Cochlospermum gossypium): a tree gum from India. J Agric Food Chem 56:2199–2207 11. Granzotto C, Sutherland K (2017) Matrix assisted laser desorption ionization mass fingerprinting for identification of acacia gum in microsamples from works of art. Anal Chem 89: 3059–3068 12. Phillips GO, Phillips AO (2011) Chapter 6: gum arabic and other exudate gums. 166–185 13. Nazarzadeh Zare E, Makvandi P, Borzacchiello A, Tay FR, Ashtari B, Padil VVT (2019) Antimicrobial gum bio-based nanocomposites and their industrial and biomedical applications. Chem Commun 55:14871–14885 14. Munir H, Bilal M, Khan MI, Iqbal HMN (2021) Gums-based bionanostructures for medical applications. Polysaccharides:385–398 15. Mirhosseini H, Amid BT (2012) A review study on chemical composition and molecular structure of newly plant gum exudates and seed gums. Food Res Int 46:387–398 16. Padil VVT, Senan C, Černík M (2015) Dodecenylsuccinic anhydride derivatives of gum Karaya (Sterculia urens): preparation, characterization, and their antibacterial properties. J Agric Food Chem. https://doi.org/10.1021/jf505783e 17. Pooja D, Panyaram S, Kulhari H, Reddy B, Rachamalla SS, Sistla R (2015) Natural polysaccharide functionalized gold nanoparticles as biocompatible drug delivery carrier. Int J Biol Macromol 80:48–56

76

V. V. T. Padil and M. Černík

18. Padil VVT, Wacławek S, Senan C, Kupčík J, Pešková K, Černík M, Somashekarappa HM (2017) Gum karaya (Sterculia urens) stabilized zero-valent iron nanoparticles: characterization and applications for the removal of chromium and volatile organic pollutants from water. RSC Adv 7:13997–14009 19. Silva SCCC, de Araujo Braz EM, de Amorim Carvalho FA, de Sousa Brito CAR, Brito LM, Barreto HM, da Silva Filho EC, da Silva DA (2020) Antibacterial and cytotoxic properties from esterified Sterculia gum. Int J Biol Macromol 164:606–615 20. Preetha BK, Vishalakshi B (2020) Microwave assisted synthesis of karaya gum based montmorillonite nanocomposite: characterisation, swelling and dye adsorption studies. Int J Biol Macromol 154:739–750 21. Murphy CA, Costa JB, Silva-Correia J, Oliveira JM, Reis RL, Collins MN (2018) Biopolymers and polymers in the search of alternative treatments for meniscal regeneration: state of the art and future trends. Appl Mater Today 12:51–71 22. Mohammadifar MA, Musavi SM, Kiumarsi A, Williams PA (2006) Solution properties of targacanthin (water-soluble part of gum tragacanth exudate from Astragalus gossypinus). Int J Biol Macromol 38:31–39 23. Nejatian M, Abbasi S, Azarikia F (2020) Gum Tragacanth: structure, characteristics and applications in foods. Int J Biol Macromol 160:846–860 24. Nazarzadeh Zare E, Makvandi P, Tay FR (2019) Recent progress in the industrial and biomedical applications of tragacanth gum: a review. Carbohydr Polym 212:450–467 25. Vinod VTP, Sashidhar RB, Suresh KI, Rama Rao B, Vijaya Saradhi UVR, Prabhakar Rao T (2008) Morphological, physico-chemical and structural characterization of gum kondagogu (Cochlospermum gossypium): a tree gum from India. Food Hydrocoll 22:899–915 26. Vinod VTP, Sashidhar RB, Sarma VUM, Vijaya Saradhi UVR (2008) Compositional analysis and rheological properties of gum kondagogu (Cochlospermum gossypium): a tree gum from India. J Agric Food Chem. https://doi.org/10.1021/jf072766p 27. Nasrollahzadeh M, Sajjadi M, Iravani S, Varma RS (2021) Starch, cellulose, pectin, gum, alginate, chitin and chitosan derived (nano)materials for sustainable water treatment: a review. Carbohydr Polym 251:116986 28. Gour A, Jain NK (2019) Advances in green synthesis of nanoparticles. Artif Cells Nanomed Biotechnol 47:844–851 29. Cerqueira MA, Bourbon AI, Pinheiro AC, Martins JT, Souza BWS, Teixeira JA, Vicente AA (2011) Galactomannans use in the development of edible films/coatings for food applications. Trends Food Sci Technol 22:662–671 30. Zare EN, Padil VVT, Mokhtari B, Venkateshaiah A, Wacławek S, Černík M, Tay FR, Varma RS, Makvandi P (2020) Advances in biogenically synthesized shaped metal- and carbon-based nanoarchitectures and their medicinal applications. Adv Colloid Interf Sci 283:102236 31. Singh J, Dutta T, Kim K-H, Rawat M, Samddar P, Kumar P (2018) ‘Green’ synthesis of metals and their oxide nanoparticles: applications for environmental remediation. J Nanobiotechnol 161(16):1–24 32. Padil VVT, Černík M (2013) Green synthesis of copper oxide nanoparticles using gum karaya as a biotemplate and their antibacterial application. Int J Nanomedicine. https://doi.org/10. 2147/IJN.S40599 33. Vinod VTP, Saravanan P, Sreedhar B, Devi DK, Sashidhar RB (2011) A facile synthesis and characterization of Ag, Au and Pt nanoparticles using a natural hydrocolloid gum kondagogu (Cochlospermum gossypium). Colloids Surf B Biointerfaces 83:291–298 34. Nguyen NHA, Padil VVT, Slaveykova VI, Černík M, Ševců A (2018) Green synthesis of metal and metal oxide nanoparticles and their effect on the unicellular alga Chlamydomonas reinhardtii. Nanoscale Res Lett 13:159 35. Vinod VTP, Sashidhar RB, Sivaprasad N, Sarma VUM, Satyanarayana N, Kumaresan R, Rao TN, Raviprasad P (2011) Bioremediation of mercury (II) from aqueous solution by gum karaya (Sterculia urens): a natural hydrocolloid. Desalination. https://doi.org/10.1016/j. desal.2011.01.027

3

Tree Gum-Based Renewable Materials and Nanoparticles

77

36. Vinod VTP, Sashidhar RB, Sreedhar B, Rama Rao B, Nageswara Rao T, Abraham JT (2009) Interaction of Pb2+ and Cd2+ with gum kondagogu (Cochlospermum gossypium): a natural carbohydrate polymer with biosorbent properties. Carbohydr Polym. https://doi.org/10.1016/j. carbpol.2009.07.025 37. Padil VVT, Wacławek S, Černík M (2016) Green synthesis: nanoparticles and nanofibres based on tree gums for environmental applications. Ecol Chem Eng S 23:533–557 38. Kothaplamoottil Sivan S, Padinjareveetil AKK, Padil VVT, Pilankatta R, George B, Senan C, Černík M, Varma RS (2019) Greener assembling of MoO3 nanoparticles supported on gum arabic: cytotoxic effects and catalytic efficacy towards reduction of p-nitrophenol. Clean Techn Environ Policy 21:1549–1561 39. El-Adawy MM, Eissa AE, Shaalan M, Ahmed AA, Younis NA, Ismail MM, Abdelsalam M (2021) Green synthesis and physical properties of gum arabic-silver nanoparticles and its antibacterial efficacy against fish bacterial pathogens. Aquac Res 52:1247–1254 40. Ihsan J, Farooq M, Khan MA, Ghani M, Shah LA, Saeed S, Siddiq M (2021) Synthesis, characterization, and biological screening of metal nanoparticles loaded gum acacia microgels. Microsc Res Tech. https://doi.org/10.1002/JEMT.23726 41. Agnihotri AS, Fatima Z, Hameed S, Nidhin M (2021) Highly surface active anisotropic silver nanoparticles as antimicrobial agent against human pathogens, Mycobacterium smegmatis and Candida albicans. ChemistrySelect 6:5466–5473 42. Al-Ansari MM, Al-Dahmash ND, Ranjitsingh AJA (2021) Synthesis of silver nanoparticles using gum arabic: evaluation of its inhibitory action on Streptococcus mutans causing dental caries and endocarditis. J Infect Public Health 14:324–330 43. Gali L, Bedjou F, Ferrari G, Donsì F (2021) Formulation and characterization of zein/gum arabic nanoparticles for the encapsulation of a Rutin-rich extract from Ruta chalepensis. Food Chem 129982 44. Emam HE, Saad NM, Abdallah AEM, Ahmed HB (2020) Acacia gum versus pectin in fabrication of catalytically active palladium nanoparticles for dye discoloration. Int J Biol Macromol 156:829–840 45. Han J, Chen F, Gao C, Zhang Y, Tang X (2020) Environmental stability and curcumin release properties of Pickering emulsion stabilized by chitosan/gum arabic nanoparticles. Int J Biol Macromol 157:202–211 46. Zamani H, Rastegari B, Varamini M (2019) Antioxidant and anti-cancer activity of Dunaliella salina extract and oral drug delivery potential via nano-based formulations of gum arabic coated magnetite nanoparticles. J Drug Deliv Sci Technol 54:101278 47. Velayati M, Hassani H, Sabouri Z, Mostafapour A, Darroudi M (2021) Biosynthesis of Se-Nanorods using Gum Arabic (GA) and investigation of their photocatalytic and cytotoxicity effects. Inorg Chem Commun 128:108589 48. Gonçalves JP, da Cruz AF, Nunes ÁM et al (2021) Biocompatible gum arabic-gold nanorod composite as an effective therapy for mistreated melanomas. Int J Biol Macromol 185: 551–561 49. Araujo FP, Trigueiro P, Honório LMC, Oliveira DM, Almeida LC, Garcia RP, Lobo AO, Cantanhêde W, Silva-Filho EC, Osajima JA (2020) Eco-friendly synthesis and photocatalytic application of flowers-like ZnO structures using Arabic and Karaya Gums. Int J Biol Macromol 165:2813–2822 50. Pauzi N, Zain NM, Yusof NAA (2020) Gum arabic as natural stabilizing agent in green synthesis of ZnO nanofluids for antibacterial application. J Environ Chem Eng 8:103331 51. Shahvalizadeh R, Ahmadi R, Davandeh I, Pezeshki A, Seyed Moslemi SA, Karimi S, Rahimi M, Hamishehkar H, Mohammadi M (2021) Antimicrobial bio-nanocomposite films based on gelatin, tragacanth, and zinc oxide nanoparticles – microstructural, mechanical, thermo-physical, and barrier properties. Food Chem 354:129492 52. Nagaraja K, Rao KM, Reddy GV, Rao KSVK (2021) Tragacanth gum-based multifunctional hydrogels and green synthesis of their silver nanocomposites for drug delivery and inactivation of multidrug resistant bacteria. Int J Biol Macromol 174:502–511

78

V. V. T. Padil and M. Černík

53. Mallakpour S, Ramezanzade V (2021) Tragacanth gum mediated green fabrication of mesoporous titania nanomaterials: application in photocatalytic degradation of crystal violet. J Environ Manag 291:112680 54. Moradnia F, Taghavi Fardood S, Ramazani A, Min C k, Joo SW, Varma RS (2021) Magnetic Mg0.5Zn0.5FeMnO4 nanoparticles: green sol-gel synthesis, characterization, and photocatalytic applications. J Clean Prod 288:125632 55. Padil VVT, Černík M (2015) Poly (vinyl alcohol)/gum karaya electrospun plasma treated membrane for the removal of nanoparticles (Au, Ag, Pt, CuO and Fe3O4) from aqueous solutions. J Hazard Mater 287:102–110 56. Reddy GB, Madhusudhan A, Ramakrishna D, Ayodhya D, Venkatesham M, Veerabhadram G (2015) Green chemistry approach for the synthesis of gold nanoparticles with gum kondagogu: characterization, catalytic and antibacterial activity. J Nanostructure Chem 5:185–193 57. Saranya KS, Padil VVT, Senan C, Pilankatta R, Saranya K, George B, Wacławek S, Černík M (2018) Green synthesis of high temperature stable anatase titanium dioxide nanoparticles using gum Kondagogu: characterization and solar driven photocatalytic degradation of organic dye. Nanomater 8:1002 58. Rastogi L, Karunasagar D, Sashidhar R, Giri A (2017) Peroxidase-like activity of gum kondagogu reduced/stabilized palladium nanoparticles and its analytical application for colorimetric detection of glucose in biological samples. Sensors Actuators B Chem 240: 1182–1188 59. Kora AJ, Sashidhar RB, Arunachalam J (2010) Gum kondagogu (Cochlospermum gossypium): a template for the green synthesis and stabilization of silver nanoparticles with antibacterial application. Carbohydr Polym 82:670–679 60. Kumar SSD, Mahesh A, Antoniraj MG, Rathore HS, Houreld NN, Kandasamy R (2018) Cellular imaging and folate receptor targeting delivery of gum kondagogu capped gold nanoparticles in cancer cells. Int J Biol Macromol 109:220–230 61. Kalaignana Selvi S, Mahesh Kumar J, Sashidhar RB (2017) Anti-proliferative activity of gum kondagogu (Cochlospermum gossypium)-gold nanoparticle constructs on B16F10 melanoma cells: an in vitro model. Bioact Carbohydrates Diet Fibre 11:38–47 62. Rastogi L, Sashidhar RB, Karunasagar D, Arunachalam J (2014) Gum kondagogu reduced/ stabilized silver nanoparticles as direct colorimetric sensor for the sensitive detection of Hg2+ in aqueous system. Talanta 118:111–117 63. Padil VVT, Cheong JY, KP A, Makvandi P, Zare EN, Torres-Mendieta R, Wacławek S, Černík M, Kim I-D, Varma RS (2020) Electrospun fibers based on carbohydrate gum polymers and their multifaceted applications. Carbohydr Polym 247:116705 64. Muñoz-Shugulí C, Vidal CP, Cantero-López P, Lopez-Polo J (2021) Encapsulation of plant extract compounds using cyclodextrin inclusion complexes, liposomes, electrospinning and their combinations for food purposes. Trends Food Sci Technol 108:177–186 65. Akshay Kumar KP, Zare EN, Torres-Mendieta R, Wacławek S, Makvandi P, Černík M, Padil VVT, Varma RS (2021) Electrospun fibers based on botanical, seaweed, microbial, and animal sourced biomacromolecules and their multidimensional applications. Int J Biol Macromol 171: 130–149 66. Topuz F, Uyar T (2020) Antioxidant, antibacterial and antifungal electrospun nanofibers for food packaging applications. Food Res Int 130:108927 67. Padil VVT, Senan C, Wacſawek S, Ŀerník M (2016) Electrospun fibers based on Arabic, karaya and kondagogu gums. Int J Biol Macromol 91:299–309 68. Silvestri D, Mikšíček J, Wacławek S, Torres-Mendieta R, Padil VVT, Černík M (2019) Production of electrospun nanofibers based on graphene oxide/gum Arabic. Int J Biol Macromol 124:396–402 69. Abdoli M, Sadrjavadi K, Arkan E, Zangeneh MM, Moradi S, Zangeneh A, Shahlaei M, Khaledian S (2020) Polyvinyl alcohol/gum tragacanth/graphene oxide composite nanofiber for antibiotic delivery. J Drug Deliv Sci Technol 60:102044

3

Tree Gum-Based Renewable Materials and Nanoparticles

79

70. Ghorbani M, Ramezani S, Rashidi MR (2021) Fabrication of honey-loaded ethylcellulose/ gum tragacanth nanofibers as an effective antibacterial wound dressing. Colloids Surf A Physicochem Eng Asp 621:126615 71. Khaledian S, Kahrizi D, Tofik Jalal Balaky S, Arkan E, Abdoli M, Martinez F (2021) Electrospun nanofiber patch based on gum tragacanth/polyvinyl alcohol/molybdenum disulfide composite for tetracycline delivery and their inhibitory effect on gram+ and gram– bacteria. J Mol Liq 334:115989 72. Ghorbani M, Mahmoodzadeh F, Yavari Maroufi L, Nezhad-Mokhtari P (2020) Electrospun tetracycline hydrochloride loaded zein/gum tragacanth/poly lactic acid nanofibers for biomedical application. Int J Biol Macromol 165:1312–1322 73. Bilal M, Munir H, Khan MI, Khurshid M, Rasheed T, Rizwan K, Franco M, HMN I (2021) Gums-based engineered bio-nanostructures for greening the 21st-century biotechnological settings. Crit Rev Food Sci Nutr. https://doi.org/10.1080/10408398.2020.1871318 74. Shin S-H, Cheong JY, Lim H, Padil VVT, Venkateshaiah A, Kim I-D (2020) Carbon anchored conducting polymer composite linkage for high performance water energy harvesters. Nano Energy 74:104827 75. Venkateshaiah A, Cheong JY, Shin S-H et al (2020) Recycling non-food-grade tree gum wastes into nanoporous carbon for sustainable energy harvesting. Green Chem 22:1198–1208 76. Oliveira RD, Pscheidt J, Santos CS, Ferreira RT, Marciniuk G, Garcia JR, Vidotti M, Marchesi LF, Pessoa CA (2020) Electrochemical performance of pH sensor based on LbL films of polyaniline-gum Arabic nanocomposite and graphene oxide. J Electrochem Soc 167:047505 77. Sivan SK, Shankar SS, N S, et al (2020) Fabrication of a Greener TiO2 @Gum Arabic-Carbon paste electrode for the electrochemical detection of Pb 2+ ions in plastic toys. ACS Omega acsomega.0c03781 78. Sadat Hosseini M, Hemmati K, Ghaemy M (2016) Synthesis of nanohydrogels based on tragacanth gum biopolymer and investigation of swelling and drug delivery. Int J Biol Macromol 82:806–815 79. Ahmed J, Auras R, Kijchavengkul T, Varshney SK (2012) Rheological, thermal and structural behavior of poly(caprolactone) and nanoclay blended films. J Food Eng 111:580–589 80. Pacheco MS, Barbieri D, da Silva CF, de Moraes MA (2021) A review on orally disintegrating films (ODFs) made from natural polymers such as pullulan, maltodextrin, starch, and others. Int J Biol Macromol 178:504–513 81. Pinto L, Bonifacio MA, De Giglio E, Santovito E, Cometa S, Bevilacqua A, Baruzzi F (2021) Biopolymer hybrid materials: development, characterization, and food packaging applications. Food Packag Shelf Life 28:100676 82. Mostafavi FS, Kadkhodaee R, Emadzadeh B, Koocheki A (2016) Preparation and characterization of tragacanth–locust bean gum edible blend films. Carbohydr Polym 139:20–27 83. Tonyali B, Cikrikci S, Oztop MH (2018) Physicochemical and microstructural characterization of gum tragacanth added whey protein based films. Food Res Int 105:1–9 84. Farahmandfar R, Mohseni M, Asnaashari M (2017) Effects of quince seed, almond, and tragacanth gum coating on the banana slices properties during the process of hot air drying. Food Sci Nutr 5:1057–1064 85. Pourmolaie H, Asl AK, Ahmadi M, Zomorodi S, Raeisi SN (2018) The effect of Guar and Tragacanth gums as edible coatings in Cheddar cheese during ripening. J Food Saf 38:e12529 86. Jafari S, Hojjati M, Noshad M (2018) Influence of soluble soybean polysaccharide and tragacanth gum based edible coating to improve the quality of fresh-cut apple slices. J Food Process Preserv 42:e13638 87. Mallakpour S, Ramezanzade V (2020) Green fabrication of chitosan/tragacanth gum bionanocomposite films having TiO2@Ag hybrid for bioactivity and antibacterial applications. Int J Biol Macromol 162:512–522 88. Liu F, Chang W, Chen M, Xu F, Ma J, Zhong F (2020) Film-forming properties of guar gum, tara gum and locust bean gum. Food Hydrocoll 98:105007

80

V. V. T. Padil and M. Černík

89. Kang S, Xiao Y, Guo X, Huang A, Xu H (2021) Development of gum arabic-based nanocomposite films reinforced with cellulose nanocrystals for strawberry preservation. Food Chem 350:129199 90. Amalraj A, Haponiuk JT, Thomas S, Gopi S (2020) Preparation, characterization and antimicrobial activity of polyvinyl alcohol/gum arabic/chitosan composite films incorporated with black pepper essential oil and ginger essential oil. Int J Biol Macromol 151:366–375 91. Yousuf B, Wu S, Gao Y (2021) Characteristics of karaya gum based films: amelioration by inclusion of Schisandra chinensis oil and its oleogel in the film formulation. Food Chem 345: 128859 92. Cao TL, Song KB (2019) Effects of gum karaya addition on the characteristics of loquat seed starch films containing oregano essential oil. Food Hydrocoll 97:105198 93. Cao TL, Song KB (2019) Active gum karaya/Cloisite Na+ nanocomposite films containing cinnamaldehyde. Food Hydrocoll 89:453–460 94. Ramakrishnan RK, Wacławek S, Černík M, Padil VVT (2021) Biomacromolecule assembly based on gum kondagogu-sodium alginate composites and their expediency in flexible packaging films. Int J Biol Macromol 177:526–534 95. Venkateshaiah A, Havlíček K, Timmins RL, Röhrl M, Wacławek S, Nguyen NHA, Černík M, Padil VVT, Agarwal S (2021) Alkenyl succinic anhydride modified tree-gum kondagogu: a bio-based material with potential for food packaging. Carbohydr Polym 266:118126 96. Zhao S, Malfait WJ, Guerrero-Alburquerque N, Koebel MM, Nyström G (2018) Biopolymer aerogels and foams: chemistry, properties, and applications. Angew Chemie Int Ed 57: 7580–7608 97. Jiang S, Agarwal S, Greiner A (2017) Low-density open cellular sponges as functional materials. Angew Chemie Int Ed 56:15520–15538 98. Ramakrishnan RK, Padil VVT, Wacławek S, Černík M, Varma RS (2021) Eco-friendly and economic, adsorptive removal of cationic and anionic dyes by bio-based Karaya gum— chitosan sponge. Polym 13:251 99. Ramakrishnan RK, Padil VVT, Škodová M, Wacławek S, Černík M, Agarwal S (2021) Hierarchically porous bio-based sustainable conjugate sponge for highly selective oil/organic solvent absorption. Adv Funct Mater 31:2100640 100. Umoren SA, Eduok UM (2016) Application of carbohydrate polymers as corrosion inhibitors for metal substrates in different media: a review. Carbohydr Polym 140:314–341 101. Peter A, Obot IB, Sharma SK (2015) Use of natural gums as green corrosion inhibitors: an overview. Int J Ind Chem 63(6):153–164 102. Okon Eddy N, Ameh P, Gimba CE, Ebenso EE (2011) GCMS studies on Anogessus leocarpus (Al) gum and their corrosion inhibition potential for mild steel in 0.1 M HCl. Int J Electrochem Sci 6:5815–5829 103. Verma C, Quraishi MA (2021) Gum Arabic as an environmentally sustainable polymeric anticorrosive material: recent progresses and future opportunities. Int J Biol Macromol 184: 118–134 104. Umoren SA, Ebenso EE, Okafor PC, Ekpe UJ, Ogbobe O (2007) Effect of halide ions on the corrosion inhibition of aluminium in alkaline medium using polyvinyl alcohol. J Appl Polym Sci 103:2810–2816 105. Umoren SA (2008) Inhibition of aluminium and mild steel corrosion in acidic medium using gum Arabic. Cellul 155(15):751–761 106. Solomon MM, Gerengi H, Umoren SA, Essien NB, Essien UB, Kaya E (2018) Gum Arabicsilver nanoparticles composite as a green anti-corrosive formulation for steel corrosion in strong acid media. Carbohydr Polym 181:43–55

4

Natural Gums for Fruits and Vegetables Preservation: A Review Nishant Kumar Mohit Singla

, Pratibha

, Anka Trajkovska Petkoska

, and

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Classification of Natural Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Plant-Based Natural Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Animal-Based Natural Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Microbial-Based Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Marine-Based Natural Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Isolation and Purification of Natural Gums . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Application of Natural Gums as Edible Coating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Effects of Natural Gums on Postharvest Shelf Life and Quality Attributes of Fruits and Vegetables . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Physiological Loss in Weight (PLW) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Total Soluble Solids (TSS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 Titratable Acidity (TA) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4 Textural Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5 Color Attributes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6 Respiration Rate . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7 Ethylene Production . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.8 Biochemical Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

83 84 84 85 89 89 90 91 92 92 98 98 99 100 101 101 102

N. Kumar (*) National Institute of Food Technology Entrepreneurship and Management, Sonipat, Haryana, India Pratibha National Institute of Technology, Kurukshetra, Haryana, India A. T. Petkoska Faculty of Technology and Technical Sciences, St. Kliment Ohridski University – Bitola, Veles, North Macedonia e-mail: [email protected] M. Singla Tezpur University, Tezpur, Assam, India © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_4

81

82

N. Kumar et al.

5.9 Enzymatic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.10 Sensorial Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

103 104 105 105

Abstract

Recently, natural gum is promising as a novel source for maintaining the postharvest quality, organoleptic properties, and extending the shelf life of fruits and vegetables during the storage period. The development of natural gum-based edible coating has increased remarkable growth in the past few decades. The use of natural gum to develop edible coating helps to improve the recyclability of packaging materials compared to synthetic packaging materials. It is also a good alternative to synthetic packaging and played an important role as a biodegradable and eco-friendly edible coating for improving postharvest characteristics and shelf life of fruits and vegetables. They are naturally occurring carbohydrate/ polysaccharide-based polymers obtained from natural/renewable sources. The natural gums are hydrocolloid in nature and used as a water binder and also act as a good carrier of natural antioxidant and antimicrobial agents. The present chapter reviewed the potential applications of different types of natural gums as novel film-forming materials/edible coating on postharvest characteristics and shelf life of fruits and vegetables. The chapter also summarized the extensive knowledge about the natural gums, their effectiveness, protection, and suitability on fruits and vegetables. Keywords

Edible packaging · Fruits and vegetables · Natural gums · Postharvest characteristics · Shelf life extension Abbreviations

AA B. bifidum CMC FAO GRAS L. acidophilus L. casei L. rhamnosus NGs PAL PLW POD PPO SOD TA TFC

Ascorbic acid Bifidobacterium bifidum Carboxy-methyl cellulose Food and Agriculture Organization Generally recognized as safe Lactobacillus acidophilus Lactobacillus casei Lactobacillus rhamnosus Natural gums Phenylalanine ammonia-lyase Physiological loss in weight Peroxidase Polyphenol oxidase Reduced superoxide dismutase Titratable acidity Total flavonoid content

4

Natural Gums for Fruits and Vegetables Preservation: A Review

TPC TSS

1

83

Total phenolic content Total soluble solids

Introduction

Recently, the interest in natural gums (NGs) has been evoked due to their properties and diversified applications in food and pharmaceutical sectors as thickener agent, encapsulated agent, binding agent, gelling agent, coating materials [1]. NGs and their derivatives are produced from plants and animal-based renewable sources, are considered hydrocolloid, carbohydrate polymer (polysaccharide), and have the ability to form gel and stabilizing emulsion with hydration capacity in water [2]. Generally, they are hydrophilic with high molecular weight and composed of monosaccharide units joined by glucosidic bonds [3]. Natural gums are an excellent replacement for synthetic polymers, produced from edible sources, biodegradable in nature, and are biocompatible, widely available, nontoxic materials with low cost [4–7]. European Commission [8] reported that 25.8 million tons of plastic-based wastes are generated per annum in Europe and rarely 30% of them are recycled. Natural Gums have been approved by FAO as GRAS and are safe for human consumption. India is the largest producer of natural gum worldwide along with China, Russia, Brazil, Indonesia and harvests approximately 2.80 lakh tons of natural gum and resin (80% gums, 19% resin). In India, the leading states in the production of natural gums are Chhattisgarh (3500 tons), Madhya Pradesh (700 tons), Gujarat (70 tons), Rajasthan, and Andhra Pradesh (800 tons) [9]. NGs have excellent properties such as emulsifier agent, gelling agent, suspending agent, laxative [10–14], film-forming agent, thickening agent [15– 19], microencapsulation [20], fast dissolving oral/drug delivery [18, 21–23], and edible packaging and carrier of active agents [24–27]. Figure 1 shows the general

Fig. 1 Characteristics of natural gums

84

N. Kumar et al.

characteristics of natural gums. Various scientists and researchers have been exploring the potential of natural gums in food, pharmaceutical, postharvest management as edible coating, and drug delivery system [24, 28]. Recently the application and demands of natural gum have been drastically increased in the field of food processing sectors as edible coating to the preservation of postharvest quality of fruits and vegetables and extending their shelf life [29].

2

Classification of Natural Gums

Around the world, various types of plant, animal, seaweeds, and microbial-based gums (albizia gum, almond gum, agar gum, acacia gum, bhara gum, cashew gum, carrageenan, guar gum, ghatti gum, gellan gum, honey locust gum, locust bean gum, okra gum, tamarind gum, xanthan gum) are found in nature [6]. The NGs are also categorized based on their surface charge and structures. Based on the surface charge, the gums have been divided into three sections: (i) anionic (e.g., agar, carrageenan, xanthan, gellan, gum arabic, alginate, karaya gum); (ii) cationic (guar gum-modified); and (iii) nonionic (cellulose, amylase, locust bean, and tamarind gum, arabinans). Furthermore, on the basis of the structures of NGs, these are categorized into two different parts: (i) linear chains (cellulose, pectin, amylase, locus bean gum) and (ii) branched chains (guar gum, gum arabic, amylopectin, karaya gum) [1, 7, 29, 30]. Figure 2 shows the different types of origin for producing natural gums [5, 24, 31–33].

2.1

Plant-Based Natural Gums

The plant-based gum is produced as a form of cellulose after the disintegration of different parts of plants of tissue by the gummosis process. It may be extracted from the epidermis of the seed and bark of plants [28, 34]. The gums contain excellent amounts of carbohydrates and pectin. The various types of gums can be produced from plant sources. The most commercial plant-based gums are guar gum and gum arabic; these gums are widely used in printing, textiles, food processing, and packaging sector and pharmaceutical sectors as an adhesive agent, emulsifying agent, disintegrates, stabilizer, suspending agent, and thickening and binding agent. Recently, the use of plant-based natural gum as an edible coating has been increased in the food packaging sector to improve the shelf life of fruits and vegetables. The various researchers have applied different types of plant-based gums as edible coating and composite edible coating to improve the postharvest shelf life of fruits and vegetables during the storage period [33, 35]. The natural gum-based edible coating is with a substantial potential to add to food packaging applications to improve the shelf life of fruits and vegetables [2]. Many researchers such as Maqbool et al. [36, 37], Tahir et al. [38] have investigated the effects of different types of natural gum as an edible coating on fruits and vegetables and improved the shelf life and postharvest characteristics of fruits and vegetables during

4

Natural Gums for Fruits and Vegetables Preservation: A Review

85

Fig. 2 Classifications of different types of natural gums

the storage period by maintaining color, delayed weight loss (PLW), firmness, texture, total soluble solids (TSS), titratable acidity (TA), ascorbic acid (AA), respiration rate, ethylene production, and sensory attributes due to barrier properties [39–43]. The NGs-based edible coating is economically affordable with excellent barrier properties and also acts as carriers of food additives such as vitamins, antioxidant, and antimicrobial compounds [14]. Previous researchers improved the postharvest characteristics and extended the shelf life of apples, tomatoes, bananas, papaya, and strawberries using plant-based natural gum (gum arabic, soy bean gum) as an edible coating [36–40, 43]. Additionally, the additives such as plant extracts, different types of essential oils, vitamins, and phenolic compounds can enhance the mechanical, barrier, physical, thermal, and biochemical properties of the edible coating. Table 1 summarizes the details about the natural source and chemical constituents of some natural gums.

2.2

Animal-Based Natural Gums

The polysaccharides of animal origin play an imperative role as their tissue composition demonstrates a significant biomedical effect [82]. The extracellular matrix in

86

N. Kumar et al.

Table 1 Source and chemical composition of some plant-based natural gums Types of gum Almond gum

Source Almond tree

Guar gum

Cympopsis tetragonoloba (guar bean)

Gum arabic (gum sudani, acacia gum, Arabic gum, gum acacia, acacia, Senegal gum, Indian gum

Acacia senegal/ seyal tree

Locust bean gum

Carob tree Ceratonia siliqua

Fenugreek mucilage

Trigonellafoenumgraceum

Hibiscus mucilage

Hibiscus rosasinensis

Honey locust gum (sweetlocust or thorny-locust)

Gleditsia triacanthos

Tara gum

Caesalpinia spinosa

Cashew gum

Anacardium occidentale

Chemical constituents Arabinose, xylose, galactose and uronic acid, galactomannan chain Galactomannan, mannose, (1 ! 4)-linked β-Dmannopyranosyl units with (1 ! 6)-linked α-Dgalactopyranosyl D-galactose, L-arabinose, L-rhamnose, D-glucuronic acid, and 4-O-methyl-Dglucuronic acid, 1–3-linked β-D-galactopyranosyl, (1–6) linked β-D-glucopyranosyl D-galacto-Dmannoglycan, pentane, proteins, cellulose, D-mannopyranose units with a side-branching unit of D-galactopyranose Mannose, galactose, xylose, 1,4-linked mannose (b-Dmannopyranosyl) L-rhamnose, D-galactose, D-galacturonic acid, and D-glucuronic acid, alpha-1,4linked D-galactosyl alpha1,2-linked L-rhamnosyl alpha-1,4-linked D-galacturonic acid Galactomannan, D-galactopyranose, D-mannopyranose Galactomannans, mannose, (1–4)-β-D-manno-pyranose linear chains, branched through (1–6) bonds with α-D-galactopyranose Galactose, arabinose, rhamnose, glucose, glucuronic acid, and other sugar residues, gum yields L-arabinose, L-rhamnose, D-galactose, and glucuronic acid, (1 ! 3)-linked β–Dgalactopyranosyl units interspersed with β-(1 ! 6) linkages

References [44]

[45]

[46]

[47, 48]

[49–51]

[52–54]

[55]

[56]

[57]

(continued)

4

Natural Gums for Fruits and Vegetables Preservation: A Review

87

Table 1 (continued) Types of gum Neem gum

Source Azadirachta indica

Aloe mucilage

Aloe barbadensis

Moringa oleifera gum

Moringa oleifera

Gum Damar

Shorea wiesneri

Gum copal

Bursera bipinnata

Moi gum

Lannea coromandelica

Kondagogu gum

Cochlospermum religiosum

Phoenix mucilage

Phoenix dactylifera Cassia tora

Cassia tora mucilage

Chemical constituents Mannose, glucosamine, arabinose, galactose, fucose, xylose, glucose, acylgucosaminyl-asparaginyl bond Arabinan, arabinorhamnogalactan, galactan, galactogalacturan, glucogalactomannan, galactoglucoarabinomannan, and glucuronic acid, mannose, L-rhamnose, aldopentose, β-(1 ! 4)-dmanose and β-(1 ! 4)-dglucose Arabinose, galactose, glucuronic, rhamnose, (1,6), (1,3) and (1,3,6) β glycosidic linkages Alpharesin, beta-resin, dammarol acid Agathic acid ciscommunic acid, transcommunic acid, polycommunic acid, sandaracopimaric, acid, agathalic acid, monomethyl ester of agathalic acid, agatholic acid, and acetoxy agatholic acid Dlepi-catechin, (+)leucocyanidin; ellagic acid, quercetin, and quercetin-3 arabinoside. Isoquercetin and morin. Beta-sitosterol, leucocyanidin, and leucodelphinidin Rhamnose, galacturonic acid, glucuronic acid, b-D galactopyranose, a-Dglucose, b-D-glucose, galactose, arabinose, mannose, and fructose Fructose, sucrose, mannose, glucose, and maltose Cinnamaldehyde, tannins, mannitol, coumarins, and essential oils (aldehydes, eugenol, and pinene)

References [58]

[59]

[60, 61]

[62, 63] [64]

[20, 65]

[66]

[67] [68–70]

(continued)

88

N. Kumar et al.

Table 1 (continued) Types of gum Bhara gum

Source Terminalia bellerica

Mimosa mucilage

Mimosa pudica

Mimosa scabrella gum

Mimosa scabrella

Hakea gum

Hakea gibbosa

Konjac Glucomannan

Amorphophallus konjac Ocimum americanum Terminalia randii

Basil seed gum Terminalia gum

Chemical constituents ß-sitosterol, gallic acid, ellagic acid, ethyl gallate, galloyl glucose, and chebulaginic acid D-xylose and D-glucuronic acid. Galactomannan, mannose, galactose Glucuronic acid, galactose, arabinose, mannose, xylose (12: 43: 32: 5: 8) D-glucose and D-mannose (1: 1.6) Xylose, arabinose, rhamnose, and galacturonic acids Galactose, arabinose, rhamnose, mannose and xylose, b-D- (1–4)galactopyranosyl unit with a side chain of single xylopyranosyl unit; D-glucopyranosyl unit through a-D- (1–6) linkage

References [71]

[72] [73] [74, 75]

[76, 77] [78, 79] [80, 81]

the animal tissues consisting of an interconnecting lattice of heteropolysaccharides and fibrous proteins are packed with a jelly-like substance that supports cell adhesion as well as cell growth [83]. This also facilitates porous pathways for the diffusion of oxygen and nutrients to the individual cells. For example, various heteropolysaccharides are well known as the glycosaminoglycans, belonging to a group of linear polymers, comprised of repeating units of disaccharides [82, 83]. Different glycosaminoglycans comprise hyaluronic acid, chondroitin sulfate, heparin and heparan sulfate, keratin sulfate, and dermatan sulfate [84]. In addition to the glycosaminoglycans, chitin and chitosan (i.e., a deacetylated derivative of chitin) also belong to the animal polysaccharides, which are widely exploited in different biomedical uses including drug delivery, tissue engineering, wound healing [85]. These offer some unique advantages like biocompatibility, biodegradability, nontoxicity, solubility in water, stability, higher degrees of swelling capability; these gums are widely used in the food processing and packaging sector and pharmaceutical sectors as an adhesive agent, emulsifying agent, disintegrates, stabilizer, suspending agent, and thickening and binding agent. Various researchers have applied chitosan and other animal-derived biopolymer-based edible coating on fruits and vegetables to extend their storage life [24].

4

Natural Gums for Fruits and Vegetables Preservation: A Review

2.3

89

Microbial-Based Gums

Microbial polysaccharides are high-molecular-weight polymers that are produced by the cell wall-anchored enzymes of microorganisms such as bacteria, molds, and yeasts [86]. Microbial gums are composed of sugar residues linked by glycosidic linkages and may be linear or highly branched. Biopolymers produced by microorganisms, including exopolysaccharides (EPSs), endo-polysaccharides, and polyhydroxyalkanoates, are neutral or acidic and have a wide range of physicomechanical characteristics. These microbial gums are composed primarily of carbohydrate components (glucose, mannose, rhamnose), noncarbohydrate components (acetate, pyruvate, succinate, phosphate), and uronic acid. Microbial polysaccharides are nontoxic compounds produced via batch submerged aerobic fermentation in two forms: EPSs and capsular polysaccharides (CPSs) [87, 88]. The advantage of microbial gums over other polymers or synthetics is their potential for production on an industrial scale. On the other hand, it requires high-technology equipment, specific substrates, adequate power and water supplies, and well-trained staff. Among the various types of microbial gums, a number of them are utilized in the preparation of gels (gellan and curdlan), thickening agents (pullulan, xanthan), and film solutions (pullulan, cellulose, and gellan) that are used as edible coating, packaging materials, and gums employed in the prevention of fruits and vegetables during the storage period by reducing undesirable effects, retarded respiration rate, ethylene production or barrier against moisture and gas transpiration. Since most biopolymers derived from microorganisms are carbohydrates in nature, films made of these biopolymers have hydrophilic structures as polysaccharides usually react strongly with water [89]. Xanthan gum has the largest microbial polysaccharide market because of its rheological features over a wide range of temperatures and pH. It is used for salad dressings, syrups, starch-based products, beverages, abrasives, texturized coatings, and enhanced oil recovery [90, 91]. Dextrans are employed in the manufacturing of molecular sieves. They are primarily produced by Leuconostoc mesenteroides and Leuconostoc dextranicum [92]. Pullulan biopolymers produced by Azotobacter pullulans are used as a filmwrap food packaging material. Bacterial cellulose is produced by Acetobacter xylinum BPR2001 using molasses as a carbon source [93]. Because these microbial polysaccharides are resistant to digestive enzymes, they can be used as substitutes for starch in low-calorie foods [94]. Numerous researchers were applied microbial natural gums-based edible coating to extend the shelf life of fruits and vegetables [95–98].

2.4

Marine-Based Natural Gums

In recent years, there has been much attention on alginate, carrageenan, agar, and other seaweed-derived hydrocolloids as raw materials for edible gums to application in the prevention of fruits and vegetables [99, 100]. These natural food ingredients

90

N. Kumar et al.

are generally regarded as safe materials and can be used as edible films and coatings in functional food products. Because they are highly hydrophilic, they can offer a good barrier to fats, oils, and also oxygen, providing protection against lipid oxidation [101]. In this particular application, alginate and carrageenan are the most commonly used hydrocolloids used in the food processing sector. Alginate and carrageenan-based coating can reduce microbial contamination and surface discoloration by delaying moisture transport [102]. Alginate and carrageenanbased edible coatings are effective as postharvest treatments to maintain the quality of fruits such as tomato, peach, sweet cherry, where the edible coatings can delay ripening and extend the shelf life of fruit products [103, 104]. For minimally processed products such as fresh-cut fruits, edible coatings can control microbial spoilage by preventing microbial proliferation and delaying respiration [105]. In addition, alginate and carrageenan-based edible coatings are applied to carry different functional agents to improve their applications [106]. Previous researchers extend the shelf life of fruits and vegetables such as pineapple [107], cantaloupe, strawberries [108], fresh-cut nectarines [109], Arbutus unedo [110], sweet cherries [111], fresh-cut apples [112], and fresh-cut melon [113] using alginate-based edible coating with maintaining the postharvest characteristics of fruits and vegetables during the storage period. On the other hands, carrageenanbased edible coating effects were also applied by the previous researchers on longan fruits [114], berries [115], papaya [103], pears [116], apples [117], and tomatoes [118] to extend their shelf life with minimum losses of physiochemical and organoleptic properties.

3

Isolation and Purification of Natural Gums

The isolation and purification methods improved the functions, that is, drug delivery, color, and flavor of the gums; they can also help in the elimination of the impurities such as protein, fiber, fat, enzymes, or other natural pigments of natural gum and improving physiochemical properties [119, 120]. The natural gums are extracted from a different natural source and can be isolated and purified using several types of methods such as heating, solvent precipitation, microwave-assisted extraction, soxhlet. The solvent precipitation methods of gum isolation and purification are considered the easiest method; in this, the gums are selected followed by drying, grinding, and sieving, then dissolved with the water, heated, and stand for 6–8 h at room temperature. The supernatant is obtained using the centrifugation process and solvent is added for the precipitation; the solution is stirred continuously and dried at 50–60  C using a vacuum dryer [1]. In addition, various types of purification methods such as precipitation using alcohols [121, 122], copper and barium-complex [123, 124], borate method [125] of natural gums have been reported by the previous researchers. The precipitation with isopropanol is the most common method which is used to purify natural gum at a commercial scale [126, 127].

4

4

Natural Gums for Fruits and Vegetables Preservation: A Review

91

Application of Natural Gums as Edible Coating

Recently the consumer awareness increases in terms of food safety, quality, and eco-friendly packaging. The edible coating is an alternative to the plastic and synthetic-based packaging for fruits and vegetables to improve their postharvest quality attributes and shelf life [24]. Natural gums are widely used in the packaging sector to develop biodegradable and eco-friendly edible coating and film. The natural gum-based edible coating and films are nontoxic, cheap processing cost, and easily available [128]. Edible coating of natural gum-based is a protective layer that interacts with the surface of fruits and vegetables and provides benefits such as delaying ripening, decreased respiration rate, economically affordable, extending shelf life, improved sensory characteristics, a barrier against water transpiration, and gas exchange [129]. The gum-based edible coating acts as carriers of bioactive compounds, plant extract, essential oils, vitamins, minerals, antioxidants, antimicrobial, and nanoparticles. Therefore, to develop edible coating and film, various types of reinforcing cohesive agents like plasticizer (glycerol, glycol, glycerin, sorbitol, sucrose, and corn syrup) have been used to improve the physical, mechanical, barrier, structural, thermal, and functional attributes of materials [26, 130– 133]. Many researchers have incorporated active ingredients to enhance the properties of edible coating as well as fruits and vegetables. Yang et al. [134] incorporated Roselle extract in gum arabic-based edible coating to extend the postharvest shelf life of blueberry. Salehi [129] successfully developed edible film using balangu, basil, cress, perfoliate pepperwort, wild sage, flaxseed, fenugreek, chia, and mesquite seeds gums; the developed edible films showed the good barrier, mechanical, and other properties and can be utilized in the food packaging sector to extend the shelf life of fruits and vegetables. Kumar et al. [135] fabricated a chitosan-pullulan composite edible film incorporated with pomegranate peel extract and characterized their physiochemical, mechanical, thermal, antioxidant, and functional properties. Echinacea extract was incorporated with basil seed gum by Moradi et al. [136] to develop an edible coating for extending postharvest shelf life of fruits and vegetables. Moring leaf extract as an antioxidant agent was incorporated in gum arabic and carboxy-methyl cellulose (CMC)-based edible coating to improve the postharvest quality attributes of avocado fruits during storage for 21 days. Pinto et al. [137] prepared a cashew- and starch gum-based edible film and tested their application on cashew nut kernel to improve their stability and properties of edible film such as mechanical strength, barrier properties. Locust gum-based edible film was prepared by Fuciños et al. [138]. The almond gum-guar gum-based composite edible film was prepared by Dhaka et al. [19]; they reported that the composite edible film showed excellent physical, mechanical, thermal, microstructural, and functional properties as compared to alone due to microphase separation and molecular interaction between the materials. The antioxidant agents such as oregano essential oil [139], cinnamic acid [95], spices extracts, fennel, bay leaf, coriander, and nigella seeds [140], were incorporated in basil-seed gum, xanthan gum, and guar gum-based edible coating and film for further application on fruits and vegetables. Recently, the incorporation

92

N. Kumar et al.

of prebiotic and probiotic in edible film and coating has drastically increased. For example, probiotic strains such as Lactobacillus acidophilus, L. casei, L. rhamnosus, and Bifidobacterium bifidum were immobilized in CMC-based edible film by Ebrahimi et al. [141] to improve the functional properties of materials. There is very limited literature that has been available on gum-based edible packaging enriched with probiotics. Table 2 summarizes the effects of different types of natural gum-based edible coating on the shelf life and quality attributes of fruits and vegetables during the storage period.

5

Effects of Natural Gums on Postharvest Shelf Life and Quality Attributes of Fruits and Vegetables

Nowadays the demand for fresh fruits and vegetables is higher in the market due to containing nutrients and valuable bioactive compounds. Approximately 30–40% of the fruits and vegetables are affected by the microorganism, insects, condition of storage, transportation, and preservation [177]. The prevention of the postharvest quality of fruits and vegetables and fresh-cut is the biggest challenge around the world. The edible coating could be considered as an effective technique to solve the postharvest losses problems of fruits and vegetables. Various types of biomaterials such as polysaccharide, protein, lipid, and their combinations are used for the formation of edible coating to prolong the shelf life of fruits and vegetables [24]. The natural gums obtained from renewable resources have been widely used in the formation of edible materials for the prevention of fruits and vegetables during the storage period. The natural gum-based edible coating has excellent barrier properties against gas and water transpiration, moisture loss, and lipid oxidation and acts as a carrier of active agents [26]. The application of natural gum-based edible coating maintains the physiochemical, textural, and organoleptic characteristics, that is, weight loss, total soluble solids, acidity, pH, respiration rate, ethylene production, textural properties, enzymatic activity, color, phenolic, antioxidant activity, and sensory characteristics of fruits and vegetables have been discussed below. The deposition methods of an edible coating such as dipping, spraying, spreading, fluidized bed, and panning methods are used for the application on food products, that is, fruits and vegetables [2, 26, 177, 178].

5.1

Physiological Loss in Weight (PLW)

Fresh vegetables are highly susceptible to weight loss. The main reason behind weight loss is vapor pressure gradient and respiration, which causes wilting and shriveling resulting in low-market value and acceptability by consumers [40]. Natural gum edible coatings act as a barrier to water loss to the atmosphere by maintaining high relative humidity in the tissue atmosphere and reducing moisture loss [179]. Similar results have been observed by various other workers for a reduction of weight loss by edible coating. Peach gum combined with sunflower

4

Natural Gums for Fruits and Vegetables Preservation: A Review

93

Table 2 Application of different natural gum-based edible coating on fruits and vegetables and their effects S.No 1

Natural gum Gum arabic

Application Banana and papaya

2

Gum arabic

Anna apples

3

Gum Arabic and almond gum

Sweet cherry

4

Gum arabic

Strawberries

5

Gum arabic

Tomatoes

6

Gum arabic

Persimmon

7

Aloe vera

Tomatoes/ grapes

Potential effects on fruits and vegetables Retarded the weight loss, improved organoleptic and postharvest characteristics, that is, delaying color, control ethylene production, respiration rate and helps to enhance the shelf life of papaya and banana Significant delayed the weight loss, firmness, acidity, TSS, improved sensory characteristics, and maintained the visual appearance of anna apples during storage at 0  C Improved the sensory characteristics and other physiochemical attributes of sweet cherries during the storage period The edible coating was found effective to maintain the quality attributes such as TSS, phenolic activity, retarded the enzymatic activity (PPO), retained higher firmness, maintain color, and sensory characteristics of strawberry fruits during storage period for 10 days at 4  1  C Retarded the ripening process and maintained the quality attributes, sensory characteristics, and antioxidant properties of tomatoes during 20 days of storage period at 20  C The gum arabic-based edible coating was the potential to significantly reduced the weight loss, leakage, TSS, the phenolic and antioxidant activity of treated persimmon as compared to control during the storage period for 20 days at 20  1  C The tomato shelf life was extended by aloe vera-based edible coating with maintaining color, firmness, TSS, acidity, pH, ascorbic acid, and lycopene during the storage period The minimum weight loss, TSS, color browning, cracking, antimicrobial, the antifungal effect were observed in grapes using aloe vera gum-based edible coating during the storage period

References [36, 37]

[39]

[41]

[38]

[40, 142]

[143]

[144, 145]

(continued)

94

N. Kumar et al.

Table 2 (continued) S.No 8

Natural gum Aloe vera

Application Cantaloupe

9

Gum arabic

Guava

10

Gum arabic

Papaya

11

Gum arabic

Plum

12

Gum arabic

Carambola

13

Gum arabic

Mango

14

Gum arabic

Avocado

Potential effects on fruits and vegetables Extended the shelf life of cantaloupe by reduction of weight loss, maintained the quality attributes such as TSS, acidity, firmness, sensory characteristics during storage at different temperature conditions at 5  C, 10  C, 15  C, 20  C and 27  C for 24, 76 and 96 h respectively The edible materials showed barrier properties against water loss, rate of respiration, oxidation. The shelf life of guava fruits was prolonged by 7 days at 28  C by reducing enzymatic activity (PPO/POD), maintained higher antioxidant activity, phenolic activity, sugar content, ascorbic acid, and flavonoid content The gum arabic coating combined with ginger oil was showed bio-fungicide effects to control anthracnose and other quality attributes of papaya fruits during the storage period Reduction of weight loss, firmness, maintained other physicochemical attributes such as color, flavor, sensory characteristics, the phenolic and antioxidant activity of plum fruits was maintained by application of gum arabic edible coating Edible coating retarded the changes in physicochemical attributes and minimized the loss of ascorbic acid, phenolic contents, with improving sensory characteristics of carambola during the storage period Reduction loss of color, mass, and ethylene production with maintaining the firmness and ascorbic acid of mango fruits using gum arabic-based edible coating The coating was the potential to inhibit the anthracnose diseases and fungal growth with maintained color, texture property, phenolic compounds, and sensory characteristics

References [146]

[147, 148]

[149]

[150]

[151]

[152]

[153]

(continued)

4

Natural Gums for Fruits and Vegetables Preservation: A Review

95

Table 2 (continued) S.No 15

Natural gum Gum arabic

Application Tomato (raw and blanched)

16

Almond gum

Tomato

17

Xanthan gum

Fresh cut pears/ Fuji apples

18

Xanthan gum

Guava/melon/ baby carrot

19

Xanthan gum

Grapes

20

Guar gum

Tomato/mango/ cherry/ cucumber

Potential effects on fruits and vegetables Extending the shelf life of tomatoes by maintaining the water activity, color properties, and reduced respiration rate The application of gum arabic and almond gum-based edible coating minimized the changes in firmness, color, TSS, weight loss, microbial load and improved the sensory characteristics Application of xanthan gum-based edible coating was found effective in delaying the color browning, prevent loss of vitamin C, retarded the loss of phenolic compounds, the antioxidant activity of fresh-cut pears during the storage period Fuji apple shelf life was extended using xanthan gum-based treatment. The α-tocopherol containing by xanthan gum was effective in retarding the color loss, firmness and reduced the growth of microbes (E. coli and salmonella sp.) yeast and molds The coating treatment was effective to maintain the quality attributes of fruits and vegetables by reducing the weight loss, maintained ascorbic acid, phenolic compounds, color, firmness, sensory characteristics, and β- carotene. The apricot fruit’s shelf life was extended by reducing the microbial growth, maintained phenolic and antioxidant activity during the storage period Treatment was significantly maintained the physiochemical (weight loss, color, firmness, antioxidant properties) and organoleptic attributes during storage at cold temperature conditions Maintained the physiochemical and organoleptic quality attributes of mango fruits for up to 24 days by reducing the respiration rate and microbial growth Improved the quality of tomatoes by

References [154]

[155]

[95, 156, 157]

[158–160]

[161]

[162–165]

(continued)

96

N. Kumar et al.

Table 2 (continued) S.No

Natural gum

Application

21

Gellan gum

Fresh cut apple/ pineapple/fresh cut Fuji apple

22

Cashew gum

Guavas

23

Guar gum/xanthan gum

Fresh cut pears

Potential effects on fruits and vegetables reducing the rate of respiration, minimizing oxidation, weight loss, reducing ethylene production, and retarded ripening during cold storage Cherry fruit’s shelf life was also prolonged with reducing the weight loss, control reduction in ascorbic acid, acidity, polyphenols, firmness by guar gum coating enriched with ginseng extract The minimum change in acidity, weight loss, and degradation in phenolic contents was reported in cucumber by using guar gum application with excellent antimicrobial and antioxidant activity The extended shelf life of apple fruits significantly reduced the color browning, maintained firmness, and reducing the rate of respiration by application of gellan gum with ascorbic acid and calcium chloride Fresh cut pineapples shelf life was extended by controlling the loss of color, firmness, sensory characteristics, reduced respiration rate, and other physiochemical attributes during storage In fresh cut apples physiochemical and organoleptic properties were improved by reducing total counts of mesophilic and psychrophilic bacteria, prevention of color degradation, and sensory attributes over the storage period The physiological loss in weight of fresh and cut red guava fruits was reduced by preventing firmness, color loss, and sensory attributes The coating was effective to control the postharvest losses of fresh-cut pears by maintaining quality attributes, sensorial property, minimized oxidation, respiration rate. The shelf life of guava fruits was extended by 9 days

References

[166–168]

[169]

[170]

(continued)

4

Natural Gums for Fruits and Vegetables Preservation: A Review

97

Table 2 (continued) S.No 24

Natural gum Arabic/ xanthan gum/pectin

Application Green bellpepper

25

Gum arabic+ chitosan

Banana

26

Gellan gum

Mushrooms

27

Chitosanpullulan

Litchi, bell pepper, tomatoes

Potential effects on fruits and vegetables The treatments were found potentially significant to maintain the quality attributes with improving postharvest shelf life, sensory characteristics, appearance, and minimizing physiological loss in weight The coating significantly improved the shelf life of banana fruits with maintained quality attributes such as control weight loss, maintained TSS, firmness, and acidity during storage at 35  C and 54% RH Edible coatings were found able to reduce total color change of mushroom, retard respiration rate, oxidation during storage on 10 days Extending the shelf life of fruits and vegetables with maintaining the postharvest characteristics at room and cold storage temperature during the 18 days of storage period

References [171]

[172]

[173]

[174–176]

oil conserved firmness reduced weight loss and delayed the changes in total acidity of cherry tomatoes during cold storage as compared with the uncoated fruits [180]. Pigeon pea polysaccharides combined with protein isolate provided a good semipermeable barrier around strawberry fruits, which decreased the weight loss [43]. This might be possible due to the reduction of oxidation rate and enzymatic activity. Numerous researchers have used different types of natural gum to retard the weight loss of guava [147, 148, 158], tomatoes [40, 142, 154, 162, 180], papaya [149], tomato slices [181, 182], banana [36], mango [152], avocado [153], sweet cherry [41], and peach [183]. Ruelas-Chacon et al. [184] reported that the application of guar gum-based edible coating significantly regulates the weight loss of treated Roma tomato as compared to control during storage at 22  C. This might be possible due to the semipermeable layers of guar gum, which allow passing small molecules but the barrier to others and also showed barrier properties against oxidation, moisture, and water losses. The physiological loss in weight was also maintained by the Mahfoudhi and Hamdi [41] in sweet cherry using almond gum and gum arabic-based edible coating at 2  C throughout the 15 days of storage period and prolonged the shelf life. Dong and Wang [164] and Minh et al. [185] were controlled the weight loss of sweet cherry and litchi fruits by the application of guar gum and gum arabic-based edible coating during the storage period. However, the literature showed that natural gum can prevent fruits and vegetables without affecting the other quality. The weight loss of the fruits and vegetables is reduced by the natural gum

98

N. Kumar et al.

application by reducing the respiration, ethylene production, enzymatic activity (PPO/POD), wilting, and microbial contamination.

5.2

Total Soluble Solids (TSS)

The level of sugar (TSS) is an important factor to determine the taste and responsible for consumer acceptance and quality of fruits and vegetables. TSS of the fruits and vegetables increased with increasing duration of storage due to hydrolysis conversion of starch to simple sugar and dependent on the interaction between sugar and metabolism [174–176]. The application of natural gum-based edible coating reduced the conversion of polysaccharides of fruits and vegetables due to barrier properties against gas and water transpiration, retarded ripening, fermentation, and oxidative stress. Tomatoes treated with rice starch-based coating had lower TSS compared to uncoated samples during storage [186]. Peach fruits treated with tara gum coating also showed the conservation and maintenance of TSS [183]. The TSS of avocado fruit was maintained by Bill et al. [153] using gum arabic-based edible coating enriched with aloe vera extract. The various researchers maintained TSS of fruits and vegetables such as cherry tomatoes [180], strawberry [43], apricot [187], orange [188–190], fresh-cut strawberry [191], and sweet cherry [164] during the storage period using natural gum-based edible coating formulated by peach gum, basil seed gum, guar gum, pea starch, gellan gum, guar gum, and locust bean gum. Tahir et al. [38] also maintained the TSS of the strawberries fruits using gum arabic during storage of 10 days at 4  1  C. The gum arabic-based edible coating was also found potential by Saleem et al. [143] to maintain TSS of treated persimmon fruits as compared to control during the storage period for 20 days at 20  1  C. Tomatoes [144], grapes [145], and cantaloupe [146] sugar content level was maintained by using aloe vera gum-based edible coating with reducing leakage and cracking of fruits and vegetables. The application of almond gum-based edible coating was found potentially effective to minimize the changes in TSS of tomatoes during the storage period as compared to control ones [155].

5.3

Titratable Acidity (TA)

The titratable acidity of the fruits and vegetables decreased during the ripening or maturity stages due to the utilization of organic acids [192]. Accumulation of organic acids is usually seen during the development stage and conversion as respiratory substrates in TCA and glycolysis pathway [193]. On the other hand, the increasing acidity of fruits and vegetables during the storage period has been occurring due to the production of organic acid during ripening stages [194, 195] due to the accumulation of malic acid caused by the activity of the malate dehydrogenase enzyme [196]. Another aspect contributing to the increasing acidity during storage could be an indication of the initiation of fermentative pathways [197]. The natural gum-based edible packaging is the potential to the delayed decrement of TA by

4

Natural Gums for Fruits and Vegetables Preservation: A Review

99

reducing the rate of respiration; the changes in the rate of acidity are dependent on the types of coating materials, produces, and storage conditions [198]. The gum arabic and chitosan-based edible coating were found effective in extending the shelf life of banana and papaya by maintaining the acidity during the storage period [36, 37]. On the other hand, Kumar et al. [174–176] applied chitosan-pullulan composite edible coating enriched with pomegranate peel extract and controlled the increasing acidity of litchi, bell pepper, and tomatoes during the storage period for 18 days at room and cold temperature by controlling fermentative activation and oxidative stress. The previous researcher extended the shelf life of fruits and vegetables such as anna apples [39], tomatoes/grapes [144, 145], cantaloupe [146] by maintaining their acidity using gum arabic and aloe vera-based edible coating. Gellangum-based edible coating was applied by Azarakhsh et al. [167] to maintain the acidity of fresh-cut pineapple by retardation of respiration rate, barrier properties against water, and gas transpiration during 16 days of storage period at cold temperature. Peach gum-based edible coating with the addition of sunflower oil delayed the changes in total acidity of cherry tomatoes during cold storage as compared with the uncoated fruits [180]. Pigeon pea polysaccharides combined with protein isolate provided a good semipermeable barrier around strawberry fruits, which decreased the change in acidity and other physicochemical properties [43]. Sweet cherry acidity was maintained using almond gum and gum arabicbased novel edible coating by delaying the ripening process and oxidation during storage for 15 days at 2  C [41].

5.4

Textural Properties

Texture properties indicated the freshness and consumer acceptance of the fruits and vegetables. Texture properties of the fruits and vegetables can be influenced by various factors such as microstructure of the tissue, adhesion force between the cells, turgor pressure; ripening of the fruits and vegetables also affects firmness. It is perceived with the sense of touch and placed in the mouth and chewed [199, 200]. As per Bourne [201], reported textural properties of the food products as a group of physical characteristics that arise from the structural elements of the foods are sensing by the touch, deformation, disintegration, flow of force measured by mass, time, and temperature. Pectic enzyme degrades pectin to protopectin resulting in loss of firmness. Texture enhancers incorporated in the edible coating can minimize loss of firmness. Firmness loss is mainly associated with the decomposition of pectins by pectin methylesterase and polygalacturonase [202]. The application of natural gum-based edible coating could be the potential to exhibit the retarded loss of firmness and other textural properties of the fruits and vegetables with maintaining higher consumer acceptability by minimizing lipid oxidation, decreasing the rate of respiration, ethylene production, others phenolic and antioxidant, and antimicrobial activities. According to Tahir et al. [38], the firmness loss of gum arabic-treated strawberry was lower than that of uncoated samples and results on decay were 8% and 35%, respectively. The combination of gellan gum and

100

N. Kumar et al.

calcium chloride conserves the firmness of fresh-cut pineapples for 16 days in cold storage [167]. A similar trend was observed when fresh-cut apples [166, 168] were coated with a combination of gellan gum and calcium chloride. The various researchers maintained the firmness of the fruits and vegetables such as mango [152], sweet cherry [164], fresh and cut guavas [169], cherry tomatoes [180], and mandarins [203] using natural gum-based edible coating i.e. gum arabic, guar gum, peach gum. The composite of starches and gums has been used in the food industry to modify and control the texture, improve moisture preservation, and control water mobility [204]. In the guar gum-pea starch system, gums increase the viscosity, which could be attributed to the interactions between gum molecules and solubilized amylose and low-molecular-weight amylopectin molecules as a possible cause of the improved mechanical barrier properties of coatings and films. Guar gum and pea starch edible coatings provided effective control in ethylene production, respiration rate, weight loss, and firmness loss of Valencia orange [188, 189]. Tomatoes, grapes, and cantaloupe firmness was maintained by the application of aloe vera-based edible coating during the storage period with the maintenance of other quality attributes such as color, acidity, sugar content, cracking of the fruits, antimicrobial, antifungal, and antioxidant activity [144–146]. Other researchers have also retained the higher textural properties of the strawberry fruits [43], mango [152], tomato [155, 176, 180], guava [158, 169], fresh-cut melon [159], baby carrot [160], apricot [187], cherry fruits [164], fresh-cut apple [166, 168], pineapple [167], fresh-cut pears [170], banana [172], litchi [174], and bell-pepper [175] using edible coating prepared using natural gum such as pigeon pea gum, gum arabic, almond gum, xanthan gum, guar gum, gellan gum, cashew gum, chitosan, pullulan and peach gum, respectively, with maintaining other quality and extension of postharvest shelf life.

5.5

Color Attributes

The color attributes of the fruits and vegetables (F and V) are the important factor for the consumer acceptability of the produces. It influenced the preferences of the consumers with ensuring the freshness of the F and V. The changes in color parameters of F and V used to determine the losses of chlorophyll and lycopene content in fruits and vegetables during storage; the degradation of these contents occurs due to the higher metabolic activity and oxidation [205, 206]. The application of natural gum-based edible coating retained the color attributes of fruits and vegetables by reducing the respiration rate, ethylene production, control enzymatic browning, and delaying pigmentation [207–211]. Almond gum and gum arabic were found effective to retain the color attributes of sweet cherry fruits during the storage period for 15 days at 2  C without any off-flavor and spoilage [41]. Gum arabicbased edible coating was applied by researchers to extend the shelf life of a banana, papaya [36, 37], strawberries [38], plum [150], mango [152], avocado [153], and tomato slices [154] by retarding the color browning. On the other hand, color properties of tomatoes and grapes were prevented by Athmaselvi et al. [144] and Chauhan et al. [145] using aloe vera-based edible coating. Numerous researchers applied xanthan gum-based edible coating to retain the color attributes and extend

4

Natural Gums for Fruits and Vegetables Preservation: A Review

101

the shelf life of fruits and vegetables such as guava [158], fresh-cut melon [159], baby carrot [160], grapes [161] fresh-cut pears/Fuji apples [95, 156, 157, 166, 168], and apricot [187]. Many researchers have also investigated the effect of gellangumbased edible coating on the color (L*, a*, b*) and color differences on pineapple [167] and mushrooms [173].

5.6

Respiration Rate

The respiration process in fruits and vegetables evolved the oxidation of sugar contents to produce heat, water, and CO2 and responsible for the loss of substrates and their postharvest shelf-life; at a lower temperature, the respiration rate of fruits and vegetables is decreased and the oxidation is delayed [212, 213]. The higher respiration rate is the main cause of the physiological disorder, increasing enzymatic activity, the vapor pressure at the surface, increasing transpiration, and pigment synthesis [214]. The rate of respiration of fruits and vegetables is dependent on the base of the commodity; storage conditions affect the respiration rate of fruits and vegetables [214, 215]. The postharvest management technique that has been used to extend the postharvest shelf life of fruits and vegetables is edible coating by reducing the rate of respiration through proper control of the concentration of gases (O2 and CO2) surrounding a commodity [216]. The application of natural gum and their derivative improved the resistance of the edible coating to gas diffusion and improved barrier properties, which is resulting in reduced respiration rate of fruits and vegetables during the storage period. Numerous researchers have applied natural gum (gum arabic combined with additives)-based edible coating to improve the shelf life and reduce the respiration rate of fruits and vegetables such as banana [36], papaya [37], strawberry [38], tomato [40, 154], sweet cherry [41], guava [147, 148], and mango [152], which might be due to barrier properties of edible coating against gas exchange and water transpiration. As gellan, the gum-based edible coating was applied on mushrooms and fresh-cut pineapple. The results demonstrated that gellan gum retarded respiration rate, oxidation during storage, lower ethylene production, and reduced weight loss during the storage for 10 days of mushroom and 16 days of fresh-cut pineapples [167, 173]. On other hand, Rojas-Graü et al. [168] reported that the gellangum-based edible coating combined with sun flower oil not showed any significance on the respiration rate of fresh-cut Fuji apples during the storage period. Guar and xanthan gum was used for minimally process on the pear to extending their shelf life by 9 days by maintaining quality attributes, sensorial property, minimized oxidation, respiration rate [170]. Almond gum and gum arabic were reported as novel edible materials by Mahfoudhi and Hamdi [41] to maintain the postharvest quality attributes of sweet cherry by reducing the respiration rate.

5.7

Ethylene Production

It is a natural gas without color produced by the plants (fruits and vegetables) and acts as a regulator of plant growth also known as death and ripening hormone.

102

N. Kumar et al.

It is responsible for the changes such as color, textural property, tissue degradation, deterioration, and others. Ethylene production has various impacts on the postharvest shelf life of fruits and vegetables and causes product losses (10–80%) effect on growth, quality, and sensory attributes [217]. Suslow [218] reported that the higher ethylene production is responsible for russet spotting of lettuce, loss of green and yellow colors of spinach, broccoli, kale, and cucumber, reduced firmness of asparagus pear and turnip, decreased and increased sprouting in potatoes, off-flavor in watermelon, pepper, summer squash, carrot, parsnips, and potatoes. The natural gum application as a postharvest management strategy is the best way to prevent the fruits and vegetables during the storage period by reducing the ethylene production, minimized reparation rate, microbial decay, reduced degradation of anthocyanin content, controlling enzymatic and metabolic activities, retained phenolic contents, reduced weight loss, and improved sensory characteristics [134]. Many researchers investigated the effects of natural gum-based edible coating on the shelf life of fruits and vegetables. They extended the shelf life of fruits and vegetables such as banana [36], tomato [40, 142], sweet cherry [41], strawberry [136], papaya [149], and mango [152] by reducing ethylene production and delaying loss of color and sensorial properties and barrier properties against water transpiration and gas exchange. The application of natural gum on fruits and vegetables creates a barrier between the surface and atmosphere which resulting in reduced weight loss, modified the internal atmosphere, and disrupted ethylene production, hence reduces respiration and delays ripening and senescence processes.

5.8

Biochemical Properties

Fruits and vegetables are good sources of polyphenols and contribute to diet as natural antioxidants and prevent and decrease the risk of many diseases [2]. Furthermore, these compounds are secondary metabolites in plants (fruits and vegetables) with the ability to protect human body tissues against oxidative attacks [219, 220]. During maturity, these compounds decrease due to the metabolic rate of vegetables. Edible coatings produce an abiotic challenge to fresh produce, modifying the metabolism and affecting the production of secondary metabolites. Under the challenge, phenylalanine ammonia-lyase (PAL) activity is enhanced, which leads to the accumulation of phenolic compounds. Frusciante et al. [221] showed that high CO2 and low O2 concentrations increase phenolic production due to oxidative challenges during the storage of fruits and vegetables. Antioxidant activity in fruits and vegetables is due to the presence of phenolics, flavonoids, lycopene, carotenoids, and glucosinolates [222]. With the application of coatings, respiration rate can be slowed, and antioxidant activity can be maintained for a longer storage period. The natural gum-based edible coating is an effective technique to modify the internal atmosphere of vegetables to slow metabolic processes. Loss of phenolic in uncoated tissues was due to senescence and breakdown of cell structure. Edible coating effectively delayed senescence by controlling the metabolic rate, retaining total phenolic content (TPC) for a longer storage period. In line with

4

Natural Gums for Fruits and Vegetables Preservation: A Review

103

these derived benefits, gum arabic was effective for the enhancement of total antioxidant in strawberry fruits, with the increase of anthocyanins and phenolic contents in fruit during cold storage [38]. Antioxidant activity in tomatoes is retained longer when coated with 10% gum arabic, as the ripening process is retarded by delaying biochemical and physiological changes [142]. Similar results were observed for guava fruit when coated with a combination of gum arabic and essential oil which showed higher total antioxidant activity, ascorbic acid, TPC, and total flavonoid content (TFC) than untreated samples [148]. Antioxidant capacities, ascorbic acid, lycopene, carotenoid, phenolics, and flavonoid of guar gum-coated green-unripe mangoes were maintained during storage [163]. Sharma and Rao [95] observed that phenolic content and antioxidant capacity increased in xanthan gum-treated fresh-cut pears after 5 days of refrigerator storage, while it slowed the rate of reduction in ascorbic acid. Similarly, retention of ascorbic acid and phenolic contents in xanthan gum-treated guava fruit was found when this was combined with carnauba wax solid lipid nanoparticles [158]. Basil-seed gum was enhanced with Origanum vulgare subsp. viride essential oil (4–6%) which helps to preserve antioxidant activity and phenolic compounds in fresh-cut apricots as compared with untreated fruits [187]. Ascorbic acid and phenolic compound contents were significantly maintained during the storage of fresh-cut apple slices treated with tragacanth gum as compared with the untreated fruits, while no significant differences were seen among the treatment and control at end of storage [223]. In orange fruit, guar gum and pea starch treatment maintained the ascorbic acid, TPC, TFC, carotenoids, anthocyanin, and antioxidant activity [188, 189]. A similar trend was observed when cucumber fruits were treated with guar gum [165].

5.9

Enzymatic Activity

Inhibition of browning in fresh tissue is one of the main concerns in fresh-cut processing. Gum edible coating has been described to have an inhibition impact on the polyphenol oxidase (PPO) and peroxidase (POD) in the tissue of fruits and vegetables. Compared to untreated strawberries, those coated with gum arabic showed lower PPO activity [38]. PPO and POD activities were inhibited in freshcut pears by xanthan gum enriched with cinnamic acid [95]. Treatment of guava fruits with a combination of gum arabic and chitosan reduced the activities of PPO and POD enzymes and showed higher antioxidant activity and polyphenol content [148]. The application of soluble soybean polysaccharide and tragacanth in fresh-cut apple slices inhibited PPO activity, which was linked to the reduction of respiration rate and the oxidative reaction of phenolic compounds [223]. Apple slices dipped in 10% of three different gums (gum arabic, xanthan gum, and karaya gum) showed a great reduction in activities of PPO and POD as well as reduced natural browning [224]. Locust bean gum solution combined with antagonistic yeasts increased the activity of POD and reduced superoxide dismutase (SOD) around the wounded mandarin, which demonstrated their contribution to the biocontrol mechanism [225]. Galindo-Pérez et al. [226] investigated the effect of different xanthan gum

104

N. Kumar et al.

coatings with nanoparticles (nanocapsules and nanospheres) on the production and oxidation of phenolic compounds produced by enzymatic activity (phenylalanine ammonia-lyase (PAL) and PPO) on fresh-cut apples stored for 21 days at 4  C. The results showed that nanoparticles containing α-tocopherol and combined with xanthan gum significantly reduced the activities of PAL and PPO enzymes as compared to untreated samples, especially the nanocapsules and nanocapsules/ xanthan gum systems, which presented the lowest catalytic activity and reduced the production and oxidation of phenolic compounds on the cut apple surfaces.

5.10

Sensorial Properties

Sensory evaluation is the important test to measure the degree of disliking and liking of fruits and vegetables for consumer’s acceptance [227]. It is a scientific method used to measure, analyze, and interpret the responses of panelists by appearance, smell, touch, hearing, and taste. They are dealing with the perception and effective response by the human. Various types of methods have been used to record the sensory evaluation score (color, flavor, taste, texture, and aroma) but consumer acceptability and sensory descriptive analysis are mostly used [228, 229]. The unipoint scales are used to measure the sensory scores of the fruits and vegetables. The sensory characteristics of fruits and vegetables are mainly losses due to the higher respiration rate, ethylene production, deterioration, enzymatic and metabolic activities, leakage and cracking of produces, higher weight loss, microbial contamination, and lower firmness [230]. The application of natural gum as a protective layer could be the potential to prevent the organoleptic, textural, and physiochemical properties of fruits and vegetables due to their hydrocolloid nature and barrier properties [38, 43]. Numerous studies have investigated the effects of natural gum-based edible coating on sensory characteristics of fruits and vegetables. For example, Minh et al. [185] reported that the application of gum arabic-based edible coating on litchi fruits was effective in maintaining a higher sensory score for overall acceptability during the storage period. Effects of gum arabic-based edible coating on sensory properties of strawberries [38], anna apples [39], tomatoes [40, 142], plum [150], carambola [151], avocado [153] were investigated and recorded that the gum arabictreated fruits and vegetables have a higher sensory score as compared to control samples. This might be possible due to the properties of gum arabic-based edible coating, which helps to retard the changes in physicochemical attributes and minimize the loss of ascorbic acid and phenolic contents. The coating was the potential to inhibit the anthracnose diseases and microbial growth with maintained color, texture property, phenolic compounds, and sensory characteristics. Aloe vera was also applied on cantaloupe by Yulianingish et al. [146] to improve their sensory characteristics and consumer acceptance at different temperature conditions at 5  C, 10  C, 15  C, 20  C, and 27  C for 24, 76, and 96 h, respectively. Guava fruit’s sensory characteristics and acceptability were improved using cashew gum by Forato et al. [169]. Litchi fruits, bell pepper, and tomatoes shelf life were extended by

4

Natural Gums for Fruits and Vegetables Preservation: A Review

105

chitosan-pullulan composite edible coating enriched with pomegranate peel extract to maintain the postharvest characteristics and consumer acceptability at room and cold storage temperature during the 18 days of storage period [174–176]. Hashemi et al. [187] demonstrated the effect of basil seed gum-based edible coating with the addition of oregano essential oil (1–6%) on fresh-cut apricot during cold storage at 4  C for 8 days. The incorporation of oregano essential oil in the edible film-forming solutions improved the WVP and mechanical properties of the film. The results indicated incorporation of 6% oregano essential oil was found most effective in reducing pathogen load to maintain sensory characteristics and quality of fresh-cut apricot for 8 days. Dong and Wang [164] also demonstrated the effects of guar gum with the addition of ginseng extract on sweet cherry. The edible coating showed a positive response in reducing weight loss, respiration rate, reduction in change of TSS, TA, AA, total anthocyanin, phenolic properties, firmness, and improved sensory characteristics of treated sweet cherry.

6

Conclusions

Natural gum is a renewable and good substitute for plastic and synthetic materials in the food processing sector, especially for fruits and vegetables. They are hydrocolloids in nature and have excellent barrier properties against water transpiration and gas exchange. They are widely used as edible coating to reduce the postharvest losses in fruits and vegetables by reducing undesirable effects, deterioration, minimizing respiration rate, ethylene production, lipid peroxidation, physiological loss in weight, maintaining TSS, acidity, controlling enzymatic and metabolic activity with retention of color properties, bioactive components, firmness, and sensory properties. They also act as carriers of active substances, composite with other biomaterials with improving materials property. The application of natural gums is also significant on fruits and vegetables. Therefore, the extending shelf life of fruits and vegetables has a big impact on the reduction of postharvest losses and achieving sustainability goals. More research should be required on natural gum-based, innovative composite/nanomaterial to extend the shelf life of fruits and vegetables.

References 1. Choudhary PD, Pawar HA (2014) Recently investigated natural gums and mucilages as pharmaceutical excipients: an overview. J Pharm 204849:1–9 2. Tahir HE, Xiaobo Z, Mahunu GK, Arslan M, Abdalhai M, Zhihua L (2019) Recent developments in gum edible coating applications for fruits and vegetables preservation: a review. Carbohydr Polym 115141:224 3. Srivastava S, Ray DP (2015) Natural gum resources in India and their commercial importance. Int J Bio-Resour Sci 2(2):151–155 4. Bhardwaj TR, Kanwar M, Lal R, Gupta A (2000) Natural gums and modified natural gums as sustained release carriers. Drug Dev Ind Pharm 26(10):1025–1038

106

N. Kumar et al.

5. Goswami S, Naik S (2014) Natural gums and its pharmaceutical application. Int J Sci Innov Res 3(1):112–121 6. Lankalapalli S, Sandhala D (2019) A review on natural gums and their use as pharmaceutical excipients. Int J Pharm Sci Res 10(12):5274–5283 7. Mohammadinejad R, Kumar A, Ranjbar-Mohammadi M, Ashrafizadeh M, Han SS, Khang G, Roveimiab Z (2020) Recent advances in natural gum-based biomaterials for tissue engineering and regenerative medicine: a review. Polymers 12(1):176 8. European Commission (2018) A European strategy for plastics in a circular economy; document 52018DC0028. Publications Office of the Europian Union, Luxembourg, pp 1–18 9. Pal G (2013) Production, export and import of natural resins and gums in India. Natural resins and gums. Rashtriya Krishi 8:30–32 10. Ofoefule SI, Chukwu A, Anyakoha N (2001) Application of Abelmoschus esculentus in solid dosage formulation: use as a binder for a poorly water soluble drug. Indian J Pharm Sci 63: 234–238 11. Ofoefule SI, Chukwu A (2001) Application of Abelmoschus esculentus gum as a mini matrix for furosemide and diclofenac sodium tablets. Indian J Pharm Sci 63:532–535 12. Oluwatoyin AO (2005) Assessment of Albizia zygia gum as a binding agent in tablet formulations. Acta Pharma 55:263–276 13. John GL, Declan MD, James EK (2006) The use of agar as a novel filler for monolithic matrices produced using hot melt extrusion. Eur J Pharm Biopharm 64:75–81 14. Salehi F (2020a) Edible coating of fruits and vegetables using natural gums: a review. Int J Fruit Sci 20(2):S570–S589 15. Kibbe H (2003) Handbook of pharmaceutical excipients. The Pharmaceutical Press and the American Pharmaceutical Association, Washington, DC, pp 271–273 16. Kale VV, Kasliwal R, Parida SK (2004) Formulation and release characteristics of guar gum matrix tablet containing metformin HCl. Int J Pharm Expt 45:75–80 17. Heda A, Shivhare U (2004) Study of some natural hydrophilic polymers as matrix forming materials for sustained release tablet formulation. Int J Pharm Expt 8:69–74 18. Sarojini S, Kunam SD, Manavalan R, Jayanthi B (2010) Effect of natural gums as a binder in the formulation of diclofenac sodium tablets. Int J Pharm Sci Res 1(3):55–60 19. Dhaka RK, Kumar N, Pratibha, Upadhyay A (2021) Optimization, characterization and influence of microfluidization on almond gum based composite edible film. Starch – Stärke 2000101:1–10 20. Nayak BS, Nayak UK, Patro KB, Rout PK (2008) Preparation and in vitro evaluation of lamivudine entrapped MOI microspheres for oral administration. Res J Pharm Technol 1(4): 437–441 21. Krishna RR, Murthy TEGK (2010) Preparation and evaluation of mucoadhesive microcapsules of glipizide formulated with gum Kondagogu: in-vitro and in-vivo. Acta Pharm Sci 52: 335–344 22. Deshmukh AS, Aminabhavi TM (2015) In: Ramawat K, Mérillon JM (eds) Pharmaceutical applications of various natural gums. polysaccharides. Springer, Berlin/Heidelberg 23. Himani, Kumar N, Prabhakar PK, Pant V (2020) Physical, mechanical, functional and thermal characterization of chitosan: maltodextrin blends edible oral film incorporated with aqueous clove extract. Starch – Stärke 73(1–2):1900220 24. Kumar N, Neeraj (2019) Polysaccharide-based component and their relevance in edible film/ coating: a review. Nutr Food Sci 49(5):793–823 25. Salehi F (2020) Effect of common and new gums on the quality, physical, and textural properties of bakery products: a review. J Texture Stud 51(2):361–370 26. Suhag R, Kumar N, Petkoska AT, Ashutosh U (2020) Film formation and deposition methods of edible coating on food products: a review. Food Res Int 136:109582 27. Koyyada A, Orsu P (2021) Natural gum polysaccharides as efficient tissue engineering and drug delivery biopolymers. J Drug Deliv Sci Technol 63:102431

4

Natural Gums for Fruits and Vegetables Preservation: A Review

107

28. Avachat AM, Dash RR, Shrotriya SN (2011) Recent investigations of plant based natural gums, mucilages and resins in novel drug delivery systems. Ind J Pharm Educ Res 45(1):86–99 29. Saha A, Tyagi S, Gupta RK, Tyagi YK (2017) Natural gums of plant origin as edible coatings for food industry applications. Crit Rev Biotechnol 37(8):959–973 30. Hamman H, Steenekamp J, Hamman J (2015) Use of natural gums and mucilages as pharmaceutical excipients. Curr Pharm Des 21:4775–4797 31. Patel S, Goyal A (2015) Applications of natural polymer gum arabic: a review. Int J Food Prop 18:986–998 32. Sarkar PC, Sahu U, Binsi PK, Nayak N, Ninan G, Ravishanker CN (2018) Studies on physicochemical and functional properties of some natural Indian gums. Asian J Dairy Food Res 37 (2):126–131 33. Galus S, Arik Kibar EA, Gniewosz M, Kraśniewska K (2020) Novel materials in the preparation of edible films and coatings-a review. Coatings 10(7):674 34. López-Franco Y, Higuera-Ciapara I, Goycoolea FM, Wang W (2009) Other exudates: tragancanth, karaya, mesquite gum and larchwood arabinogalactan. In: Handbook of hydrocolloids, 2nd edn. Woodhead Publishing Series in Food Science, Technology and Nutrition, Duxford, pp 495–534 35. Jemilakshmi TV, Rakshana L, Priya SK, Aishwarya B, Anithaee C (2020) Postharvest quality enhancement of fruits and vegetables using edible coatings: a review. J Crit Rev 7(7):786–790 36. Maqbool M, Ali A, Alderson PG, Mohamed MTM, Siddiqui Y, Zahis N (2011a) Postharvest application of gum arabic and essential oils for controlling anthracnose and quality of banana and papaya during cold storage. Postharvest Biol Technol 62:71–76 37. Maqbool M, Ali A, Alderson PG, Zahid N, Siddiqui Y (2011b) Effect of a novel edible composite coating based on gum arabic and chitosan on biochemical and physiological responses of fbill fruits during cold storage. J Agric Food Chem 59(10):5474–5482 38. Tahir HE, Xiaobo Z, Jiyong S, Mahunu GK, Zhai X, Mariod AA (2018) Quality and postharvest-shelf life of cold-stored strawberry fruit as affected by gum arabic (Acacia senegal) edible coating. J Food Biochem 42:e12527 39. El-Anany AM, Hassan GFA, Ali FMR (2009) Effects of edible coatings on the shelf-life and quality of Anna apple (Malus domestica Borkh) during cold storage. J Food Technol 7:5–11 40. Ali A, Maqbool M, Ramachandran S, Alderson PG (2010) Gum arabic as a novel edible coating for enhancing shelf-life and improving post-harvest quality of tomato (Solanum lycopersicum L.) fruit. Postharvest Biol Technol 58:42–47 41. Mahfoudhi N, Hamdi S (2015) Use of almond gum and gum arabic as novel edible coating to delay postharvest ripening and to maintain sweet cherry (Prunus avium) quality during storage. J Food Process Preserv 39:1499–1508 42. Bashir M, Haripriya S (2016) Assessment of physical and structural characteristics of almond gum. Int J Biol Macromol 93:476–482 43. Robles-Flores G, Abud-Arcgilla M, Ventura-Canseco LMC, Meza-Gordillo R, GrajalesLagunes A, Ruiz-Cabrera MA, Gutiérrez-Miceli FA (2018) Development and evaluation of a film and edible coating obtained from the Cajanus cajan seed applied to fresh strawberry fruit. Food Bioprocess Technol 11:2172–2181 44. Mahfoudhi N, Chouaibi M, Donsi F, Ferrari G, Hamdi S (2012) Chemical composition and functional properties of gum exudates from the trunk of the almond tree (Prunus dulcis). Food Sci Technol Int 18(3):241–250 45. Mudgil D, Barak S, Khatkar BS (2014) Guar gum: processing, properties and food applications – a review. J Food Sci Technol 51(3):409–418 46. Pech-Canul ADLC, Ortega D, García-Triana A, González-Silva N, Solis-Oviedo RL (2020) A brief review of edible coating materials for the microencapsulation of probiotics. Coatings 10 (3):197 47. Jain A, Gupta Y, Jain SK (2007) Perspectives of biodegradablenatural polysaccharides for sitespecific drug delivery to the colon. J Pharm Pharm Sci 10(1):86–128

108

N. Kumar et al.

48. Malik K, Arora G, Singh I (2011) Locust bean gum as superdisintegrant – formulation and evaluation of nimesulide orodispersible tablets. Polim Med 41(1):17–28 49. Petropoulos GA (2002) Fenugreek: the genus Trigonella. In: Petropoulus GA (ed) Botany. Taylor & Francis, London, pp 9–17 50. Ali N, Hossein N, Afagh K, Tarifeh S, Hadi V, Ford JL (2008) An in vitro evaluation of fenugreek mucilage as a potential excipient for oral controlled-release matrix tablet. Drug Dev Ind Pharm 34(3):323–329 51. Zandi P, Basu SK, Khatibani LB, Balogun MO, Aremu MO, Sharma M, Cetzal-Ix W (2014) Fenugreek (Trigonella foenum-graecum L.) seed: a review of physiological and biochemical properties and their genetic improvement. Acta Physiol Plant 37(1):1714 52. Jenita JJL, Vijaya K, Suma R, Raj B (2010) Formulation and evaluation of compression coated tablets of mesalazine for colon delivery. Int J Pharmtech Res 2(1):535–541 53. Jani GK, Shah DP (2008) Assessing Hibiscus rosa-sinensis Linn as an excipient in sustainedrelease tablets. Pharm Technol 32(1):62–75 54. Kassakul W, Praznik W, Viernstein H, Hongwiset D, Phrutivorapongkul A, Leelapornpisid P (2014) Characterization of the mucilages extracted from Hibiscus rosa-sinensis Linn and Hibiscus mutabilisLinn and their skin moisturizing effect. Int J Pharm Pharm Sci 6(11): 453–457 55. Üner M, Altınkurt T (2004) Evaluation of honey locust (Gleditsia triacanthos Linn.) gum as sustaining material in tablet dosage forms. Il Farmaco 59(7):567–573 56. Final Assessment Report (2006) Application A546 Tara gum as a food additive, food standards, Australia New Zealand, 2006. Reports are available for viewing and downloading from the FSANZ website www.foodstandards.gov.au 57. Lima RDN, Lima JR, de Salis CR, Moreira RA (2002) Cashew-tree (Anacardium occidentale L.) exudate gum: a novel bioligand tool. Biotechnol Appl Biochem 35(1):45–53 58. Gangurde AB, Malode SS, Bhambar RS (2008) Preliminary evaluation of neem gum as tablet binder. Indian J Pharm Educ 42(4):344–347 59. Choi S, Chung MH (2003) A review on the relationship between Aloe vera components and their biologic effects. Semin Integr Med 1(1):53–62 60. Si S, Swain S, Kanungo SK, Gupta R (2006) Preparation and evaluation of gels from gum of Moringa oleifera. Indian J Pharm Sci 68(6):777–780 61. Badwaik HR, Al Hoque A, Kumari L, Sakure K, Baghel M, Giri TK (2020) Moringa gum and its modified form as a potential green polymer used in biomedical field. Carbohydr Polym 249: 116893 62. Morkhade DM, Fulzele SV, Satturwar PM, Joshi SB (2006) Gum copal and gum damar: novel matrix forming materials for sustained drug delivery. Indian J Pharm Sci 68(1):53–58 63. Morkhade DM, Joshi SB (2007) Evaluation of gum damar as a novel microencapsulating material for ibuprofen and diltiazem hydrochloride. Indian J Pharm Sci 69(2):263–268 64. Osete-Cortina L, Doménech-Carbó MT (2005) Analytical characterization of diterpenoid resins present in pictorial varnishes using pyrolysis–gas chromatography–mass spectrometry with on line trimethylsilylation. J Chromatogr A 1065(2):265–278 65. Venkaiah K, Shah JJ (1984) Distribution, development and structure of gum ducts in Lannea coromandelica (Houtt.) merril. Ann Bot 54(2):175–186 66. Janaki B, Sashidhar RB (2000) Subchronic (90-day) toxicity study in rats fed gum kondagogu (Cochlospermum gossypium). Food Chem Toxicol 38(6):523–534 67. Ngwuluka NC, Idiakhoa BA, Nep EI, Ogaji I, Okafor IS (2010) Formulation and evaluation of paracetamol tablets manufactured using the dried fruit of Phoenix dactylifera Linn as an excipient. Res Pharma Biotechnol 2(3):25–32 68. Soni PL, Pal R (1996) Industrial gum from Cassia tora seeds. Trends Carbohydr Chem 2:33–44 69. Singh S, Bothara DSB, Singh S (2010) Pharmaceutical characterization of Cassia tora of seed mucilage in tablet formulations. Sch Res J 2(5):54–61 70. Mann AS, Jain NK, Kharya MD (2007) Evaluation of the suspending properties of Cassia tora mucilage on sulphadimidine suspension. Asian J Exp Sci 21(1):63–67

4

Natural Gums for Fruits and Vegetables Preservation: A Review

109

71. Nayak BS, Nayak UK, Patro KB, Rout PK (2008b) Design and evaluation of controlled release bhara gum microcapsules of famotidine for oral use. Res J Pharm Technol 1(4):433– 436 72. Singh K, Kumar A, Langyan N, Ahuja M (2009) Evaluation of Mimosa pudica seed mucilage as sustained-release excipient. AAPS PharmSciTech 10(4):1121–1127 73. Vendruscolo CW, Andreazza IF, Ganter JLMS, Ferrero C, Bresolin TMB (2005) Xanthan and galactomannan (from M. scabrella) matrix tablets for oral controlled delivery of theophylline. Int J Pharm 296(1–2):1–11 74. Peter FK, Alistair MS, Shirley CC (1993) Molecular structures of gum exudates from Hakea species. Phytochemistry 34(3):709–713 75. Alur HH, Pather SI, Mitra AK, Johnston TP (1999) Evaluation of the gum from Hakea gibbosa as a sustained-release and mucoadhesive component in buccal tablets. Pharm Dev Technol 4 (3):347–358 76. Davé V, McCarthy SP (1997) Review of konjac glucomannan. J Environ Polym Degrad 5(4): 237–241 77. Alvarez-Mancenido F, Landin M, Lacik I, Martínez-Pacheco R (2008) Konjac glucomannan and konjac glucomannan/xanthan gum mixtures as excipients for controlled drug delivery systems. Diffusion of small drugs. Int J Pharm 349(1–2):11–18 78. Chopra RN, Nayar SL, Chopra IC (1956) Glossary of Indian medicinal plants, 1st edn. Council of Scientific & Industrial Research, New Delhi 79. Sheth NS, Shah NV, Shah NC (2010) Extraction of mucilage from Ocimum americanum Linn and its role as disintegrant in tablets formulation. J Glob Pharm Technol 2(12):26–31 80. Bamiro OA, Sinha VR, Kumar R, Odeku OA (2010) Characterization and evaluation of Terminalia randii gum as a binder in carvedilol tablet formulation. Acta Pharm Sci 52(3): 254–262 81. Bamiro OA, Odeku OA, Sinha VR, Kumar R (2012) Terminalia gum as a directly compressible excipient for controlled drug delivery. AAPS PharmSciTech 13(1):16–23 82. Li Q, Niu Y, Xing P, Wang C (2018) Bioactive polysaccharides from natural resources including Chinese medicinal herbs on tissue repair. Chin Med 13(1):1–11 83. DeAngelis PL (2012) Glycosaminoglycan polysaccharide biosynthesis and production: today and tomorrow. Appl Microbiol Biotechnol 94(2):295–305 84. Ray S, Sinha P, Laha B, Maiti S, Bhattacharyya UK, Nayak AK (2018) Polysorbate 80 coated crosslinked chitosan nanoparticles of ropinirole hydrochloride for brain targeting. J Drug Del Sci Tech 48:21–29 85. Verma A, Dubey J, Verma N, Kumar NA (2017) Chitosan-hydroxypropyl methylcellulose matrices as carriers for hydrodynamically balanced capsules of moxifloxacin HCl. Curr Drug Del 14(1):83–90 86. Morris V (2006) Chapter 12: Bacterial polysaccharides. In: Food polysaccharides and their applications. Taylor & Francis Group, Boca Raton, pp 413–443 87. Sutherland IW (2001) Microbial polysaccharides from Gram-negative bacteria. Int Dairy J 11 (9):663–674 88. Sutherland IW (2006) Biotechnology of microbial polysaccharides in food. Food Sci Technol 148:193 89. Alizadeh-Sani M, Ehsani A, Kia EM, Khezerlou A (2019) Microbial gums: introducing a novel functional component of edible coatings and packaging. Appl Microbiol Biotechnol 103 (17):6853–6866 90. Chaitali M, Kapadi M, Suraishkumar GK, Gudi RD (2003) Productivity improvement in xanthan gum fermentation using multiple substrate optimization. Biotechnol Prog 19(4):1190–1198 91. Yang ST, Lo YM, Min DB (1996) Xanthan gum fermentation by Xanthomonas campestris immobilized in a novel centrifugal fibrous-bed bioreactor. Biotechnol Prog 12(5):630–637 92. Behravan J, Fazly Bazzaz BS, Salimi Z (2003) Optimization of dextran production by Leuconostoc mesenteroides NRRL B-512 using cheap and local sources of carbohydrate and nitrogen. Biotechnol Appl Biochem 38(3):267–269

110

N. Kumar et al.

93. Bae S, Shoda M (2004) Bacterial cellulose production by fed-batch fermentation in molasses medium. Biotechnol Prog 20(5):1366–1371 94. Domań-Pytka M, Bardowski J (2004) Pullulan degrading enzymes of bacterial origin. Crit Rev Microbiol 30(2):107–121 95. Sharma S, Rao RTV (2015) Xanthan gum based edible coating enriched with cinnamic acid prevents browning and extends the shelf-life of fresh-cut pears. LWT Food Sci Technol 62(1): 791–800 96. Lara G, Sana Y, Cherry MV, Kunihiko U, Isao K, Chieko T, Mitsutoshi N, Marcos AN (2020) Spray technology applications of xanthan gum-based edible coatings for fresh-cut lotus root (Nelumbo nucifera). Food Res Int 137:109723 97. Wu S, Chen J (2013) Using pullulan-based edible coatings to extend shelf-life of fresh-cut ‘Fuji’apples. Int J Biol Macromol 55:254–257 98. Eroglu E, Torun M, Dincer C, Topuz A (2014) Influence of pullulan-based edible coating on some quality properties of strawberry during cold storage. Packag Technol Sci 27(10):831–838 99. Tavassoli-Kafrani E, Shekarchizadeh H, Masoudpour-Behabadi M (2016) Development of edible films and coatings from alginates and carrageenans. Carbohydr Polym 137:360–374 100. Cian RE, Salgado PR, Drago SR, González RJ, Mauri AN (2014) Development of naturally activated edible films with antioxidant properties prepared from red seaweed Porphyra columbina biopolymers. Food Chem 146:6–14 101. Varela P, Fiszman SM (2011) Hydrocolloids in fried foods – a review. Food Hydrocoll 25: 1801–1812 102. Nussinovitch A (2009) Biopolymer films and composite coatings. In: Kasapis S, Norton IT, Ubbink JB (eds) Modern biopolymer science: bridging the divide between fundamental treatise and industrial application. Elsevier, London 103. Hamzah HM, Osman A, Tan CP, Ghazali FM (2013) Carrageenan as an alternative coating for papaya (Carica papaya L. cv. Eksotika). Postharvest Biol Technol 75:142–146 104. Moldao-Martins M, Beirao-da-Costa SM, Beirao-da-Costa ML (2003) The effects of edible coatings on postharvest quality of the “Bravo de Esmolfe” apple. Eur Food Res Technol 217 (4):325–328 105. Mastromatteo M, Conte A, Del Nobile MA (2012) Packaging strategies to prolong the shelf life of fresh carrots (Daucus carota L.). Innov Food Sci Emerg Technol 13:215–220 106. Millette MCLT, Le Tien C, Smoragiewicz W, Lacroix M (2007) Inhibition of Staphylococcus aureus on beef by nisin-containing modified alginate films and beads. Food Control 18(7): 878–884 107. López-Córdoba A, Aldana-Usme A (2019) Edible coatings based on sodium alginate and ascorbic acid for application on fresh-cut pineapple (Ananas comosus (L.) Merr). Agron Colomb 37(3):317–322 108. Senturk PT, Lindner M, Rothkopf I, Schmid M, Müller K (2019) The development of a uniform alginate-based coating for cantaloupe and strawberries and the characterization of water barrier properties. Foods 8(6):203 109. Chiabrando V, Giacalone G (2016) Effect of chitosan and sodium alginate edible coatings on the postharvest quality of fresh-cut nectarines during storage. Fruits 71(2):79–85 110. Guerreiro AC, Gago CM, Faleiro ML, Miguel MG, Antunes MD (2015) The effect of alginatebased edible coatings enriched with essential oils constituents on Arbutus unedo L. fresh fruit storage. Postharvest Biol Technol 100:226–233 111. Zam W (2019) Effect of alginate and chitosan edible coating enriched with olive leaves extract on the shelf life of sweet cherries (Prunus avium L.). J Food Qual:8192964. https://doi.org/10. 1155/2019/8192964 112. Hu W, Jiang A, Xiu Z, Feng K (2018) Effect of thyme oil–alginate-based coating on quality and microbial safety of fresh-cut apples. J Sci Food Agric 98(6):2302–2311 113. Raybaudi-Massilia RM, Mosqueda-Melgar J, Martín-Belloso O (2008) Edible alginate-based coating as carrier of antimicrobials to improve shelf-life and safety of fresh-cut melon. Int J Food Microbiol 121(3):313–327

4

Natural Gums for Fruits and Vegetables Preservation: A Review

111

114. Lin MG, Lasekan O, Saari N, Khairunniza-Bejo S (2018) Effect of chitosan and carrageenanbased edible coatings on post-harvested longan (Dimocarpus longan) fruits. CyTA-J Food 16 (1):490–497 115. Falcó I, Randazzo W, Sánchez G, López-Rubio A, Fabra MJ (2019) On the use of carrageenan matrices for the development of antiviral edible coatings of interest in berries. Food Hydrocoll 92:74–85 116. Moraes KSD, Fagundes C, Melo MC, Andreani P, Monteiro AR (2012) Conservation of Williams pear using edible coating with alginate and carrageenan. Food Sci Technol 32(4): 679–684 117. Lee JY, Park HJ, Lee CY, Choi WY (2003) Extending shelf-life of minimally processed apples with edible coatings and antibrowning agents. LWT-Food Sci Technol 36(3):323–329 118. Baraiya NS, Gol NB, Rao TR (2012) Influence of polysaccharide-based edible coatings on the shelf life and nutritional quality of tomato fruit. Food 6(1):22–27 119. Kakrani HK, Jain NK (1981) A study on investigated as drug retarding agents, each presenting a binding properties of guggal gum. Ind J Hosp Different Approach Matrix Syst 18(Based on the Pharmacist 3):100–102 120. Kulkarni GT, Gowthamarajan K, Dhobe RR, Yohanan F, Suresh B (2005) Development of controlled release spheriods using natural polysaccharide as release modifier. Drug Deliv 12 (4):201–206 121. Baveja SK, Rao KVR, Arora J (1988) Examination of natural gums and mucilages as sustaining materials in tablet dosage forms. Indian J Pharm Sci 50:89–92 122. Kokate DCK, Purohit AP, Gokhale SB (2008) Pharmacognosy, 29th edn. Nirali, Pune 123. Wahi SP, Sharma VD, Jain VK, Sinha P (1985) Studies on suspending property of mucilage of Hygrophila spinosa T. Anders and Hibiscus Esculentas Linn. Indian Drugs 22:500–502 124. Khandelwal KR (2008) Practical pharmacognosy, techniques and experiments. Nirali, Maharashtra 125. Mazumder R, Nath LK, Haque A, Maity T, Choudhury PK, Shrestha B, Chakraborty M, Pal RN (2010) Formulation and in vitro evaluation of natural polymers based microspheres for colonic drug delivery. Int J Pharm Pharm Sci 2(1):211–219 126. Hirose K, Endo K, Hasegawa K (2004) A convenient synthesis of lepidimoide from okra mucilage and its growth-promoting activity in hypocotyls. Carbohydr Res 339(1):9–19 127. Kumar R, Patil MB, Patil SR, Paschapur MS (2009) Evaluation of Abelmoschus esculentus mucilage as suspending agent in paracetamol suspension. Int J Pharmtech Res 1(3):658–665 128. Gahruie HH, Safdarianghomsheh R, Zamanifar P, Salehi S, Niakousari M, Hosseini SMH (2020) Characterization of novel edible films and coatings for food preservation based on gum Cordia. J Food Qual 8883916:1–7 129. Salehi F (2019) Characterization of new biodegradable edible films and coatings based on seeds gum: a review. J Packag Technol Res 3(2):193–201 130. Borges JA, Romani VP, Cortez-Vega WR, Martins VG (2015) Influence of different starch sources and plasticizers on properties of biodegradable films. Int Food Res J 22: 2346–2351 131. Jeyasubramanian K, Balachander R (2016) Starch bioplastic film as an alternative foodpackaging material. J Achiev Mater Manuf Eng 75:78–84 132. Zakaria NH, Muhammad N, Sandu AV, Abdullah MMAB (2018) Effect of mixing temperature on characteristics of thermoplastic potato starch film. Iop Conf Ser Mater Sci Eng 374:012083 133. Rahman R (2019) Bioplastics for food packaging: a review. Int J Curr Microbiol App Sci 2019 (8):2311–2321 134. Yang Z, Zou X, Li Z, Huang X, Zhai X, Zhang W, Shi J, Tahir HE (2019) Improved postharvest quality of cold stored blueberry by edible coating based on composite gum Arabic/Roselle extract. Food Bioprocess Technol 12:1537–1547 135. Kumar N, Neeraj, Ojha A, Singh R (2019) Preparation and characterization of chitosan – pullulan blended edible films enrich with pomegranate peel extract. React Funct Polym 144: 104350

112

N. Kumar et al.

136. Moradi F, Emamifar A, Ghaderi N (2019) Effect of basil seed gum based edible coating enriched with echinacea extract on the postharvest shelf life of fresh strawberries. Food Measure 13:1852–1863 137. Pinto AMB, Santos TM, Caceres CA, Lima JR, Ito EN, Azeredo HMC (2015) Starch-cashew tree gum nanocomposite films and their application for coating cashew nuts. LWT Food Sci Technol 62:549–554 138. Fuciños C, Míguez M, Cerqueira MA, Costa MJ, Vicente AA, Rúa ML, Pastrana LM (2015) Functional characterisation and antimicrobial efficiency assessment of smart nanohydrogels containing natamycin incorporated into polysaccharide-based films. Food Bioprocess Technol 8:1430–1441 139. Hashemi SMB, Khaneghah AM (2017) Characterization of novel basil-seed gum active edible films and coatings containing oregano essential oil. Prog Org Coat 110:35–41 140. Naeem A, Abbas T, Ali TM, Hasnain A (2019) Application of guar gum-based edible coatings supplemented with spice extracts to extend post-harvest shelf life of lemon (Citrus limon). Qual Assur Saf Crop Foods 11(3):241–250 141. Ebrahimi B, Mohammadi R, Rouhi M, Mortazavian AM, Shojaee-Aliabadi S, Koushki MR (2018) Survival of probiotic bacteria in carboxymethyl cellulose-based edible film and assessment of quality parameters. LWT Food Sci Technol 87:54–60 142. Ali A, Maqbool M, Alderson PG, Zahid N (2013) Effect of gum arabic as an edible coating on antioxidant capacity of tomato (Solanum lycopersicum L.) fruit during storage. Postharvest Biol Technol 76:119–124 143. Saleem MS, Shaghef E, Muhammad AA, Aamir N, Safina N, Sajjad H, Sajid A, İhsan C (2020) Postharvest application of gum arabic edible coating delays ripening and maintains quality of persimmon fruits during storage. J Food Process Preserv 44(8):e14583 144. Athmaselvi KA, Sumitha P, Reathy B (2013) Development of Aloe vera based edible coating for tomato. Int Agrophy 27:369–375 145. Chauhan S, Gupta KC, Agrawal M (2014) Application of biodegradable Aloe vera gel to control post harvest decay and longer the shelf life of grapes. Int J Curr Microbiol Appl Sci 3 (3):632–642 146. Yulianingish R, Maharani DM, Hawa LC, Sholikhan L (2013) Physical quality observation of edible coating made from Aloe vera on cantaloupe minimally processed. Pak J Nutr 12(9): 800–805 147. Murmu SB, Mishra HN (2017) Optimization of the arabic gum based edible coating formulations with sodium caseinate and tulsi extract for guava. LWT-Food Sci Technol 80:271–279 148. Murmu SB, Mishra HN (2018) The effect of edible coating based on Arabic gum, sodium caseinate and essential oil of cinnamon and lemon grass on guava. Food Chem 245:820–828 149. Ali A, Hei GK, Keat YW (2016) Efficacy of ginger oil and extract combined with gum arabic on anthracnose and quality of papaya fruit during cold storage. J Food Sci Technol 53(3): 1435–1444 150. Andrade SCA, Baretto TA, Arcanjo NMO, Madruga MS, Meireles B, Cordeiro ÂM, Barbosa de Lima MA, de Souza EL, Magnani M (2017) Control of Rhizopus soft rot and quality responses in plums (Prunus domestica L.) coated with gum arabic, oregano and rosemary essential oils. J Food Process Preserv 41(6):e13251 151. Gol NB, Chaudhari ML, Rao TVR (2015) Effect of edible coatings on quality and shelf life of carambola (Averrhoa carambola L.) fruit during storage. J Food Sci Technol 52(1):78–91 152. Khaliq G, Mohamed MT, Ali A, Ding P, Ghazali HM (2015) Effect of gum arabic coating combined with calcium chloride on physico-chemical and qualitative properties of mango (Mangifera indica L.) fruit during low temperature storage. Sci Hortic 190:187–194 153. Bill M, Sivakumar D, Korsten L, Thompson AK (2014) The efficacy of combined application of edible coatings and thyme oil in inducing resistance components in avocado (Persea americana Mill.) against anthracnose during post-harvest storage. Crop Prot 64:159–167 154. Adiamo OQ, Eltoum YAI, Babiker EE (2019) Effects of gum arabic edible coatings and sun-drying on the storage life and quality of raw and blanched tomato slices. J Culin Sci Technol 17(1):1–14

4

Natural Gums for Fruits and Vegetables Preservation: A Review

113

155. Mahfoudhi N, Chouaibi M, Hamdi S (2014) Effectiveness of almond gum trees exudate as a novel edible coating for improving postharvest quality of tomato (Solanum lycopersicum L.) fruits. Food Sci Technol Int 20(1):33–43 156. Zambrano-Zaragoza M, Mercado-Silva E, Gutiérrez-Cortez E, Cornejo-Villegas M, Quintanar-Guerrero D (2014) The effect of nano-coatings with α-tocopherol and xanthan gum on shelf-life and browning index of fresh-cut “red delicious” apples. Innov Food Sci Emerg Technol 22:188–196 157. Freitas IR, Cortez-Vega WR, Pizato S, Prentice-Hernández C, Borges CD (2013) Xanthan gum as a carrier of preservative agents and calcium chloride applied on fresh-cut apple. J Food Saf 33(3):229–238 158. García-Betanzos CI, Hernández-Sánchez H, Bernal-Couoh TF, Quintanar-Guerrero D, de la Luz Zambrano-Zaragoza M (2017) Physicochemical, total phenols and pectin methylesterase changes on quality maintenance on guava fruit (Psidium guajava L.) coated with candeuba wax solid lipid nanoparticles-xanthan gum. Food Res Int 101:218–227 159. Zambrano-Zaragoza ML, Quintanar-Guerrero D, Del Real A, Piñon-Segundo E, ZambranoZaragoza JF (2017) The release kinetics of β-carotene nanocapsules/xanthan gum coating and quality changes in fresh-cut melon (cantaloupe). Carbohydr Polym 157:1874–1882 160. Mei Y, Zhao Y, Yang J, Furr HC (2002) Using edible coating to enhance nutritional and sensory qualities of baby carrots. J Food Sci 67(5):1964–1968 161. Golly MK, Ma H, Sarpong F, Dotse BP, Oteng-Darko P, Dong Y (2019) Shelf-life extension of grape (Pinot noir) by xanthan gum enriched with ascorbic and citric acid during cold temperature storage. J Food Sci Technol 56:4867–4878 162. Naeem A, Abbas T, Ali TM, Hasnain A (2018a) Effect of antioxidant and antibacterial properties of guar gum coating containing spice extracts and its application on tomatoes (Solanum lycopersicum L.). J Food Meas Charact 12(4):2725–2734 163. Naeem A, Abbas T, Ali TM, Hasnain A (2018b) Effect of guar gum coatings containing essential oils on shelf life and nutritional quality of green-unripe mangoes during low temperature storage. Int J Biol Macromol 113:403–410 164. Dong F, Wang X (2018) Guar gum and ginseng extract coatings maintain the quality of sweet cherry. LWT Food Sci Technol 89:117–122 165. Saha A, Tyagi S, Gupta RK, Tyagi YK (2016) Guar gum based edible coating on cucumber (Cucumis sativus L.). Eur J Pharm Med Res 3(9):558–570 166. Moreira MR, Tomadoni B, Martín-Belloso O, Soliva-Fortuny R (2015) Preservation of freshcut apple quality attributes by pulsed light in combination with gellan gum-based prebiotic edible coatings. LWT Food Sci Technol 64(2):1130–1137 167. Azarakhsh N, Osman A, Ghazali HM, Tan CP, Mohd Adzahan N (2014) Effects of gellanbased edible coating on the quality of fresh-cut pineapple during cold storage. Food Bioprocess Technol 7(7):2144–2151 168. Rojas-Graü MA, Tapia MS, Martín-Belloso O (2008) Using polysaccharide-based edible coatings to maintain quality of fresh-cut Fuji apples. LWT Food Sci Technol 41(1): 139–147 169. Forato LA, de Britto D, de Rizzo JS, Gastaldi TA, Assis OBG (2015) Effect of cashew gum-carboxymethylcellulose edible coatings in extending the shelf-life of fresh and cut guavas. Food Packag Shelf Life 5:68–74 170. Mohamed A, Aboul-Anean H, Amal M (2013) Utilization of edible coating in extending the shelf life of minimally processed prickly pear. J Appl Sci Res 9(2):1202–1208 171. Ochoa-Reyes E, Martínez-Vazquez G, Saucedo-Pompa S, Montañez J, Rojas-Molina R, LeonZapata MAD, Rodríguez-Herrera R, Aguilar CN (2021) Improvement of shelf life quality of green bell peppers using edible coating formulations. J Microbiol Biotechnol Food Sci 2: 2448–2451 172. La DD, Nguyen-Tri P, Le KH, Nguyen PT, Nguyen MDB, Vo AT, Nguyen MT, Chang SW, Tran LD, Chung WJ, Nguyen DD (2021) Effects of antibacterial ZnO nanoparticles on the performance of a chitosan/gum arabic edible coating for post-harvest banana preservation. Prog Org Coat 151:106057

114

N. Kumar et al.

173. Criado P, Fraschini C, Shankar S, Salmieri S, Lacroix M (2021) Influence of cellulose nanocrystals gellan gum-based coating on color and respiration rate of Agaricus bisporus mushrooms. J Food Sci 86(2):420–425 174. Kumar N, Neeraj, Pratibha, Singla M (2020) Enhancement of storage life and quality maintenance of litchi (Litchi chinensis Sonn.) fruit using chitosan: pullulan blend antimicrobial edible coating. Int J Fruit Sci 20(3):S1662–S1680 175. Kumar N, Pratibha N, Ojha A, Upadhyay A, Singh R, Kumar S (2021) Effect of active chitosan- pullulan composite edible coating enrich with pomegranate peel extract on the storage quality of green bell pepper. LWT Food Sci Technol 138:110435 176. Neeraj K, Neeraj, Pratibha, Petkoska AT (2021) Improved shelf life and quality of Tomato (Solanum lycopersicum L.) by using chitosan-pullulan composite edible coating enriched with pomegranate peel extract. ACS Food Sci Technol. https://doi.org/10.1021/acsfoodscitech. 0c00076 177. Raghav PK, Agarwal N, Saini M (2016) Edible coating of fruits and vegetables: a review. Int J Sci Res Mod Educ 1(1):188–204 178. Yanyun Z (2011) Application of commercial coatings. In: Edible coatings and films to improve food quality. CRC Press, Boca Raton, pp 319–331 179. Olivas GI, Rodriguez JJ, Barbosa-Canovas GV (2003) Edible coatings composed of methylcellulose, stearic acid, and additives to preserve quality of pear wedges. J Food Process Preserv 27:299–320 180. Li C, Tao J, Zhang H (2017) Peach gum polysaccharides-based edible coatings extend shelf life of cherry tomatoes. Biotech 7(3):168 181. Babiker EE, Eltoum YAI (2014) Effect of edible surface coatings followed by dehydration on some quality attributes and antioxidants content of raw and blanched tomato slices. Food Sci Biotechnol 23(1):231–238 182. Eltoum YAI, Babiker EE (2014) Changes in antioxidant content, rehydration ratio and browning index during storage of edible surface coated and dehydrated tomato slices. J Food Process Preserv 38(3):1135–1144 183. Pizato S, Cortez-Vega WR, Souza JTA, Prentice-Hernández C, Borges CD (2013) Effects of different edible coatings in physical, chemical and microbiological characteristics of minimally processed peaches (Prunus persica L. batsch). J Food Saf 33(1):30–39 184. Ruelas-Chacon X, Contreras-Esquivel JC, Montañez J, Aguilera-Carbo AF, Reyes-Vega ML, Peralta-Rodriguez RD, Sanchéz-Brambila G (2017) Guar gum as an edible coating for enhancing shelf-life and improving postharvest quality of Roma tomato (Solanum lycopersicum L.). J Food Qual 8608304:1–9 185. Minh PN, Nhi TYT, Vien TBL, Ha TTT, Yen TKN (2019) Effect of arabic gum coating on postharvest quality of litchi (Litchi chinensis) fruits. J Pharm Sci Res 11(4):1464–1468 186. Das DK, Dutta H, Mahanta CL (2013) Development of a rice starch-based coating with antioxidant and microbe-barrier properties and study of its effect on tomatoes stored at room temperature. LWT Food Sci Technol 50(1):272–278 187. Hashemi SMB, Mousavi KA, Ghaderi GM, Eş I (2017) Basil-seed gum containing Origanum vulgare subsp. viride essential oil as edible coating for fresh cut apricots. Postharvest Biol Technol 125:26–34 188. Saberi B, Golding JB, Chockchaisawasdee S, Scarlett CJ, Stathopoulos CE (2018a) Effect of biocomposite edible coatings based on pea starch and guar gum on nutritional quality of “Valencia” orange during storage. Starch 70(5–6):1700299 189. Saberi B, Golding JB, Marques JR, Pristijono P, Chockchaisawasdee S, Scarlett CJ, Stathopoulos CE (2018b) Application of biocomposite edible coatings based on pea starch and guar gum on quality, storability and shelf life of ‘Valencia’ oranges. Postharvest Biol Technol 137:9–20 190. Kharchoufi S, Parafati L, Licciardello F, Muratore G, Hamdi M, Cirvilleri G, Cristina R (2018) Edible coatings incorporating pomegranate peel extract and biocontrol yeast to reduce Penicillium digitatum postharvest decay of oranges. Food Microbiol 74:107–112

4

Natural Gums for Fruits and Vegetables Preservation: A Review

115

191. Tomadoni B, Moreira MR, Pereda M, Ponce AG (2018) Gellan-based coatings incorporated with natural antimicrobials in fresh-cut strawberries: microbiological and sensory evaluation through refrigerated storage. LWT Food Sci Technol 97:384–389 192. Eshetu A, Ibrahim MA, Forsido FS, Kuyu GC (2019) Effect of beeswax and chitosan treatments on quality and shelf life of selected mango (Mangifera indica L.) cultivars. Heliyon 5(1):1–22 193. Etienne A, Génard M, Lobit P, Mbeguié-A-Mbéguié D, Bugaud C (2013) What controls fleshy fruit acidity? A review of malate and citrate accumulation in fruit cells. J Exp Bot 64(6):1451–1469 194. GutiéRrez M, Lahoz JM, Sola M, Pascual L, Vargas AM (1994) Postharvest changes in total soluble solids and tissue pH of cherimoya fruit stored at chilling and non-chilling temperatures. J Horti Sci 69(3):459–463 195. Manríquez DA, Muñoz-Robredo P, Gudenschwager O, Robledo P, Defilippi BG (2014) Development of flavor-related metabolites in cherimoya (Annona cherimola Mill.) fruit and their relationship with ripening physiology. Postharvest Biol Technol 94:58–65 196. Muñoz T, Sanchez-Ballesta MT, Ruiz-Cabello J, Escribano MI, Merodio C (2004) The acid metabolism of Annona fruit during ripening. J Hortic Sci Biotech 79(3):472–478 197. Kanellis AK, Tonutti P, Perata P (2009) Biochemical and molecular aspects of modified and controlled atmospheres. In: Yahia EM (ed) Modified and controlled atmospheres for the storage, transportation, and packaging of horticultural commodities. CRC Press, Boca Raton, pp 553–567 198. Fagundes C, Palou L, Monteiro AR, Pérez-Gago MB (2014) Effect of antifungal hydroxypropyl methylcellulose-beeswax edible coatings on gray mold development and quality attributes of cold-stored cherry tomato fruit. Postharvest Biol Technol 92:1–8 199. Lásztity R, SEBŐK A, Major J (1992) Textural properties of fruits and vegetables and their changes during freezing and storage at low temperatures. Period Polytech Chem Eng 36(4): 225–238 200. Barrett DM, Beaulieu JC, Shewfelt R (2010) Color, flavor, texture, and nutritional quality of fresh-cut fruits and vegetables: desirable levels, instrumental and sensory measurement, and the effects of processing. Crit Rev Food Sci Nutr 50(5):369–389 201. Bourne MC (1982) Food texture and viscosity, 1st edn. Academic, New York 202. Barbagallo RN, Chisari M, Caputa G (2012) Effects of calcium citrate and ascorbate as inhibitors of browning and softening in minimally processed ‘Birgah’ eggplants. Postharvest Biol Technol 73:107–114 203. Rojas-Argudo C, del Río MA, Pérez-Gago MB (2009) Development and optimization of locust bean gum (LBG)-based edible coatings for postharvest storage of ‘Fortune’ mandarins. Postharvest Biol Technol 52(2):227–234 204. Appelqvist IAM, Debet MRM (1997) Starchbiopolymer interactions – a review. Food Rev Int 13(2):163–224 205. Artes F, Gomez P (2003) Packaging and color control: the case of fruit and vegetables. In: Avenhainen R (ed) Novel food packaging techniques. CRC Press/Woodhead Publishing, Boca Raton, p 416 206. Mohammadi A, Hashemi M, Hosseini SM (2016) Postharvest treatment of nanochitosanbased coating loaded with Zataria multiflora essential oil improves antioxidant activity and extends shelf-life of cucumber. Innov Food Sci Emerg Technol 33:580–588 207. Ali A, Muhammad MTM, Sijam K, Siddiqui Y (2011) Effect of chitosan coatings on the physicochemical characteristics of Eksotika II papaya (Carica papaya L.) fruit during cold storage. Food Chem 124(2):620–626 208. Dilmacunal T, Koyunchu MA, Aktas H, Bayindir D (2011) The effect of several post-harvest treatments on shelf life, quality of bunch tomatoes. Not Bot Horti Agrobot 39:209–213 209. Escamilla-García M, Rodríguez-Hernández JM, Hernández-Hernández MH, DelgadoSánchez FL, García-Almendárez EB, Amaro-Reyes A, Regalado-González C (2018) Effect of an edible coating based on chitosan and oxidized starch on shelf life of Carica papaya L., and its physicochemical and antimicrobial properties. Coatings 8(318):1–14

116

N. Kumar et al.

210. Mandal D, Lalrinpuii S, Hazarika KT, Amritesh SC (2018) Effect of edible coating on shelf life and quality of local mango cv. Rangkuai of Mizoram. Res Crop 19(3):419–424 211. Sharma L, Saini S, Sharma C, Harish K (2019) Biocomposite edible coatings based on cross linked-sesame protein and mango puree for the shelf life stability of fresh-cut mango fruit. J Food Process Eng 42(1):1–9 212. Halachmy IB, Mannheim CH (1991) Modified atmosphere packaging of fresh mushrooms. Packag Technol Sci 4(5):279–286 213. Becker BR, Fricke BA (1996) Transpiration and respiration of fruits and vegetables. Sci Tech Froid 6:110–121 214. Silva E (2010) Respiration and ethylene and their relationship to postharvest handling. Organic Agriculture 215. Gaffney JJ, Baird CD, Chau KV (1985) Influence of airflow rate, respiration, evaporative cooling, and other factors affecting weight loss calculations for fruits and vegetables. ASHRAE Trans 91(1B):690–707 216. Gonzalez-Aguilar GA, Valenzuela-Soto E, Lizardi-Mendoza J, Goycoolea F, Martínez-Téllez MA, Villegas-Ochoa MA, Monroy-García IN, Ayala-Zavala JF (2009) Effect of chitosan coating in preventing deterioration and preserving the quality of fresh-cut papaya ‘Maradol’. J Sci Food Agric 89:15–23 217. Keller N, Ducamp MN, Robert D, Keller V (2013) Ethylene removal and fresh product storage: a challenge at the frontiers of chemistry. Toward an approach by photocatalytic oxidation. Chem Rev 113(7):5029–5070 218. Suslow TV (2000) Post-harvest handling for organic crops. Organic vegetable production in California series. Pub. 7254. University of California Davis. Available online at: https:// anrcatalog.ucanr.edu/pdf/7254.pdf. Verified 24 Dec 2019 219. Bhattacharya A, Sood P, Citovsky V (2010) The roles of plant phenolics in defence and communication during Agrobacterium and Rhizobium infection. Mol Plant Pathol 11(5):705–719 220. Swallah MS, Sun H, Affoh R, Fu H, Yu H (2020) Antioxidant potential overviews of secondary metabolites (polyphenols) in fruits. Int J Food Sci 9081686:1–8 221. Frusciante L, Carli P, Ercolano MR, Pernice R, Di Matteo A, Fogliano V, Pellegrini N (2007) Antioxidant nutritional quality of tomato. Mol Nutr Food Res 51:609–617 222. Kaur C, Kapoor HC (2001) Antioxidant in fruits and vegetables – the millennium's health. Int J Food Sci Technol 36(7):703–725 223. Jafari S, Hojjati M, Noshad M (2018) Influence of soluble soybean polysaccharide and tragacanth gum based edible coating to improve the quality of fresh-cut apple slices. J Food Process Preserv 42(6):e13638 224. Sarpong F, Oteng-Darko P, Golly MK, Amenorfe LP, Rashid MT, Zhou C (2018) Comparative study of enzymes inactivation and browning pigmentation of apple (Malus domestica) slices by selected gums during low temperature storage. J Food Biochem 42(6):e12681 225. Parafati L, Vitale A, Restuccia C, Cirvilleri G (2016) The effect of locust bean gum (LBG)based edible coatings carrying biocontrol yeasts against Penicillium digitatum and Penicillium italicum causal agents of postharvest decay of mandarin fruit. Food Microbiol 58:87–94 226. Galindo-Pérez MJ, Quintanar-Guerrero D, Mercado-Silva E, Real-Sandoval SA, ZambranoZaragoza ML (2015) The effects of tocopherol nanocapsules/Xanthan gum coatings on the preservation of fresh-cut apples: evaluation of phenol metabolism. Food Bioprocess Technol 8 (8):1791–1799 227. Tuorila H, Monteleone E (2009) Sensory food science in the changing society: opportunities, needs, and challenges. Trends Food Sci Technol 20:54–62 228. Peryam DR, Pilgrim FJ (1957) Hedonic scale method of measuring food preferences. Food Technol 11:9–14 229. Lawless HT, Heymann H (2010) Introduction. In: Lawless HT, Heymann H (eds) Sensory evaluation of food: principles and practices, 2nd edn. Springer Science and Business Media, New York 230. Barth M, Hankinson TR, Zhuang H, Breidt F (2009) Microbiological spoilage of fruits and vegetables. In: Compendium of the microbiological spoilage of foods and beverages. Springer, New York, pp 135–183

5

Application of Guar Gum and Its Derivatives in Agriculture Manar El-Sayed Abdel-raouf, Asmaa Sayed, and Mai Mostafa

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Guar Plant . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Global Distribution of Guar Crop . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Extraction of Guar Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Chemical Structure of Guar Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Physical Properties of Guar Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Chemical Modification of Guar Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Modified Guar Gum in Agriculture . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Soil Amendment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Water-Saving . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Sustained Release and Delivery System . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

118 120 120 120 121 122 123 124 125 128 128 129 130

Abstract

Guar gum is one of the most abundant carbohydrate polymers. This polymer finds tremendous areas of application due to its biodegradability, high functionality, and hydrophilic nature. Moreover, it pertains to some unique physical properties that make guar an excellent candidate as a thickening agent and a gellating material. Due to its high functionality, guar gum can be adapted into various forms to fit different applications. The most significant feature of guar is the ease of extraction from its natural source as a pure white powder. Herein, we introduce an idea of guar extraction and purification, the physical and chemical properties of guar, and different guar derivatives. Moreover, we discuss the application of M. E.-S. Abdel-raouf (*) Petroleum Application Department, Egyptian Petroleum Research Institute, Cairo, Egypt e-mail: [email protected] A. Sayed · M. Mostafa Polymer Chemistry Department, National Center for Radiation Research and Technology, Egyptian Atomic Energy Authority, Cairo, Egypt © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_5

117

118

M. E.-S. Abdel-raouf et al.

guar gum and its modified derivatives such as guar gum-based hydrogels, guar gum-based composites, and hydrogel nanocomposites in the agriculture field from the point of high water absorption, excellent retention capacity, and effective controlled release. Keywords

Agriculture · Biodegradable · Green polymers · Guar gum

1

Introduction

There are numerous polymeric materials that can be extracted from animals or plants, Fig. 1. Guar gum is one of the most important polysaccharide polymers of plant origin. The significant importance of guar gum has emerged since the green chemistry concept is established. Guar gum is in the form of a white smooth powder obtained from seeds of a drought-tolerant legume plant, i.e. (Cyamopsis tetragonoloba) of family Fabaceae, Fig. 3, [1–3]. It was commonly used as food for castles in developing countries. Recently, it has become a universal crop for industry. It is widely used in pharmaceutical applications, petroleum sector, as thickening, in

Sources of natural polymers Plant origin Srarch strachy plants such as potatoes, sweet potatoes, rice, wheat

Animal origin Gelatin

Cellulose The peels of ome fruits such as banana and pometranates

Pectin The peels of citruc fruits

gums Acasia gum, Arabic gum, Guar gum

legnin

Fig. 1 Sources of natural polymers

Chitin glycogen Collagen

5

Application of Guar Gum and Its Derivatives in Agriculture

Fig. 2 Different applications of guar gum

119

Pharmaceuticals and biomedical

Agriculture

Oil and gas industries

Cosmetics

Food and beverages

Fig. 3 Guar plant, guar pods, and guar powder

the paper industry, and wastewater treatment (Fig. 2). Guar gum can be adapted chemically into a wide number of guar gum derivatives through modification of the reactive hydroxyl groups present along with the guar gum monomer unit. A list of the most important guar gum derivatives is given below [4–8]: • • • • • •

Carboxymethyl guar gum. Hydroxymethyl guar gum. Hydroxypropylethyl guar gum. O-carboxymethyl-O-hydroxypropyl guar gum (CMHPG). Ammonium hydroxyl propyl trimethyl chloride of guar gum. O-carboyxymethyl-O-2 hydroxy-3-(trimethylammonia propyl) (CMHTPG). • Acryloyloxy guar gum.

guar

gum

120

M. E.-S. Abdel-raouf et al.

• Methacryloyl guar gum. • Guar gum esters. These derivatives are widely applied in various industries.

2

Guar Plant

Guar is a drought-tolerant plant that grows best in sandy soils and needs moderate, intermittent rainfall with lots of sunshine. Guar gum roots develop well in the lateral direction also. The Guar plant has a single stem, fine branching, or basal branching, and grows as high as 45–100 cm. The flowers are tiny white. The pods are oblong and 5–10 cm in length. Pods normally contain 5–12 seeds of oval or cube shape of variable size and color according to the plant origin, Fig. 3, [9–11]

2.1

Global Distribution of Guar Crop

The guar or cluster bean is an agricultural crop grown in tropical areas such as West and North-West India, Pakistan, Sudan, and some parts of the USA, Fig. 4. The major global production is achieved by India which produces over 850,000 tons or 85% of the total guar produced. About 75% of the guar gum or its derivatives produced in India are exported, mainly to the USA and to European countries [12].

2.2

Extraction of Guar Gum

Guar is a pod-bearing plant. Each seed consists of hull, endosperm, and germ parts, in a weight percentage of l5%, 40%, and 45%, respectively. The germ portion is chiefly protein, and the endosperm is mainly guar galactomannan or guar gum. Germ and hull are consumed as animal feedstuff after proper treatment [13–15]. Fig. 4 Global distribution of guar production

India

Pakistan

Others

5

Application of Guar Gum and Its Derivatives in Agriculture

Cleaning

Grading

Dehusking

separation of the endosperm

121

grinding and purification of GG powder

Fig. 5 The overall process of extraction of guar gum

The three components are separated during processing. Finally, the guar gum powder is obtained after removing the hull and germ from the seed and grinding the endosperm into fine powder. The endosperm ranges from 32 to 42% depending on the variety and maturity of the crop [16]. Therefore, the main unit operations involved in the processing of guar seeds are cleaning, grading, dehusking, splitting, and separation of endosperm, grinding, and purification of powder. On arrival at the processing plant, seeds are screened for removal of dirt, stones, sand, metal debris, chaffs, and broken seeds. Standard seed cleaning vibrators, electromagnets, and shifters are used for cleaning [17]. The flowchart of the entire process is given in Fig. 5.

2.3

Chemical Structure of Guar Gum

Guar gum is a galactomannan polymer consisting of α (1, 4)-linked β-Dmannopyranose backbone with branch points from their 6-positionslinked to α-Dgalactose (i.e., 1, 6-linked-α-D-galactopyranose), Fig. 6, [15, 18,19] The ratio of mannose to galactose unit (M/G) ranges from 1.8:1 to 2:1 due to the distinction in geographical origins. Guar is hydrophilic due to the numerous hydroxyl groups along with the main chain and the side branches. This feature afforded guar with some unique features such as high ability to form intermolecular hydrogen bondings. This makes guar gum is an excellent gelling agent and used as an outstanding candidate in many industries related to this feature. Moreover, the high functionality of guar enables a tremendous number of modification strategies and offers numerous guar derivatives [20–22].

122

M. E.-S. Abdel-raouf et al.

Fig. 6 Chemical structure of guar gum Fig. 7 Chemical modification of guar gum

2.4

Crosslinking

Derivatization

Hydrogels

partial hydrolysis

composites

carboxymthylation

Hydrogel nanocompoites

sulphonation, carboxylation

Physical Properties of Guar Gum

Guar gum exhibits some fabulous physical properties that make guar one of the most applicable carbohydrate polymers (Fig. 7). These are as follows [24–28]: • It is strong water-soluble in both hot and cold water but insoluble in most organic solvents. • It has a significant ability of hydrogen bonding formation. • It has excellent thickening, emulsifying, Stabilizing, and film-forming properties. • At very low concentration, Guar Gum has excellent settling (flocculation) properties, and it acts as a filter aid. • It is non-ionic and maintains a constant high viscosity over a broad range of pH. • It is compatible with a variety of inorganic and organic substances including certain dyes and various constituents of food. • The viscosity of Guar Gum solution increases gradually with increasing concentration of Guar Gum in water.

5

Application of Guar Gum and Its Derivatives in Agriculture

123

• The viscosity of Guar Gum solution is dependent on temperature, pH, presence of salts, and other solids. • It has an excellent ability to control rheology by economic water phase management. • Guar gum powder and solution is odorless and has a bland taste. • Guar gum is compatible with many other hydrocolloids used in food formulations.

2.5

Chemical Modification of Guar Gum

The two main modifications routes for guar gum are derivatization and crosslinking. Below each of them, there are many classes of guar-based materials that can be produced. All these routes take place on the hydroxyl groups distributed along with guar monomer. In sustained release applications, guar-based hydrogels are most common due to their remarkable swelling capacity, distinct water retention, and smart behavior [29].

2.5.1 Derivatization of Guar Gum Carboxymethyl guar gum is the most common guar gum derivative that is being used in delivery systems. Moreover, carboxymethyl guar gum nanoparticles were prepared for pharmaceutical uses. Other chemically modified water-soluble guar gum derivatives are illustrated in Fig. 8. These derivatives have strong thickening properties and are used in sustained release applications. Some active derivatives of guar gum including hydroxymethyl guar gum, hydroxypropyl guar gum, ammonium hydroxyl propyltrimethyl chloride of guar gum, acryloyloxy guar gum, methacryloyl guar gum, carboxymethylated guar gum, sulfated guar gum, guar gum esters, etc. have been prepared, characterized, and examined for application in different fields [30–35]. 2.5.2 Hydrogel Formation Hydrogels are three-dimensional network structures with numerous pores [36–38]. These pores are responsible for holding aqueous media while the active functional groups of the gel components can chelate different species such as metal cations, nutrients such as phosphate fertilizers. Guar gum can form hydrogels by crosslinking with different acrylate monomers or polymers in presence of a suitable crosslinker. Commonly used crosslinking agents include derivatives of methylene-bis-acrylamide, derivatives of ethylene-glycol-di(meth)acrylate, di-vinyl-benzene, glutaraldehyde, etc. The crosslinker is a highly functional compound that possesses at least two active sites which undergo intermolecular bonding with hydroxyl groups of polymer chains to form a closed-loop-like structure. Some acrylates can induce certain responsive behavior to the hydrogel. For instance, crosslinking with polyacrylic acid produces pH-responsive hydrogel whereas crosslinking with polyacrylamide brings thermoresponsive behavior. Moreover, guar gum can be self-crosslinked in the presence of certain crosslinkers such as borax. In this work, Nandkishore et al. utilized the claimed

124

M. E.-S. Abdel-raouf et al.

Fig. 8 Chemical structure of some water-soluble guar gum derivatives

hydrogels as adsorbents for water purification purposes [12], Fig. 9. Moreover, Kono et al. [26] prepared hydrogels from guar gum (GG) via esterification with 1,2,3,4butanetetracarboxylicdianhydride (BTCA) for sustained release applications.

2.5.3 Guar Gum-Based Hydrogel Composites and Nanocomposites Several guar gum-based hydrogel composites and nanocomposites were prepared and evaluated for sustained release and wastewater treatment applications. Many materials used for composite formation including cloisite, magnetic nanoparticles, muscovite and attapulgite. Recently, Chanon et al. introduced guar gum hydrogels, crosslinked with borax, and loaded with silver nanoparticles, that are injectable, exhibit rapid self-healing, and show antibacterial properties toward both grampositive and gram-negative bacteria. Deka et al. introduced AgNPs containing polyvinyl alcohol (PVA)-guar gum (GG) smart hydrogel composite for catalytic and biomedical application [9].

3

Modified Guar Gum in Agriculture

The utilization of hydrogels in agriculture is known as agrohydrogels. The main roles of guar gum hydrogels in the field of agriculture are summarized in Fig. 10.

5

Application of Guar Gum and Its Derivatives in Agriculture

125

Fig. 9 Proposed scheme of borax-crosslinked guar gum [12] Fig. 10 Applications of guar gum in agriculture

Sustained release and delivery systems

Water saving

Soil amendment

3.1

Soil Amendment

Hydrogels based on guar gum are either neutral or charged according to the type of the chemical adaptation regime. However, both types can interact with the soil components in many ways. For instance, cationic hydrogels can bind to clay particles and act as flocculants. Anionic hydrogels connect to the clay and other negatively charged particles through ionic bridges such as calcium and magnesium. The effective attraction between the gel matrix and surrounding solutes and soil

126

M. E.-S. Abdel-raouf et al.

Fig. 11 Water absorption of hydrogels

particles improves the water absorption, creates aggregates, and stabilizes soil structure [39, 40]. Dry and desert lands that represent over 70% of the total land area have a loose structure, poor impacts, very low fertility, and inadequate water retention. However, practicing the proper water management methodologies can increase the productivity of these soils as others. The addition of soil conditioners was found to be more effective than adding clays or organic manures and composts to soils. Soil conditioners retain the soil humidity and thus recover hydrophysical properties in such soils by the following effects [41–44]: • Increasing the soil holding capacity of water by absorbing large quantities of water, Fig. 11. • Improving the soil compactness and reducing erosion runoff, Fig. 12. • Adapting soil permeability and infiltration. Hydrogel act as a slow release of water in the soil by forming an amorphous gelatinous mass on hydration and thus result in absorption and desorption of water over a long period [45–47]. Water will be removed from these reservoirs according to the root demand through osmotic pressure difference. Guar gum-based hydrogels were investigated for soil amendment by capturing a huge amount of water for regular irrigation and soil fixation [48–52]. In this regard, Thombare et al. [53] introduced novel guar gum hydrogels via grafting guar gum with acrylic acid and crosslinking with ethylene-glycol-di methacrylic acid (EGDMA). Synthesized hydrogel (GG-AA-EGDMA) was confirmed to be biodegradable with a half-life period of 77 days through soil burial biodegradation studies. Different soil properties such as bulk density, porosity, water absorption, and retention capacity. It was found that the prepared guar gum super absorbent hydrogels improved soil porosity, moisture absorption, and retention capacity

5

Application of Guar Gum and Its Derivatives in Agriculture

127

Fig. 12 Roles of hydrogels in agriculture

significantly which proves the applicability of the claimed hydrogels as effective soil conditioners. In most cases, the hydrogels are tested as soil conditioners and as carriers at the same time. Chandrika et al. [5] investigated the potential of some crosslinked guar gum-g-polyacrylate (cl-GG-g-PA) superabsorbent hydrogels soil conditioners and carriers. The hydrogels were prepared by in situ grafting polymerization and crosslinking of acrylamide onto a natural GG followed by hydrolysis. The swelling behavior of a candidate hydrogel [GG-superabsorbent polymer (SAP)] in response to external stimuli, namely, salt solutions, fertilizer solutions, temperature, and pH, was studied [54]. The GG-SAP displayed substantial swelling in various environments. The effect of GG-SAP on water absorption and the retention characteristics of sandy loam soil and soil-less medium was also considered as a function of temperature and moisture tensions. The addition of GG-SAP significantly improved the moisture characteristics of plant growth media (both soil and soil-less), showing that it has tremendous potential for diverse applications in moisture stress agriculture. In our previous work [1], two sets of smart guar gum-based hydrogels were prepared by grafting guar gum onto acrylic acid/ acrylamide and acrylic acid/ N-isopropylacrylamide copolymers by using persulphate radical as an initiator and N,N methylenebisacrylamide as a crosslinker. The effect of some composition variables on the swelling performance of PA-GG hydrogel was carefully verified. Furthermore, swelling behavior was monitored as a function of temperature and electrolyte concentration. A lab experiment was conducted to investigate the effect of the optimum hydrogels on the growth of guava plants in sandy soil. In this experiment, the soil was well irrigated then it has been subjected to drought conditions for 15 days. It was found that the addition of hydrogel material into the

128

M. E.-S. Abdel-raouf et al.

soil improved the total vegetative parts of the plants in drought conditions which reflects the modification of the water holding capacity of the soil and the improvement of the soil compactness.

3.2

Water-Saving

The ability of soil to retain water is an important feature for healthy plant growth. The continuous leakage of water from the soil is predominantly due to the disintegration of the soil particles [55]. The addition of the hydrogel increases the soil impactness, modifies the adhesion forces, and reduces the interarticular spaces. Moreover, the addition of organic materials enhances water retention and increases nutrient availability. In most cases, green hydrogels such as guar gum – when added to the soil – display all the functions of hydrogels: Improving the physico-chemical feature of the soil, enhancing water retention and delivery of certain chemicals such as nutrients and pesticides [55]. In this regard, Upadhyay and Warker [56] synthesized a series of eco-friendly hydrogel formulations that can absorb and reserve a huge amount of water for a longer period to achieve lesser irrigation, supporting the cause of water conservation. To support in recognizing the utility of efficient materials in water delivery for agricultural applications. The claimed hydrogels were based on varying proportions of carboxymethyl guar gum (CMG), and sodium polyacrylate, and a crosslinker. The swelling and water retention behavior of synthesized hydrogels were verified versus time, temperature, and pH. The hydrogels showed a noticeable response in relation to pH, temperature, and more importantly with respect to the growth of plants.

3.3

Sustained Release and Delivery System

The hydrogels which are applied for delivery applications and carrier systems are characterized by a smart behavior, i.e., they release the encaptured materials under certain environmental stimuli such as a change in temperature and pH of the medium. These are known as smart or stimuli-responsive hydrogels. Several smart guar-gum-based hydrogels are known as delivery candidates. For instance, Lang et al. [27] investigated some thermo- and pH-sensitive hydrogels that were synthesized using N-isopropylacrylamide and Guar gum (GG) and crosslinked with glutaraldehyde (GA) for their drug release potency. Sinomenine hydrochloride (SH-HCl) was employed as the model drug. The lower critical solution temperature (LCST) of the poly(N-isopropylacrylamide)-g-Guar gum (PNIAAm-g-GG) was shown to be approximately 37.5  C due to the presence of PNIMAM as a thermoresponsive polymer, and the release rate of SH-HCl was shown to be faster below the LCST. Then, when the temperature was changed across the LCST, reversible and thermoresponsive release behavior was detected. Also, at a pH 6.8 or a high salt concentration, the release rate of SH-HCl from the hydrogel was slower than in

5

Application of Guar Gum and Its Derivatives in Agriculture

129

pH 1.0 HCl. When pH changed across 1.0–6.8, reversible and pH-responsive release behavior was also shown. Many other parameters such as hydrogel strength, permeability, and viscosity were verified, and the results were discussed in terms of the nature of the polymer. Chandrika et al. [4] introduced a new series of eco-friendly crosslinked guar gum-g-poly(acrylate)porous superabsorbent hydrogels by in situ grafting polymerization and crosslinking onto a guar gum macromolecule utilizing N,N-methylene bis acrylamide as crosslinker. A detailed swelling investigation was performed for the optimized hydrogel (SPH) in response to external stimuli namely, salt solutions, fertilizer solutions, temperature, and pH. The investigated hydrogels exhibited high swelling capacities in various environments. The obtained data proved that the prepared hydrogels could serve as excellent carriers of pesticides and fertilizers. They can be uploaded with antimicrobial formulations to protect the plants from different agriculturally important microbes such as phytopathogenic fungus Pythium aphanidermatum. Moreover, Wang et al. [57] studied the swelling properties and delivery activity of some superabsorbent nanocomposites based on natural guar gum and cationmodified vermiculite. The prepared hydrogel nanocomposites were very effective in delivering several types of fertilizers to the soil. In addition, Wang et al. [58] incorporated the medical stone in an efficient formulation within carboxymethyl guar gum/ polyacrylic acid as superabsorbent composites. The data demonstrated that the incorporation of 20 wt% MS enhanced the water absorption by 100% (from 317 to 634 g/g). The advanced composites showed improved swelling rate and swelling/deswelling characteristics in various pH solutions, saline solution, and hydrophilic organic solvents, which represented interesting and reversible pH-, saline-, and hydrophilic organic solvent-responsive characteristics. In another work, Gupta and Warker [19] studied the swelling properties of poly (acrylamide-Cl carboxymethyl guar gum) hydrogels for agriculture purposes. They found that there is an optimum acrylamide/carboxymethyl guar gum ratio that fulfills maximum swelling while retaining the hydrogel matrix impacted. This is a very important parameter in judging the workability of the hydrogels [59].

4

Conclusions

Guar gum is a highly functional carbohydrate polymer containing numerous hydroxyl groups as well as a linear chain with side branches. This unique arrangement acquired guar gum many features such as the high ability of hydrogen bonding formation, gelation at high concentration, and film-forming features. Guar gum can be modified via numerous strategies to produce different derivatives that find great importance in wide applications. For agriculture, modified guar gum can be adapted into hydrogel materials which can hold a huge amount of water or aqueous solutions containing nutrients and pesticides and deliver them under certain conditions at a regulated rate of release [60–63].

130

M. E.-S. Abdel-raouf et al.

References 1. Abdel-Raouf ME, El-Saeed SM, Zaki EG, Al-Sabagh AM (2018) Green chemistry approach for preparation of hydrogels for agriculture applications through modification of natural polymers and investigating their swelling properties. Egypt J Pet 27(4):1345–1355 2. Abdel-Raouf ME (2019) Guar gum based hydrogels for sustained water release applications in agriculture, a review. Curr Res Biopolymers 2:111 3. Ahmed EM (2015) Hydrogel: preparation, characterization, and applications: a review. J Adv Res 6(2):105–121 4. Chandrika KSVP, Singh A, Rathore A, Kumar A (2016) Novel cross linked guar gum-G-poly (acrylate) porous superabsorbent hydrogels: characterization and swelling behaviour in different environments. Carbohydr Polym 149:175–185 5. Chandrika KSVP, Singh A, Sarkar DJ, Rathore A, Kumar A (2014) Ph-sensitive crosslinked guar gum-based superabsorbent hydrogels: swelling response in simulated environments and water retention behavior in plant growth media. J Appl Polym Sci 131(22) 6. Cheng Y, Prud’Homme RK, Chik J, Rau DC (2002) Measurement of forces between galactomannan polymer chains: effect of hydrogen bonding. Macromolecules 35(27):10155– 10161 7. Chowdhary M, White W (2002) Guar gum powder possessing improved hydration characteristics. Google Patents 8. Dall’Alba V, Silva FM, Antonio JP, Steemburgo T, Royer CP, Almeida JC, Gross JL, Azevedo MJ (2013) Improvement of the metabolic syndrome profile by soluble fibre–guar gum–in patients with type 2 diabetes: a randomised clinical trial. Br J Nutr 110(9):1601–1610 9. Deka R, Sarma S, Patar P, Gogoi P, Sarmah JK (2020) Highly stable silver nanoparticles containing guar gum modified dual network hydrogel for catalytic and biomedical applications. Carbohydr Polym 248:116786 10. Dodi G, Hritcu D, Popa MI (2011) Carboxymethylation of guar gum: synthesis and characterization. Cellul Chem Technol 45(3):171 11. Dodi G, Pala A, Barbu E, Peptanariu D, Hritcu D, Popa MI, Tamba BI (2016) Carboxymethyl guar gum nanoparticles for drug delivery applications: preparation and preliminary in-vitro investigations. Mater Sci Eng C 63:628–636 12. Dong C, Tian B (1999) Studies on preparation and emulsifying properties of guar galactomannan ester of palmitic acid. J Appl Polym Sci 72(5):639–645 13. Elshafie HS, Camele I (2021) Applications of absorbent polymers for sustainable plant protection and crop yield. Sustainability 13(6):3253 14. Ercelebi EA, Ibanoglu EJIJOFP (2010) Stability and rheological properties of egg yolk granule stabilized emulsions with pectin and guar gum. Int J Food Prop 13(3):618–630 15. George P, Manuel J (2013) Low cost tissue culture technology for the regeneration of some economically important plants for developing countries. Int J Agric Environ Biotechnol 6 (Special Issue):703–711 16. Gittings MR, Cipelletti L, Trappe V, Weitz DA, In M, Lal J (2001) The effect of solvent and ions on the structure and rheological properties of guar solutions. Chem A Eur J 105(40): 9310–9315 17. Gong H, Liu M, Chen J, Han F, Gao C, Zhang B (2012) Synthesis and characterization of carboxymethyl guar gum and rheological properties of its solutions. Carbohydr Polym 88(3): 1015–1022 18. Gupta AP, Verma DK (2014) Guar gum and their derivatives: a research profile. Int J Adv Res 2 (1):680–690 19. Gupta AP (2014) Preparation and characterization of carboxymethyl guar gum nanoparticles. Int J Biol Macromol 68:247–250 20. Gupta AP, Warkar SG (2015) Synthesis, characterization and swelling properties of poly (acrylamide-cl-carboxymethylguargum) hydrogels. Int J Pharm Bio Sci 6(1):516–529 21. Hasan AMA, Abdel-Raouf ME (2018) Applications of guar gum and its derivatives in petroleum industry: a review. Egypt J Pet 27(4):1043–1050

5

Application of Guar Gum and Its Derivatives in Agriculture

131

22. He L-S, Jiang B, Wang K (2008) Determination of the degree of the substitution of hydroxyethyl guar gum. Carbohydr Polym 72(3):557–560 23. Huettermann A, Orikiriza LJB, Agaba H (2009) Application of superabsorbent polymers for improving the ecological chemistry of degraded or polluted lands. Clean Soil Air Water 37(7): 517–526 24. Jing H, Feng J, Shi J, He L, Guo P, Guan S, Hai F, Ao Y (2021) Ultra-stretchable, selfrecovering, self-healing cationic guar gum/poly (stearyl methacrylate-co-acrylic acid) hydrogels. Carbohydr Polym 256:117563 25. Johnson W Jr, Heldreth B, Bergfeld WF, Belsito DV, Hill RA, Klaassen CD, Liebler DC et al (2015) Safety assessment of galactomannans as used in cosmetics. Int J Toxicol 34(1_suppl):35S–65S 26. Kono H, Otaka F, Ozaki M (2014) Preparation and characterization of guar gum hydrogels as carrier materials for controlled protein drug delivery. Carbohydr Polym 111:830–840 27. Lang YY, Li SM, Pan WS, Zheng LY (2006) Thermo-and Ph-sensitive drug delivery from hydrogels constructed using block copolymers of poly (N-Isopropylacrylamide) and guar gum. J Drug Deliv Sci Technol 16(1):65–69 28. Lapasin R, De Lorenzi L, Pricl S, Torriano G (1995) Flow properties of hydroxypropyl guar gum and its long-chain hydrophobic derivatives. Carbohydr Polym 28(3):195–202 29. Lapasin R, Pricl S, Tracanelli P (1991) Rheology of hydroxyethyl guar gum derivatives. Carbohydr Polym 14(4):411–427 30. Li X, Wang X, Han T, Hao C, Han S, Fan X (2021) Synthesis of sodium lignosulfonate-guar gum composite hydrogel for the removal of Cu2+ and Co2+. Int J Biol Macromol 175:459–472 31. Likhitha M, Sailaja RRN, Priyambika VS, Ravibabu MV (2014) Microwave assisted synthesis of guar gum grafted sodium acrylate/cloisite superabsorbent nanocomposites: reaction parameters and swelling characteristics. Int J Biol Macromol 65:500–508 32. Mestechkina NM, Egorov AV, Shcherbukhin VD (2006) Synthesis of galactomannan sulfates. Appl Biochem Microbiol 42(3):326–330 33. Mishra S, Thombare N, Ali M, Swami S (2018) Applications of biopolymeric gels in agricultural sector. In: Polymer gels. Springer, New York, pp 185–228 34. Mittal H, Maity A, Ray SS (2016) Synthesis, characterization, and adsorption properties of gum polysaccharide-based graft copolymers. In: Advances in polymer materials and technology. CRC Press, Boca Raton, pp 559–580 35. Mudgil D, Barak S, Khatkar BS (2014) Guar gum: processing, properties and food applications—a review. J Food Sci Technol 51(3):409–418 36. Oblonšek M, Šostar-Turk S, Lapasin R (2003) Rheological studies of concentrated guar gum. Rheol Acta 42(6):491–499 37. Paixão MVG, de Carvalho Balaban R (2018) Application of guar gum in brine clarification and oily water treatment. Int J Biol Macromol 108:119–126 38. Pal S, Patra AS, Ghorai S, Sarkar AK, Mahato V, Sarkar S, Singh RP (2015) Efficient and rapid adsorption characteristics of templating modified guar gum and silica nanocomposite toward removal of toxic reactive blue and Congo red dyes. Bioresour Technol 191:291–299 39. Paluszek J, Zembrowski W (2008) Improvement of water-air properties of eroded soils in a loess landscape after the application of agrohydrogel. Ann Warsaw Univ Life Sci Land Reclam 39:85–93 40. Pandey VS, Verma SK, Behari K (2014) Graft [partially carboxymethylated guar gum-G-poly N-(hydroxymethyl) acrylamide] copolymer: from synthesis to applications. Carbohydr Polym 110:285–291 41. Parija S, Misra M, Mohanty AK (2001) Studies of natural gum adhesive extracts: an overview. J Macromol Sci C Polym Rev 41(3):175–197 42. Pasha M, Ngn S (2008) Derivatization of guar to sodium carboxymethyl hydroxypropyl derivative: characterization and evaluation. Pak J Pharm Sci 21(1):40–44 43. Robinson G, Ross-Murphy SB, Morris ER (1982) Viscosity-molecular weight relationships, intrinsic chain flexibility, and dynamic solution properties of guar galactomannan. Carbohydr Res 107(1):17–32

132

M. E.-S. Abdel-raouf et al.

44. Sabahelkheir Murwan K, Abdalla Abdelwahab H, Nouri H, Sulafa. (2012) Quality assessment of guar gum (endosperm) of guar (Cyamopsis tetragonoloba). ISCA J Biol Sci 1:67–70 45. Sahoo JK, Aniket K, Juhi R, Tanuja M, Priyabrat D, Harekrushna S (2017) Guar gum-coated iron oxide nanocomposite as an efficient adsorbent for Congo red dye. Desalin Water Treat 95: 342–354 46. Shenoy MA, D’Melo DJ (2010) Synthesis and characterization of acryloyloxy guar gum. J Appl Polym Sci 117(1):148–154 47. Shi H-Y, Zhang L-M (2007) New grafted polysaccharides based on O-carboxymethyl-Ohydroxypropyl guar gum and N-isopropylacrylamide: synthesis and phase transition behavior in aqueous media. Carbohydr Polym 67(3):337–342 48. Shi X, Wang W, Wang A (2011) Synthesis and enhanced swelling properties of a guar gum-based superabsorbent composite by the simultaneous introduction of styrene and Attapulgite. J Polym Res 18(6):1705–1713 49. Slavin JL, Greenberg NA (2003) Partially hydrolyzed guar gum: clinical nutrition uses. Nutrition 19(6):549–552 50. Soumya RS, Ghosh S, Abraham ET (2010) Preparation and characterization of guar gum nanoparticles. Int J Biol Macromol 46(2):267–269 51. Srichamroen A (2013) Influence of temperature and salt on viscosity property of guar gum. Naresuan Univ J Sci Technol 15(2):55–62 52. Talodthaisong C, Boonta W, Thammawithan S, Patramanon R, Kamonsutthipaijit N, Hutchison JA, Kulchat S (2020) Composite guar gum-silver nanoparticle hydrogels as self-healing, injectable, and antibacterial biomaterials. Mater Today Commun 24:100992 53. Thombare N, Jha U, Mishra S, Siddiqui MZ (2017) Borax cross-linked guar gum hydrogels as potential adsorbents for water purification. Carbohydr Polym 168:274–281 54. Thombare N, Sumit Mishra MZ, Siddiqui UJ, Singh D, Mahajan GR (2018) Design and development of guar gum based novel, superabsorbent and moisture retaining hydrogels for agricultural applications. Carbohydr Polym 185:169–178 55. Tripathy S, Das M (2013) Guar gum: present status and applications. J Pharm Sci Innov 4: 24–28 56. Upadhyay A, Warkar SG (2021) Synthesis and study of a novel carboxymethyl guar gum/polyacrylate polymeric structured hydrogel for agricultural application. In: Advances in manufacturing and industrial engineering. Springer, New York, pp 1073–1084 57. Wang WB, Xu JX, Wang AQ (2011) A pH-, salt-and solvent-responsive carboxymethylcelluloseG-poly (sodium acrylate)/medical stone superabsorbent composite with enhanced swelling and responsive properties. eXPRESS Polym Lett 5(5) 58. Wang W, Kang Y, Wang A (2010) Synthesis, characterization and swelling properties of guar gum-G-poly (sodium acrylate-co-styrene)/muscovite superabsorbent composites. Sci Technol Adv Mater 11:025006 59. Wang W, Zhai N, Wang A (2011) Preparation and swelling characteristics of a superabsorbent nanocomposite based on natural guar gum and cation-modified vermiculite. J Appl Polym Sci 119(6):3675–3686 60. Xia S, Zhang L, Davletshin A, Li Z, You J, Tan S (2020) Application of polysaccharide biopolymer in petroleum recovery. Polymers 12(9):1860 61. Xiao W, Dong L (2011) Novel excellent property film prepared from methacryloyl chloridegraft-guar gum matrixes. Paper presented at the 2011 international conference on consumer electronics, communications and networks (CECNet) 62. Yoon S-J, Chu D-C, Juneja LR (2008) Chemical and physical properties, safety and application of partially Hydrolized guar gum as dietary fiber. J Clin Biochem Nutr 42(1):1–7 63. Zhang L-M, Zhou J-F, Hui PS (2005) A comparative study on viscosity behavior of watersoluble chemically modified guar gum derivatives with different functional lateral groups. J Sci Food Agric 85(15):2638–2644

6

Exudate Gums Deepak Mudgil and Sheweta Barak

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Acacia Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Tragacanth Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Karaya Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Ghatti Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Mesquite Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

134 135 136 138 139 141 142 142

Abstract

Gums are high molecular weight polysaccharides that form a gel with water. Exudate gums are obtained from the plants and are named so because these gums ooze out from the tree bark on the physical injury on it. Exudate gums are very beneficial to human beings and are greatly been used since ancient times. Due to their gel-forming property and water-binding activities, these gums are used in several food and non-food applications. These are used in various industries such as pharma, food, textile, paper, cosmetics, etc. This chapter discusses the physical and chemical properties, applications, and health benefits of exudate gums. Keywords

Acacia gum · Exudate gum · Ghatti gum · Karaya gum · Mesquite gum · Tragacanth gum Abbreviations

cP FDA

Centi poise Food and Drug Administration

D. Mudgil (*) · S. Barak Mansinhbhai Institute of Dairy & Food Technology (MIDFT), Mehsana, Gujarat, India © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_6

133

134

D. Mudgil and S. Barak

GRAS HLB KDa LBG NMR PDI RTE

1

Generally recognized as safe Hydrophilic–lipophilic balance Kilo Dalton (1000 Dalton) Locust bean gum Nuclear Magnetic Resonance Polydispersity index Ready-to-eat

Introduction

Trees have been valuable resources, providing many useful agro-based commodities, to the human population. Plants are excellent sources of gums in the form of seed gums [1–6] and exudate gums [7–9]. Plant seed gums are the high-molecularweight polysaccharides that are obtained principally from seeds of the plants, whereas exudate gums are the high-molecular-weight complex carbohydrates that are secreted by the plant bark when it is exposed to certain physical injuries such as cuts and incisions [7]. When the tree gets a physical injury, it secretes a sticky and viscous fluid from the opening of the injury site, and this fluid covers and seals the cut or opening [10]. These gums are the products of natural phenomena of normal plant metabolism and the defense mechanism of the plants which are released after physical injury or in adverse climatic conditions like heat and drought [11]. This fluid when coming in contact with the external environment dries with time and becomes hard, brittle, semi-transparent, and glazed. These gums are exuded in the form of amorphous lumps or tear-shaped nodules with streaks which on drying transforms to hard glassy lumps and hard opaque ribbons. Mesquite gum and karaya gum are found in the form of hard glassy lumps, whereas tragacanth gum is found in the form of hard and opaque ribbons. Exudate gums vary in color such as red-amber (mesquite gum), light-gray to dark-brown (karaya gum), and white to dark-brown (tragacanth) [7]. These gums have numerous food and industrial applications. These are used by human beings from ancient times to date due to their unique characteristics related to water phase management. The Bible also mentions the use of exudate gums in food [12]. In ancient times, Australian natives also utilized wattle gum (Acacia gum) with fish. The availability of exudate gums is the main reason behind their uses by humans in ancient times. Exudate gum collection by hands is an earning source for rural people in India, Africa, Turkey, Iran, etc., and to a limited extent in Mexico also. Isolation of water-soluble arabinogalactan or larch gum from larch trees also provides income to rural people of northern USA. Exudate gums collection, drying, and transportation helped in the availability of these gums to the non-gum-producing area. There are certain factors including environmental conditions which affect the yield of exudate gums. Exudate gums yield can be increased with the incorporation of incisions and cuts on the bark of gum-producing trees. The various steps involved in the exudate gum production include knocking or making cuts on the trees, collecting gum, drying of gum, sorting and packing, and transportation to gum’s

6

Exudate Gums

135

processors. In gum processing plants, large granules of crude exudate gums are subjected to grinding, sieving, and purification (dry or wet process). Dry purification of exudate gums include air purification, whereas wet purification of exudate gums include spray drying processing for the removal of insoluble impurities. In comparison to other gums, exudate gum is non-replaceable with alternative gums because of their unique functional characteristics. There are several examples of exudate gums such as Acacia gum, tragacanth gum, karaya gum, ghatti gum, mesquite gum, larch arabinogalactan, Acacia nilotica gum, etc. Acacia gum is the most popular among these exudate gums due to its availability and its unique physicochemical characteristics and applications. Other exudate gums also possess specific physicochemical characteristics which makes them useful in several foods and non-food applications [13].

2

Acacia Gum

Acacia gum or Arabic gum is excreted by Acacia trees found chiefly in Africa. These trees have heights upto 7–8 meters and gum is collected after making incisions on the bark of the tree. Acaica gum has a complex structure [14]. The main backbone chain of the gum is composed of β-1,3- and β-1,6-linked D-galactose along with β-1,6-linked D-glucopyranosyl uronic acid units. β-D-glucuronic acid, α-Lrhamnopyranose, α-L-arabinofuranosyl, and β-D-galactopyranose units are present as side chains linked with (1 ! 3), (1 ! 4), and (1 ! 6) glycosidic linkages. In comparison to other exudate, Acacia gum is low viscous and highly water-soluble in nature. This low viscosity and high water solubility of Acacia gum being attributed to its low molecular weight and greatly branched structure [15]. In the Acacia gum molecule, carbohydrate chains are also covalently associated with protein molecules which provide it unique characteristics. Protein molecules of Acacia gum are rich in proline, hydroxyproline, and serine. These protein molecules in Acacia gum provide unique characteristics such as emulsifying property, foaming property, and surface activity [16]. Acacia gum exhibits low viscosity in an aqueous solution at low concentrations. At high gum concentration (up to 30%), its aqueous solution shows Newtonian flow. At a very high concentration (i.e., above 30%), it shows pseudoplastic nature. At a pH value of 6, Acacia gum solution shows the highest viscosity [17]. Acacia gum leads to gel formation at a very acidic pH value ( 0.05; f2 ¼ 90) in drug release (80.52  3.41%) between the developed formulation and the commercially available formulation (79.65  4.08%) after 12 h [189]. Priyanka Mankotia and coworkers manufactured neem gum-based site-specific hydrogel-drug delivery for methotrexate (an antitumor drug) at diverse pH conditions. The neem gums contribute great loading capacity and exhibited 90% and 93% drug entrapment efficiency at pH 6.8 and pH 7.4. The hydrogel network demonstrated lower drug release at diverse pH, indicating that the sustained release of methotrexate from the hydrogels may be acceptable drug carriers for the delivery of antitumor drugs [190]. Asghar et al. have developed a novel neem gum-coated Fe3O4 nanoparticles by simple sonochemical approach for the target site-specific delivery of doxorubicin. The drug release of doxorubicin depend on the pH and showed better entrapment efficiency and in vitro release. The synthesized nanobiocomposite possesses good thermal, magnetic controllability, and chemical stability behaviors, which is useful for the site-specific doxorubicin delivery to the slightly acidic tumor site. Finally, this study has concluded that innovative neem gum and Fe3O4 based nanobiocomposite characteristics were found to be appropriate magnetic nanocarrier systems for cancer therapy [191]. Due to their microbial biodegradation in the colonic microenvironment, the polysaccharide-based hydrogel can be employed for colon-targeted delivery via the oral route. Hydrogels based on neem gum exhibited pH-responsive behavior which supports colon-targeted drug delivery. Methyl prednisolone-loaded neem gum hydrogels showed delayed release into colonic inflammation with improved therapeutic effects and decreased adverse effects than the conventional formulation [192– 194]. Neem has been shown to act as native insulin-producing beta cell stimulator. Numerous investigations in stimulated-diabetic experimental rat models have shown that neem extracts can restore glucose-6-phosphate-dehydrogenase function in hyperglycemic conditions [195–199]. Vijayavani et al. have developed an oral mucoadhesive microsphere system loaded with sildenafil citrate for extending the residence and improving the drug’s bioavailability. According to this study, the researchers state that the Azadirachta indica gum act as a promising candidate to be a mucoadhesive polymer in the controlled-drug delivery systems for oral administration [200]. Ogunjimi et al. has reported the coprocessing of neem gum with lactose/rice starch at varied ratios. For the evaluation of both native and new excipients, morphological and physical property evaluations showed the size and shape of the particles is mainly depend upon the quantity of lactose/rice starch added in the co-processed recipients [201]. Neem gum-based available formulations are listed in Table 3.

4.4

Cashew Gum

Cashew is a multipurpose tree crop, from which almost all parts (roots, stem, bark, leaves, apples, and nuts) are used [210]. Availability of all essential amino acids in cashew nuts rewards it as nutrition-dense crop, providing cashew nuts in the form of dry fruits. Cashew apple bagasse is rich in organic nature and could be a potent

158

S. Muruganantham et al.

Table 3 Neem gum-based pharmaceutical formulations Formulation S.No type 1 Tablet 2 Tablet

Drug loaded Paracetamol Propranolol HCl

Gum properties Faster release Retardant release

Biocompatibility and water dispersibility Dispersing agent (solid dispersion) Emulsifier

3

Hydrogel

Methotrexate

4

Tablet

Aceclofenac

5

Emulsions

Ciprofloxacin Hcl

6

Microspheres loaded gel

Neem extract

Antibacterial activity

7

Cream

Azadirachta indica leaves

8

Sustained release matrix tablet

Fluvastatin

Insecticides, antiinflammatory, and antioxidant Matrix-forming agent

9

Noneffervescent floating tablet

Metronidazole

Binding agent

10

Shampoo

Neem seeds

Insecticidal activity

Therapeutic applications Used as a binder Suitable for sustainedrelease tablets Improved sitespecific drug delivery Enhanced bioavailability Controlled release for ocular drug delivery Used for the treatment of topical bacterial infections Skin care treatment Improved extended drug release of drug Sustained drug delivery and prolonged (GRT) gastric retention time Treatment of head lice infection

Reference [202] [189]

[190]

[203] [204]

[205]

[206]

[207]

[208]

[209]

source of lignocellulosic material for the production of bioethanol and other microbial products through biological processes. Cashew nut shell liquid (CNSL) is enriched with numerous phenolic compounds and has potential benefits for usage in the preparation of coatings and laminates. Cashew nut is among the most important agro-industrial crop in India, Brazil, Vietnam, and African countries. The primary product of cashew crop processing yields cashew nuts which is a highly nutritive profile providing all essential amino acids. These cashew by-products are industrially significant as they can be processed to form several bioactive compounds, polymers, and other products, thus making the process and products economic and environmentally friendly, and sustainable [211]. Cashew nutshell has an energy content of 20.42 MJ/kg which is similar to that of wood. Cashew nutshell can be successfully used in the domestic gasifier. Cashew apple pomace, a major byproduct of cashew plantations and processing units, has the potential to be used

7

Gums as Pharmaceutical Excipients: An Overview

159

as a vital source of nutritive components [212]. Cashew apple pomace powder (CAPP) is loaded with huge amounts of essential minerals, antioxidants, and nutrients. Cashew tree exudate and cashew gum have great potential to be used as a carbon source to produce bacterial cellulose [213]. Cashew tree gum (CG) is a biological macromolecule that has been proposed to be used as an emulsifier in beverage emulsions [214]. Cashew nut protein isolate (CNPI) has higher water and oil absorption capacity, emulsifying stability index, foam capacity and stability, and least gelation capacity [215]. Cashew gum is extracted from the exudate of the giant cashew tree. Tablets were produced with a cashew gum isolated and purified by the direct compression method, and it was shown that the tablets produced with the purified cashew gum obtained better mechanical properties (hardness and friability) and less disintegration time than tablets made with the gum of cashew isolated, suggesting the use of purified cashew gum as a diluent for this type of pharmaceutical form. The flow properties of purified cashew gum were found to be reasonable, providing suitable conditions for the use of such material as a diluent of tablets obtained by direct compression [216]. The acetylated cashew gum had higher values of solubility, viscosity, and swelling index as 113.40% at 80oC, 53.4cs, and 49.54%, respectively, while the native gum had solubility, viscosity, and swelling index as 50.10% at 80oC, 20.20cs, and 10.94%, respectively [217]. The nut contains an acrid compound which is a powerful vesicant that is abrasive to the skin. Starch was extracted from the cashew nuts and used as binding agent at a concentration of 2% w/v, 4% w/v, 6% w/v, and 8% w/v. The tablets were formulated by using famotidine drug, and they were further evaluated for various parameters like weight variation, hardness, friability, disintegration time, in vitro and in vivo drug release. The results show that all parameters were found within the given Indian pharmacopeial limits. The in vitro release studies were performed in 0.1 N HCl using dialysis methods. This shows that tablets containing 2% of cashew starch showed maximum drug release (89%) compared to other formulations. The optimized formulation was further used for in vivo study and results showed better bioavailability compared to marketed products [218]. Crude and purified cashew gums were evaluated for their physicochemical properties and were found to be acidic with satisfactory moisture content and insoluble characteristics. Atomic absorption spectrophotometric analysis of the gums showed that the crude gum had higher metallic ion content than the purified gum. This may be attributed to the purification process. The gums had relatively high levels of calcium, followed by magnesium, iron, and zinc. Potassium and sodium were in trace amounts. Purified cashew gum was investigated as an emulsifying, suspending, and binding agent [219, 220]. The emulsifying property of the gum was investigated by wet/dry gum methods. The results obtained demonstrated that stable emulsions could be prepared with the mineral oil and fixed oil with ease but not with the volatile oil. Investigation of the gum as a binding agent in metronidazole tablets included the formulation of tablets with different concentrations of cashew gum using the wet granulation technique. The binding property of cashew gum was compared to that of acacia, a standard binding agent. The flow properties of the granules were evaluated and the physical

160

S. Muruganantham et al.

Table 4 Cashew gum-based pharmaceutical formulations Formulation S.No type 1. Orabase formulation

2.

Nanoemulsion

3.

Sustained release dosage form

4.

Nanoparticles

5.

Nanoparticles

Drug loaded CG-P150 (150 mg CG-P/1 g orabase gel) cashew gum polysaccharide (CG-P) Cashew nut shell liquid (CSNL) (1%) into 0.1% polysorbate 80 Diclofenac sodium with cashew gum (CG)

Zinc oxide nanoparticles with cashew gum (CG) and carboxymethylated cashew gum (CMCG) Epiisopiloturine

Gum properties Decrease in myeloperoxidase activity of the gingival tissue. Antiproliferative and targetspecific killing of cells. Effectively used for the preparation of sustained-release tablets Inhibition towards yeasts of Candida parapsilosis

Drug delivery vehicle

Therapeutic applications Treatment of periodontitis

Reference [222]

Targetedcancer therapy

[223]

Effective alternative to synthetic polymers

[224]

Effective in antifungal treatments.

[225]

Potential drug delivery system.

[226]

properties of the compressed tablets, namely uniformity of weight, hardness, friability, and disintegration time and dissolution rate determined [221]. Cashew gum polysaccharide-based topical treatment decreased alveolar bone loss, relative mRNA expression of TNF-, IL-1, and RANKL, and the RANKL/OPG ratio in periodontal tissue of rats with periodontitis, and caused a decrease in myeloperoxidase (MPO) activity. As a result, CG-P in orabase could be a novel biotechnological discovery as well as a potential adjuvant drug in the treatment of periodontitis [222].The antiproliferative and morphological effects of the cashew nut shell liquid (CSNL) nanoemulsions appear to be cell-killing on a target-specific basis [223]. Sustainedrelease tablets with cashew gum as the controlled-release polymer are formulated and evaluated; diclofenac sodium was used as the standard drug. Therefore, natural gums can be used as an effective alternative to synthetic polymers [224]. Cashew gum-based available formulations are listed in Table 4.

4.5

Fenugreek Gum

Fenugreek native to southern Europe and Asia is an annual herb with white flowers and hard, yellowish-brown, and angular seeds, known from ancient times for its

7

Gums as Pharmaceutical Excipients: An Overview

161

nutritional value besides its medicinal effects. Fenugreek seeds are a rich source of gum, fiber, alkaloid, flavonoids, saponin, and volatile content [227]. Fenugreek (Trigonella foenum graecum) is an annual plant that belongs to the family Leguminosae. It is a famous spice in human food. The seeds and green leaves of fenugreek are used in food as well as in medicinal applications. It has been used to increase the flavoring and color, and also modifies the texture of food materials. Seeds of fenugreek show medicinal properties such as hypocholesterolemic, lactation aid, antibacterial, gastric stimulant, for anorexia, antidiabetic agent, galactagogue, hepatoprotective effect, and anticancer. These beneficial physiological effects including the antidiabetic and hypocholesterolemic effects of fenugreek are mainly attributable to the intrinsic dietary fiber constituent that have promising nutraceutical value [228]. The dietary fiber of fenugreek seed is about 25% which changes the texture of food. The protein of fenugreek is found to be more soluble at alkaline pH [229]. Fenugreek is having a beneficial influence on digestion and also has the ability to modify food. Fenugreek has antidiabetic, antifertility, anticancer, antimicrobial, antiparasitic, lactation stimulant, and hypocholesterolemic effects. Fenugreek has been found to have important bioactive compounds. Fenugreek has been used as a food stabilizer, food adhesive, food emulsifier, and gum [230]. Fenugreek contains diosgenin, a steroidal saponin, has been investigated for its medicinal uses, and fenugreek has been reported as a source of raw material for the production of steroidal hormones. Noteworthy, fenugreek can be a more suitable alternative for diosgenin production than the conventional method using yams, due to ease of production, short life cycle, and low cost. Fenugreek seed gum (FSG) is a promising natural, biodegradable, economical, and eco-friendly film former, mainly when masking of taste or objectionable odor in a solid dosage formulation is desired. It can be used as a carrier in sustained release formulation. Fenugreek seed gum can be used for the development of visual qualities of dosage forms, masking disagreeable taste or odor, easing digestion, improving stability, and modifying the drug release characteristics of the drug. FSG has been used as a release retarding agent in matrix tablet formulation with water-soluble and insoluble drugs. Water-soluble drug release rate can be better controlled by cross-linking derivative of FSG. Natural crosslinking derivative FSG can play a significant role in the development of sustained-release dosage with water-soluble drugs [231]. Polysaccharide mucilage derived from the seeds of fenugreek, Trigonella foenum-graecum (family Fabaceae), was investigated for use in matrix formulations containing propranolol hydrochloride. Extracts of fenugreek appear to have major potential for use as a controlled release excipient [232]. It has been shown to acutely lower postprandial glucose levels, but the long-term effect on glycemia remains uncertain [233]. It has been used for numerous indications, including labor induction, aiding digestion, and as a general tonic to improve metabolism and health. Mucilaginous fiber present in fenugreek seeds may bind bile acids to reduce cholesterol and fat absorption. The plant protein in fenugreek might exert a lipid-lowering effect. Steroidal saponin, alkaloids, and 4-hydroxy-isoleucine may promote glucose metabolism and inhibit the absorption of cholesterol. Furthermore, some chemical constituents of fenugreek may directly stimulate insulin secretion from beta-cells resulting in blood sugar

162

S. Muruganantham et al.

reduction. Its cardioprotective effects are attributed to its modulating effect on blood lipid levels and antioxidant properties [234, 235]. Seed extract of fenugreek showed both anti-glycation and glycation reversing activity in the BSA glucose glycation model. Glycation reversing activity of fenugreek seed extract is a novel finding having therapeutically potential [236]. The clinical applications of fenugreek are also attributed to its diverse chemical composition, which makes this plant strong to alleviate the dependence on various synthetic drugs for curing the diseases. Fenugreek seeds contain a substantial amount of fiber, phospholipids, glycolipids, oleic acid, linolenic acid, linoleic acid, choline, vitamins A, B1, B2, C, nicotinic acid, niacin, and many other functional elements. Fenugreek significantly improves highdensity lipoprotein to low-density lipoprotein ratios also decreases hepatic expression of fatty acid-binding protein 4 and increases subcutaneous inguinal adipose tissue expression of adiponectin. Fenugreek glycoside (FG) supplementation demonstrated significant anabolic and androgenic activity as compared with the placebo [237–239]. Fenugreek glycoside (FG) treated subjects showed significant improvements in body fat without a reduction in muscle strength or repetitions to failure. The Fenu-FG supplementation was found to be safe and well-tolerated. Fenu-FG supplementation showed beneficial effects in male subjects during resistance training without any clinical side effects. The purified fenugreek gum was found to reduce surface tension lower than guar gum. The fenugreek gum can adsorb (or “precipitate”) on the oil interface forming a relatively thick interfacial film. Fenugreek seed mucilage and Ocimum basilicum gum could be used in tablet dosage forms for a variety of applications, and they could be explored as high functionality excipients for future applications as superdisintegrants [240, 241]. The antioxidant defense and detoxification systems were shown to be profoundly affected by repeated-dose curcumagalactomannoside (CGM) administration for 30 days, as evidenced by significant increases in endogenous antioxidant defense markers and reduction in lipid peroxidation. Participants in the CGM group experienced a significant reduction in perceived stress, anxiety, and fatigue, resulting in better quality of life (QoL), showing that bioavailable free curcuminoids are more efficient [242]. The bioavailability of BR213 curcumagalactomannoside, curcuminimpregnated soluble fiber, and dispersions was enhanced when administered orally. The improved absorption is due to the amorphous nature and superior hydrophobic– hydrophilic balance, as well as a slow release of stable colloidal curcumin [243]. Fenugreek gum-based available formulations are listed in Table 5.

4.6

Almond Gum

Exudate almond gum (padam pisin/padam gum) is natural, anionic, biodegradable, arabinogalactan structured polysaccharides with high molecular weight. It is also called a natural body coolant and is mainly collected from the almond trees Amygdalus scoparia Spach (Family: Rosaceae), a genus Prunus species. It is majorly observed in subtropical climatic zones, particularly in the region of Mediterranean, Middle East, and South East Asia [246–251]. It is mostly made up of

Emulsion

Shampoo

4.

5.

Formulation S.No type 1. Fast dissolving tablet 2. Oral formulation 3. Dispersions

Basic shampoo formulation with fenugreek extract

Elevation in endogenous antioxidant defense markers and reduction in lipid peroxidation Improved absorption

Curcumin with fenugreek dietary fiber BR213 curcumagalactomannoside with fenugreek fiber Fenugreek emulsion Good thixotropy property

Improvement in mechanical parameters

Gum properties Superdisintegrants

Drug loaded Amlodipine besylate with fenugreek seed mucilage

Table 5 Fenugreek gum-based pharmaceutical formulations

Improvement in skin elasticity, ageing, hydration, and fatigue Better wettability and conditioning property

Reduction in perceived stress, anxiety, and fatigue Enhanced bioavailability

Therapeutic applications In tablet dosage forms as superdisintegrants

[245]

[244]

[243]

[242]

Reference [241]

7 Gums as Pharmaceutical Excipients: An Overview 163

164

S. Muruganantham et al.

65.75% hemicelluloses, 18.66% aqueous-soluble polysaccharides, as well as relatively small amounts of 3.8%, 1.2%, 0.7% of cellulose, insoluble lignin, and acidsoluble lignin, respectively, in which the significant quantities of proteins and fatty acids to generate a viscous, adhesive sticky gel [54, 252]. Because of their protein composition, molecular weight, and solubility, they showed extremely varied operational as well as biological properties. Biocompatibility, biodegradability, waterbinding potential, nontoxic in nature, and antibacterial activities are a few qualities that have sparked attention in its applications including food industry as an emulsifying agent, suspending agent, glazing agent, thickening agent, adhesive agent, preservative, and stabilizer [248, 251, 253–255]. This gum’s quality is determined by the percentage of soluble arabinogalactan in the gum’s structure (water-soluble fraction vs. water-insoluble fraction). In addition, this unique polysaccharide has a simple extraction procedure and is very inexpensive compared to other common hydrocolloids (pectin, sodium alginate, and xanthan) [256, 257]. Many studies and applications have been conducted based on almond gum [258–261]. Using almond gum as a drug delivery vehicle, the drug release kinetics was shown to be non-Fickian diffusion when compared to the synthetic gum. For colontargeting abilities, 5-aminosalicylic acid is designed as a compressed coated tablet employing Prunus amygdalus gum at various concentrations because 5-aminosalicylic acid gets degradation at acidic pH. In vitro release measurements indicated that produced tablets were strong enough to withstand drug release in pH 1.2 buffer, and over 10 h, only 50% of the drug was released. Researchers determined that Prunus gum could make an excellent tablet coating gum polysaccharides for drug delivery systems in a sustained manner. These gums also have high binding properties for uncoated tablet formulation with potent retardant drug release [262, 263]. On the other hand, it had higher emulsification efficiency than gum arabic (Acacia senegal) and therefore can also be employed as a delivery method for temperature-sensitive therapeutic agents. In another study, it was shown that sweet cherries’ shelf life may be extended by coating them with almond gum [54, 253, 264]. Almond gum’s mucoadhesive properties also suggest that it could be used for the buccal route of administrations. In this connection, formulated metoprolol succinate mucoadhesive tablet for hypertension treatment showed greater area under the curve (AUC) and mean residence time (MRT) values, with a percent relative bioavailability of 159.19, compared to markedly extended-release tablet of Gudpress XL-25 [250]. In 2018, Ruchi Sunayana et al. have prepared indomethacinloaded sustained release matrix tablets using almond gum as a sustained release coating material, and the pre- and post-compression evaluations have shown the values with acceptable pharmacopeial ranges. The SEM analysis showed that the tablet’s matrix was eroding at 2, 4, and 8 h, thus indicating the rise in the size of the pores that enhance release profile from the flat distribution of the polymeric matrix tablet formulation [265]. In a recent study, when ground or minced beef is stored at 4  C, oligosaccharides produced from almond gum have shown to be efficient in preventing or lowering the formation of free radicals and microbial development, and showed high 2,2-diphenyl1-picrylhydrazyl scavenging antioxidant activity with 6.6  0.7 mg/mL IC50

7

Gums as Pharmaceutical Excipients: An Overview

165

(half maximal inhibitory concentration) that demonstrates plant-derived polysaccharide gums contain electron-donor elements that react with free radicals to interrupt the radical chain processes and terminate to form more stable compounds. In another study, almond gum has been revealed enhanced antioxidant effects. In addition, almond gum polysaccharides showed higher total antioxidant activity [251, 266– 268]. Hashemi et al. have investigated the effects of conjugation of almond gum (soluble fraction) with sodium caseinate on probiotic yogurt and showed the developed conjugates with greater stabilizing applications in yogurts and related products. While studying the preservation of Lactobacillus acidophilus La5 in a tomato juice under refrigeration, Kazeruni and Hosseini discovered that almond gum with soluble fractions had the significant prebiotic potential [269]. At the same time, the addition of almond gum with apple juice reduces blood triglycerides as well as body mass, body mass index, and insulin hormone resistance in obese adults with hyperlipidemic disease. The existence of phytochemical compounds in almond gum has been implicated in its benefits, and it may be a useful dietary supplement to control obesity and hyperlipidemia in the future, according to certain studies [270]. In nanocarrier systems, almond gum would be a promising candidate for synthesizing and delivering therapeutic agents. Hussain et al. have synthesized polysaccharide almond gum grafted poly(acrylamide) based silver nanoparticles loaded semi-interpenetrating hydrogel via free radical polymerization. The prepared hydrogels have exhibited potent antimicrobial and antibacterial activity against Escherichia coli, Staphylococcus aureus, as well as Pseudomonas aeruginosa; in this, the almond gum act as an antibacterial agent itself, thus enhancing the silver ion’s activity against pathogenic microorganisms. Thermogravimetric analysis showed degradation of the hydrogel at 230  C and increases up to 500  C with the good thermal stability of the developed formulation [271]. Atefe Rezaei et al. developed vanillin embedded almond gum/polyvinyl alcohol electrospun nanofibers and observed greater thermal stability compared to plain vanillin, rendering the mixture appropriate for normal cooking heating ranges of 180  C and higher. Furthermore, natural gum’s property of mimic extracellular matrix, almond gum-based superparamagnetic nanoparticles iron oxide nanoparticles has attained great impacts [249]. Jaison et al. has synthesized doxorubicin-loaded magnetic polymeric conjugate by using an anti-solvent precipitation technique. In vitro studies have revealed the greater activity of doxorubicin with cell viability reduction at 24 h, and showed a high amount of doxorubicin release in acidic pH (5.5), and concluded that the gum-based nanoparticles could be a better alternative for cancer treatment. Theophil Anand G et al. in fabricated Prunus dulcis based green synthesized zinc oxide nanoparticles with 25 nm average particle size. Antimicrobial evaluations demonstrated excellent antimicrobial activity zone of inhibition against Staphylococcus aureus, Klabriella pneumonia, Salmonella para typhi, Escherichia coli, and Proteus mirabilius [272]. Anushiravani et al. have conducted a study with a herbal formulation containing almond gum combined with Plantago major seed for the treatment of asthma. In this study, there were 28 participants involved with a mean age of 54.7  11.2 years old, and 4 volunteers dropped from the experiment due to sensitivities to the natural herbal preparation. As a result of this study, when

166

S. Muruganantham et al.

Table 6 Almond gum-based pharmaceutical formulations Formulation S.No type 1 Sachet

Drug loaded Fermentable oligo-, di-, monosaccharides and polyols Paracetamol

Gums properties Active ingredients

2

Tablet

Disintegrant

3

Tablet

Diclofenac sodium

Tablet binder

4

Gel

Glycosmis pentaphylla extract

Gellants

5

Tablet

Metoprolol succinate

6

Tablets

Diclofenac sodium

Buccoadhesive, control-release polymer Tablet binder

7

Floating tablets

Propranolol HCl

8

Nanoparticles Quercetin

Nanocarrier

9

Nanoparticles Quercetin

Nanocarriers

10

Nanoparticles Doxorubicin, daunorubicin

Chemotherapy

Controlled release polymer

Therapeutic application To treat irritable bowel syndrome

Reference [274]

Increased drug disintegration Increased binding capacity in uncoated tablet dosage form Increase the wound healing effect of active ingredient Increased bioavailability

[275]

Better binding capacity in tablet formulation Improved the drug dissolution with controlled release Improved encapsulation efficiency Enhanced absorption Treat cancer

[278]

[276]

[277]

[250]

[279]

[260]

[257] [280]

compared to the baseline, the forced vital capacity (FVC) post-intervention and forced expiratory volume (FEV in one second) have increased, where as the number of volunteers with wheezing gets decreased. Finally, this study demonstrated the combination of almond gum and Plantago major seed would be a promising therapeutic candidate for patients with refractory asthma [273]. Almond gum-based available formulations are listed in Table 6.

5

Patents in Gum-Based Pharmaceutical Products

Gums and mucilages, owing to their various valuable properties, are becoming a significant component in commercial pharmaceutical products. Modifications of these gums have led them to enter various advanced formulation technologies as well as in pharmaceutical market. Several natural gums like cashew gum, almond

7

Gums as Pharmaceutical Excipients: An Overview

167

gum, fenugreek gum, etc., find applications in diverse drug delivery systems. Employing the various beneficial physicochemical characteristics of the gums, they have been successfully utilized as a drug delivery vehicle, sustained release agent, penetration enhancer, etc., and these products have been patented as shown in Table 7 [280–289].

6

Current Clinical Trials in Gum-Based Pharmaceutical Products

Natural gums are increasingly being used in the pharmaceutical arena either as an excipient or as an active ingredient as they inherently have certain activities. Hence several types of research are being focused on using these natural gums in pharmaceutical formulations for various diseases. Clinical trials are also being conducted to bring the use of these gums to daily life as medicines. The list of such clinical trials is given in Table 8.

7

Challenges and Opportunities for the Natural Gum

The application of agro–polysaccharides in pharmaceuticals has enlarged due to their abundance, biodegradable, nature, and their crucial role in drug delivery as a vehicle. Several natural polymers like guar gum, xanthan gum, gellan gum, neem gum, cashew gum, albizia gum, khaya gum, aloe mucilage were used as a diluent, gelling agent, stabilizing agent, disintegrants, lubricants, etc., in order to afford controlled release, pH-dependent, and sustained release applications [306– 308]. Mankotia et al. have attempted site-specific applications by designing pH-dependent neem gum-based hydrogel matrix loaded with methotrexate for the treatment of cancer. The hydrogels showed greater drug loading efficiency (90%) with better release characteristics at pH 7.4 than 6.8 with non-Fickian behavior. Thus, the regimen may be suitable for anticancer drug delivery applications. The choice of gums must depend on the characteristics of the drug, compatibility, toxicity limits, desired dissolution, and degradation pattern for the effective drug delivery as they determine the quality of the final product [190]. Each novel, potent, and economic value gums as polymer must meet the regulatory stipulations for their employability in the commercial formulations. Thus, the natural-based gums find various applications in the food processing industry, predominantly expand the spectrum of compatibility with various bioactive components in the pharmaceutical industry, and find a major role in immediate, extended, gastrointestinal, and sustained release of drugs by topical, mucosal, rectal, transdermal, ocular, gene delivery systems for treatment of various diseases [309]. The novel drug delivery systems like micro particles, beads, cross-linked hydrogels, etc., combined with the natural polymer has become an emerging trend in addressing the permeation, bioavailability, and solubility of many bioactive substances [310]. Woldu et al. used Aloe elegans mucilage as a suspending agent and formulated paracetamol suspension to evaluate the suspending capacity of mucilage. They prepared

US2009022767A1 United States patent 22-01-2009

US2013029905A1 United States patent 31-01-2013

3

4

2

Patent details IN1825/MUM/ 2015 Indian patent 08.11.2019 WO2018104971A1 14-06-2018

S.No 1

Formulation containing curuminoids exhibiting enhanced bioavailability

Composition, device, and method for transdermal delivery of insect repellent

Fabrication of Aloe vera nano-cellulose via mechanical method

Patent name Property of cashew gum as sustained release polymer in sustained release tablet

Table 7 Patented Gum-based Pharmaceutical Products

Gel matrixforming agent

Penetration enhancer

Drug delivery vehicle

Pharmaceutical use Sustained-release agent

Fabrication of Aloe vera nano-cellulose drug vehicle using cryocrushing and ultrasonic methods. Transdermal patch comprising vitamin B1 as an insect repellant, urethane backing layer and a lining layer, adhesive layer, and Aloe vera, accelerates the drug diffusion into the bloodstream. Curcuminoids microencapsulated fenugreek-based soluble matrix exhibits a slow-release pattern in the colon with good efficacy.

Description Cashew gum at 4–8% w/w was effectively employed as a binding agent in aceclofenac tablet formulation.

[284]

[283]

[282]

Reference [280]

168 S. Muruganantham et al.

IN2986MU2013A Indian patent 09-10-2015 IN3084DE2015A Indian patent 23-10-2015

US500190A United States 19-03-1996

CN103054932A China 24-04-2013

6

8

9

7

1540/MUM/2007 Indian patent 29.05.2009

5

Application of Albizia chinensis extract in preparation of a medicament for treating gastric ulcer

Anion exchange resin compositions containing almond paste for taste improvement.

A natural extract-based polymeric prodrug for sustaining the release of a drug

An orally administrative gastro-retentive drug delivery system

Fenugreek gum-based colonic drug delivery

Excipient

Flavoring agents

Natural polymer

Natural polymer

Drug delivery

Diclofenac sodium matrix tablets formulation using fenugreek gum as novel drug carrier showed site-specific colonic delivery. Oral administrable gastro retentive drug formulation comprising Sterculiafoetida gum and xanthan gum as polymer. Ceftriaxone prodrug based orally active sustained release formulation using sweet almond polysaccharide as an excipient. Almond based anion exchange resin comprising of colestipol and cholestyramine with improved properties for the treatment of hypercholesterolemia Material in the treatment of chronic gastritis as all pharmacological evaluation showed high proton pump inhibition activity [289]

[288]

[287]

[286]

[285]

7 Gums as Pharmaceutical Excipients: An Overview 169

Investigator-initiated randomized openlabel comparative study of Britomar (prolonged release Torasemide) and Diuver (Torasemide) to assess effects on natriuresis and central hemodynamics.

4

3

The influence of personal care products on the skin microbiome Efficacy and safety of PRO-148 versus Systane ®, in patients with mild to moderate dry eye

2

S.No Title 1 Determination of the efficacy and safety of Psirelax in the relief of the disease in psoriasis

Thickener or active component for PRO-148 – xanthan gum, gelling agent for Systane ® – hydroxypropyl guar Excipient- guar gum, maize starch

PRO-148, Systane ®

Prolonged release Torasemide (Britomar)

Burt’s Bees serum

Gums used and its function Natural absorption aids – jojoba oil, vegetable squalene, natural thickening agents – bee wax, aloe vera, medicinal Vaseline, guar gum, borax Thickener – xanthan gum

Pharmaceutical product Psirelax

Table 8 Clinical trials in gum-based product

Arterial hypertension, chronic heart failure

Dry eye

Microbiome

Condition/disease Mild to moderate psoriasis

Unknown

Completed

Completed

Status Completed

Phase 4

Phase 3

–

Phase Phase 2

Society of specialists in heart failure

Laboratorios Sophia S.A de C.V.

University of California, Davis

Study sponsors Etwal Ltd.

[293]

[292]

[291]

Reference [290]

170 S. Muruganantham et al.

Vitamin D’s effect on physical performance in the elderly The effect of 2-DeNT Oral topical powder on minor recurrent Aphthous ulcer Plant sterol INtervention for cancer prevention (PINC)

8

10

9

7

6

Effects of sage extracts on cognitive function during aerobic exercise To check effectiveness of Medistus Antivirus lozenges for cough Protected pea protein extract and satiety hormone release

5

Dietary supplement: cholesterol reducing strawberry yogurt drink (Tesco Ltd)

Dietary supplement: Bio-D-Mulsion Forte ® 2-DeNT powder

Dietary supplement: Saturn

Dietary supplement: sage extract Cognivia Medistus Antivirus lozenges

Hypercholesterolemia, breast cancer, obesity

Health

Emulsifier base – gum arabic

Thickener – carob gum

Obesity, overweight

Excipient – acacia gum 381A or 396I

Minor recurrent Aphthous stomatitis lesions

Throat infection, pharyngitis, sore throat

Protective film formation – gum arabic

MucoadhesiveKaraya gum

Health

Encapsulation – gum acacia

Ongoing

Completed

Completed

Completed

Completed

Completed

–

Early phase 1

–

–

Phase 3

–

University of Leeds

Texas A&M University

Maastricht University Medical Center University of Miami

Nutrin GmbH

University of Burgundy

(continued)

[299]

[298]

[297]

[296]

[295]

[294]

7 Gums as Pharmaceutical Excipients: An Overview 171

13

12

Physiological flow of liquids in head and neck cancer patients: A pilot study Effect of Aloe vera mouthwashes on the oral health of children

S.No Title 11 Arabic gum-absorption study

Table 8 (continued)

Aloe vera mouthwash

Pharmaceutical product Dietary supplement: menaquinone-7 from arabic gum capsules Xanthan-gum thickened liquids Deglutition disorders, oropharynx cancer

Oral health

Drug – Aloe vera

Condition/disease Bioavailability

Thickener – xanthan gum

Gums used and its function Delivery vehicle – arabic gum

Completed

Completed

Status Completed

–

–

Phase –

Damascus University.

University Health Network, Toronto

Study sponsors Maastricht University Medical Center

[302]

[301]

Reference [300]

172 S. Muruganantham et al.

16

15

14

Gum arabic as antioxidant, antiinflammatory and fetal hemoglobin inducing agent in sickle cell anemia patients (GA&SCA) Treatment of chronic constipation in Parkinson’s disease (PHGG-PD) An assessment of the glyconutrient Ambrotose™ on immunity, gut health, and safety in men and women

Stick pack containing PHGG and hyaluronic acid Dietary supplement: Ambrotose LIFE

Dietary supplement: Acacia Senegal extract

Health

Parkinson’s disease

Drug – partially hydrolyzed guar gum (PHGG) Provides glycoprotein – Ghatti gum, gum tragacanth

Sickle cell anemia in children

Powder – gum arabic

Completed

Completed

Ongoing

IRCCS San Raffaele

University of Memphis

–

Al-Neelain University

Phase 2

Phase 2

[305]

[304]

[303]

7 Gums as Pharmaceutical Excipients: An Overview 173

174

S. Muruganantham et al.

suspensions at five different concentrations and suspending potential was compared with xanthan gum, and observed a drug release of 85% within 45 min. Thus, Aloe elegans mucilage could be a better alternative suspending agent in pharmaceutical suspensions. Similarly, chemical modifications of the gums resulted in the expansion of the applications [311]. Oliveira et al. chemically modified cashew gum and evaluated it for its multifactorial applications [312]. The phthalated cashew gum was reported by conjugation with benznidazole. The nanoparticles were characterized by various analytical tools and results suggested that this mode of drug delivery may improve the treatment of Chagas disease. Thus, although the natural polysaccharides are admitted in all sorts of developed dosage forms, in the nearby future, the global demand for this technology would elevate, improve the performance of many BCS class drugs, ensuring the health stability as it is a better alternative for the synthetic polymer.

8

Conclusion

Natural gums due to their advantageous properties like biodegradability, non-toxicity, wide availability, and their suitability to be used in drug delivery systems have made them a promising material to be applied in the pharmaceutical field. These natural polysaccharides have benefits over synthetic ones and are being used as both excipients and as key components in formulations. Natural gums and their modifications are also being explored in pharmaceutical applications like gene delivery and nanotechnology, thereby expanding the scope in formulations. For various drug delivery systems, there is a rising need of exploring materials of natural origin to reduce the impact on the environment and make it safer. Hence natural gums will continuously be of interest in developing and designing better drug delivery systems. Acknowledgment The authors gratefully acknowledge the Department of Science and Technology (DST) (GoI), New Delhi, supported National Facility for Drug Development for Academia, Pharmaceutical and Allied Industries (NFDD) (Ref No. VI- D&P/349/10-11/TDT/1 Dt: 21.10.2010), and DST (GoI), New Delhi, supported project entitled “Development of Nano based Smart Pesticide Formulation for high Agricultural Productivity Project” (Ref No. DST/TDT/ AGRO47/2020; Dt: 29.09.2020).

References 1. Bhardwaj TR, Kanwar M, Lal R, Gupta A (2000) Natural gums and modified natural gums as sustained-release carriers. Drug Dev Ind Pharm 26:1025–1038 2. Nep EI, Conway BR (2011) Physicochemical characterization of grewia polysaccharide gum: effect of drying method. Carbohydr Polym 84(1):446–453 3. Ahmad S, Ahmad M, Manzoor K, Purwar R, Ikram S (2009) A review on latest innovations in natural gums based hydrogels: preparations & applications. Int J Biol Macromol 136:870–890

7

Gums as Pharmaceutical Excipients: An Overview

175

4. Prajapati VD, Jani GK, Moradiya NG, Randeria NP (2003) Pharmaceutical applications of various natural gums, mucilages and their modified forms. Carbohydr Polym 92(2):1685– 1699 5. Hamdani AM, Wani IA, Bhat NA (2019) Sources, structure, properties and health benefits of plant gums: a review. Int J Biol Macromol 135:46–61 6. Kulkarni GT, Gowthamarajan K, Satish KMN, Suresh B (2002) Gums and Mucilages: therapeutic and pharmaceutical applications. Nat Pro Radiance 10–17 7. Rana V, Rai P, Tiwary AK, Singh RS, Kennedy JF, Knill CJ (2011) Modified gums: approaches and applications in drug delivery. Carbohydr Polym 83:1031–1047 8. Li JM, Nie SP (2016) The functional and nutritional aspects of hydrocolloids in foods. Food Hydrocoll 53:46–61 9. Saha A, Tyagi S, Rajinder KG, Tyagi YK (2017) Natural gums of plant origin as edible coatings for food industry applications. Crit Rev Biotechnol 37(8):959–973 10. Javidi F, Razavi SMA, Behrouzian F, Alghooneh A (2016) The influence of basil seed gum, guar gum and their blend on the rheological, physical and sensory properties of low fat ice cream. Food Hydrocoll 52:625–633 11. Salamanca CH, Yarce CJ, Moreno RA, Prieto V, Recalde J (2018) Natural gum-type biopolymers as potential modified nonpolar drug release systems. Carbohydr Polym 189:31–38 12. Sharma G, Naushad M, Al-Muhtaseb AH, Kumar A, Khan MR, Kalia S, Shweta M, Bala A, Sharma (2017) Fabrication and characterization of chitosan-crosslinked-poly(alginic acid) nanohydrogel for adsorptive removal of Cr(VI) metal ion from aqueous medium. Int J Biol Macromol 95:484–493 13. Sharma G, Sharma S, Kumar A, Ala’a H, Naushad M, Ghfar AA, Mola GT, Stadler FJ (2018) Guar gum and its composites as potential materials for diverse applications: a review. Carbohydr Polym 199:534–545 14. George A, Shah PA, Shrivastav PS (2018) Guar gum: versatile natural polymer for drug delivery applications. Eur Polym J 112:722–735 15. Williams PA (2011) Renewable resources for functional polymers and biomaterials: polysaccharides, proteins and polyesters. RSC polymer chemistry series. Royal Society of Chemistry, Cambridge, pp 1–14 16. Knudsen KEB (2001) The nutritional significance of dietary fibre analysis. Anim Feed Sci Technol 90:3–20 17. Upadhyay RK (2017) Nutritional, therapeutic, and pharmaceutical potential of plant gums: a review. Int J Green Pharm 11:S30–S48 18. Layek B, Mandal S (2020) Natural polysaccharides for controlled delivery of oral therapeutics: a recent update. Carbohydr Polym 230:115617 19. Srivastava M, Kapoor VP (2005) Seed galactomannans: an overview. Chem Biodivers 2:295– 317 20. Thombare N, Jha U, Mishra S, Siddiqui M (2016) Guar gum as a promising starting material for diverse applications: a review. Int J Biol Macromol 88:361–372 21. Mudgil D, Barak S, Khatkar BS (2014) Guar gum: processing, properties and food applications – a review. J Food Sci Technol 51:409–418 22. Panagopoulou A, Georgarakis M (2008) Effect of compression and diluent on drug release from mastix matrix tablets. A statistical analysis. Drug Dev Ind Pharm 16(4):637–649 23. Morkhade DM (2017) Evaluation of gum mastic (Plastacia lentiscus) as a microencapsulating and matrix forming material for sustained drug release. Asian J Pharm Sci 12:424–432 24. Avachat AM, Dash RR, Shrotriya SN (2011) Recent investigations of plant based natural gums, Mucilages and resins in novel drug delivery systems. Indian J Pharm Educ Res 45(1): 86–99 25. Cerqueira MA, Bourbon AI, Pinheiro AC, Martins JT, Souza BWS, Teixeira JA, Vicente AA (2011) Galactomannans use in the development of edible films/coatings for food applications. Trends Food Sci Technol 22:662–671 26. Koychev S, Dommisch H, Chen H, Pischon N (2017) Antimicrobial effects of mastic extract against Oral and periodontal pathogens. J Periodontol 88(5):511–517

176

S. Muruganantham et al.

27. Deshpande RD, Gowda DV, Mahammed N (2013) Design of Plastacia lentiscus (mastic gum) controlled release spheroids and investigating the influence of roll compaction. Ind Crop Prod 44:603–610 28. Rehman A, Jafari SM, Tong Q, Riaz T, Assadpour E, Aadil RM, Niazi S, Khan IM, Shehzad Q, Ali A, Khan S (2020) Drug nanodelivery systems based on natural polysaccharides against different diseases. Adv Colloid Interf Sci 284:102251 29. Raza A, Rasheed T, Nabeel F, Hayat U, Bilal M, Iqbal HMN (2019) Endogenous and exogenous stimuli-responsive drug delivery systems for programmed site-specific release. Molecules 24(6):1117 30. Tian B, Liu Y, Liu J (2020) Smart stimuli-responsive drug delivery systems based on cyclodextrin: a review. Carbohydr Polym 251:116871 31. Soleimani K, Derakhshankhah H, Jaymand M, Samadian H (2021) Stimuli-responsive natural gums-based drug delivery systems for cancer treatment. Carbohydr Polym 254:117422 32. Dai S, Ravi P, Tam KC (2008) pH-responsive polymers: synthesis, properties and applications. Soft Matter 4(3):435–449 33. Praphakar RA, Jeyaraj M, Mehnath S, Higuchi A, Ponnamma D, Sadasivuni KK, Rajan M (2018) A pH-sensitive guar gum-grafted-lysine-β-cyclodextrin drug carrier for the controlled release of 5-flourouracil into cancer cells. J Mater Chem B6(10):1519–1530 34. Alle M, Kim TH, Park SH, Lee SH, Kim JC (2020) Doxorubicin-carboxymethyl xanthan gum capped gold nanoparticles: microwave synthesis, characterization, and anti-cancer activity. Carbohydr Polym 229:115511 35. Hemmati K, Ghaemy M (2016) Synthesis of new thermo/pH sensitive drug delivery systems based on tragacanth gum polysaccharide. Int J Biol Macromol 87:415–425 36. Sayadnia S, Arkan E, Jahanban-Esfahlan R, Sayadnia S, Jaymand M (2021) Tragacanth gum-based pH-responsive magnetic hydrogels for “smart” chemo/hyperthermia therapy of solid tumors. Polym Adv Technol 32:262–271 37. Shafiee S, Ahangar HA, Saffar A (2019) Taguchi method optimization for synthesis of Fe3O4 @chitosan/Tragacanth gum nanocomposite as a drug delivery system. Carbohydr Polym 222: 114982 38. Renaud M, Belgacem MN, Rinaudo M (2005) Rheological behaviour of polysaccharide aqueous solutions. Polymer 46:12348–12358 39. Wang F, Wen Y, Bai T (2016) The composite hydrogels of polyvinyl alcohol–gellan gum-Ca2+ with improved network structure and mechanical property. Mater Sci Eng C69:268–275 40. Osmałek T, Froelich A, Tasarek S (2014) Application of gellan gum in pharmacy and medicine. Int J Pharm 466:328–340 41. Yang J, Zhang YS, Yue K, Khademhosseini A (2017) Cell-laden hydrogels for osteochondral and cartilage tissue engineering. Acta Biomater 57:1–25 42. El-Sherbiny IM, Yacoub MH (2013) Hydrogel scaffolds for tissue engineering: progress and challenges. Glob Cardiol Sci Pract 3:316–342 43. Mokhtarzadeh A, Alibakhshi A, Hejazi M, Omidi Y, Dolatabadi JEN (2016) Bacterial-derived biopolymers: advanced natural nanomaterials for drug delivery and tissue engineering. TrAC Trends Anal Chem 82:367–384 44. Rinaudo M (2008) Main properties and current applications of some polysaccharides as biomaterials. Polym Int 57:397–430 45. Milcovich G, Lettieri S, Antunes FE, Medronho B, Fonseca AC, Coelho JF, Marizza P, Perrone F, Farra R, Dapas B (2017) Recent advances in smart biotechnology: hydrogels and nanocarriers for tailored bioactive molecules depot. Adv Colloid Interf Sci 249:163–180 46. Khan F, Ahmad SR (2013) Polysaccharides and their derivatives for versatile tissue engineering application. Macromol Biosci 13(4):395–421 47. Kumar A, Rao KM, Han SS (2018) Application of xanthan gum as polysaccharide in tissue engineering: a review. Carbohydr Polym 180:128–144 48. Aadil KR, Nathani A, Sharma CS, Lenka N, Gupta P (2019) Investigation of poly (vinyl) alcohol-gellan gum based nanofiber as scaffolds for tissue engineering applications. J Drug Deliv Sci Technol 54:101276

7

Gums as Pharmaceutical Excipients: An Overview

177

49. Maciel JS, Azevedo S, Correia CR, Costa AM, Costa RR, Magalhaes FA, de Sousa Monteiro AA, Costa JFG, de Paula RCM, Feitosa JP (2019) Oxidized cashew gum scaffolds for tissue engineering. Macromol Mater Eng 1800574 50. Burdick JA, Prestwich GD (2011) Hyaluronic acid hydrogels for biomedical applications. Adv Mater 23:H41–H56 51. Lu KY, Lin YC, Lu HT, Ho YC, Weng SC, Tsai ML, Mi FL (2019) A novel injectable in situ forming gel based on carboxymethyl hexanoyl chitosan/hyaluronic acid polymer blending for sustained release of berberine. Carbohydr Polym 206:664–673 52. Kim K, Choi H, Choi ES, Park MH, Ryu JH (2019) Hyaluronic acidcoated nanomedicine for targeted cancer therapy. Pharmaceutics 11:301 53. Yarom N, Hovan A, Bossi P, Ariyawardana A, Jensen SB, Gobbo M, Pentenero M (2019) Systematic review of natural and miscellaneous agents for the management of oral mucositis in cancer patients and clinical practice guidelines – part 1: vitamins, minerals, and nutritional supplements. Support Care Cancer 27(10):3997–4010 54. Rezaei A, Nasirpour A, Tavanai H (2016) Fractionation and some physicochemical properties of almond gum (Amylgdalus communis L.) exudates. Food Hydrocoll 60:461–469 55. Williams PA, Philips GO (1998) Gums and stabilisers for the food industry, 9th edn. IRL Press at Oxford University Press, Oxford, UK 56. Todd R (2008) Guar gum and similar soluble fibers in the regulation of cholesterol metabolism: current understandings and future research priorities. Vasc Health Risk Manag 4(5): 1023–1033 57. Phillips GO (1998) Acacia gum (Gum Arabic): a nutritional fibre; metabolism and calorific value. Food Addit Contam 15(3):251–264 58. Dhingra D, Michael M, Rajput H, Patil RT (2012) Dietary fibre in foods: a review. J Food Sci Technol 49(3):255–266 59. Flint HJ, Scott KP, Duncan SH, Louis P, Forano E (2012) Microbial degradation of complex carbohydrates in the gut. Gut Microbes 3(4):289–306 60. Fiszman S, Varela A (2013) The role of gums in satiety/satiation: a review. Food Hydrocoll 32: 147–154 61. Elleuch M, Bedigian D, Roiseux O, Besbes S, Blecker C, Attia H (2011) Dietary fiber and fiber rich by-products of food processing: characterization, technological functionality and commercial applications: a review. Food Chem 124:411–421 62. Theuwissen E, Mensink RP (2008) Water soluble dietary fibres and cardiovascular disease. Physiol Behav 94:285–292 63. Slavin J, Green H (2007) Dietary fibre and satiety. Nutr Bull 32:32–42 64. Choudhary PD, Pawar HA (2014) Recently investigated natural gums and mucilages as pharmaceutical excipients: an overview. J Pharm (Cairo) 2014:204849 65. Karmakar K (2016) Application of natural gum as a binder in modern drug delivery. J Anal Pharm Res 3(4):00061 66. Sarkar PC, Upali S, Binsi PK, Natasha N, George N, Ravishanker CN (2018) Studies on physico-chemical and functional properties of some natural Indian gums. Asian J Dairy Food Res 37(2):126–131 67. Jindal M, Kumar V, Rana V, Tiwary AK (2013a) Exploring potential new gum source Aeglemarmelosfor food and pharmaceuticals: physical, chemical and functional performance. Ind Crop Prod 45:312–318 68. Vasile FE, Martinez MJ, Ruiz-Henestrosa VMP, Judis MA, Mazzobre MF (2016) Physicochemical, interfacial and emulsifying properties of a nonconventional exudate gum (Prosophis alba) in comparison with gum arabic. Food Hydrocoll 56:245–253 69. Daoub RMA, Elmubarak AH, Misran M, Hassan EA, Osman ME (2000) Characterization and functional properties of some natural acacia gums. J Saudi Soc Agri Sci 17(3): 241–249 70. Hamdani AM, Wani IA, Gani A, Bhat NA, Masoodi FA (2017) Effect of gamma irradiation on physicochemical, structural and rheological properties of plant exudate gums. Innov Food Sci Emerg Technol 44:74–82

178

S. Muruganantham et al.

71. Hamdani AM, Wani IA, Gani A, Bhat NA (2018) Effect of gamma irradiation on the physicochemical and structural properties of plant seed gums. Int J Biol Macromol 106: 507–515 72. Cerqueira MA, Pinherio AC, Souza BW, Lima AM, Ribeiro CM, Miranda C, Teixeira JA, Moreira RA, Coimbra MCA, Goncalves MP (2009) Vicente, extraction, purification and characterization of galactomannan from non-traditional source. Carbohydr Polym 75(3):408–414 73. Sibaja-Hernandez R, Román-Guerrero A, Sepulveda-Jimenez G, Rodriguez-Monroy M (2015) Physicochemical, shear flow behaviour and emulsifying properties of Acacia cochicantha and Acacia farnesianagums. Ind Crop Prod 67:161–168 74. Bhushette PR, Annapure US (2018) Physicochemical, functional and rheological investigation of Soymida febrifuga exudate gum. Int J Biol Macromol 111:1116–1123 75. Wu Y, Ding W, Jia L, He Q (2015) The rheological properties of tara gum (Caesalpinia spinosa). Food Chem 168:366–371 76. Marcotte M, Hoshahili T, Ramaswamy AR (2001) Rheological properties of selected hydrocolloids as a function of concentration and temperature. Food Res Int 34:695–704 77. Sanchez C, Renard D, Robert P, Schmitt C, Lefebvre J (2002) Structure and rheological properties of acacia gum dispersions. Food Hydrocoll 16(3):257–267 78. Whistler Royl L (1993) Industrial Gums In Exudate Gums 12:309–339 79. Chandran N, Sarathchandran C, Thomas S (2009) Introduction to rheology. In: Rheology of polymer blends and nanocomposites: theory, modelling and applications, pp 1–17 80. Munoz J, Rincon F, Carmen Alfaro M, Zapata I, de la Fuente J, Beltran O (2007) Rheological properties and surface tension of Acacia tortuosa gum exudate aqueous dispersions. Carbohydr Polymn 70(2):198–205 81. Chenlo F, Moreira R, Blanco CS (2010) Rheological behaviour of aqueous systems of tragacanth and guar gums with storage time. J Food Eng 96(1):107–113 82. Mudgil D, Barak S, Khatkar BS (2012) X-ray diffraction, IR spectroscopy and thermal characterization of partially hydrolyzed guar gum. Int J Biol Macromol 50(4):1035–1039 83. Synytsya A, Copíkova J, Matejka P, Machovic V (2003) Fourier transform Raman and infrared spectroscopy of pectins. Carbohydr Polym 54(1):97–106 84. Espinosa-Andrews H, Sandoval-Castilla O, Vazquez-Torres H, Vernon-Carter EJ, LobatoCalleros C (2010) Determination of the gum Arabic-chitosan interactions by Fourier transform infrared spectroscopy and characterization of the microstructure and rheological features of their coacervates. Carbohydr Polym 79(3):541–546 85. Duus J, Gotfredsen CH, Bock K (2000) Carbohydrate structural determination by NMR spectroscopy: modern methods and limitations. Chem Rev 100(12):4589–4614 86. Tosin S, Fernanda F, Ruth BR, Ferreira M, Werner D, Maria Fernanda de P, Cristiane CH, Ricardo W, Fhernanda SR, Elaine CR, Guilherme SL, Marcello I, Philip AJ (2014) Glucuronoarabinoxylan from coconut palm gum exudate: chemical structure and gastroprotective effect. Carbohydr Polym 107:65–71 87. Brown ME, Gallagher PK (2008) Introduction to recent advances, techniques and applications of thermal analysis and calorimetry. In: Brown ME, Gallagher PK (eds) Handbook of thermal analysis and calorimetry, 1st edn. Elsevier, Amsterdam, pp 1–12 88. Muller AJ, Michell RM (2016) Differential scanning calorimetry of polymers. In: Polymer morphology: principles, characterization, and processing. Wiley, Hoboken, pp 72–99 89. Vinod VTP, Sashidhar RB, Suresh KI, Rao BR, Saradhi UVRV, Rao TP (2008) Morphological, physico-chemical and structural characterisation of gum Kondagogu (Cochlospermum gossypium): a tree gum from India. Food Hydrocoll 22:899–915 90. Martins E, Omoyeme I, Christiana I, Ofoefule S, Olobayo K (2009) Isolation, characterization and compaction properties of Afzelia Africana gum exudates in hydrochlorothiazide tablet formulations. Afr J Phar Pharmacol 3(5):265–272 91. Huanbutta K, Sittikijyothin W (2018) Use of seed gums from Tamarindus indica and Cassia fistula as controlled-release agents. Asian J Pharma Sci 13(5):398–408

7

Gums as Pharmaceutical Excipients: An Overview

179

92. Bashir M, Haripriya S (2016) Assessment of physical and structural characteristics of almond gum. Int J Biol Macromol 93:476–482 93. Aroshi S, Bhushette PR, Uday AS (2020) Purification and physicochemical characterization of Prunus domestica exudate gum polysaccharide. Carbohydr Polym 1(1):100003 94. He Y, Wang Q, Ye Y, Liu Z, Sun H (2020) The ethnopharmacology, phytochemistry, pharmacology and toxicology of genus Albizia: a review. J Ethnopharmacol 257:112677 95. Odeku OA, Fell JT (2005) In-vitro evaluation of khaya and albizia gums as compression coatings for drug targeting to the colon. J Pharm Pharmacol 57(2):163–168 96. Bhaskar DA, Uttam KJ, Singh AM, Jayram CM, Bhanudas SR (2013) Plant exudates and mucilage as pharmaceutical excipients. J Adv Pharm Edu Res 3(4):387–402 97. Mahlangu ZP, Botha FS, Madoroba E, Chokoe K, Elgorashi EE (2017) Antimicrobial activity of Albizia gummifera (J.F.Gmel.) C.A.Sm leaf extracts against four Salmonella serovars. S Afr J Bot 108:132–136 98. Tang W, Eisenbrand G (2011) Handbook of Chinese medicinal plants. Wiley, Weinheim 99. Pharmacopoeia Committee of China (2015) Chinese pharmacopoeia (part I). China Medical Science Press, Beijing 100. Ramya Devi D, Sowmiya Lakshna S, Veena Parvathi S, Vedha Hari BN (2018) Investigation of wound healing effect of topical gel of Albizia amara leaves extract. S Afr J Bot 119: 400–409 101. Saidu Y, Nwachukwu FC, Bilbis LS, Faruk UZ, Abbas AY (2010) Hypoglycaemic and hypolipidemic effects of root extracts of Albizzia chevalieriin alloxan induced diabetic rats. Nigerian J Basic Appl Sci 18:72–78 102. Kumar D, Kumar S, Kohli S, Arya R, Gupta J (2011) Antidiabetic activity of methanolic bark extract of Albizia odoratissima Benth. in alloxan induced diabetic albino mice. Asian Pac J Trop Med 4:900–903 103. Nurul IM, Mizuguchi H, Shahriar M, Venkatesh P, Maeyama K, Mukherjee PK, Hattori M, Choudhuri MS, Takeda N, Fukui H (2011) Albizzia lebbecksuppresses histamine signalling by the inhibition of hisamine H1 receptor and histidine decarboxylase gene transcriptions. Int Immunopharmacol 11:1766–1772 104. Al-Massarani SM, El Gamal AA, Abd El Halim MF, Al-Said MS, Abdel Kader MS, Basudan OA, Alqasoumi SI (2017) New acyclic secondary metabolites from the biologically active fraction of Albizia lebbeckflowers. Saudi Pharm J 25:110–119 105. Meshram GG, Kumar A, Rizvi W, Tripathi CD, Khan RA (2016) Evaluation of the antiinflammatory activity of the aqueous and ethanolic extracts of the leaves of Albizzia lebbeck in rats. J Tradit Complement Med 6:172–175 106. Ogbiti VM, Akindele AJ, Adeyemi OO (2017) Analgesic, anti-inflammatory, and antipyretic activities of hydroethanolic stem bark extract of Albizia glaberrima. J Herb Spices Med Plants 23:44–67 107. Dabhade AR, Mokashe NU, Patil UK (2016) Purification, characterization, and antimicrobial activity of nontoxic trypsin inhibitor from Albizia Amara Boiv. Process Biochem 51(5): 659–674 108. Bakasatae N, Kunworarath N, Takahashi Yupanqui C, Voravuthikunchai SP, Joycharat N (2018) Bioactive components, antioxidant, and anti-inflammatory activities of the wood of Albizia myriophylla. Rev Bras 28(4):444–450 109. Adebesin IF, Akindele AJ, Adeyemi OO (2015) Evaluation of neuropharmacological effects of aqueous leaf extract of Albizia glaberrima(Leguminosae) in mice. J Ethnopharmacol 160: 101–108 110. Sun HX, He SW, Shi MH (2014) Adjuvant-active fraction from Albizia julibrissinsaponins improves immune responses by inducing cytokine and hemokines at the site of injection. Int Immunopharmacol 22:346–355 111. Du J, Jin J, Wang J, Sun H (2020) Mechanisms of mixed Th1/Th2 responses in mice induced by Albizia julibrissinsaponin active fraction by in silico analysis. Vaccine 8(1):48

180

S. Muruganantham et al.

112. Pachuau L, Mazumder B (2012) Albizia procera gum as an excipient for oral controlled release matrix tablet. Carbohydr Polym 90(1):289–295 113. Veenus Seelan T, Henry LJK, Narra K, Lalduhsanga P, Kandasamy R (2016) Design and development of Albizia stipulata gum based controlled-release matrix tablets in cancer therapeutics. Int J Biol Macromol 92:972–980 114. Adeniyi AT, Daniel GA (2017) Characterization of native and graft copolymerized albizia gums and their application as a flocculant. J Polym 2017:1–8 115. Odeku OA, Fell JT (2004) Evaluation of khaya gum as a directly compressible matrix system for controlled release. J Pharm Pharmacol 56(11):1365–1370 116. Bonsu MA, Ofori-Kwakye K, Kipo SL, Boakye-Gyasi ME, Fosu MA (2016) Development of oral dissolvable films of diclofenac sodium for osteoarthritis using Albizia and Khaya gums as hydrophilic film formers. J Drug Deliv 2016:1–11 117. Oluwatoyin AO (2005) Assessment of Albizia zygia gum as a binding agent in tablet formulations. Acta Pharma 55:263–276 118. Femi-Oyewo MN, Adedokun MO, Olusoga TO (2007) Evaluation of the suspending properties of Albizia zygia gum on sulphadimidine suspension. Trop J Pharm Res 3(1):279–284 119. Maan AA, Nazir A, Khan MKI, Ahmad T, Zia R, Murid M, Abrar M (2018) The therapeutic properties and applications of Aloe vera: a review. J Herb Med 12:1–10 120. Surjushe A, Vasani R, Saple D (2008) Aloe vera: a short review. Indian J Dermatol 53(4):163– 166 121. Akinyele BO, Odiyi AC (2007) Comparative study of the vegetative morphology and the existing taxonomic status of Aloe vera. J Plant Sci 2(5):558–563 122. Misir JH, Brishti FM, Hoque M (2014) Aloe vera gel as a novel edible coating for fresh fruits: a review. Am J Food Sci Technol 2(3):93–97 123. He Q, Changhong L, Kojo E, Tian Z (2005) Quality and safety assurance in the processing of Aloe vera gel juice. Food Control 16(2):95–104 124. Elbandy MA, Abed SM, Gad SSA, Abdel-Fadeel MG (2014) Aloe vera gel as a functional ingredient and natural preservative in mango nectar. World J Dairy Food Sci 9(2):191–203 125. Eshun K, He Q (2004) Aloe vera: a valuable ingredient for the food, pharmaceutical and cosmetic industries: a review. Crit Rev Food Sci Nutr 44(2):91–96 126. Rodriguez ER, Martin JD, Romero CD (2010) Aloe vera as a functional ingredient in foods. Crit Rev Food Sci Nutr 50(4):305–326 127. Pushkala R, Srividya N (2011) Influence of aloe gel enrichment on the physicochemical, textural and sensory characteristics of dahi. J Food Sci Eng 1:141–153 128. Valverde JM, Valero D, Martinez-Romero D, Guillen F, Castillo S, Serrano M (2005) Novel edible coating based on Aloe vera gel to maintain table grape quality and safety. J Agric Food Chem 53(20):7807–7813 129. Benitez S, Achaerandio I, Pujola M, Sepulcre F (2015) Aloe vera as an alternative to traditional edible coatings used in fresh-cut fruits: a case of study with kiwifruit slices. LWT Food Sci Technol 61(1):184–193 130. Jain N, Vijayaraghavan R, Pant SC, Lomash V, Ali M (2010) Aloe vera gel alleviates cardiotoxicity in streptozocin-induced diabetes in rats. J Pharm Pharmacol 62(1):115–123 131. Lad VN, Murthy ZVP (2013) Rheology of Aloe barbadensis Miller: a naturally available material of high therapeutic and nutrient value for food applications. J Food Eng 115(3):279– 284 132. Tarameshloo M, Norouzian M, Zarein-Dolab S, Dadpay M, Mohsenifar J, Gazor R (2012) Aloe vera gel and thyroid hormone cream may improve wound healing in Wistar rats. Anatomy Cell Biol 45:170–177 133. Mansour G, Ouda S, Shaker A, Abdallah HM (2014) Clinical efficacy of new Aloe vera and myrrh-based oral mucoadhesive gels in the management of minor recurrent aphthous stomatitis: a randomized, double-blind, vehicle-controlled study. J Oral Pathol Med 43:405–409 134. Radha MH, Laxmipriya NP (2015) Evaluation of biological properties and clinical effectiveness of Aloe vera: a systematic review. J Tradit Complement Med 5(1):21–26

7

Gums as Pharmaceutical Excipients: An Overview

181

135. El-Shemy HA, Aboul-Soud MAM, Nassr-Allah AA, Aboul-Enein KM, Kabash A, Yagi A (2010) Antitumor properties and modulation of antioxidant enzymes activity by Aloe vera leaf active principles isolated via supercritical carbon dioxide extraction. Curr Med Chem 17:129–138 136. Huseini HF, Kianbakht S, Hajiaghaee R, Dabaghian FH (2012) Anti-hyperglycemic and antihypercholesterolemic effects of Aloe vera leaf gel in hyperlipidemic type 2 diabetic patients: a randomized double-blind placebo-controlled clinical trial. Planta Med 78:311–316 137. Lopez A, de Tangil MS, Vega-Orellana O, Ramirez AS, Rico M (2013) Phenolic constituents, antioxidant and preliminary antimycoplasmic activities of leaf skin and flowers of Aloe vera (L.) Burm. f. (syn. A. barbadensis Mill.) from the Canary Islands (Spain). Molecules 18(5): 4942–4954 138. Mulay S (2014) Aloe vera – a Review. Int J Pharm Phytopharmacol Res 3(3):203–211 139. Sujatha G, Kumar GS, Muruganandan J, Prasad TS (2014) Aloe vera in Dentistry. J Clin Diagnostic Res 8(10):1–2 140. Olatunya OS, Olatunya AM, Anyabolu HC, Adejuyigbe EA, Oyelami OA (2012) Preliminary trial of Aloe vera gruel on HIV infection. J Altern Complement Med 18:850–853 141. Koul A, Bala S, Goyal Y, Arora N (2014) Aloe vera affects changes induced in pulmonary tissue of mice caused by cigarette smoke inhalation. Environ Toxicol 30(9):1–15 142. Chen CP, Wang BJ, Weng YM (2010) Physiochemical and antimicrobial properties of edible aloe/gelatin composite films. Int J Food Sci Technol 45(5):1050–1055 143. Mendy TK, Misran A, Mahmud TMM, Ismail SI (2019) Antifungal properties of Aloe vera through in vitro and in vivo screening against postharvest pathogens of papaya fruit. Sci Hortic 257:108767 144. Soraya G, Majid M, Mahnaz MR (2016) Encapsulation of Aloe vera extract into natural Tragacanth gum as a novel green wound healing product. Int J Biol Macromol 93:344–349 145. Vinson JA, Al Kharrat H, Andreoli L (2005) Effect of Aloe vera preparations on the human bioavailability of vitamins C and E. Phytomedicine 12:760–765 146. Dudhatra GB, Mody SK, Awale MM, Patel HB, Modi CM, Kumar A, Kamani DR, Chauhan BN (2012) A comprehensive review on pharmacotherapeutics of herbal bioenhancers. Sci World J 2012:1–33 147. Vashisth I, Ahads A, Aqil M, Agarwal SP (2014) Investigating the potential of essential oils as penetration enhancer for transdermal losartan delivery: effectiveness and mechanism of action. Asian J Pharm Sci 9(5):260–267 148. ClinicalTrials.govIdentifier:NCT02462993. https://clinicaltrials.gov/ct2/show/NCT02462993 149. Joshy KS, Chandra PS, Nandakumar K, Sandeep K, Sabu T, Laly AP (2016) Evaluation of in-vitro cytotoxicity and cellular uptake efficiency of zidovudine-loaded solid lipid nanoparticles modified with Aloe vera in glioma cells. Mater Sci Eng C 66:40–50 150. Chakraborty T, Gupta S, Nair A, Chauhan S (2021) Wound healing potential of insulin-loaded nanoemulsion with Aloe vera gel in diabetic rats. J Drug Deliv Sci Technol 64:102601 151. Nayebi I, Rajabi O, Chamani J, Izi S (2020) In vitro evaluation of biophysical properties of an artificial saliva produced from Aloe vera gel. J Herb Med 19:100307 152. Silva SS, Popa EG, Gomes ME, Cerqueira M, Marques AP, Caridade SG, Teixeira P, Sousa C, Mano JF, Reis RL (2013) An investigation of the potential application of chitosan/aloe-based membranes for regenerative medicine. Acta Biomater 9(6):6790–6797 153. Silva SS, Caridade SG, Mano JF, Reis RL (2013) Effect of crosslinking in chitosan/aloe verabased membranes for biomedical applications. Carbohydr Polym 98(1):581–588 154. Saibuatong O-A, Phisalaphong M (2010) Novo Aloe vera–bacterial cellulose composite film from biosynthesis. Carbohydr Polym 79(2):455–460 155. Singh B, Sharma V, Dhiman A, Devi M (2012) Design of Aloe vera-alginate gastroretentive drug delivery system to improve the pharmacotherapy. Polym Plast Technol Eng 51(13):1303– 1314 156. Mohan Raj R, Duraisamy N, Raj V (2020) Drug loaded chitosan/Aloe vera nanocomposite on Ti for orthopedic applications. Mater Today Proc. Available at online 24 December 2020. https://doi.org/10.1016/j.matpr.2020.10.772

182

S. Muruganantham et al.

157. Aghamohamadi N, Sanjani NS, Majidi RF, Nasrollahi SA (2019) Preparation and characterization of Aloe vera acetate and electrospinning fibers as promising antibacterial properties materials. Mater Sci Eng C 94:445–452 158. Jambwa T, Viljoen A, Hamman J (2011) Matrix forming excipients from natural origin for controlled release matrix type tablets. J Drug Deliv Sci Technol 21(5):433–439 159. Cole L, Heard C (2007) Skin permeation enhancement potential of Aloe vera and a proposed mechanism of action based upon size exclusion and pull effect. Int J Pharm 333(1–2):10–16 160. Wallis L, Malan M, Gouws C, Steyn D, Ellis S, Abay E, Wiesner L, Otto DP, Hamman J (2016) Evaluation of isolated fractions of Aloe vera gel materials on Indinavir pharmacokinetics: in vitro and in vivo studies. Curr Drug Deliv 13(3):471–480 161. de Bruyn S, Willers C, Dewald S, Jan S, Josias H (2018) Development and evaluation of a double-phase multiple-unit dosage form for enhanced insulin intestinal delivery. Drug Deliv Lett 8(1):52–60 162. Habibur R (2016) Aloe vera mucilage as solubility enhancer in tablet formulation. J Nutr Food Sci 6:5 163. Aslani A, Ghannadi A, Raddanipour R (2015) Design, formulation and evaluation of Aloe vera chewing gum. Adv Biomed Res 4:175 164. Pereira GG, Guterres SS, Balducci AG, Colombo P, Sonvico F (2014) Polymeric films loaded with vitamin E and Aloe vera for topical application in the treatment of burn wounds. BioMed Res Int 2014:1–9 165. Yalavarthi P, Haritha K, Satyanarayana R, Vandana KR, Bindu D, Vinesha V, Vadlamudi Dr HC (2015) Formulation and characterization of Aceclofenac -Aloe vera Transemulgel. Curr Drug Deliv 12:703–708 166. Jouybar A, Seyedjafari E, Ardeshirylajimi A, Zandi-Karimi A, Feizi N, Khani M-M, Pousti I (2017) Enhanced skin regeneration by herbal extract-coated poly-L-lactic acid nanofibrous scaffold. Artif Organs 41(11):E296–E307 167. Farhadiana N, Godinyb M, Mansourib A, Moradic S, Tajehmirid A, Shahlaei M (2020) Hydrophilic natural polymers for sustained-controlled release of calcium hydroxide. Iran J Pharm Res 19(2):323–332 168. Serincay H, Ozkan S, Yılmaz N, Kocyigit S, Uslu I, Gurcan S, Arısoy M (2013) PVA/PAAbased antibacterial wound dressing material with Aloe vera. Polym Plast Technol Eng 52(13): 1308–1315 169. Kamaraj C, Gandhi PR, Elango G, Karthi S (2018) Novel and environmental friendly approach; impact of neem (Azadirachta indica) gum nano formulation (NGNF) on helicoverpa armigera (Hub.) and spodoptera litura (Fab.). Int J Biol Macromol 107:59–69 170. Velusamy P, Das J, Pachaiappan R, Vaseeharan B, Pandian K (2015) Greener approach for synthesis of antibacterial silver nanoparticles using aqueous solution of neem gum (Azadirachta indica L.). Ind Crop Prod 66:103–109 171. Malviya R, Sharma PK, Dubey SK (2018) Stability facilitation of nanoparticles prepared by ultrasound assisted solvent-antisolvent method: effect of neem gum, acrylamide grafted neem gum and carboxymethylated neem gum over size, morphology and drug release. Mater Sci Eng C 91:772–784 172. Moniem ME, Hassan EA, Osaman ME (2018) Characterization and rheological behavior of neem gum (Azadirachta indica). Int J Chem Stud 6:1977–1981 173. Upadhyay SN, Charu K, Parshad TG (1990) Antifertility effects of neem (Azadirachta indica) oil by single intrauterine administration:a novel method for contraception. Proc R Soc Lond B 242:175–179 174. Malviya R, Sharma PK, Dubey SK (2017) Antioxidant potential and emulsifying properties of neem (Azadirachita indica, family Meliaceae) gum polysaccharide. Pharm Anal Acta 8(8): 100559 175. Hindustan AA, Kumar CS, Kumar AB (2010) Fabrication and evaluation of Nimesulide Azadirachta indica fruit mucilage based sustained release matrix tablets. Int J ChemTech Res 2(2):937–941

7

Gums as Pharmaceutical Excipients: An Overview

183

176. Rupani R, Chavez A (2018) Medicinal plants with traditional use: ethnobotany in the Indian subcontinent. Clin Dermatol 36(3):306–309 177. Chen J, Fan X, Zhu J, Song L, Li Z, Lin F, Yu R, Xu H, Zi J (2018) Limonoids from seeds of Azadirachta indica A. Juss. and their cytotoxic activity. Acta Pharma Sin B 8(4):639–644 178. Soares DG, Godin AM, Menezes RR, Nogueira RD, Brito AMS, Melo ISF, Machado RR (2014) Anti-inflammatory and antinociceptive activities of azadirachtin in mice. Planta Med 80(8–9):630–636 179. Mohammad AA (2016) Therapeutics role of Azadirachta indica (neem) and their active constituents in diseases prevention and treatment. Evid Based Complement Alternat Med 2016:1–11 180. Al Akeel R, Mateen A, Janardhan K, Gupta VC (2017) Analysis of anti-bacterial and anti oxidative activity of Azadirachta indica bark using various solvents extracts. Saudi J Biol Sci 24(1):11–14 181. Quelemes PV, Perfeito MLG, Guimaraes MA, Dos Santos RC, Lima DF, Nascimento C, Silva MPN, Maria JDS, Ropke CD, Eaton P, de Moreas J, Leite JRSA (2015) Effect of neem (Azadirachta indicaA. Juss) leaf extract on resistant Staphylococcus aureus biofilm formation and Schistosoma mansoni worms. J Ethnopharmacol 175:287–294 182. Asif M (2013) A review on spermicidal activities of Azadirachta indica. J Pharmacogn Phytochem 1(5):61–79 183. SaiRam M, Ilavazhagan G, Sharma SK, Dhanraj SA, Suresh B, Parida MM, Jana AM, Kumar D, Selvamurthy W (2000) Anti-microbial activity of a new vaginal contraceptive NIM-76 from neem oil (Azadirachta indica). J Ethnopharmacol 71(3):377–382 184. Kaur I, Sharma N, Kumari V (2013) Modification of fiber properties through grafting of acrylonitrile to rayon by chemical and radiation methods. J Adv Res 4(6):547–557 185. Peng P, Zhai MZ, She D, Gao YF (2015) Synthesis and characterization of carboxymethyl xylan-g-poly(propylene oxide) and its application in films. Carbohydr Polym 133:117–125 186. Pillay V, Seedat A, Choonara YE, du Toit LC, Kumar P, Ndesendo VM (2013) A review of polymeric refabrication techniques to modify polymer properties for biomedical and drug delivery applications. AAPS Pharm Sci Tech 14:692–711 187. Bhattacharyaa A, Misra BN (2004) Grafting: a versatile means to modify polymers techniques, factors and applications. Prog Polym Sci 29(8):767–814 188. Prakashkumar N, Vignesh M, Brindhadevi K, Nguyen-TriPhuong, Pugazhendhi A, Suganthy N (2021) Enhanced antimicrobial, antibiofilm and anticancer activities of biocompatible neem gum coated palladium nanoparticles. Prog Org Coat 151:106098 189. Bhagwat Durgacharan A, Kolekar Vandana R, NadafSameer J, Choudhari Prafulla B, More Harinath N, KilledarSuresh G (2020) Acrylamide grafted neem (Azadirachta indica) gum polymer: screening and exploration as a drug release retardant for tablet formulation. Carbohydr Polym 229:115357 190. Mankotia P, Choudhary S, Sharma K, Kumar V, Kaur Bhatia J, Parmar A, Sharma S, Sharma V (2019) Neem gum based pH responsive hydrogel matrix: a new pharmaceutical excipient for the sustained release of anticancer drug. Int J Biol Macromol 145:742–755 191. Asghar K, Qasim M, Das D (2019) Synthesis and characterization of neem gum coated superparamagnetic nanoparticle based novel nanobiocomposite. Ceram Int 45(18): 345–356 192. Madan J, Gundala SR, Baruah B, Nagaraju M, Yates C, Turner T, Rangari Hamelberg D, Reid MD, Aneja R (2014) Cyclodextrin complexes of reduced bromonoscapine in guar gum microspheres enhance colonic drug delivery. Mol Pharm 11(12):4339–4349 193. Yadav M, Sand A, Mishra DK, Behari K (2010) A study toward the physicochemical properties of graft copolymer (partially carboxymethylated guar gum-g-NN0 -dimethylacrylamide): synthesis and characterization. J Appl Polym Sci 117:974–981 194. Huanbutta K, Sangnim T, Limmatvapirat S, Nunthanid J, Sriamornsak P (2016) Design and characterization of prednisolone-loaded nanoparticles fabricated by electrohydrodynamic atomization technique. Chem Eng Res Des 109:816–823

184

S. Muruganantham et al.

195. Chauhan AS, Chalasani KB, Surapanini S, Yandrapu SK, Kataram, R, Chary GM, Raghavan KV (2006) Therapeutic/edible compositions comprising herbal ingredients and methods for treating hyperglycemia. Patent no. US6989160B2, USPTO 196. Joshi BN, Bhat M, Kothiwale SK, Tirmale AR, Bhargava SY (2011) Antidiabetic properties of Azardiracta indica and bougainvillea spectabilis: in vivo studies in murine diabetes model. Evid Based Complement Alternat Med 2011:1–9 197. Pushpangadan P, Prakash D (2006) Herbal nutraceutical formulation for diabetics and process for preparing the same. Patent no. US7014872. USPTO 198. Upreti J, Ali S, Basir SF (2013) Effect of lower doses of vanadate in combination with Azadirachta indica leaf extract on hepatic and renal antioxidant enzymes in streptozotocininduced diabetic rats. Biol Trace Elem Res 156(1):202–209 199. Basir S, Shailey S (2012) Strengthening of antioxidant defense by Azadirachta indica in alloxan-diabetic rat tissues. J Ayurveda Integr Med 3(3):130–135 200. Vijayavani SC, Vidyavathi M (2018) Azadirachita indicagum based sildenafil citrate mucoadhesive microspheres – design and optimization. J Drug Deliv Sci Technol 47:499–513 201. Ogunjimi AT, Alebiowu G (2013) Flow and consolidation properties of neem gum coprocessed with two pharmaceutical recipients. Powder Technol 246:187–192 202. Ogunjimi AT, Alebiowu G (2014) Neem gum as a binder in a formulated paracetamol tablet with reference to acacia gum BP. AAPS Pharm Sci Tech 15(2):500–510 203. Nagpal M, Aggarwal G, Sharma P, Mahan P, Thakur GS (2017) Neem gum based solid dispersion in development of Aceclofenac tablet with enhanced bioavailability. Drug Deliv Lett 7(2):115–124 204. Quereshi D, Dhal S, Das D, Mohanty B, Anis A, Shaikh H, Hanh Nguyen TT, Kim D, Sarkar P, Pal K (2019) Neem seed oil and gum arabic-based oil-in-water emulsions as potential ocular drug delivery system. J Dispers Sci Technol 41(13):1911–1924 205. Raju D, Jose J (2019) Development and evaluation of novel topical gel of neem extract for the treatment of bacterial infections. J Cosmet Dermatol 18(6):1776–1783 206. Chandrasekar R, Sivagami B (2018) Formulation and evaluation of a poly herbal skin care cream containing neem and Tulsi. Res J Topic Cosmet Sci 9(1):25–32 207. Sandhala D, Lankalapalli S (2019) Preparation and evaluation of fluvastatin extended release tablets using neem gum. Int Res J Pharm 10(10):64–69 208. Ovenseri AC, Michael UU (2021) Formulation of non-effervescent floating dosage form of metronidazole using sintering and sublimation technique. J Pharm Sci 20(1):11–17 209. Heukelbach J, Oliveira FAS, Speare R (2006) A new shampoo based on neem (Azadirachta indica) is highly effective against head lice in vitro. Parasitol Res 99(4):353–356 210. Kapinga FA, Kasuga LJ, Kafiriti EM (2017) Growth and production of cashew nut. In: Soils, plant growth and crop production 211. Sharma P, Gaur VK, Sirohi R, Larroche C, Kim SH, Pandey A (2020) Valorization of cashew nut processing residues for industrial applications. Ind Crop Prod 152:112550 212. Dineshkumar R, Begum, K, Ramanathan A (2021) Comprehensive characterization of cashew nutshell for biomass gasification. Mat Today: Proc 46(19):9837–9843 213. Preethi P, Mangalassery S, Shradha K, Pandiselvam R, Manikantan MR, Reddy SV, Devi SR, Nayak MG (2021) Cashew apple pomace powder enriched the proximate, mineral, functional and structural properties of cereal based extrudates. LWT 139:110539 214. Pacheco G, Nogueira CR, Meneguin AB, Trovatti E, Silva MC, Machado RT, Ribeiro SJ, Da Silva Filho EC, Barud HD (2017) Development and characterization of bacterial cellulose produced by cashew tree residues as alternative carbon source. Ind Crop Prod 107:13–19 215. Porto BC, Augusto PE, Terekhov A, Hamaker BR, Cristianini M (2015) Effect of dynamic high pressure on technological properties of cashew tree gum (Anacardium occidentale L.). Carbohydr Polym 129:187–193 216. Ogunwolu SO, Henshaw FO, Mock HP, Santros A, Awonorin SO (2009) Functional properties of protein concentrates and isolates produced from cashew (Anacardium occidentale L.) nut. Food Chem 115(3):852–858

7

Gums as Pharmaceutical Excipients: An Overview

185

217. Pinto AP, Holanda e Silva KG, Mansur CR (2018) Evaluation of the application of cashew gum as an excipient to produce tablets. Polimeros 28:302–308 218. Adeyanju O, Nwanta UC, Shuaibu Y, Hussaini Y, Adejoh AI (2016) Effect of acetylation on physicochemical characteristics of cashew exudate gum (Anacardium occidentale), a potential excipient. J Pharm Appl Chem 2(3):201–204 219. Nandi BK (1997) Cashew nut nutritional aspects. Inexpert consultation on integrated production practices in cashew in asia. Bangkok, pp 7–9 220. Kushwaha A (2019) Cashew nut starch as natural excipient for improved bioavailability of drugs. Int J Pharm Sci Nanotechnol 12(4):4616–4622 221. Asantewaa Y (2011) Evaluation of Anacardium occidentale (cashew) gum as a pharmaceutical excipient. Dissertation, College of Health Sciences 222. Souza Filho MD, Medeiros JV, Vasconcelos DF, Silva DA, Leódido AC, Fernandes HF, Silva FR, França LF, Lenardo D, Pinto GR (2018) Orabase formulation with cashew gum polysaccharide decreases inflammatory and bone loss hallmarks in experimental periodontitis. Int J Biol Macromol 107:1093–1101 223. Al-Hazzani A, Periyasamy V, Subash-Babu P, Alshatwi AA (2012) Formulation of cashew nut shell liquid (CSNL) nanoemulsions, a potent inhibitor of human MCF-7 breast cancer cell proliferation. Med Chem Res 21(7):1384–1388 224. Rohit RB, Riyaz Ali MO, Padmaja C, Afrasim MO (2015) Formulation and evaluation of sustained release dosage form using modified cashew gum. Int J Pharm Pharm Sci 7: 141–150 225. Jessica Maria TS, de Araujo AR, de Carvalho AMA, das Graças Nascimento Amorim A, Daboit TC, de Souza de Almeida Leite JR, da Silva DA, Eaton P (2020) Sustainably produced cashew gum-capped zinc oxide nanoparticles show antifungal activity against Candida parapsilosis. J Clean Prod 247:119085 226. Do Amaral Rodrigues J, de Araujo AR, Pitombeira NA, Placido A, de Almeida MP, Veras LMC, Delerue-Matos C, Lima FCDA, Batagin-Neto A, Monteiro RC, de Paula J, Feitosa PA, Eaton P, Leite JRSA, da Silva DA (2019) Acetylated cashew gum-based nanoparticles for the incorporation of alkaloid epiisopiloturine. Int J Biol Macromol 128:965–972 227. Khorshidian N, Yousefi Asli M, Arab M, Adeli Mirzaie A, Mortazavian AM (2016) Fenugreek: potential applications as a functional food and nutraceutical. Nutr Food Sci Res 3(1):5– 16 228. Srinivasan K, Ramarao P (2007) Animal model in type 2 diabetes research: an overview. Indian J Med Res 125(3):451 229. Murlidhar M, Goswami TK (2012) A review on the functional properties, nutritional content, medicinal utilization and potential application of fenugreek. J Food Process Technol 9: 1000181 230. Wani SA, Kumar P (2018) Fenugreek: a review on its nutraceutical properties and utilization in various food products. J Saudi Soc Agric Sci 17(2):97–106 231. Basu SK, Acharya SN, Bandara MS, Friebel D, Thomas JE (2009) Effects of genotype and environment on seed and forage yield in fenugreek (‘Trigonella foenum-graecum L.’) grown in western Canada. Aust J Crop Sci 3(6):305–314 232. Shukla AK, Yadav A, Vishwakarma RK, Mishra SK (2020) Applications, isolation and characterization of fenugreek seed gum as pharmaceutical excipient. J Med Pharm Allied Sci 9:2484–2491 233. Nokhodchi A, Nazemiyeh H, Khodaparast A, Sorkh-Shahan T, Valizadeh H, Ford JL (2008) An in vitro evaluation of fenugreek mucilage as a potential excipient for oral controlled-release matrix tablet. Drug Dev Ind Pharm 34(3):323–329 234. Neelakantan N, Narayanan M, de Souza RJ, van Dam RM (2014) Effect of fenugreek (Trigonella foenum-graecum L.) intake on glycaemia: a meta-analysis of clinical trials. Nutr J 13(1):1–1 235. Al-Asadi JN (2014) Therapeutic uses of fenugreek (Trigonella foenum-graecum L.). Am J Soc Issues Hum 2:21–36

186

S. Muruganantham et al.

236. Abeysekera WK (2018) Anti-glycation and glycation reversing potential of fenugreek (Trigonella foenum-graecum) seed extract. Biomed J Sci Tech Res 3(1):1–5 237. Syed QA, Rashid Z, Ahmad MH, Shukat R, Ishaq A, Muhammad N, Rahman HU (2020) Nutritional and therapeutic properties of fenugreek (Trigonella foenum-graecum): a review. Int J Food Prop 23(1):1777–1791 238. Ahmad A, Alghamdi SS, Mahmood K, Afzal M (2016) Fenugreek a multipurpose crop: potentialities and improvements. Saudi J Biol Sci 23(2):300–310 239. Knott EJ, Richard AJ, Mynatt RL, Ribnicky D, Stephens JM, Bruce-Keller A (2017) Fenugreek supplementation during high-fat feeding improves specific markers of metabolic health. Sci Rep 7(1):1–5 240. Wankhede S, Mohan V, Thakurdesai P (2016) Beneficial effects of fenugreek glycoside supplementation in male subjects during resistance training: a randomized controlled pilot study. J Sport Health Sci 5(2):176–182 241. Sukhavasi S, Kishore VS (2012) Formulation and evaluation of fast dissolving tablets of amlodipine besylate by using Fenugreek seed mucilage and Ocimum basilicum gum. Int Curr Pharm J 1(9):243–249 242. Sudheeran SP, Jacob D, Mulakal JN, Nair GG, Maliakel A, Maliakel B, Kuttan R, Krishnakumar IM (2016) Safety, tolerance, and enhanced efficacy of a bioavailable formulation of curcumin with fenugreek dietary fiber on occupational stress: a randomized, doubleblind, placebo-controlled pilot study. J Clin Psychopharmacol 36(3):236–243 243. Krishnakumar IM, Ravi A, Kumar D, Kuttan R, Maliakel B (2012) An enhanced bioavailable formulation of curcumin using fenugreek-derived soluble dietary fibre. J Funct Foods 4(1): 348–357 244. Trop P, Akhtar N, Waqas MK, Mahmood A, Tariq S, Ghulam M, Rasool A, Aamir MN, Shujaat K, Bhatti NS, Atif A (2010) Effect of cream formulation of fenugreek seed extract on some mechanical parameters of human skin. Trop J Pharm Res 9(4):329–337 245. Noudeh GD (2011) Formulation of herbal conditioner shampoo by using extract of fenugreek seeds and evaluation of its physicochemical parameters. Afr J Pharm Pharmacol 5(22):2420– 2427 246. Khanniri E, Yousefi M, Khorshidian N (2019) Development of an efficient stabiliser mixture for physical stability of nonfat un fizzy doogh. Int J Dairy Technol 72(1):8–14 247. Abbasi S, Mohammadi S (2013) Stabilization of milk-orange juice mixture using Persian gum: efficiency and mechanism. Food Biosci 2:53–60 248. Abbasi S (2017) Challenges towards characterization and applications of a novel hydrocolloid: Persian gum. Curr Opin Colloid Interface Sci 28:37–45 249. Rezaei A, Tavanai H, Nasirpour A (2016) Fabrication of electrospun almond gum/PVA nanofibers as a thermostable delivery system for vanillin. Int J Biol Macromol 91:536–543 250. Mylangam CK, Beeravelli S, Medikonda J, Pidaparthi JS, Kolapalli VRM (2016) Badam gum: a natural polymer in mucoadhesive drug delivery. Design, optimization, and biopharmaceutical evaluation of badam gum-based metoprolol succinate buccoadhesive tablets. Drug Deliv 23(1):195–206 251. Bouaziz F, Helbert CB, Romdhane MB, Koubaa M, Bhiri F, Kallel F, Chaari F, Driss D, Buon L, Chaabouni SE (2014) Structural data and biological properties of almond gumoligosaccharide: application to beef meat preservation. Int J Biol Macromol 72:472–479 252. Bouaziz F, Koubaa M, Jeddou KB, Kallel F, Helbert CB, Khelfa A, Ghorbel RE, Chaabouni SE (2016) Water-soluble polysaccharides and hemicelluloses from almond gum: functional and prebiotic properties. Int J Biol Macromol 93:359–368 253. Mahfoudhi N, Chouaibi M, Donsi F, Ferrari G, Hamdi S (2012) Chemical composition and functional properties of gum exudates from the trunk of the almond tree (Prunus dulcis). Food Sci Technol Int 18:241–250 254. Mahfoudhi N, Sessa M, Chouaibi M, Ferrari G, Donsi F, Hamdi S (2014) Assessmentof emulsifying ability of almond gum in comparison with gum arabic using response surface methodology. Food Hydrocoll 37:49–59

7

Gums as Pharmaceutical Excipients: An Overview

187

255. Pal K, Bera D (2020) Natural polymers, gums and mucilages as efficacious green emissaries of essential therapeutics. MOL2NET 6 Available at: http://sciforum.net/conference/mol2net-06 256. Aji MDR, Ali SD, Vipul G, Mohd Dona BS, Davy VW, Paul VM, Koen D (2020) Stability and functionality of xanthan gum–shellac nanoparticles for the encapsulation of cinnamon bark extract. Food Hydrocoll 100:105377 257. Doost AS, Kassozi V, Grootaert C, Claeys M, Dewettinck K, Van Camp J, Van der Meeren P (2019) Self-assembly, functionality, and in-vitro properties of quercetin loaded nanoparticles based on shellac-almond gum biological macromolecules. Int J Biol Macromol 129: 1024–1033 258. Kazeruni AR, Hosseini E (2017) Effect of bitter almond gum (Amygdalus scoparia Spach) on the survival of lactobacillus acidophilus La5 in tomato juice during refrigeration storage and exposure to simulated gastric juice. J Maz Univ Med Sci 27(147):75–86 259. Bouaziz F, Ben Romdhane M, Boisset Helbert C, Buon L, Bhiri F, Bardaa S, Driss D, Koubaa M, Fakhfakh A, Sahnoun Z, Rebai T, Kallel F, Kacem I, Ghorbel R, Zghal N, Ellouz Chaabouni S (2014) Healing efficiency of oligosaccharides generated from almond gum in dermal wounds of adult rats. J Tissue Viability 23:98–108 260. Doost AS, Muhammad DRA, Stevens CV, Dewettinck K, Van der Meeren P (2018) Fabrication and characterization of quercetin loaded almond gum-shellac nanoparticles prepared by antisolvent precipitation. Food Hydrocoll 83:190–201 261. Sedaghat Doost A, Nikbakht Nasrabadi M, Kassozi V, Dewettinck K, Stevens CV, Van der Meeren P (2019) Pickering stabilization of thymol through green emulsification using soluble fraction of almond gum – whey protein isolate nano-complexes. Food Hydrocoll 88: 218–227 262. Koushal D, Vandana A, Kulkarni GT (2017) Formulation of Prunus amygdalus (family: Rosaceae) gum based compression coated tablet for colon targeted delivery of 5-Aminosalicylic acid. Nov Appro Drug Des Dev 2(4):555591 263. Bani-Jaber A, Al-Ghazawi M (2005) Sustained release characteristics of tablets prepared with mixed matrix of sodium carrageenan and chitosan: effect of polymer weight ratio, dissolution medium, and drug type. Drug Dev Ind Pharm 31(3):241–247 264. Mahfoudhi N, Hamdi S (2014) Use of almond gum and gum arabic as novel edible coating to delay postharvest ripening and to maintain sweet cherry (Prunus avium) quality during storage. J Food Process Preserv 39(6):1–10 265. Ruchi SS, Gowda D, Vishal GN, Praveen S, Manjunath M (2018) Formulation development and evaluation of almond gum based sustained release matrix tablet of indomethacin. Asian J Pharm Clin Res 11(12):166–169 266. Kardosova A, Machova E (2006) Antioxidant activity of medicinal plant polysaccharides. Fitoterapia 77:367–373 267. Yao X-C, Cao Y, Wu S-J (2013) Antioxidant activity and antibacterial activity of peach gum derived oligosaccharides. Int J Biol Macromol 62:1–3 268. Ranjbar-Mohammadi M, Bahrami SH, Joghataei MT (2013) Fabrication of novel nanofiber scaffolds from gum tragacanth/poly(vinyl alcohol) for wound dressing application: in vitro evaluation and antibacterial properties. Mater Sci Eng C Mater Biol Appl 33:4935–4943 269. Khaterehsadat H, Ebrahim H (2021) The stabilizing and prebiotic potential of water-soluble phase of bitter almond gum exudate in probiotic yogurt drink. Carbohydr Polym 255:117395 270. Negar C, Ebrahim H, Shahidul IM, Ali Reza R (2019) Bitter almond gum reduces body mass index, serum triglyceride, hyperinsulinemia and insulin resistance in overweight subjects with hyperlipidemia. J Funct Foods 55:343–351 271. Hussain SA, Jaisankar V (2017) An eco-friendly synthesis, characterisation and antibacterial applications of novel almond gum – poly(acrylamide) based hydrogel silver nanocomposite. Polym Test 62:154–161 272. Jaison D, Chandrasekaran G, Mothilal M (2018) pH-sensitive natural almond gum hydrocolloid based magnetic nanocomposites for theragnostic applications. Int J Biol Macromol 154: 256–266

188

S. Muruganantham et al.

273. Majid A, Jabbari AF, Ali T, Majid M, Jalil TA, Roshanak S, Javad NM, Maryam K, Roger ME, Kaboli FM (2019) The effect of Plantago major seed and almond gum on refractory asthma: a proof-of-concept study. J Herb Med 19:100297 274. Darvishmoghadam S, Ansari M, Ahmadipour H, Azimipour M, Esmaeilzade M, Zahedi MJ, Sharififar F (2019) Assessment of the effect of sachet formulation of almond (Amygdalus dulcis L.) on diarrhea prominent irritable bowel syndrome (IBS-D) symptoms: a clinical trial. Complement Ther Med 45:242–247 275. Gayathri M, Chandrasekaran M, Radhakrishnan A, Kuppusamy G, Singh SK (2020) Optimizing Badam gum towards tableting excipients. Res J Pharm Tech 13(12):6176–6181 276. Sarojini S, Kunam DS, Manavalan R, Jayanthi B (2010) Effect of natural almond gum as a binder in the formulation of diclofenac sodium tablets. Int J Pharm Sci Res 1(3):55–60 277. Gowda DV, Arvind Ram AS, Gowrav MP, Sivadasu P, Sebastian G, Osmani RM, Srivastava A (2016) Fabrication, characterization and evaluation of Glycosmis pentaphylla gel using almond gum for wound healing activity. Int J Pharm Sci Rev Res 39(2):58–65 278. Rahim H, Sadiq A, Khan S, Khan MA, Amin F, Jan NU, Chishti KA (2018) Prunus armeniaca and Prunus domestica gums: exploring their synergistic binding potential in tablets. Lat Am J Pharm 37(8):1672–1683 279. Meka VS, Nali SR, Songa AS, Kolapalli VRM (2012) Characterization and in vitro drug release studies of a natural polysaccharide Terminalia catappa gum (Badam gum). AAPS Pharm Sci Tech 13(4):1451–1464 280. Naz M, Nasiri N, Ikram M, Nafees M, Qureshi MZ, Ali S, Tricoli A (2017) Eco-friendly biosynthesis, anticancer drug loading and cytotoxic effect of capped ag-nanoparticles against breast cancer. Appl Nanosci 7(1):793–802 281. BhagyashreeTulashidas C (2019) Property of cashew gum as sustained release polymer in sustained release tablet. IN1825/MUM/2015 282. Gill P, MehraniSabet J (2018) Fabrication of Aloe veranano-cellulose via mechanical method. WO2018104971A1 283. Fisher KC, Garrett KW, Tompkins PZ (2009) Composition, device and method for transdermal delivery of insect repellent. US2009022767A1 284. Dinesh K, Illathu MK, Balu PM, Abhilas R (2013) Formulation containing curuminoids exhibiting enhanced bioavailability. US2013029905A1 285. Amit T, Bihari GV, Singh RM (2009) Fenugreek gum based colonic drug delivery. 1540/ MUM/2007 286. Shashikant SB, Vijay DG, Shailendra SG et al (2015) An orally administrative gastro retentive drug delivery system. IN2986MU2013A 287. Annamalai P, Puneet G, Lal KR et al (2015) A natural extract based polymeric prodrug for sustaining the release of a drug. IN3084DE2015A 288. Andre JR, Colliopoulos JA (1996) Anion exchange resin compositions containing almond paste for the taste improvement. US500190A 289. Chengxue J, Shuanggang M, Ruiming X et al (2013) Application of Albizia chinensis extract in preparation of medicament for treating gastric ulcer. CN103054932A 290. https://clinicaltrials.gov/ct2/show/NCT01000714 291. https://clinicaltrials.gov/ct2/show/NCT03819179 292. https://clinicaltrials.gov/ct2/show/NCT01657253 293. https://clinicaltrials.gov/ct2/show/NCT02087332 294. https://clinicaltrials.gov/ct2/show/NCT04804657 295. https://clinicaltrials.gov/ct2/show/NCT04612829 296. https://clinicaltrials.gov/ct2/show/NCT01877057 297. https://clinicaltrials.gov/ct2/show/NCT02066441 298. https://clinicaltrials.gov/ct2/show/NCT02142543 299. https://clinicaltrials.gov/ct2/show/NCT04147767 300. https://www.clinicaltrials.gov/ct2/show/NCT00858767 301. https://clinicaltrials.gov/ct2/show/NCT04112940

7

Gums as Pharmaceutical Excipients: An Overview

189

302. https://clinicaltrials.gov/ct2/show/NCT04009616 303. https://clinicaltrials.gov/ct2/show/NCT04191213 304. https://clinicaltrials.gov/ct2/show/NCT04569656 305. https://clinicaltrials.gov/ct2/show/NCT04386226 306. Singh P, Mahmood T, Shameem A, Bagga P, Ahmad N (2016) A review on herbal excipients and their pharmaceutical applications. Sch Acad J Pharm 5(3):53–57 307. Nayak AK, Hasnain MS (2019) Plant polysaccharides-based multiple-unit systems for oral drug delivery. Springer briefs in applied sciences and technology, plant polysaccharides in drug delivery applications, pp 19–23 308. Kumar T, Gupta S, Prajapati M, Tripathi DK (2012) Natural excipients: a review. Int J Pharm Biol Arch 3(5):1028–1034 309. Saripilli R, Prasanthi T, Sudha N, Ranjit Prasad S, Satyajit P, Goka V (2017) Natural polymers: a recent review. World J Pharm Pharm Sci 6(8):472–494 310. Shirwaikar A, Annie S, Sl P, Ga K (2008) Herbal excipients in novel drug delivery systems. Indian J Pharm Sci 70(4):415 311. Woldu G, Baymot B, Tesfay D, Demoz GT (2021) Evaluation of Aloe elegans mucilage as a suspending agent in paracetamol suspension. In: Kontos CK (ed). BioMed Research International, pp 1–12 312. de Oliveira ACJ, Chaves LL, de Ribeiro FOS, de Lima LRM, Oliveira TC, García-Villén F, Viseras C, de Paula RCM, Rolim-Neto PJ, Hallwass F, Silva-Filho EC, Silva DA, SoaresSobrinho JL, Roca Soares MFL (2020) Microwave-initiated rapid synthesis of phthalated cashew gum for drug delivery systems. Carbohydr Polym 254:117226

Part II Plant Gums

8

Chemistry, Biological Activities, and Uses of Moi Gum Sumit Mishra, Ch. Jamkhokai Mate, and Nandkishore Thombare

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Chemistry of Moi Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Plant Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Biology, Habitat, and Uses of Moi Tree . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Modifications of a Polysaccharide Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Development of Moi Gum–Based Hydrogel and its Applications in Dye Removal for Environmental Remediation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Synthesis of Moi Gum Hydrogel and Experimental Plan . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Biodegradation Study and Determination of Half-Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Results and Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Synthesis and Purification of Cross-Linked Moi Gum Hydrogel . . . . . . . . . . . . . . . . . . . . 4.2 Characterization Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Adsorption Experiments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Biodegradation Study and Calculation of Half-Life . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Applications of Moi Gum Matrices for Nutrient Release Studies for Agricultural Applications . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Synthesis of Micronutrients-Loaded Hydrogel . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Results and Discussions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

194 195 196 196 197 199 199 203 203 203 204 206 209 210 212 214 217 217

Abstract

Moi gum is a well-known minor gum found abundantly in tropical and subtropical climates. Based upon its chemical and biological properties, it is modified by available techniques and put to use in different applications. Its modified derivatives are used in many applications. Here, its synthesis as a cross-linked hydrogel and its applications for dye removal is highlighted. The synthesized hydrogel (Moi-g-PAM-cl-NN’MBA) was studied for dye removal applications for brilliant S. Mishra (*) · C. J. Mate · N. Thombare Department of Chemistry, Birla Institute of Technology, Mesra, Ranchi, India e-mail: [email protected] © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_8

193

194

S. Mishra et al.

green dye and its adsorption kinetics is reported. It is biodegradable in 180 days which shows its immense potential as dye removing hydrogel. Along with it, its application as a potential matrix for drug release or nutrient release is emphasized. It was found that modified gum derivatives can be used for controlled nutrient release applications along with their release mechanism presented here. Overall, it can be concluded that based upon the chemical and biological properties of Moi gum, it can be used for many applications. It is low cost, nontoxic, easily available, easily modifiable, and it can be further explored in many applications of miscellaneous nature to suit our various requirements. Keywords

Agricultural applications · Cross-linking · Dye removal · Grafting · Moi gum · Nutrient release Abbreviations

AM BG dye FTIR GE mM Mn PAM PFO Ppm PSO RE SAP SEM TGA XRD

1

Acrylamide Brilliant green dye Fourier transform infrared Grafting efficiency Milli molar Molecular weight Polyacrylamide Pseudo-first order Parts per million Pseudo-second order Dye removal efficiency Super absorbent polymers Scanning electron microscopy Thermogravimetric analysis X-ray diffraction

Introduction

Moi gum exudates from cracks and crevices of the bark of the Moi gum plant, (biological name: Lannea coromandelica [Houtt]). It readily oozes out in huge amounts upon any cut or cracks caused to the plant. Other common vernacular names of Moi gum are Moiingan, Joel, or Odina depending upon the local habitat. It is a deciduous tree found up to an altitude of 1000 m in tropical regions [1]. Moi gum tree is seen in considerable amounts in countries with tropical climates like India, Bangladesh, and many parts of Africa. It is widely distributed in many regions of the Indian subcontinent. The gum exudates from the stem and bark as yellowish-white sap initially but slowly oxidizes to the brown coloration on prolonged exposure to

8

Chemistry, Biological Activities, and Uses of Moi Gum

195

sunlight. The gum has not been extensively explored and our research group has explored it for environmental and biomedical applications, some of which are summarized in this communication. Still, some available reports suggest its use as an emulsifier and as a substitute for guar gum and gum arabic, and as a flocculant for wastewater treatment [2, 3]. It is also used for making incense sticks as a binding agent [3]. It is also used as a matrix for controlled drug delivery applications in pharmaceutical research, on the basis of its suitability with the human physiological systems [4]. It has been modified and used as a microencapsulating agent and as a controlled release matrix formulation for drug lamivudine which is used for the treatment of HIV/AIDS [5]. Some studies report applications of Moi gum in the pharmaceutical sector. It was used to synthesize drug-based microspheres which were of desired size and uniform morphology. This helped toward the continuous sustained release of the drug for more than 10 hours which was quite high as compared to other gums [6]. It is also reported to be used as a controlled retardant for drug release [7] so that it can be used for sustained drug delivery applications [8, 9].

1.1

Chemistry of Moi Gum

The commonly found arabinogalactan polysaccharide is an important constituent of this gum. As in other places of its occurrence, here also it is found in primary walls of plant tissues. Arabinogalactan occurs in two major forms: arabinogalactans I and arabinogalactan II. Type I category of arabinogalactan consists of: 1. Main backbone composed of (1–4)-linked β-D-Galp unit 2. Side chain at the C3 position consisting of 1–5-linked α-Araf [10] On the other hand, type II arbinogalactan has a more complex structure which consists of: 1. Main backbone of 1, 3-linked β-D-Galp unit 2. Side chains of 1, 6 β -D Galp or in less frequent occurrence 1, 3 α – L-Araf or 1, 6-D- glucopyranosyl uronic acid [11, 12] Hence, the Moi gum is composed of two types of arabinogalactans, mainly D-galactose (63.7%) as major constituents, L-arabinose (19.5%), and some uronic acids (11.5–17%) in varying proportions, which contribute toward the polyanionic character of the gum, D-galactouronic acid and aldobiouronic acid [8, 9]. The chemical structure consists of a 1, 6-linked β-D-galactopyranosyl unit with few side chains in form of singly branched galactopyranose units. These are linked at C1, C3, and C6 positions while double branches are attached to the C1, C3, C4, and C6 positions of the main chain. A single side unit chain of uronic acid is also attached to the C3 unit of this galactose residue [13–15]. These branched arabinose

196

S. Mishra et al.

Fig. 1 Chemical structure of Moi gum

units are attached to the main chain at C1, C3, and C5 positions [14, 15]. This is represented as a chemical structure in Fig. 1. Certain studies report the molecular weight of Moi gum to be around 1.68
105 Kda as determined by the static light scattering method [15]. If we try to compare it with other contemporary gums, it is somewhat chemically similar to inulin because of the presence of β -type glycoside linkages [16]. This background information about the structural linkage and molecular weight makes it possible to modify it for better-suited applications. The presence of many hydroxyl and carboxylic groups in the gum polysaccharides enhances their chances of being modified and better suited toward desired applications in miscellaneous ways.

1.2

Plant Description

Scientific name: Family: Order Genus Species Vernacular names:

1.3

Lannea coromandelica (Houttuyn) Merrill Anacardiaceae (Spondiadae) Sapindales Lannae L. coromandelica Indian ash tree, Wodier, Moi, Joel, Moi, Mohin

Biology, Habitat, and Uses of Moi Tree

Moi tree is also called by various common/vernacular names like Moi, Wodier, or better known as Indian ash tree. It is a deciduous tree found in the Indian subcontinent, including Pakistan, Bangladesh as well as in many regions of the African subcontinent. There are accounts of information in traditional practices which suggest its use in the treatment of many ailments like impotence, vaginal infections, ulcers, heart disease, dysentery, etc. [17, 18]. Plant leaves are also used for the treatment of injuries, cuts, wounds, hematochezia, and other skin infections [19, 20]. Leaf and flower have quercetin-3-arabinoside and ellagic acid constituents which are beneficial for some such kinds of treatments [21]. Leaves also contain compounds like leucocyanidin, leucodelphinidin, polyphenols, flavonoids, tannin, quercetin, and rutin [22, 23]. The whole plant parts are also used in conventional medicinal practices like plant twigs as tooth stick; bark boiled in water or as sap for treating

8

Chemistry, Biological Activities, and Uses of Moi Gum

197

skin diseases, dyspepsia, general debility, gout, dysentery [24–28], wounds, ulcers, sore eyes, tooth ache, and dental caries; and tender leaves and roots decoction for treatment of stomach ache [29]. The leaves are boiled in water to prepare a decoction or paste to be applied in local swelling and body ache [24]. This decoction or plant extract is also used in the treatment of high blood pressure and wound healing [25, 26]. Along with this, the bark is also claimed to be associated with hepatoprotective activity and used for liver treatment [30], which is attributed to the chemical constituent dihydroflavonols in it [31]. The presence and identification of terpenoids, flavonoids, polyphenols, and pigments/compounds like phlobatannins, β- sitosterol, physcion, physcionanthraxnol B, dl-epicatechin, and leucocyanidin attribute its antioxidant properties. Among other claims, a lotion made from the Moi bark is reported to be helpful in the treatment of even leprous ulcers [32, 33], which is an acute skin ailment. The heartwood of the plant contains leucocyanidin pigment in good amounts. The flowers also contain quercetin, quercetin-3-arabinoside, ellagic acid, marin, and isoquercetin. The fruit sap is used for the treatment of common cold and cough for gargling and inhalation. In addition to all this, the tree also contains some amounts of sterols [1]. So, to sum up the biological and pharmaceutical properties as reported in the literature, the Moi tree and its parts have the potential of antimicrobial, wound healing, and antiinflammatory [34] activities. In local instances which being documented and largely undocumented, it is used for the treatment of general debility, dyspepsia, dysentery, cholera, diarrhea, ulcers [35], sore eyes, bruises, skin infections, leprosy, sprains, tooth-related diseases, and elephantiasis [36]. Overall, the tree seems to have a very good source of bark gum exudate from the plant. This gum extracted from the plant is like a resource that can be used in the treatment of many ailments as discussed here. Even, some reports suggest its use for cancer treatment [37]. Some reports also refer to antineoplastic property but no clinical trials have been conducted for it [38, 39].

2

Modifications of a Polysaccharide Gum

In order to improve the function of polysaccharides, any kind of modification or copolymerization is carried out. This allows the incorporation of the desired amount of different monomers or other substituents in the copolymer. This can vary according to the nature and concentration of the monomer units. Graft copolymers are synthesized by adding a monomer to a preexisting different polymer backbone chain. Grafting yields a newly formed polymer with desirable properties of the base polymer and new properties of incorporated monomer in the newly grafted polymer. There are various methods to attain grafting, such as (1) chemical/conventional technique [40–42], (2) radiation-induced technique, (3) high-energy radiation technique [43], (4) UV radiation technique [44, 45], and (5) microwave radiation technique (Scheme 1). Conventional method: Conventional method of synthesis relies on free radical initiators such as redox reagents (Fenton’s reagent (Fe+2/H2O2), persulphate, and

198

S. Mishra et al.

Scheme 1 Schematic diagram depicting various techniques for copolymerization synthesis

peroxides) [46–48]. However, this method has low reproducibility, is time consuming, requires an inert atmosphere, and is not suitable for commercial-scale graft copolymer synthesis [48]. Radiation-based modifications: Recently, in the past two decades, new methods have been explored for graft copolymerization techniques. Advancement in these has been radiation-induced grafting. The excited electrons by these radiations have sufficient energy to cause chemical bonds to cleave and give way for the initiationpropagation-termination type of radical polymerization phenomenon [41]. Grafting by high-energy radiations: High-energy radiations have been explored for graft polymerization in the 1960s and they have continued to attract tremendous interest in search of easy and reproducible polymerization techniques. The main source of high-energy radiation is γ rays and ion beams. As radiation bombards the macromolecules, it produces free radicals, cations, and anions which make it pass through any one of these pathways [49]. Yet, this method is not deemed suitable for graft copolymerization synthesis reactions because of its extremely high energy. The impact of this high-energy radiation often damages the polysaccharide backbone called radiolysis of the backbone [50–55]. Still, it can be used in the case of fluropolymers which are otherwise difficult to work with due to their exceptional high stability [56–64]. UV-radiation-induced grafting: UV radiations are unable to penetrate deep into solutions. Hence, in presence of a suitable photosensitizer, a UV radiation source can also be utilized to initiate grafting reactions. Yet, UV rays have low penetration which makes them the right medium for localized surface grafting [65]. Microwave radiation–induced grafting: However, the most efficient technique often employed is microwave radiation. Microwave radiation lies in the frequency range of 0.3–300GHz. The technique employed “selective excitation” of polar bonds of the medium which come under restricted rotation. This kind of restricted rotation leads to the rupture or cleavage from the sites which experience this tension and lead to the formation of free radicals at various places along with the backbone polymer.

8

Chemistry, Biological Activities, and Uses of Moi Gum

199

Since the “C– C” backbone of the main polymer, Moi gum, in this case, is nonpolar, it remains inert to microwave irradiation. Therefore, microwave radiation–based grafting reactions have the virtues of being fast, highly reproducible, and give the desired percentage of grafting [66, 67]. Based upon the type and time of exposure, microwave irradiation–based synthesis is classified into two types, i.e., (1) microwave-initiated synthesis and (2) microwave-assisted synthesis. Microwave-initiated technique employs microwave irradiation alone as a means for grafting. It excludes the use of any other agent in this process. This process is suitable and highly reproducible for the synthesis of graft copolymers. It is proved that by using this method control and reproducibility of percentage grafting can be achieved which may lead to its possibility of commercialization [68]. In microwave-assisted technique the use of a free radical initiator is carried out. This method yields a higher percentage of grafting than microwave-initiated and conventional synthesis. The product synthesized adopting this technique increases in hydrodynamic volume and decreases insolubility of the macromolecule. Here, we are discussing the applications of Moi gum in two applications: 1. Development of Moi gum–based hydrogel and its applications in dye removal for environmental remediation. 2. Applications of Moi gum matrices for nutrient release studies for agricultural applications.

3

Development of Moi Gum–Based Hydrogel and its Applications in Dye Removal for Environmental Remediation

3.1

Synthesis of Moi Gum Hydrogel and Experimental Plan

Moi gum hydrogel (Moi-g-PAM-cl-NN’MBA) was synthesized by using microwave-assisted technique [69, 70], with acrylamide (AM) monomer, NN’methylenebisacrylamide (NN’MBA) cross-linker, and ceric ammonium nitrate (CAN) chemical-free radical initiator. The synthesized hydrogel was kept in acetone for 72 hours [71], dried, sieved, and characterized through various analytical techniques. Characterization The determination of the contents of C, H, N, and O percentage in crude Moi gum and product hydrogel (Moi-g-PAM-cl-NN’MBA) was carried out by elemental analyzer (Make –M/s Elementar, model: Vario EL III, Germany). FTIR analysis was done by FTIR spectrophotometer (Make –Shimadzu Corporation, Model: IRPrestige21, Japan). Analysis conditions: 400–4000 cm1, 4 cm1 resolution by standard KBr pellet method. The XRD phase identification was done by using Cu Kα radiation and scan range of 10–80 2θ (Make: Bruker axis diffractometer Model: D8-Advance).

200

S. Mishra et al.

Adsorption Experiments Factors Affecting Adsorption An adsorption study was conducted adopting the batch equilibrium technique. It was optimized in terms of many factors like dye concentration (5–80 mg/L), adsorbent dose (0.1–0.8 g), pH (2.5–12), agitation time (60–600 minutes), and temperature (10–55  C). The concentration of dye concerning all these parameters after adsorption was measured by UV-VIS (model: Cecil Aquarius CE 7200 Double Beam) at λmax626 nm [72]. The standard calibration curve of BG dye (1-80 mg/L) was prepared and percent adsorption and equilibrium capacity of dye “qe” (mg/L) were determined by the following equation [73, 74]:

% Dye removal efficiency ð% adsorptionÞ ¼

qe ¼

ðCo  Ce ÞV m

ðCo  Ce Þ
100 Co

ð1Þ

ð2Þ

Co and Ce stand for initial and equilibrium dye concentration (mg/L), respectively, V is dye volume (L), and “m” is dosage adsorbent (g). Adsorption Isotherms These are the standard models to express the interdependence and extent of interaction between adsorbates with adsorbents [75]. A preoptimized dosage of 0.6 g of adsorbent was taken and added to 100 ml of dye at a concentration range of 5–60 mg/L at different temperatures (25  C, 35  C, and 45  C) and optimized pH conditions. The solution was vigorously agitated in an incubator shaker (model: GeNei™) for 420 minutes. Equilibrium adsorption (qe)/unit mass of adsorbent (mg/g) was calculated and finally fitted for Langmuir, Freundlich, and Temkin isotherm models. Langmuir Isotherm This model is applicable in conditions where a monolayer is formed at equilibrium between the adsorbate and adsorbent and the adsorbed molecules do not interact. The linear formula representing this model is given [76] as: Ce 1 C ¼ þ e qe Qm K L Qm

ð3Þ

The plot of Ce/qe vs Ce helps to determine the values of Qm (maximum adsorption capacity) and KL (Langmuir constant) and RL (separation factor) being calculated by the equation given below: RL ¼

1 1 þ K L Co

ð4Þ

8

Chemistry, Biological Activities, and Uses of Moi Gum

201

RL value gives the feasibility of this model. If RL > 1, it gives an unfavorable isotherm; for RL ¼ 1, linear isotherm is applicable, but in case RL ¼ 0, the isotherm becomes irreversible. In case RL values lies between 0 and 1 range (0 < RL < 1), the model is considered favorable [77]. Freundlich Isotherm This isotherm is applicable on the assumption that adsorption is being carried upon the heterogeneous adsorbent surface. Its equation is given as [78]: log qe ¼ log kF þ

1 log Ce n

ð5Þ

The plot log qe vs log Ce gives KF (Freundlich constant or adsorption capacity) and the “n.” “n” value indicates heterogeneity of adsorption reaction. If the “n” value lies in the 0–10 range value, adsorption is considered favorable. The higher “n” value means stronger adsorption intensity [79]. Temkin Isotherm The linear equation for the Temkin isotherm model is represented as [80, 81]: qe ¼ Bt ln ðK T Þ þ Bt ln ðCe Þ

ð6Þ

BT (Temkin constant as given by heat of adsorption) and KT (equilibrium constant) values were calculated from the qe vs lnCe plot. Adsorption Kinetics The experiment to determine adsorption kinetics was carried out by adding 0.6 g of adsorbent into a known concentration of dye solution (10 mg/L) in a 100 ml glass beaker. Adsorption was carried out in an incubator shaker rotating at 120 rpm at a normal room temperature of 25  C. The value of qt was calculated by the equation [78]: qt ¼

ðCo  Ct ÞV m

ð7Þ

where qt is the dye adsorbed per unit mass of adsorbent at any given time “t” and Ct is the concentration of dye (mg L1). The data were fitted to various kinetic equations as discussed below: Pseudo-First-Order Kinetics The linear equation for this model is given as [82]: log ðqe  qt Þ ¼ log qe 

K1t 2:303

ð8Þ

The rate constant (K1) and qe values were calculated from the ln (qe-qt) vs “t” plot.

202

S. Mishra et al.

Pseudo-Second-Order Kinetics The equation for this model is given as [83]: t 1 t ¼ þ qt k2 q2e qe

ð9Þ

The rate constant (k2) and qe values were calculated from the linear plot of t/qt vs t. Intraparticle Diffusion Model This model explains the diffusion mechanism involved during the entire sorption process. This model is based on the assumption that qt is dependent on t0.5 and not on contact time (t) as given by this equation below [84]: qt ¼ K diff t0:5 þ C

ð10Þ

The plot of qt vs t0.5 gave the value diffusion rate constant “kdif” and thickness of the boundary layer “C” [85]. Elovich Model The equation for this model is given below as follows: [86]

qt ¼

ln ðαβÞ ln ðtÞ þ β β

ð11Þ

Here, α is the initial sorption rate and β is the desorption constant which depends on the extent of surface covered and activation energy involved in the sorption process. The values of α and β are calculated by the plot of qt vs ln (t). This model describes pseudo-second-order kinetics and chemisorption [87] for heterogeneous adsorbing surface model [88]. Thermodynamic Properties The spontaneity and feasibility of the adsorption process were determined from the plot of log K0vs 1/T as given below [89]:

log K o ¼

ΔSo ΔH o  2:303 R 2:303 RT

ΔGo ¼ ΔH o  ΔTS o where K0 is Ce/qe and T is the temperature (Kelvin).

ð12Þ ð13Þ

8

Chemistry, Biological Activities, and Uses of Moi Gum

3.2

203

Biodegradation Study and Determination of Half-Life

Biodegradability is an important aspect for designing materials for water treatment and pharmaceutical formulation or any other such enterprise [90]. Therefore, modified polysaccharides are necessary because their mechanical properties are high and show better biodegradability than any other synthetic or native materials [91]. The biodegradability of the synthesized hydrogel was studied by measuring the weight loss in soil [92]. For this study, a fixed amount of hydrogel was put inside a 60-mesh nylon sieve bag and buried in the soil of desired thickness. The soil moisture content was maintained at one-third of its water retention capacity. The hydrogel sample was removed at fixed intervals, washed with water, and dried till constant weight was obtained [93]. The change in the surface morphology was recorded by SEM. Dry matter percentage of remaining hydrogel after every sampling period was determined using the formula: % DM remaining ¼

Weight of dry matter at particular period
100 ð14Þ Weight of initial matter

The decomposition rate constant (k) was determined by Olson single exponential model [94]: W t ¼ W o ekt

ð15Þ

It can be expressed as linear equation also: ln ½Wt ¼ kt þ ln ½Wo  where Wt ¼ weight after time (t), Wo ¼ initial dry matter, k ¼ decomposition rate constant, and t ¼ time. Half-life (t50) of hydrogel sample under decomposition was estimated by the formula: t50 ¼ 0.693/k.

4

Results and Discussion

4.1

Synthesis and Purification of Cross-Linked Moi Gum Hydrogel

Microwave-assisted technique was adopted for the synthesis of Moi gum hydrogel (Moi-g-PAM-cl-NN’MBA). In this method, 1 g Moi gum was added to 50 ml distilled water under continuous stirring conditions. Monomer acrylamide (7 g) was also added into the same solution and stirring continued. Then 0.01 g of initiator CAN and 0.01 g of cross-linker NN’MBA were added into the solution till a homogenized solution was obtained. This reaction beaker was kept in a microwave reactor to expose intermittent irradiation of 700 W (model: Catalyst TM system CATA 4 R) to it. This was stopped when a gel-like material was visible in the beaker at 70  C. This gel-like product was precipitated under excess acetone for 72 h to

204

S. Mishra et al.

eliminate the possibility of any competing homopolymer formation reaction [71]. After complete precipitation, the final product was collected, dried, and pulverized for further use. This aqueous microwave-based synthesis technique for polymer grafting reactions is effective and very convenient to carry out [95, 96]. The Mechanism Involved in the Synthesis of Cross-Linked Moi Gum Hydrogel Ceric ammonium nitrate is a free radical initiator. It gives Ce (IV) ions which can furnish free radicals on the -OH group by direct oxidation mechanism [96]. These free radicals are formed on the backbone of Moi gum and after this, an alkoxy radical is formed on the substrate with some active sites on which further monomer branches shall be attached. Thus, a free radical polymerization reaction is triggered via the initiation-propagation-termination route till a polyacrylamide-grafted free radical is formed which combines with NN’MBA to give a grafted cross-linked type of hydrogel. Another possible route might be through the bond formation of polyacrylamide-grafted Moi free radical and cross-linker by free radicals present on the backbone of Moi gum. Alternatively, Moi free radicals might react simultaneously with monomer and cross-linker to produce a grafted cross-linked hydrogel. All these possible routes of hydrogel synthesis are depicted in Scheme 2.

4.2

Characterization Results

Elemental Analysis Nitrogen was absent in crude Moi gum but it was present in a synthesized hydrogel which confirms grafting reaction. Though carbon, hydrogen and oxygen are present in 38.64%, 5.602%, and 54.54%, respectively, and nitrogen was absent in Moi gum, but their ratio changes to 42.23%, 6.023%, 35.54%, and 16.2%, respectively, in synthesized hydrogel (Moi-g-PAM-cl-NN’MBA). FTIR Moi gum spectra (Fig. 2a) showed peaks at 3309 cm1and 2947 cm1 due to O-H and C-H stretching, respectively. The peak at 1068 cm1 and 1600 cm1 were by C-O-C stretching vibrations and O-H bending mode [97]. The peak at 1419 cm1 was due to carbonyl stretching of glucuronic acids. For hydrogel spectrum, 3309 cm1 peak (O-H stretching) was reduced and shifted to 3350 cm1. This confirms the involvement of the hydroxyl group in covalent bond formation with NN’MBA. Absorption bands at 1600 (H-O-H bending) present in Moi gum also got vanished. Two peaks at 1323 cm1 and 1689 cm1 were due to C¼N and C¼O stretching, respectively. A new 660 cm1 peak was found in the hydrogel spectrum due to the wagging vibration of N-H and NH2 (hydrogen bonded) [98] which was absent in Moi gum. Qualitative X-Ray Diffractometry XRD analysis (Fig. 2b) shows that Moi gum was slightly crystalline with three crystalline peaks in the 2θ range of 9.6 , 19.16 , and 43.29 , respectively due to the

8

Chemistry, Biological Activities, and Uses of Moi Gum

205

Scheme 2 The proposed mechanism involved in microwave-assisted synthesis of Moi-g-PAM-clNN’MBA

a

b

Fig. 2 (a) FTIR spectra and (b) XRD pattern of crude Moi gum and hydrogel (Moi-g-PAM-clNN’MBA)

206

S. Mishra et al.

intermolecular interaction of hydroxyl (OH) group. However, synthesized hydrogel displayed only one weak peak at 2θ values of 21.8. This confirmed that the crystalline structure was converted to an amorphous form, an indication of successful grafting.

4.3

Adsorption Experiments

Dye adsorption efficiency can be maximized by regulating certain parameters in the external or local environment. This may include concentration range of dye under test, a dose of adsorbent, medium, pH, temperature, the extent of adsorption, number of cycles, and others which may be optimized by investigating the role of each of these factors one by one first and then together as a system. So, the optimization of these parameters was carried out with all these parameters. Initial Dye Concentration A wide range (5–80 mg/L) of BG dye solutions was prepared and a fixed amount hydrogel dose was added to each of these solutions. Adsorption studies were carried out at 120 rpm in an incubator shaker (model: GeNei™) at normal room temperature. No other parameter was altered, pH was also the same as the prepared dye solution. Adsorption decreased progressively from lower to higher concentration. This was due to less concentration of dye molecules concerning available adsorption sites and hence adsorption could occur at its pace. However, as the dye concentration increased, active sites of hydrogel were already occupied by dye adsorption which decreased dye removal efficiency by hydrogel [99]. This is also presented in Fig. 3a. Adsorbent Amount Fig. 3b shows the effect of adsorbent amount on the adsorption of the dye. This was optimized by taking a varying dose of adsorbent from 0.1 to 0.8 g. Initially, the adsorption efficiency increased with the increase in adsorbent dose up to a certain extent. Once an optimized dose was reached (0.6 g/100 ml), the efficiency remained constant with no change even when the adsorbent dosage was increased. This may be due to the agglomeration of hydrogel without any change in its previous surface area [100, 101]. The pH of the Medium pH is an important parameter while optimizing adsorbent dosage and dye removal efficiency. So, dye samples were prepared covering a broad pH range from acidic to alkaline solutions. Different pH solutions were prepared using 0.1 M NaOH and 0.1 M HCl. pH was measured using a pH meter (model: Orion 920A) for all the solutions. An amount of 0.6 g of fixed adsorbent was added to each of the solutions at room temperature. After comparing dye removal at all pH, it was found that slightly alkaline pH (8.3) gave the best results for dye removal.

8

Chemistry, Biological Activities, and Uses of Moi Gum

a

b

d

207

c

e

Fig. 3 (a-e) Various factors effecting adsorption of BG dye from aqueous solution onto the hydrogel

This may be due to the repulsion of H+ ions in an acidic medium with ¼ N+ dye moiety which reduces adsorption. At alkaline pH, carboxylic groups are present as carboxylate ions (-COO) which are attracted to ¼ N+ moiety and get drawn toward it [102]. Other available reports also suggest the same [103–105] about the removal of cationic dyes in alkaline pH conditions. Agitation Time The dye solutions were subjected to vigorous agitation at room temperature at the varying time (1–10 h) in incubator shaker (model: GeNei™). Initially, adsorption increased and settled down later. This may be due to more available vacant sites initially which might have filled as time elapsed. Also, the repulsion chances of the liquid phase and solute molecules may be there [79]. Finally, time was optimized to 420 minutes (7 h) as shown in Fig. 3d. Temperature Adsorption studies were carried out in different temperature range of 10  C, 15  C, 25  C, 37  C, 45  C, and 55  C under preoptimized dose, dye concentration, and agitation time. The adsorption process improved with rising in temperature (Fig. 3e). The temperature rise contributed to the interaction of dye molecules with active

208

S. Mishra et al.

adsorbent sites [106]. Also, the viscosity decreased with temperature increasing the diffusion process [107]. Adsorption Isotherms Calculated values of various isotherms parameters are given in Table 1. The value of Qm (monolayer adsorption capacity at equilibrium) of Langmuir isotherm was found to increase from 4.99 to 7.75 as we move from 25o–45  C. This suggested that higher temperature favored more dye adsorption. The calculated RL value falls within the 0–1 range satisfying the model. The high correlation coefficient (R2) of Langmuir isotherm in all the temperatures studied indicated the applicability of the model. This means monolayer adsorption was favorable. As for the Freundlich isotherm, the KF value was found to be within the range of 2.26–2.69. The “n” value greater than unity in all the cases suggested the applicability of the model. The higher R2 value of Freundlich recommended that adsorption fit best with the model. Therefore, it could be proposed that heterogeneous and multilayer adsorption was the dominant mode of the sorption process [108]. The value of Bt (Temkin constant) was found to increase from 2.74 to 3.11 as temperature increased from 25o–45  C. The low R2 value does not give much information about the adsorption process. Of all the models, Temkin fits poorest whereas Freundlich model fits best in explaining the adsorption process. The same type of conclusion has been reported by many researchers using decomposable organic material and natural plant exudate-based hydrogel [103, 104]. Contrary to the present finding, results in favor of the Langmuir model have also been reported using activated carbon and modified chitosan as adsorbents [109]. Adsorption Kinetics Table 2 presents all the values of kinetic parameters. The correlation coefficient (R2) helps to explain the best adsorption. The rate constant for pseudo-first-order kinetics was found to be 7
103(min1) with an R2 value of 0.9649. For pseudo-secondTable 1 Calculated values of Langmuir, Freundlich, and Temkin model parameters in different temperature Langmuir

Freundlich

Temkin

Parameters Qm(mg/g) KL(L mg1) RL R2 KF (mg g1) N R2 Bt (J/mol) KT (L mg1) R2

25  C 4.99 0.55 0.002–0.038 0.993 2.26 2.82 0.996 2.74 1.69 0.9068

37  C 7.42 0.194 0.002–0.026 0.997 2.57 2.43 0.997 2.83 1.811 0.9253

45  C 7.75 0.08 0.001–0.025 0.998 2.69 2.32 0.999 3.11 1.83 0.9415

8

Chemistry, Biological Activities, and Uses of Moi Gum

209

Table 2 Comparison of various kinetic parameters governing adsorption of BG dye onto Moi gum hydrogel: pseudo-first-order, pseudo-second-order, Weber-Morris, and Elovich models Model Pseudo-first order Pseudo-second order Elovich Weber-Morris

Isotherm constant KI (min1) 7 x 103 K2(g mg1 min1) 8 x 104 α(mgg1 min1) 19.49 Kdiff (mg/(gmin0.5) 0.089

qe(cal) 2.35 qe(cal) 3.14 β(g mg1) 1.64 C 0.205

R2 0.9649 R2 0.9968, R2 0.9956 R2 0.9362

order kinetic, the rate constant was found to be 8
104 (g mg1 min1) with an R2 value of 0.9968. Thus, a high R2 value with pseudo-second-order kinetics is the best fit to explain the adsorption of BG dye onto Moi gum hydrogel. Therefore, ionic dye groups interact with hydrogel sites to yield maximum adsorption [110]. As for the intraparticle diffusion model, the R2 value of 0.9362 with 0.205 intercept gives boundary layer thickness. Thus, intraparticle diffusion model chemical interaction and pore diffusion together lead to adsorption. The high correlation coefficient of the Elovich model (R2 > 0.99) hints toward diffusion being a dominating factor for adsorption [111] with pseudo-second-order kinetics for heterogeneous surfaces [87, 88, 112]. Thermodynamic Properties Table 3 shows factors effecting BG dye adsorption. The value of ΔH0 was found to be 6.68 kJmol1. Positive ΔH0 suggests an endothermic process, appreciable at high temperature, as confirmed in this study. The negative value ΔS0 suggested that there was a decrease in randomness at the solid-liquid interface. Similar results have been reported by many researchers working in azo dyes [113, 114]. The positive value of ΔG which increased from 30.86 to 32.58 kJmol1as temperature increased suggested favorable adsorption at higher temperature and nonspontaneous nature. Contrary to the present finding, an exothermic process has been reported using activated carbon [115]. Therefore, it can be concluded that the adsorption process was not governed by the dye itself but depends on the nature of the adsorbent.

4.4

Biodegradation Study and Calculation of Half-Life

The two-phase biodegradation curve is shown in Fig. 4a. The first phase has slow degradation with 6% weight loss in 30 days. This may be due to water absorption which makes anaerobic conditions not suitable for microorganisms [116]. The second phase of 30–180 days witnesses rapid breakdown of the hydrogel by microbial activities, leaching, and other factors. This was confirmed from SEM

210

S. Mishra et al.

Table 3 Calculated values of different thermodynamic constants Temperature (K) 298 310 318

a

ΔGo(kJmol1) 30.86 31.82 32.58

ΔHo(kJmol1) 6.68

ΔSo(kJK1 mol1) 0.0811

R2 0.994

b

Fig. 4 (a) Decay curve of Moi-g-PAM-cl-NN’MBA in the soil and (b) SEM analysis buried under soil after 30 days

studies (Fig. 4b) that the surface of hydrogel left extensive signs of erosion and broken structure. The value of the decomposition rate constant (k) was calculated to be 0.0123. And the half-life was found to be 56 days.

5

Applications of Moi Gum Matrices for Nutrient Release Studies for Agricultural Applications

Moi Hydrogel for Controlled Release of Boron and Zinc Micronutrients Proper crop nutrition management is extremely important for the maximum yield of the crops. It is necessary to understand what the plant needs under different conditions. After all, without proper management of essential nutrients, there would not be any yields. Plant nutrients are broadly classified as macronutrients and micronutrients based on the requirement of the plant [117] (Table 4). In this regard, micronutrients are often neglected and in many cases, the crop yield can be hampered without timely intervention. Their requisite presence is indispensable for plant growth and cannot be compensated by any other nutrient [118]. One micronutrient

8

Chemistry, Biological Activities, and Uses of Moi Gum

211

Table 4 List of essential macro- and micronutrients [117] Essential plant nutrients Primary macronutrients Nitrogen (N) Phosphorus (P) Potassium (K)

Secondary macronutrient Calcium (Ca) Magnesium (Mg) Sulphur (S)

Micronutrients Boron (B) Zinc (Zn) Iron (Fe) Manganese (Mn) Copper (Cu) Molybdenum (Mo) Chlorine (Cl)

that has a profound role in the plant is boron which has an integral role in cell wall synthesis and in maintaining structural integrity. Plants take up boron in the form of small uncharged boric acid (H3BO3) or B(OH)3 [119, 120]. About 50% of the world’s potentially arable soils are acidic. In such soils, deficiencies of anionic plant nutrients boron (B) through fixation and leaching are foremost factors limiting crop production. Boron deficiency also leads to considerable yield reduction in many annual, cereal, legume/pulse, oilseeds, and perennial crops [121, 122]. Zinc is another essential micronutrient that is necessary for plant growth and development. Zinc is present in many forms: as a free ion, incorporated in complex form, and as part of proteins, enzymes, or other bioinorganic molecules. Its role may be to regulate structural and functional features as a supporting cofactor in enzymes. These features may be responsible for gene expression control, maintaining RNA and DNA structure, as well as regulation of DNA synthesizing enzymes and RNA degrading enzymes [123]. In general, Zn-deficient plants are more susceptible to diseases [124, 125]. Globally zinc and boron are classified as one of the most major nutrient deficiencies in the soil [126]. It is necessary to supplement them externally. Furthermore, the presence of one element can impede the availability of other elements or have a synergistic effect. It is therefore essential to know the antagonism-synergism effect of various elements while formulating fertilizers or micronutrients. Based on Mulder’s chart [127] it is unlikely that B and Zn would have antagonism-synergism interaction when they are applied together. Control release formulation (CRF) is widely used in agriculture applications. This can deliver nutrients to plant at desire dosage and rates over an extended period [92, 128–130]. The best approach is through matrix formulation in which plant nutrients are dispersed in the matrix and diffused through pores or channels. Hydrogels because of their excellent properties have been used for the controlled release of nutrients and fertilizers in the field of agriculture [131, 132]. In this study, we prepared a controlled release formulation of micronutrients, boron, and zinc using the Moi hydrogel grades (Moi-g-AM-cl-NN’MBAs). The whole experimental setup is depicted in Scheme 3.

212

S. Mishra et al.

Scheme 3 Steps involved in nutrient release study in water and soil

Table 5 Synthesis of different grades of Moi hydrogel (Moi-g-AM-cl-NN’MBA) Grades Moi-g-AM-cl-NN’MBA 1 Moi-g-AM-cl-NN’MBA 2 Moi-g-AM-cl-NN’MBA 3 Moi-g-AM-cl-NN’MBA 4 Moi-g-AM-cl-NN’MBA 5

5.1

Amount of monomer (g) 5 5 5 5 5

Amount of cross-linker (g) 0.1 0.2 0.3 0.4 0.5

Synthesis of Micronutrients-Loaded Hydrogel

In situ incorporation of boric acid (H3BO3) and zinc sulphate (Zn2SO4) in Moi gum solution and reacting with other reagents (acrylamide monomer, NN’MBA-crosslinker, and CAN initiator) yielded hydrogel with uniformly distributed B and Zn throughout the gel network. Table 5 shows different hydrogel grades.

8

Chemistry, Biological Activities, and Uses of Moi Gum

213

Fig. 5 Standard calibration curve of boron and zinc

Release Study Nutrient release study of B and Zn in water at 25  C was done following USP drug dissolution study protocol [131]. Release studies were carried out using two different experimental sets: continuous releasing in water and soil. The number of micronutrients released from hydrogel in the water was determined using an atomic UV-VIS spectrophotometer at λmax ¼ 430 nm for zinc [132] and 420 nm for boron [133], respectively (Fig. 5). The cumulative release (%) was calculated as [134]:

Cumulative releaseð%Þ ¼

Mt
100 M1

ð16Þ

where Mt and M1 are the amounts of micronutrients released at time t and initial loaded micronutrient contents, respectively. A released study was also performed in the soil to see its application in the field of agriculture. For this hydrogel was put into permeable tea pouches which were buried in a plastic beaker containing 200 g of dry soil at 2.0 cm depth. Then, 150 mL of distilled water was added to each beaker and kept at room temperature. One package was removed every day after every 24 h (1 day). The hydrogel was put in 100 mL distilled water. The number of micronutrients extracted from the hydrogel into the water was estimated by UV-VIS spectrophotometer using the above Eq. (16). Thus, the number of released micronutrients into the soil was calculated using Eq. 16 [134, 135]. Kinetic Study Similarly, the drug release kinetics in water was determined using the well-known equation [136, 137]:

214

S. Mishra et al.

Mt ¼ k  tn M1

ð17Þ

where Mt, is the amount of micronutrient release at time “t” and M1 initial loaded micronutrient contents, respectively. And k is releasing factor describing the type of diffusion. The above equation can be linearized as [136, 137]: log

Mt ¼ log k þ n log t M1

ð18Þ

where n, k, and R2values are obtained from log (Mt/M1) vs log (t) plots for all matrix tablets. The Eq. (18) holds only when 60% of drug release occurs from the tablet Mt/M1  0.6; log Mt/M1  0.22 [138]. If the calculated “n” value is less than 0.5, then the release pattern follows Fickian diffusion where diffusion is less relaxed [139]. If “n” is between 0.5 and 1.0, it is non-Fickian diffusion (same diffusion and relaxation rate) [139]. For “n” ¼ 1, the diffusion is zero-order kinetics for most erosion-prone matrices.

5.2

Results and Discussions

Release Behavior Figure 6a and b represent the release behavior of the B and Zn micronutrient in water from various hydrogel grades. It was observed that the cumulative release of B from

a

b

Fig. 6 (a) Release pattern of boron and (b) zinc micronutrients from hydrogel (Moi-g-AM-clNN’MBAs) in water

8

Chemistry, Biological Activities, and Uses of Moi Gum

215

hydrogel grades was 51–58% during 3 days. In the case of Zn, the cumulative release was found to be 59–68% during 3 days. The low release of born was due to low solubility of boric acid (5.7 g/100 ml at 25  C) in water when compared with zinc whose solubility is higher (57.7 g/100 ml at 25  C). Furthermore, the release rates of all hydrogels were increased regularly and then became more or less constant after 54 hrs in both cases. It was also observed that cross-linking density which increased with an increase in cross-linker in the hydrogel also affects the release rate. The release behavior of boron and zinc from hydrogel into the soil is shown in Fig. 7a and b. The cumulative release of boron into the soil ranges from 62% to 74% for all the grades for 8 days beyond which the release is constant. It is also possible that a small fraction of boron (H3BO3 and H2BO3) is fixed on soil colloid either physically or chemically [140, 141]. In the case of zinc, it was found to be 52–58% for 8 days beyond which the release was more or less constant. The cumulative release of zinc was far lower than boron because zinc (II) cations are strongly adsorbed by negative clay colloids [132]. Kinetic Study The diffusion exponent “n” and diffusion constant “k” of boron and zinc release from hydrogels in water and soil are given in Table 6. It was observed that the value of “n” for boron was all less than 0.5. This indicates that Moi-g-AM-cl-NN’MBAs hydrogel follows Fickian release behavior. This means the nutrient release in the hydrogel is predominantly controlled by the rate of relaxation of the hydrogel while diffusion is the secondary means of nutrient release [138]. Furthermore, it was observed that the half-life is dependent on cross-linking density which was highest for Moi-g-AM-cl-NN’MBA 5 (t50 ¼ 62 h).

a

b

Fig. 7 (a) Release pattern of boron and (b) zinc micronutrients from hydrogel (Moi-g-AM-clNN’MBAs) in the soil

216 Table 6 Calculated values of different parameters of boron release kinetic in water and soil with T50 (half-life)

S. Mishra et al.

Boron release kinetic profile in water Grades n k Half-life (hrs) Moi-g-AM-cl-NN’MBA 1 0.225 0.218 39 Moi-g-AM-cl-NN’MBA 2 0.231 0.21 42 Moi-g-AM-cl-NN’MBA 3 0.245 0.194 46 Moi-g-AM-cl-NN’MBA 4 0.255 0.179 48 Moi-g-AM-cl-NN’MBA 5 0.265 0.167 62 Zinc release kinetic profile in water Moi-g-AM-cl-NN’MBA 1 0.342 0.162 27 Moi-g-AM-cl-NN’MBA 2 0.360 0.147 30 Moi-g-AM-cl-NN’MBA 3 0.381 0.132 34 Moi-g-AM-cl-NN’MBA 4 0.401 0.118 38 Moi-g-AM-cl-NN’MBA 5 0.408 0.106 43 Boron release kinetic profile in soil (half-life in days) Moi-g-AM-cl-NN’MBA 1 0.54 0.158 5.2 Moi-g-AM-cl-NN’MBA 2 0.56 0.162 5.6 Moi-g-AM-cl-NN’MBA 3 0.58 0.177 5.9 Moi-g-AM-cl-NN’MBA 4 0.59 0.197 6.2 Moi-g-AM-cl-NN’MBA 5 0.63 0.204 6.5 Zinc release kinetic profile in soil (half-life in days) Moi-g-AM-cl-NN’MBA 1 0.51 0.19 5.5 Moi-g-AM-cl-NN’MBA 2 0.54 0.169 5.9 Moi-g-AM-cl-NN’MBA 3 0.71 0.117 6.4 Moi-g-AM-cl-NN’MBA 4 0.85 0.077 6.9 Moi-g-AM-cl-NN’MBA 5 0.98 0.052 8.3

Fig. 8 SEM image for modification of hydrogel

Likewise, the kinetic release of boron and zinc in the soil revealed “n” values to be higher than 0.5. This means both boron and zinc follow a non-Fickian mechanism in the soil which means the rate release is controlled by diffusion and relaxation of the hydrogel. The half-life was found to be 5.2–6.5 days in boron and 5.5–8.3 days in zinc. Thus, it can be said that for all the hydrogel grades, the total cumulative release

8

Chemistry, Biological Activities, and Uses of Moi Gum

217

value in water is far higher than in soil [142, 143]. In the soil, the nutrients are released from hydrogel when hydrogel got swollen by soil solution [144, 145]. The solution, then, dissolves the soluble part of the nutrient, and the nutrient molecules slowly diffuse through the hydrogel pores and release into the soil. This is also evidenced from SEM analysis of hydrogel before and after incorporation in the soil (Fig. 8a, b). After three days of burial in the soil, the hydrogel displayed structural changes with numerous pores where micronutrients diffused which is visible when magnified.

6

Conclusion

Moi gum cross-linked hydrogel (Moi-g-PAM-cl-NN’MBA) was synthesized using NN’MBA as a cross-linker through microwave-assisted technique. The synthesized hydrogel was characterized by analytical techniques. Adsorption isotherm and kinetics studies reveal that experimental data were best fitted to the Freundlich model (R2 > 0.99) and pseudo-second-order kinetic. The adsorption process was found to be endothermic and nonspontaneous with decreasing entropy. Moreover, the hydrogel was found to degrade 88% in 180 days with a half-life of 56 days. The overall study indicates that synthesized hydrogel can be employed for remediation of anionic BG dye on a large scale. The rate of release of zinc is faster than boron in water as zinc sulphate is more soluble than boric acid. It was observed that cross-linking density affects the release rate in all the cases. The kinetics study suggested that the release of boron and zinc follows the Fickian mechanism in water where nutrient release is largely controlled by relaxation of the hydrogel. However, in the soil, it follows a non-Fickian mechanism where release rate is controlled by relaxation of hydrogel and diffusion method. Overall, it can be concluded that based upon the chemical and biological properties of Moi gum, it can be used for many applications. It is low cost, nontoxic, easily available, easily modifiable, and it can be further explored in many applications of miscellaneous nature to suit our various requirements.

References 1. Reddy AK, Jyothi MJ, Ashok Kumara CK (2011) Lannea coromandelica the Researcher’s tree. J Pharm Res 4(3):577–579 2. Samanta A, Ojha D, Mukherjee B (2010) Stability analysis of primary emulsion using a new emulsifying agent gum Odina. Nat Sci 2(5):494–505 3. Mate CJ, Mishra S (2020) Exploring the potential of Moi Gum for diverse applications: a review. J Polym Environ 28(6):1579–1591 4. Mate CJ, Mishra S, Srivastava PK (2020) In vitro release kinetics of graft matrices from Lannea coromandelica (Houtt) gum for treatment of colonic diseases by 5-ASA. Int J Biol Macromol 149:908–920

218

S. Mishra et al.

5. Nayak BS, Nayak UK, Balakrishna PK, Kumar RP (2008) Preparation and in vitro evaluation of lamivudine entrapped MOI microspheres for oral administration. Res J Pharm Technol 1: 437–441 6. Sowdhamini VURM, Sirisha B, Pratyusha A (2015) An overview on natural polymers as pharmaceutical excipient. Intercont J Pharm Investig Res 2:35–48 7. Venkaiah K, Shah JJ (1984) Distribution, development and structure of gum ducts in Lannea coromandelica (Houtt.) merril. Ann Bot 54:175–186 8. Roy PS, Samanta A, Mukherjee M, Roy B, Mukherjee A (2013) Designing novel pH-induced chitosangum Odina complex Coacervates for colon targeting. Ind Eng Chem Res 52: 15728–15745 9. Aditya KJ, Mousumi D, Arnab DE, Samanta A (2014) Determination of efficacy of a natural tablet binder: characterization and invitro release study. Asian J Pharm Clin Res 7(3):164–168 10. Perez S, Mazeau K, Herve du Penhoat C (2000) The three-dimensional structures of the pectic polysaccharides. Plant Physiol Biochem 38:37–55 11. Verbeken D, Dierckx S, Dewettinck K (2003) Exudate gums: occurrence, production, and applications. Appl Microbiol Biotechnol 63:10–21 12. Anderson DMW, Stoddart JF (1996) Studies on uronic acid materials. Carbohydr Res 2: 104–114 13. Mate CJ, Mishra S, Srivastava PK (2020) Design of low-cost Jhingan gum-based flocculant for remediation of wastewater: flocculation and biodegradation studies. Int J Environ Sci Technol 17:2545–2562 14. Bhattacharyya AK, Rao CVN (1964) Gum Jeol: the structure of the degraded gum derived from it. Can J Chem 42:107–112 15. Bhattacharyya AK, Mukherjee AK (1964) Structural studies of the Gum Jeol polysscahrides. Bull Chem Soc Jpn 37(10):1425–1429 16. Nair KK, Kharb S, Thompkinson DK (2010) Inulin dietary fiber with functional and health attributes—a review. Food Rev Int 26:189–203 17. Duppala L, Hema Naga Durga D, Ramana Murthy KV (2017) Physico-chemical and microbial studies of Lannea gum. Int Res J Pharm 8(4):50–58 18. Yusuf M, Choudhury JU, Wahab MA, Begum J (1994) Medicinal plants of Bangladesh, Bangladesh Centre for Scientific and Industrial Research, Dhaka, Bangladesh, p 146 19. Yusuf M, Begum J, Hoque MN, Chowdhury JU (2009) Medicinal plants of Bangladesh, vol 318. Bangladesh Council of Scientific and Industrial Research, Dhaka, pp 217–224 20. Zheng XL, Xing FW (2009) Ethnobotanical study on medicinal plants around Mt. Yinggeling, Hainan Island. China J Ethnopharm 124:197–210 21. Subramanian SS, Nair AGR (1971) Polyphenols of Lannea coromandelica. Phyto Chem 10: 1939–1940 22. Ghani A (2003) Medicinal plants of Bangladesh with chemical constituents and uses, 2nd edn. Asiatic Society of Bangladesh, Dhaka, p 274 23. Kantamreddi VSSN, Lakshmi YN, Kasapu VVVS (2010) Preliminary phytochemical analysis of some important Indian plant species. Int J Pharm Biol Sci:B358 24. Chopra RN, Nayar SL, Chopra IC (1956) Glossary of Indian medicinal plants. CSIR, New Delhi, (reprinted 1992) 25. Singh S, Singh GB (1996) Hypotensive activity of Lannea coromandelica bark extract. Phytother Res 10:429–430 26. Sathish R, Mohd HA, Natarajan K, Lalitha KG (2010) Evaluation of wound healing and antimicrobial activity of Lannea coromandelica (Houtt) Merr. J Pharm Res 3(6):1225–1228 27. Kadir MF, Sayeed MSB, Mia MMK (2013) Ethno-pharmacological survey of medicinal plants used by traditional healers in Bangladesh for gastrointestinal disorders. J Ethnopharmacol 147: 148–156 28. Singh S, Singh GB (1994) Anti-inflammatory activity of Lannea coromandelica bark extract in rats. Phytother Res 8:311–313

8

Chemistry, Biological Activities, and Uses of Moi Gum

219

29. Franco FM, Narasimhan D (2009) Plant names and uses as indicators of knowledge patterns. Indian J Trad Knowledge 8:645–648 30. Jain SK (1994) Ethnobotany and research on medicinal plants in India. Ciba Found Symp 185: 153–164 31. Islam MT, Tahara S (2000) Dihydroflavonols from Lannea coromandelica. Phytochemistry 54:901–907 32. Kumar BK (1998) Handbook of medicinal plants pointer publishers, Jaipur (India), p 201 33. Thyagarajan R, Jaibala S, Balakrishnan GA (1975) Hand book of common remedies in Siddha system of medicine, Central council for research in Indian medicine and Homoeopathy, Ministry of health and family planning, Govt. of India 34. Saravanan S, Dhasarathan P, Indira V, Venkataraman R (2010) Screening of anti-inflammatory potential of chosen medicinal plants using swiss albino mice. Aust J Basic Appl Sci 4: 6065–6068 35. Jain SK, Tarafder CR (1970) Medicinal plants-lore of the sandals – a revival of PO Bodding’s work. Econ Bot 24:241–278 36. Shah GL, Yadav SS, Badri N (1983) Medicinal plants from Dahanu forest division in Maharashtra state. J Econ Taxon Bot 4:141–151 37. Venkata PK, Venkata R, Venkata RR (2008) Preliminary phytochemical evaluation of certain anticancer crude drugs used by Adivasis of Rayalaseema region, Andhra Pradesh, India. Ethnobot Leafl 12:693–697 38. Carvalho M, Ferreira PJ, Mendes VS, Silva R, Pereira JA, Jeronimo C, Silva BM (2010) Human cancer cell anti-proliferative and antioxidant activities of Juglans regia L (containing Quercetin-3-arabinoside). Food Chem Toxicol 48:441–447 39. Rastogi R, Dhawan BN (1990) Anticancer and antiviral activity in Indian medicinal plant Lannea coromandelica. Drug Dev Res 19:1–12 40. Voit B (2000) New developments in hyper branched polymers. J Polym Sci Part A Polym Chem 38(14):2505–2525 41. Rani GU, Konreddy AK, Mishra S, Sen G (2014) Synthesis and applications of polyacrylamide grafted agar as a matrix for controlled drug release of 5-ASA. Int J Biol Macromol 65:375–382 42. Rahul R, Jha U, Sen G, Mishra S (1961) A novel polymeric flocculant based on polyacrylamide grafted inulin: aqueous microwave assisted synthesis. Carbohyd Polym 99:11–21 43. Odian G, Sobel M, Rossi A, Klein R (1961) Radiation-induced graft polymerization: the trommsdorff effect of methanol. J Polym Sci 55(162):663–673 44. Wang X, Ruther RE, Streifer JA, Hamers RJ (2010) UV-induced grafting of alkenes to silicon surfaces: photoemission versus excitons. J Am Chem Soc 132(12):4048–4049 45. Kim S, Kim E, Kim A, Kim W (2005) Surface modification of silica nanoparticles by UV-induced graft polymerization of methyl methacrylate. J Colloid Interface Sci 292:93–98 46. Nayak PL, Lenka S (1980) Redox polymerization initiated by metal ions. J Macromol Sci Polym Rev 19(1):83–134 47. Misra GS, Bajpai UD (1982) Redox polymerization (review). Prog Polym Sci 8:61–131 48. Temel O, Ismail C (2007) Synthesis of block copolymers via redox polymerization process: a critical review. Iranian Polym J 16(8):561–581 49. Bhattacharya A, Rawlins JW, Ray P (eds) (2008) Polymer grafting and crosslinking. John Wiley & Sons, New York 50. Adams S (1983) Recent advances in radiation chemistry of carbohydrates. In: Elias PS, Cohen AJ (eds) Recent advances in food irradiation. Elsevier Biomedical Press, Amsterdam, pp 149–170 51. Edimecheva IP, Kisel RM, Shadyro OI, Kazem K, Murase H, Kagiya T (2005) Homolytic cleavage of the O-glycoside bond in carbohydrates: a steady-state radiolysis study. J Radiat Res 46:319–324 52. Grubb DT (1974) Radiation damage and electron microscopy of organic polymers. J Mater Sci 9:1715–1736

220

S. Mishra et al.

53. Fink D (2004) Determination of radiation damage in polymers, fundamentals of Ion-irradiated polymers. Springer 63, p. 66 54. Pietraner MSA, Narvaiz P (2001) Examination of some protective conditions on technological properties of irradiated food grade polysaccharide. Radiat Phys Chem 60:195–201 55. Kim BN, Lee DH, Han DH (2008) Thermal, mechanical and electrical properties on the styrene-grafted and subsequently sulfonated FEP film induced by electron beam. Polym Degrad Stab 93:1214–1221 56. Dargaville TR, George GA, Hill DJT, Whittaker AK (2003) High energy radiation grafting of fluoropolymers. Prog Polym Sci 28:1355–1376 57. Farquet P, Padeste C, Solak HH, Gursel SA, Scherer GG, Wokaun A (2008) Extreme UV radiation grafting of Glycidyl methacrylate nanostructures onto fluoropolymer foils by RAFTmediated polymerization. Macromolecules 41:6309–6316 58. Guilmeau I, Esnouf S, Betz N, Le MA (1997) Kinetics and characterization of radiationinduced grafting of styrene on fluoropolymers. Nucl Instrum Methods Phys Res, Sect B 131(1997):270–275 59. Kimura Y, Asano MJ, Chen Y, Maekawa R, Katakai M (2008) Yoshida, influence of grafting solvents on the properties of polymer electrolyte membranes prepared by γ-ray pre-irradiation method. Radiat Phys Chem 77:864–870 60. Ameduri B, Boutevin B (2004) Well-architectured fluoropolymers, 1st edn. Elsevier, Amsterdam 61. Gubler L, Slaski M, Wallasch F, Wokaun A, Scherer GG (2009) Radiation grafted fuel cell membranes based on co-grafting of α-methylstyrene and methacrylonitrile into a fluoropolymer base film. J Membr Sci 339:68–77 62. Lappan U, Geißler U, Uhlmann S (2005) Radiation-induced grafting of styrene into radiationmodified fluoropolymer films. Nucl Instrum Methods Phys Res, Sect B 236:413–419 63. Chen J, Asano M, Maekawa Y, Yoshida M (2007) Polymer electrolyte hybrid membranes prepared by radiation grafting of p-styryltrimethoxysilane into poly (ethylene-co-tetrafluoroethylene) films. J Membr Sci 296:77–82 64. Tzanetakis N, Varcoe JR, Slade RCT, Scott K (2005) Radiation-grafted PVDF anion exchange membrane for salt splitting. Desalination 174:257–265 65. Odian G (2002) Principles of polymerization, 3rd edn. John Wiley & Sons, New York 66. Sinha S, Mishra S, Sen G (2013) Microwave initiated synthesis of polyacrylamide grafted casein (CAS-g-PAM)–its application as a flocculant. Int J Biol Macromol 60:141–147 67. Mishra S, Rani GU, Sen G (2012) Microwave initiated synthesis and application of polyacrylic acid grafted carboxymethyl cellulose. Carbohyd Polym 87:2255–2262 68. Sen G, Pal S (2009) Microwave initiated synthesis of polyacrylamide grafted carboxymethylstarch (CMS-g-PAM): application as a novel matrix for sustained drug release. Int J Biol Macromol 45(1):48–55 69. Sanghi R, Bhatttacharya B, Singh V (2006) Use of Cassia javahikai seed gum and gum-gpolyacrylamide as coagulant aid for the decolorization of textile dye solutions. Bioresour Technol 97:1259–1264 70. Ruehrwein RA, Ward DW (1952) Mechanism and clay aggregation by polyelectrolytes. Soil Sci 73:485–492 71. Kongparakul S, Prasassarakich P, Rempel LG (2008) Effect of grafted methylmethacrylate on the catalytic hydrogenation of natural rubber. Eur Polym J 44:915–1920 72. Ragab A, Inas A, Bader D (2019) The removal of brilliant green dye from aqueous solution using Nano hydroxyapatite/chitosan composite as a sorbent. Molecules 24:847 73. Mittal H, Maity A, Ray SS (2015) Synthesis of co-polymer-grafted gum karaya and silica hybrid organic-inorganic hydrogel nanocomposite for the highly effective removal of methylene blue. Chem Eng J 279:166–179 74. Mahida VP, Patel MP (2016) Removal of heavy metal ions from aqueous solution by superabsorbent poly (NIPAAm/DAPB/AA) amphoteric nanohydrogel. Desal WatTreat 57(29):13733–13746

8

Chemistry, Biological Activities, and Uses of Moi Gum

221

75. Tofighy AM, Mohammadi T (2011) Adsorption of divalent heavy metal ions from water using carbon nanotube sheets. J Hazard Mater 185:140–147 76. Langmuir I (1918) The adsorption of gases on plane surfaces of glass, mica and platinum. J Am Chem Soc 40(9):1361–1403 77. Hall KR, Eagleton LC, Acrivos A, Vermeulen T (1966) Pore-and solid-diffusion kinetics in fixed-bed adsorption under constant-pattern conditions. Ind Eng Chem Fundam 5(2):212–223 78. Freundlich HMF (1906) Over the adsorption in solution. J Phys Chem 57:385–470 79. Ahmad MA, Alrozi R (2011) Removal of malachite green dye from aqueous solution using rambutan peel-based activated carbon: equilibrium, kinetic and thermodynamic studies. Chem Eng J 171(2):510–516 80. Tempkin MJ, Pyzhev V (1940) Recent modification to Langmuir isotherms. Acta Physiochem USSR 12:217–222 81. Ghasemi M, Naushad M, Ghasemi N, Khosravifard Y (2014) A novel agricultural waste based adsorbent for the removal of Pb (II) from aqueous solution: kinetics, equilibrium and thermodynamic studies. J Ind Eng Chem 20:454–461 82. Lagergren S, Svenska K (1898) About the theory of so-called adsorption of soluble substances. Kong Vetensk Acad Handl 24(2):1–39 83. Ho YS (2006) Review of second-order models for adsorption systems. J Hazard Mater 136(3): 681–689 84. Weber WJ, Morris JC (1962) Advances in water pollution research: removal of biologically resistant pollutant from wastewater by adsorption. Proceedings of the International Conference on Water Pollution Symposium, Pergamon Press Oxford, UK vol 2, pp. 231–266 85. Li K, Li Y, Zheng Z (2010) Kinetics and mechanism studies of p-nitroaniline adsorption on activated carbon fibers prepared from cotton stalk by NH4H2PO4 activation and subsequent gasification with steam. J Hazard Mater 178(1):553–559 86. Aharoni C, Ungarish M (1977) J Chem Soc Faraday Trans 73(3):456–464 87. Zhang J, Stanforth R (2005) Slow adsorption reaction between aresenic species and geohite (α-FeOOH): diffusion or heteregenous surface reaction control. Langmuir 21(7):2895–2901 88. Namasivayam C, Kavitha D (2002) Removal of Congo red from water b adsorption onto activated carbon prepared from coir pith, an agricultural solid waste. Dyes Pigments 54: 47–58 89. Zhou Y, Zhang M, Hu X, Wang X, Niu J, Ma T (2013) Adsorption of cationic dyes on a cellulose-based multicarboxyl adsorbent. J Chem Eng Data 58:413–421 90. Mittal H, Mishra SB, Mishra AK, Kaith BS, Jindal R (2013) Flocculation characteristics and biodegradation studies of gum ghatti based hydrogels. Int J Biol Macromol 58:37–46 91. Pandey VS, Verma SK, Behari K (2014) Graft [partially carboxymethylated guar gum-g-poly N-(hydroxymethyl) acrylamide] copolymer: from synthesis to applications. Carbohyd Polym 110:285–291 92. Ni B, Liu M, Lü S (2009) Multifunctional slow-release urea fertilizer from ethylcellulose and superabsorbent coated formulations. Chem Eng J 155(3):892–898 93. El-Mohdy HLA, Ghanem S (2009) Biodegradability, antimicrobial activity and properties of PVA/PVP hydrogels prepared by γ-irradiation. J Polym Res 16:1–10 94. Olson JS (1963) Energy storage and the balance of producers and decomposers in ecological systems. Ecology 2(44):322–331 95. Rani GU, Mishra S, Sen G, Jha U (2012) Polyacrylamide grafted agar: synthesis and applications of conventional and microwave assisted technique. Carbohyd Polym 90(2): 784–791 96. Rani GU, Dey KP, Bharti S, Mishra S (2014) Controlled drug release of 5-amino salicylic acid by poly (2-hydroxyethylmethacrylate) grafted agar. Front Chem Sci Eng 8(4):465–470 97. Prasad SS, Rao KM, Reddy PR, Reddy NS, Rao KK, Subha MCS (2012) Synthesis and characterization of guar gum-g-poly (acrylamide-glycolic acid) by redox initiator. Indian J Adv Chem Sci 1(1):28–32

222

S. Mishra et al.

98. Krȩglewski M, Winther F (1992) High-resolution infrared spectrum of methyl amine: assignment and analysis of the wagging state. J Mol Spectrosc 156(2):261–291 99. Fu F, Wang Q (2011) Removal of heavy metal ions from wastewaters: a review. J Environ Manag 92:407–418 100. Barka N, Qouzal S, Assabbane A, Nounhan A, Ichou YA (2011) Removal of reactive yellow 84 from aqueous solutions by adsorption onto hydroxyapatite. J Saudi Chem Soc 15:263–267 101. Ozacar M, Sengil IA (2005) Adsorption of metal complex dyes from aqueous solutions by pine sawdust. Bioresour Technol 96:791–795 102. Feng D, Bai B, Wang H, Suo Y (2018) Novel fabrication of PAA/PVA/yeast superabsorbent with interpenetrating polymer network for pH-dependent selective adsorption of dyes. J Polym Environ 26(2):567–588 103. Rehman R, Mahmud T, Irum M (2015) Brilliant green dye elimination from water using Psidium guajava leaves and Solanum tuberosum peels as adsorbents in environmentally benign way. J Chem 126036, 8 104. Mate CJ, Mishra S (2020) Synthesis of borax cross-linked Jhingan gum hydrogel for remediation of Remazol brilliant blue R (RBBR) dye from water: adsorption isotherm, kinetic, thermodynamic and biodegradation studies. Int J Biol Macromol 151:677–690 105. Ishaq M, Sultan S, Ahmad I, Saeed K (2017) Removal of brilliant green dye from aqueous medium by untreated acid treated and magnetite impregnated bentonite adsorbents. J Chem Soc Pakistan 39(5):780–787 106. Hameed BH, El-Khaiary MI (2008) Batch removal of malachite green from aqueous solutions by adsorption on oil palm trunk fibre: equilibrium isotherms and kinetic studies. J Hazard Mater 154(1–3):237–244 107. Ahmad MA, Rahman NK (2011) Equilibrium, kinetics and thermodynamic of Remazol Brilliant Orange 3R dye adsorption on coffee husk-based activated carbon. Chem Eng J 170(1):54–161 108. Ozcan A, Omeroglu C, Erdogan Y, Ozcan AS (2007) Modification of bentonite with a cationic surfactant: an adsorption study of textile dye reactive blue 19. J Hazard Mater 140(1–2):173–179 109. Ahmad AF, ElChaghaby GA (2018) Palm fronds activated carbon for the removal of brilliant green dye from wastewater. Wat Desal Res J 2(1) 110. Bayramoglu G, Altintas B, Arica MY (2009) Adsorption kinetics and thermodynamic parameters of cationic dyes from aqueous solutions by using a new strong cation exchange resin. Chem Eng J 152(2):339–346 111. Pavlatou A, Polyzopolus NA (1988) The role of diffusion in the kinetics of phosphate desorption: the relevance of the Elovich equation. Eur J Soil Sci 39(3):425–436 112. Yakout SM, Elsherif E (2010) Batch kinetics, isotherm and thermodynamic studies of adsorption of strontium from aqueous solutions onto low cost rice-straw based carbons. Carbon Sci Technol 1:144–153 113. Abramian L, El-Rassy H (2009) Adsorption kinetics and thermodynamics of azo-dye Orange II onto highly porous titania aerogel. Chem Eng J 150(2–3):403–410 114. Mate CJ, Mishra S, Srivastava PK (2021) Design of pH sensitive low-cost adsorbent from the exudate of Lannea coromandelica (Houtt) for remediation of malachite green dye from aqueous solution. Polym Bull 78:3459–3487 115. Karthika M, Vasuki M (2017) Removal of artificial dye solution of brilliant green over a low-cost physically activated carbon prepared from coconut Shell by adsorptive technique. Mod Chem App 5(4):2–4 116. Xia L (1999) Cellulase production by solid state fermentation on corn cob residue from xylose manufacture. Process Biochem 34:909–912 117. Etienne P, Diquelou S, Prudent M, Salon C, Maillard A, Ourry A (2018) Macro and micronutrient storage in plants and their remobilization when facing scarcity: the case of drought. Agriculture 8:14 118. Shaviv A (2001) Advances in controlled-release fertilizers. Adv Agron 71:1–49

8

Chemistry, Biological Activities, and Uses of Moi Gum

223

119. Goldbach HE, Wimmer MA, Findeklee P (2000) Discussion paper: boron – how can the critical level be defined. J Plant Nutr Soil Sci 163:115–121 120. Mengel K, Kirkby EA (1982) Principles of plant nutrition, 3rd edn. International Potash Institute, Worblaufen-Bern 121. Haynes RJ, Mokolobate MS (2001) Amelioration of Al toxicity and P deficiency in acid soils by additions of organic residues: a critical review of the phenomenon and the mechanisms involved. Nutr Cycl Agroecosys 59(1):47–63 122. Singh MV (2008) Micronutrient deficiencies in crops and soils in India. In: Micronutrient deficiencies in global crop production Dordrecht. Springer, Dordrecht, pp 93–125 123. Brown PH, Cakmak I, Zhang Q (1993) Form and function of zinc in plants. Chap 7. In: Robson AD (ed) Zinc in soils and plants. Kluwer Academic Publishers, Dordrecht, pp 90–106 124. Grewal HS, Graham RD, Rengel Z (1996) Genotypic variation in zinc efficiency and resistance to crown rot disease ( fusarium graminearum Schw group 1) in wheat. Plant Soil 186: 219–226 125. Streeter TC, Rengel Z, Neate SM, Graham RD (2001) Zinc fertilisation increases tolerance to Rhizoctonia solani (AG 8) in Medicago truncatula. Plant Soil 228:233–242 126. Suri VK, Choudhary AK, Chander G, Verma TS (2011) Influence of vesicular arbuscular mycorrhizal fungi and applied phosphorus on root colonization in wheat and plant nutrient dynamics in a phosphorus–deficient acid alfisol of Western Himalayas. Commun Soil Sci Plant Anal 42(10):1077–1186 127. Rietra RPJJ, Heinen M, Dimkpa C, Bindraban PS (2015) Effects of nutrient antagonism and synergism on fertilizer use efficiency. VFRC Report 2015/5. Virtual Fertilizer Research Center, Washington, DC, p 42 128. Guilherme MR, Reis AV, Paulino AT, Moia TA, Mattoso LHC, Tambourgi EB (2010) Pectinbased polymer hydrogel as a carrier for release of agricultural nutrients and removal of heavy metals from wastewater. J Appl Polym Sci 117(6):3146–3154 129. Ni B, Liu M, Lü S, Xie L, Wang Y (2011) Environmentally friendly slow-release nitrogen fertilizer. J Agric Food Chem 59(18):10169–10175 130. Davidson DW, Verma MS, Gu FX (2013) Controlled root targeted delivery of fertilizer using an ionically crosslinked carboxymethyl cellulose hydrogel matrix. Springerplus 2(1):318 131. Aouada FA, de Moura MR, de Menezes AE, de Nogueira AR, Mattoso LHC (2008) Hydrogel synthesis and kinetics of ammonium and potassium release. Rev Bras Cenc Solo 32(4): 1643–1649 132. Cong Z, Yazhen S, Changwen D, Jianmin Z, Huoyan W, Xiaoqin C (2010) Evaluation of waterborne coating for controlled-release fertilizer using wurster fluidized bed. Ind Eng Chem Res 49(20):9644–9647 133. USP (2003) General Chapter Dissolution, USP 27, The United States Pharmacopeial Convention, Inc., Rockville, p 2303 134. Nagarjuna Reddy D, Vasudeva Reddy K, Hussain Reddy K (2011) Simple and sensitive spectrophotometric determination of Zn (II) in biological and pharmaceutical samples with 2-Benzoylpyridine thiosemicarbazone (BPT). J Chem Pharm Res 3(3):205–213 135. Anitha MS, Anil Kumar KS, Prashantha GM (2015) Distribution of plant available boron in major soil types and their correlation with other properties of the soil. Ecol Environ Conserv 21:S143–S148 136. Ma Z, Jia X, Hu J, Liu Z, Wang H, Zhou F (2013) Mussel-inspired thermosensitive polydopaminegraft- poly(N-isopropylacrylamide) coating for controlled-release fertilizer. J Agric Food Chem 61(50):12232–12237 137. Jamnongkan T, Kaewpirom S (2010) Potassium release kinetics and water retention of controlled release fertilizers based on chitosan hydrogels. J Polym Environ 18(3):413–421 138. Peppas NA, Franson NM (1983) The swelling interface number as a criterion for prediction of diffusional solute release mechanisms in swellable polymers. J Polym Sci Polym Phys Edition 21:983–997

224

S. Mishra et al.

139. Ritger PL, Peppas NAA (1987) Simple equation for description of solute release II. Fickian and anomalous release from swellable devices. J Control Release 5(1):37–42 140. Singh B (2007) Psyllium as therapeutic and drug delivery agent. Int J Pharm 334(1–2):1–14 141. Song CX, Labhasetwar L, Levy RJ (1997) Controlled release of U-86983 from double-layer biodegradable matrices: effect of additives on release mechanism and kinetics. J Control Release 45(21):177–192 142. Chaudhary DR, Shukla LM, Gupta A (2005) Boron equilibria in soil - A review. Agric Rev 26(4):288–294 143. Biggar JW, Fireman M (1960) Boron adsorption and release by soils. Soil Sci Soc Am J 24(2):115 144. Bajpai AK, Giri A (2002) Swelling dynamics of a macromolecular hydrophilic network and evaluation of its potential for controlled release of agrochemicals. React Funct Polym 53(2–3):125–141 145. Sankar C, Mishra B (2003) Development and in vitro evaluation of gelatin a microspheres of ketorolac tromethamine for intranasal administration. Acta Pharma 53:101–110

9

Chemistry, Biological Activities, and Uses of Locust Bean Gum Neha Duhan, Sheweta Barak, and Deepak Mudgil

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Processing of Locust Bean Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Acid-Based Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Thermal or Heat-Based Process . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 LBG Chemistry and Composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Biological Activities of LBG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Properties of LBG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Hydration and Solubility . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Rheological Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 Water Adsorption Isotherm . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Uses of LBG . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

226 227 229 229 229 230 232 232 233 234 234 236 237

Abstract

Locust bean gum (LBG) is a galactomannan-based natural biopolymer. LBG is extensively used commercially in food and other industries. Besides being a high value additive that brings about desired functional attributes upon usage, it is reported to have several health benefits as well. Processing of seed coat is required to separate the gum from germ and hull so as to access the gum portion of carob (locust) seeds. To obtain high-quality gum from seed, it is crucial to minimize impurities. Upon hydration, LBG forms a gel-like structure, being soluble in warm water. This and other changes associated with the solubility of LBG result in high demand for such products. This chapter is created to provide a basic intuitive overview of locust bean gum and various aspects related to it. N. Duhan Centre for Rural Development and Technology, Indian Institute of Technology Delhi, New Delhi, India S. Barak · D. Mudgil (*) Mansinhbhai Institute of Dairy & Food Technology (MIDFT), Mehsana, Gujarat, India © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_9

225

226

N. Duhan et al.

Keywords

Dietary fiber · Edible coating · Food · Locust bean gum · Pharmaceuticals · Processing · Rheology · Solubility Abbreviations 

C Fig G’ G” KDa LBG OTR w/w WVTR α β Κ

1

Degree Celsius Figure Storage modulus Loss modulus Kilo Dalton (1000 Dalton) Locust bean gum Oxygen transmission rate Weight by weight Water vapor transmission rate Alpha Beta kappa

Introduction

Trees have been valuable resources, providing many useful agro-based commodities, to the human population. One fine example in the category is the carob or locust bean tree, also known by the scientific name Ceratonia siliqua. Basically a legume tree native to the Mediterranean region, it is heavily cultivated in Spain, Italy, Morocco, Lebanon, Tunisia, Cyprus, Turkey, Portugal, and Greece [1, 2]. These trees have been significant in ecological context for reforestation of these areas and for limiting wild fire spread in the areas [3]. Locust bean tree provides products of industrial use and therefore holds high commercial value. Ayache et al. [4] were able to identify more than 50 phytochemical and volatile compounds while studying biological activity in an aqueous extract from the pulp and seed portion of the locust tree. In other words, locust bean seed and pulp were found to exhibit analgesic, antioxidant, and proapoptotic properties. Various studies in recent years have reported locusts to have antibacterial, antitumor, and antioxidant properties [5, 6]. Therefore, the locust bean tree is considered a commercially valuable crop with various parts such as seed, pulp, and extract, finding huge application-based usage in food and allied industries [7]. Locust seed is an extensively used ingredient of traditional medicine systems in some countries, for anticonstipation, antiglycemic, analgesic, and antidiarrhea effects on the body [8]. Germ, endosperm, and husk are the structural components of locust seed. The endosperm of the seed portion is a reservoir of a white creamcolored powdered substance commercially referred to as locust bean gum (LBG). Before going further to understand locust bean gum with respect to chemistry,

9

Chemistry, Biological Activities, and Uses of Locust Bean Gum

227

biological activity, and uses, it is imperative to understand the term gums and hydrocolloids in context to carbohydrates. When existing in polysaccharide, nonstarch form, carbohydrates are known to show partial or full solubility towards the water. Gum is a very frequently used term to denote such polysaccharides. To put it simply, nonstarch polysaccharides that can form viscous solution or gel with water are classified under the term “gum” [9]. When used as an ingredient in the preparation of processed food, gums are referred to as hydrocolloids [10]. As a result of gel or viscous solution formation ability, gums thicken and stabilize the system in which these are incorporated. However, the functional attributes imparted to the system upon incorporation, depending on the chemical structure of the gum molecules as in the case of other polymers. Other factors that play a deciding role in the resulting functional attributes of the system are the concentration and chemical properties of other solutes and salts present, temperature, preparation methodology, and pH of the system [10]. Due to unique water-binding and emulsion forming ability, gums are considered structure frameworks providing, water-binding entities. Gums are used to contributing to qualitative attributes such as texture, rheology, shape, and sensory properties. In context to nutritional value, gums being polysaccharides are roughage and dense nutrient source [11]. All these features result in the high commercial value of gums as a functional food ingredient. Industrially, gums are used as emulsifiers, thickening agents, gelling agents, texture improvers, wall material for encapsulation of bio-active substances, and stabilizers [12]. Locust bean gum (LBG) is galactomannan-based, a gum that is high in demand for its quality attributes. LBG is a high-value bio-polymer that is used in various food, health, and medicine sector-based applications due to being a biodegradable, easily available, and toxin-free product [13]. Locust bean gum finds usage in food and allied industries of packaging, cosmetics, and pharmaceuticals owing to its compatibility with water in the form of absorption, solubility, and hydrogen-bond forming ability, water being the common base for application-based formulations [14]. Adding further to the profile are functional, health benefits associated with locust bean gum. The gum has been found effective in providing roughage and hence, relief from lifestyle issues like irregular digestion, heart disorders, diabetes, gut health issues, and various types of cancer [15]. A detailed overview of LBG properties and associated usage has been provided within the forthcoming sections, to develop a qualitative overall understanding of LPG.

2

Processing of Locust Bean Gum

Gums serve as a source of energy for the seeds during germination. Locust bean gum is obtained from endosperm by breaking the locust seeds to access endosperm followed by further processing. Hull and seed coat breaking followed by sifting

228

N. Duhan et al.

and milling enables the endosperm separation from the rest of the seed constituents. Grinded and powdered endosperm obtained in this way is yet crude and is sold as crude flour at times [16]. The first step in the processing, that is, husk removing, is done by chemical, mechanical or thermo-mechanical means [15]. Next in line is germ separation through splitting the de-husked/peeled seed along the length. As a result, endosperm gets isolated for further sequential steps, that is, size reduction, sifting, and grading before the final step of packaging (Fig. 1). Common impurities in the case of LBG are germ and husk portions that are often reflected in tests as elevated levels of insoluble ash (indicative of husk) and proteins (germ-based impurity). As revealed by studies, in impure, crude form, LBG roughly consists of around 80% galactomannan. Protein found in impurities as a result of germ residues is present in form of glutelin (around 68%) and globulin and albumin (collectively around 32%) [17]. The presence of impurity affects the properties of LBG, and therefore, to obtain a high-end quality product, every step of processing becomes a key point for quality control, impurity removal, and removing the possibility of accidental contamination. For further clarification, the gum is dissolved in hot water and precipitated using isopropanol or ethanol (Fig. 1). Postclarification, it is very crucial to ensure that no effluent remains there in LBG, to minimize impurity. Locust seeds are hard to break owing to the tough seed coat. Therefore, to keep the germ and endosperm

Fig. 1 Flow-chart for locust bean gum (LBG) processing

9

Chemistry, Biological Activities, and Uses of Locust Bean Gum

229

undamaged in the process, a special peeling process is followed, which can be done by two means, described in detail in the following subsections. Quality and yield percentage of LBG obtained are found to be dependent on the process used for peeling and separation of endosperm from the rest of the seed constituents.

2.1

Acid-Based Process

In this process, sulfuric acid is used for seed kernels at a specific temperature. As a result, carbonization of the seed coat happens, resulting in reduced strength and easy peeling of the seed coat. Seed coat gets fragmented and cracked as a result of the method, making it easy to remove it efficiently. The clean, intact endosperm portion is accessed after brushing and rinsing away the seed coat portion. Upon drying, the peeled portion is cracked open, and the crushed germ portion is removed from the intact endosperm. LBG obtained from this method is found to have high viscosity and light white color as reported [13]. Acid-based treatment results in a respectively lower yield of LBG (37 to 48% w/w) as reported by Dakia et al. [18].

2.2

Thermal or Heat-Based Process

Instead of acid, heat treatment is used to crack and remove seed coats in this method. Seed kernels are roasted in a rotation-induced furnace. The seed coat gets cracked open and the husk is burned as a result of subjecting to the high temperature of roasting. The endosperm is easily separated from the crashed germ and recovered. Compared to the acid-based method, the thermal process results in zero effluent due to the absence of chemicals. LBG obtained from this method is found to be darker in color as reported [13]. Thermal or boiling water treatment for processing results in a relatively higher yield of LBG (around 51 to 61% w/w) as reported by Dakia et al. [18]. The product is reported to be yellowish.

3

LBG Chemistry and Composition

As mentioned earlier, LBG is a galactomannan-based polysaccharide. Thus, in order to understand the structural and chemical properties of LBG, it becomes imperative to understand the structure of galactomannans. Galactomannans come under the linear polysaccharide class of carbohydrates. LBG galactomannans comprise galactose and mannose units (Fig. 2). Galactomannan in plant-based sources comprises linear β-(C1-C4) linkage-based mannose polymer linked with α-galactose units [19]. LBG conforms to the pattern like other plant-based sources with β mannosebased backbone and side chain of single α-(C1-C6) linkage galactopyranosyl units [20]. LBG comes under poly-disperse macromolecules with varying molecular weight, depending upon the type of components attached to the main backbone. Molecular weight for gums varies depending upon harvesting, processing, and

230

N. Duhan et al.

Fig. 2 Chemical structure of locust bean gum (LBG) Table 1 The basic composition of LBG, as studied and reported by Prajapati et al. [13]

Constituent name Moisture Acid soluble ash Ash Protein

Commercial LBG (% w/w) 5 to 12% 1.7 to 5% 0.4 to 1% 3 to 7%

Clarified LBG (% w/w) 3 to 10% 0.1 to 3% 0.1 to 1% 0.1 to 0.7%

purification treatments [21]. Molecular weight of LBG lies roughly within the range of 50 to 300 KDa as determined by gel permeation-based chromatography. Nonuniform distribution of side linkage and other interlinked side materials result in variation in properties to some extent. The ratio of mannose to galactose is one of the major differentiating characteristics between galactomannans on basis of water solubility. High galactose content results in increased solubility. The ratio of mannose to galactose is found to be 4:1 for LBG which is high compared to other plant-based gums. Thus, in order to reach maximum solubility of LBG in water, application of high temperature is required [14]. LBG is a nonionic gum which means that, unlike other gums, LBG-based solutions are not destabilized by the presence of salt or pH change [15]. Morphological study of galactomannan reveals that it exists roughly in ribbon kind of shape normally. Upon solubilizing, it displays the coil shape (Table 1).

4

Biological Activities of LBG

LBG is a natural bio-resorbable and bio-compatible natural polymer. According to the expert committee on food additives (WHO/FAO), LBG is nonmutagenic and nonteratogenic [22]. Locust seed has been extensively used in traditional medicine systems for its pharmacological impact (anticonstipation, antiglycemic, analgesic, and antidiarrhea) effect on the body [8]. LBG is a functional bio-polymer and ingredient that is used in nutraceuticals, food, health, and medicine-based products. It is a biodegradable, easily available, and toxin-free product which makes it a riskfree choice [13].

9

Chemistry, Biological Activities, and Uses of Locust Bean Gum

231

Dietary fibers are known to exhibit a filler effect on the body, providing satiety. Moreover, soluble fibers, turning viscous and gel type upon hydration, provide aid in digesting heavier components of food such as proteins and fats, gently. The gum has been found effective in providing roughage and hence, relief from lifestyle issues like irregular digestion, heart disorders, diabetes, gut health issues, and various types of cancer [15]. Due to the effective swelling and gelling property of LBG and other gums, intake of these results in the slow, efficient movement of food through the digestive tract. As a result, not only do the macro- and micronutrients in food get released in blood in an optimum manner, but it also acts as a buffer medium between digestive tract lining and food. Due to this, the added selective filtration provides more time to the entire system for regulation of sugar and other components, for balanced inclusion in the system. LBG, being the source of dietary fiber, reduces LDL, whereas its high gelling ability helps aid in the regulation of sugar levels in the blood (Table 2). Certain harmful substances that may find their way to our digestive tract due to unhealthy food choices or preservatives also are screened out by the fibrous network of LBG and other gums present, by the virtue of binding such ingredients within followed by complete expulsion from the system in the stool. Due to this, studies have reported LBG to be effective against ulcer colitis and Crohn’s disease as well. Moreover, such a densely nutrient-packed dosage of food intake helps curb cravings for empty calories, getting a reputation as an obesity and

Table 2 Biological activities of locust bean gum Biological activity Nonmutagenic Nonteratogenic Anticonstipation Antiglycemic Analgesic Prebiotic

Reason No active metabolites to impair genetic material No metabolites to impair the growth of the fetus Gelling property, resulting in softening of stool Regulation of digestion duration and controlled release of sugar in blood vessels The laxative effect through active site binding Provides roughage

Anti-inflammation

Selective filter for transport of food from the digestive tract

Anti-proliferative and apoptotic activity Hypo-lipidemic effect

Screen off harmful substances in digestion, from entering blood vessels Providing roughage for efficient digestion process and regulation of lipid level in blood

Advantage Used as food-grade additive Safe for pregnant ladies Aid with bowel movement Healthy for diabetic patients Reduce pain Satiety and digestion improvement Added protection and removal of harmful products Protection against cancer

Reduce LDL, preventive against cardiac problems

232

N. Duhan et al.

weight control functional ingredient [23]. LBG and other soluble fibers that turn viscous upon hydration are effective at flattening postprandial glycemia than insoluble ones. LBG is found to have a healthy dietary effect with antiinflammation properties. LBG provides roughage and hence, relief from lifestyle issues like irregular digestion, heart disorders, diabetes, gut health issues, and various types of cancer. The good synergy of LBG with other polysaccharides makes it a suitable active ingredient for bio-pharmaceutical product designing. Thus, LBG can be utilized as a wall material for encapsulation and controls the release of active ingredients as well.

5

Properties of LBG

Properties and corresponding functional attributes exhibited by LBG depend directly on the level of synergy LBG has, with the solvent medium in which it is present and other ingredients that are a part of the system. Major properties that are crucial in bringing about functional attributes for high-end product applications are described below.

5.1

Hydration and Solubility

Hydration kinetics depends on certain factors. Key intrinsic factors that control hydration rate are the level of impurities or quality of the product and particle size. Some extrinsic factors that determine the hydration rate include the temperature of water used for the process and the time duration given for forming a stable gel. It has been found that LBG requires an approximately optimum temperature of 80  C for half-hour to reach maximum hydration. For maximum viscosity development, a duration of 2 h of hydration is required [24]. It has been observed that fine is the particle size, more is the hydration which is in line with simple rules of solution formation. The smaller is the particle size, the more is the potential of water interaction owing to the increased surface area and better distribution, resulting in high kinetics of hydration (Table 3). As mentioned earlier, given the high mannose to galactose ratio, for optimal and stable gelling, it becomes imperative to use hot water for solubilizing LBG. However, too high a temperature can also result in depolymerization. Thus, an optimal temperature that is neither too high nor too low is required. Another parameter important to bring about beneficial attributes is pH that needs to be in the range of 4 to 9 for a stable solution. The solubility of LBG is found to be around 70 to 85% when water is available at 80  C temperature for solution preparation [18]. Compared to other plant-based gums, LBG has less solubility owing to the high mannose to galactose ratio [25]. Solubility of LBG is a function of other factors as well such as purity level, granulation, and particle size [26].

9

Chemistry, Biological Activities, and Uses of Locust Bean Gum

233

Table 3 List of LBG properties, respective functional attributes, and use Properties Rheology

Emulsifying and gelling Waterbinding capacity

WVTR and OTR

5.2

Functional attribute (a) Mouthfeel (b) Spreadability (c) Thickening (a) Syneresis prevention (b) Gel stabilizer (a) Moisture retention (b) Crystal formation control (c) Antistaling Quality retention of product

Use Sandwich spreads, sauces, dairy products, baked foods, puree, pastes, canned products, soup, low-fat products Emulsions, pastes, yogurt, soup, beverages, and fruit-based processed products, low-fat products Frozen products like ice-cream

Edible coating

Rheological Properties

Gums swell upon hydration, forming a gel network, resulting in a viscous emulsion. This gel formation and resultant thickening of the solution is a function of several deciding factors. Namely, the factors deciding the viscosity development potential are the molecular weight of the gum, particle size distribution, strength or amount of gum used, solution making process adopted, magnitude and mode of force applied in the process, as well as the purity level of gum used. Detailed flow behavior study using Mark–Houwink–Sakurada model reveals that exponent for power-law for LBG comes out to be around 0.77. Gum solution of LBG is found to be showing non-Newtonian behavior when subjected to a high range of shear rates. However, at lower values of shear rate (applied force), Newtonian fluid behavior is displayed. A possible explanation of this might be that, at lower stress magnitude, disruption of bonds might be balanced by reformation and recovery of the solution, not leading to a visible difference in viscosity. However, with a gradual increase in force beyond a limit, irreversible structure disruption happens. As a result, the integrity of emulsion in terms of stability and strength reduces, causing lower viscosity and hence the visible shear thinning behavior [27]. Solutions having LBG strength of 0.5 to 1% exhibit higher values of loss modulus (G”) compared to storage modulus value (G’) in the lower frequency range while the opposite is true in the case of the high-frequency range. Storage modulus is indicative of stored energy or recoverable energy just after deformation for each cycle. On the other hand, loss modulus G” is a measure of the magnitude of energy lost in dissipation per deformation cycle [28]. As reported in studies, the viscous nature of solution dominates in terms of rheology, at lower frequency, whereas at a higher frequency, the solid irreversible phase transition is seen in the case of LBG [29].

234

5.3

N. Duhan et al.

Water Adsorption Isotherm

As we know beforehand, the water interacts with biological and food systems in various ways, resulting in adsorption, desorption, absorption, humidification, drying, etc. Understanding the adsorption isotherm is important for optimizing shelf-life, stability, and anticipating the moisture change that is likely to happen during the storage of LBG [30]. Adsorption isotherm has been studied for LBG for temperatures between 20 and 65  C by Torres et al. [31]. As a result of the study, it was found that the process followed type-II shape in alignment with Brunauer classification. LBG equilibrium moisture content was found to be reduced with an increase in temperature for every water activity level. Increased temperature results in a high energy level for water molecules, resulting in detachment from water binding sites of LBG due to reduced stability. Isosteric heat for sorption is reported to be decreasing with an increase in equilibrium moisture content for LBG. LBG is found to be less hygroscopic compared to other gums, showing a high value of sorption heat (27 kJ mol 1) [31].

6

Uses of LBG

LBG, being a bio-degradable and toxic-free polymer, finds application in a lot of industries. LBG contributes towards high-end usage by providing functional attributes as emulsifier, binder, modifier for controlled drug release, thickener, viscosity modifier, stabilizer, coating material, solubilizer, disintegrators, gelling agents, wall material and bio-adhesive [32]. Major sectors that extensively utilize LBG to create useful products on a commercial-scale are food, cosmetics, pharmaceuticals, textiles, paint and décor, mining, oil drilling, construction, paper, pet food, and packaging industries (Table 4). The pharmaceutical sector utilizes LBG in the formation of beads, nano- and micro-particles, monolithic matrix system design, inject and inhale-based systems, micro-gel-based formulations, and direct viscous liquid form (Fig. 3). Gelling ability and good synergy of LBG with other polysaccharides make it a suitable active ingredient for bio-pharmaceutical product designing. Oral delivery systems such as hydrogels, multipart systems, and tablets are among the major application-based utilization areas for LBG. LBG is also known to show a hypolipidemic effect. Table 4 Application-based examples of LBG in the field of edible coating Coating components LBG, beeswax, and glycerol LBG and lipid/ hydrocolloid LBG, Guar gum and wax

Advantage Improved appeal, improved shelf life More firm, crispier, and juicier

Coated sample Mandarin

References [33]

Golden apple

[34]

Improved quality and texture

Citrus fruit

[35]

9

Chemistry, Biological Activities, and Uses of Locust Bean Gum

235

Fig. 3 Application of LBG in food, pharmaceutical, and biomedical uses

Therefore, being a source of dietary fiber, LBG helps reduce LDL cholesterol. Locust bean gum also reduces or controls diabetes due to its high gelling ability which on ingestion causes satiety sensation [36]. LBG is amid the most extensively used additives in food-based products owing to the potential of LBG use for providing thickening and stabilizing the emulsion (Fig. 3). Hydrocolloids or water-soluble gums are utilized in form of packaging films, thickener, gelling agents, dietary fiber, and coating agents [37–39]. LBG is used extensively in fruits and vegetables edible coating because of having good binding, viscosity building, and barrier properties [9]. Edible coating results in better regulation in case of migration of carbon dioxide, oxygen, aroma, moisture, and lipids while it also improves sensorial attributes of the food [40]. LBG and Κ-carrageenan blend is an effective edible packaging film material as evident from the study by Martins et al. [41]. The synergistic effect of blending the gums is evident from the detailed physico-chemical analysis of the developed film. X-ray diffraction, Fourier transform infrared spectroscopy, thermo-gravimetric analysis, and dynamic mechanical analysis techniques were used to understand the interactional results of blending the two gums. Adding Κ-carrageenan resulted in enhanced barrier properties for the film, causing a decrease in water vapor permeability. Tensile strength is also found to be improved by the blending. Studies have shown the possibility of successful use of gums in cakes, bread, pasta, and biscuits [42–44]. Gums have been known to improve the water holding capacity of the overall system. In celiac disease, digestion of gluten is not possible. The only solution in this case is a gluten-free food. A lot of gluten-free products use applied gums to replicate the same viscoelastic properties as gluten. Gums are often used as dough improvers for bakery-based products as well for improved texture and sensorial quality [45]. Özboy [46] reported that five different gums/blend of gums (LBG, carrageenan, guar–carrageenan blend, xanthan–guar blend, xanthan–

236

N. Duhan et al.

Table 5 Some selective examples of application-based use of LBG in the food sector Application Edible coating

Beverages

Bakery

Frozen deserts Low-fat dairy products

Why (property) Edibility biodegradability WVTR OTR Thickening Stabilizing Solubility Texture modulation Antistaling Gluten-replacement Swelling index control Viscosity Crystallization control Texture modulation Water holding capacity

Where Fruits, vegetables

References [47, 48]

Instant hot chocolate drinks

[49]

Cookies Bread Noodles

[50, 51]

Ice-cream

[52–54]

Low-fat yogurt

[55–57]

carrageenan) were used to prepare low phenylalanine bread for phenylketonuria patients successfully (Table 5). As reported by Turabi et al. [58] for rice cakes prepared using gums, usage of LBG resulted in higher viscosity, as required, in formulations. When used in combination with gluco/fructo-oligosaccharide (prebiotic fibers), LBG exhibited the ability to delay staling in bread during storage [59]. Further, usage of LBG is found to be associated with less proof time requirement in frozen dough. Adding LBG at a level of 1 to 3% showed greater extension resistance, softer crumb, and high volume in bread [60]. As reported by Khemakhem et al. [61], LBG and other plant-based gums can be combined with egg white to obtain gels with varying functional attributes and physico-chemical properties. Interaction between nonionic gums like LBG and ionic gluten and starch bonding sites has the potential for optimizing pasting, rheological, and fermentation aspects [62]. The use of LBG has been reported to improve the water retention and holding capacity for noodle dough and improved the overall quality of final cooked noodles [63]. LBG is reported to have a protective effect on bioactive compounds like anthocyanin. As reported by Hubbermann et al. [64], the application of LBG led to improved color stability of anthocyanin in black current and elder berry samples. LBG has several food and industrial applications [65, 66].

7

Conclusions

LBG is a valuable biodegradable polymer. As evident from earlier studies, functional attributes of LBG are highly useful from a commercial standpoint. LBG is a nontoxic, safe to use healthy source of dense nutrients as well. Thus, it is heavily used in food and pharmaceuticals, not only to bring about desired textural and

9

Chemistry, Biological Activities, and Uses of Locust Bean Gum

237

sensorial changes but also as a dietary fiber source. LBG is a novel drug delivery wall material that can be used in controlled release-based products. It can be used for encapsulation of bio-active substances as well as thickener and emulsifier.

References 1. Haddarah A, Bassal A, Ismail A, Gaiani C, Ioannou I, Charbonnel C, Hamieh T, Ghoul M (2014) The structural characteristics and rheological properties of Lebanese locust bean gum. J Food Eng 120:204–214 2. Papaefstathiou E, Agapiou A, Giannopoulos S, Kokkinofta R (2018) Nutritional characterization of carobs and traditional carob products. Food Sci Nutr 6:2151–2161 3. Barracosa P, Osorio J, Cravador A (2007) Evaluation of fruit and seed diversity and characterization of carob (Ceratonia siliqua L.) cultivars in Algarve region. Sci Hortic 114:250–257 4. Ayache SB, Saafi EB, Emhemmed F, Flamini G, Achour L, Muller CD (2020) Biological activities of aqueous extracts from carob plant (Ceratonia siliqua L.) by antioxidant, analgesic and proapoptotic properties evaluation. Molecules 25:3120 5. Custódio L, Fernandes E, Escapa AL, López-Avilés S, Fajardo A, Aligué R, Albericio F, Romano A (2009) Antioxidant activity andin-vitroinhibition of tumor cell growth by leaf extracts from the carob tree (Ceratonia siliqua L.). Pharm Biol 47:721–728 6. Meziani S, Oomah BD, Zaidi F, Simon-Levert A, Bertrand C, Zaidi-Yahiaoui R (2015) Antibacterial activity of carob (Ceratonia siliqua L.) extracts against phytopathogenic bacteria Pectobacterium atrosepticum. Microb Pathog 78:95–102 7. Durazzo A, Turfani V, Narducci V, Azzini E, Maiani G, CarceaM (2014) Nutritional characterization and bioactive components of commercial carobs flours. Food Chem 153:109–113 8. Rtibi K, Selmi S, Grami D, Amri M, Eto B, El-Benna J, Sebai H, Marzouki L (2017) Chemical constituents and pharmacological actions of carob pods and leaves (Ceratonia siliqua L.) on the gastrointestinal tract: a review. Biomed Pharmacother 93:522–528 9. Saha A, Tyagi S, Gupta RK, Tyagi YK (2017) Natural gums of plant origin as edible coatings for food industry applications. Crit Rev Biotechnol 37:959–973 10. BeMiller J (2008) Gums and related polysaccharides. In: Fraser-Reid BO, Tatsuta K, Thiem J (eds) Glycoscience. Springer, Berlin, Heidelberg 11. Knudsen KEB (2001) The nutritional significance of dietary fibre analysis. Anim Feed Sci Technol 90:3–20 12. Baldwin EA, Hagenmaier R, Bai J (2011) Edible coatings and films to improve food quality. CRC Press, Boca Raton 13. Prajapati VD, Jani GK, Moradiya NG, Randeriaa NP, Nagar BJ (2013) Locust bean gum: a versatile biopolymer. Carbohydr Polym 94:814–821 14. Maier H, Anderson M, Karl C, Magnuson K (1993) Guar, locust bean, tara and fenugreek gums. In: Whistler RL, BeMiller JN (eds) Industrial gums – polysaccharides and their derivatives. Academic Press, New York 15. Barak S, Mudgil D (2014) Locust bean gum: processing, properties and food applications – a review. Int J Biol Macromol 66:74–80 16. Bouzoita N, Khaldi A, Zgoulli S, Chebil L, Chekki R, Chaabouni M (2007) The analysis of crude and purified locust bean gum: a comparison of samples from different carob tree populations in Tunisia. Food Chem 101:1508–1515 17. Smith BM, Bean SR, Schober TJ, Tilley M, Herald TJ, Aramouni F (2010) Composition and molecular weight distribution of carob germ protein fractions. J Agric Food Chem 58:7794– 7800 18. Dakia PA, Blecker C, Robert C, Wathelet B, Paquot M (2008) Composition and physicochemical properties of locust bean gum extracted from whole seeds by acid or water dehulling pre-treatment. Food Hydrocoll 22:807–818

238

N. Duhan et al.

19. Stick RV, Williams SJ (2009) Disaccharides, oligosaccharides and polysaccharides. In: Stick RV, Williams SJ (eds) Carbohydrates: the essential molecules of life, 2nd edn. Elsevier 20. Daas P, Grolle K, Vliet T, Schols H, de Jongh H (2002) Toward the recognition of structure function relationships in galactomannans. J Agric Food Chem 50:4282–4289 21. Picout D, Ross-Murphy S, Jumel K, Harding S (2002) Pressure cell assisted solution characterization of polysaccharides. 2. Locust bean gum and tara gum. Biomacromolecules 3:761–767 22. Paramita D, Biswanath SA, Sabyasachi M (2011) Carboxymethyl ethers of locust bean gum: a review. Int J Pharm Pharm Sci 3:4–7 23. Ferguson LR, Harris PJ (2005) Dietary fibres and human health. Mol Nutr Food Res 49:517–517 24. Srivastava M, Kapoor VP (2005) Seed galactomannans: an overview. Chem Biodivers 2:295–317 25. Mudgil D, Barak S, Khatkar BS (2012) Effect of enzymatic depolymerization on physicochemical and rheological properties of guar gum. Carbohydr Polym 90:224–228 26. Pollard MA, Kelly R, Wahl C, Fischer P, Windhab E, Eder B, Amadó R (2007) Investigation of equilibrium solubility of a carob galactomannan. Food Hydrocoll 21:683–692 27. Sittikijyothin W, Torres D, Gonçalves MP (2005) Modelling the rheological behaviour of galactomannan aqueous solutions. Carbohydr Polym 59:339–350 28. Duhan N, Sahu JK, Naik SN (2018) Temperature dependent steady and dynamic oscillatory shear rheological characteristics of Indian cow milk (desi) ghee. J Food Sci Technol 55:4059–4066 29. Wu Y, Cui W, Eskin NAM, Goff HD (2009) An investigation of four commercial galactomannans on their emulsion and rheological properties. Food Res Int 42:1141–1146 30. Andrade P, Ricardo D, Lemus M, Roberto P’e C, Carmen E (2011) Models of sorption isotherms for food: uses and limitations. Vitae 18:325–334 31. Torres MD, Moreira R, Chenlo F, Vázquez MJ (2012) Water adsorption isotherms of carboxymethyl cellulose, guar, locust bean, tragacanth and xanthan gums. Carbohydr Polym 89:592–598 32. Beneke C, Viljoen A, Hamman J (2009) Polymeric plant-derived excipients in drug delivery. Molecules 14:2602–2620 33. Rojas-Argudo C, Del Rio MA, Perez-Gago MB (2009) Development and optimization of locust bean gum (LBG)- based edible coatings for postharvest storage of ‘fortune’ mandarins. Postharvest Biol Technol 52:227–234 34. Conforti FD, Totty JA (2007) Effects of three lipid/hydrocolloid coatings on shelf life stability of golden delicious apples. Int J Food Sci Tech 42:1101–1106 35. Chen S, Nussinovitch A (2000) Galactomannans in disturbances of structured wax hydrocolloid-based coatings of citrus fruit (easy-peelers). Food Hydrocoll 14:561–568 36. Brennan CS (2005) Dietary fibre, glycaemic response, and diabetes. Mol Nutr Food Res 49: 560–570 37. Salehi F (2019b) Characterization of new biodegradable edible films and coatings based on seeds gum: a review. J Pack Tech Res 1:1–10 38. Salehi F, Kashaninejad M (2014b) Kinetics and thermodynamics of gum extraction from wild sage seed. Int J Food Eng 10:625–632 39. Williams PA, Phillips GO (2000) Introduction to food hydrocolloids. In: Phillips GO, Williams PA (eds) Handbook of hydrocolloids. CRC Press, New York 40. Bourtoom T (2008) Edible films and coatings: characteristics and properties. Int Food Res J 15: 1–12 41. Martins JT, Cerqueira MA, Bourbon AI, Pinheiro AC, Souza BWS, Vicente AA (2012) Synergistic effects between k-carrageenan and locust bean gum on physicochemical properties of edible films made thereof. Food Hydrocoll 29:280–289 42. Bojnanska T, Smitalova J, Vollmannova A (2016) Effect of the addition of hydrocolloids on the rheological and baking properties of the products with added spelt flour (Triticum spelta L.). Potravinarstvo 10:157–163 43. Anton AA, Artfield SD (2008) Hydrocolloids in gluten-free breads: a review. Int J Food Sci Nutr 59:11–23

9

Chemistry, Biological Activities, and Uses of Locust Bean Gum

239

44. Gomez M, Ronda F, Caballero PA, Blanco CA, Rosell CM (2007) Functionality of different hydrocolloids on the quality and shelf-life of yellow layer cakes. Food Hydrocoll 21:167–173 45. Salehi F (2019) Improvement of gluten-free bread and cake properties using natural hydrocolloids: a review. Food Sci Nutr 7:3391–3402 46. Özboy Ö (2002) Development of corn starch-gum bread for phenylketonuria patients. Food Nahrung 46:87–91 47. Cerqueira MA, Bourbon AI, Pinheiro AC, Martins JT, Souza BWS, Teixeira JA, Vicente AA (2011) Galactomannans use in the development of edible films/coatings for food applications. Trends Food Sci Technol 22:662–671 48. Vargas M, Pastor C, Chiralt A, McClements DJ, González-Martínez C (2008) Recent advances in edible coatings for fresh and minimally processed fruits. Crit Rev Food Sci Nutr 48:496–511 49. Dogan M, Toker OS, Goksel M (2011) Rheological behavior of instant hot chocolate beverage: part 1. Optimization of the effect of different starches and gums. Food Biophys 6:512–518 50. Gallagher E, Gormley TR, Arendt EK (2004) Recent advances in the formulation of gluten-free cereal-based products. Trends Food Sci Technol 15:143–152 51. Silva E, Birkenhake M, Scholten E, Sagis LMC, van der Linden E (2013) Controlling rheology and structure of sweet potato starch noodles with high broccoli powder content by hydrocolloids. Food Hydrocoll 30:42–52 52. Schorsch C, Jones MG, Norton IT (1999) Thermodynamic incompatibility and microstructure of milk protein/locust bean gum/sucrose systems. Food Hydrocoll 13:89–99 53. Rodd AB, Davis CR, Dunstan DE, Forrest BA, Boger DV (2000) Rheological characterisation of ‘weak gel’ carrageenan stabilised milks. Food Hydrocoll 14:445–454 54. Thaiudom S, Goff HD (2003) Effect of κ-carrageenan on milk protein polysaccharide mixtures. Int Dairy J 13:763–771 55. Sanchez C, Zuniga-Lopez R, Schmitt C, Despond S, Hardy J (2000) Microstructure of acid– induced skim milk–locust bean gum–xanthan gels. Int Dairy J 10:199–212 56. Fiszman SM, Lluch MA, Salvador A (1999) Effect of addition of gelatin on microstructure of acidic milk gels and yoghurt and on their rheological properties. Int Dairy J 9:895–901 57. Ünal B, Metin S, Işıklı ND (2003) Use of response surface methodology to describe the combined effect of storage time, locust bean gum and dry matter of milk on the physical properties of low-fat set yoghurt. Int Dairy J 13:909–916 58. Turabi E, Sumnu G, Sahin S (2008) Rheological properties and quality of rice cakes formulated with different gums and an emulsifier blend. Food Hydrocoll 22:305–312 59. Angioloni A, Collar C (2009) Gel, dough and fibre enriched fresh breads: relationships between quality features and staling kinetics. J Food Eng 91:526–532 60. Sharadanant R, Khan K (2003) Effect of hydrophilic gums on the quality of frozen dough: II. Bread characteristics. Cereal Chem 80:773–780 61. Khemakhem M, Attia H, Ayadi MA (2019) The effect of pH, sucrose, salt and hydrocolloid gums on the gelling properties and water holding capacity of egg white gel. Food Hydrocoll 87: 11–19 62. Li J, Zhu Y, Yadav MP, Li J (2019) Effect of various hydrocolloids on the physical and fermentation properties of dough. Food Chem 271:165–173 63. Tan H, Chen W, Liu Q, Yang G, Li K (2018a) Pectin oligosaccharides ameliorate colon cancer by regulating oxidative stress and inflammation-activated signaling pathways. Front Immunol 9:1504 64. Hubbermann EM, Heins A, Stӧckmann H, Schwarz K (2006) Influence of acids, salt, sugars and hydrocolloids on the colour stability of anthocyanin rich black currant and elderberry concentrates. Euro Food Res Tech 223:83–90 65. Barak S, Mudgil D, Taneja S (2020) Exudate gums: chemistry, properties and food applications–a review. J Sci Food Agric 100:2828–2835 66. Mudgil D, Barak S, Khatkar BS (2014) Guar gum: processing, properties and food applications—a review. J Food Sci Technol 51:409–418

Chemistry, Biological Activities, and Uses of Moringa Gum

10

Leena Kumari, Madhuri Baghel, Subhamay Panda, Kalyani Sakure, Tapan Kumar Giri, and Hemant Badwaik

Contents 1 2 3 4 5

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Source, Collection, Isolation, Extraction, and Purification of Moringa Gum . . . . . . . . . . . . . . Chemistry of Moringa Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Physicochemical Properties of Moringa Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Derivatization of Moringa Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.1 Carboxymethylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.2 Grafting . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.3 Etherification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.4 Thiolation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.5 Cross-Linking . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.6 Acryloylation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5.7 Acid Hydrolysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Biological Activities of Moringa Gum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Applications of Moringa Gum in Pharmaceutical, Biomedical, and Other Fields . . . . . . . . 7.1 As Polymer Electrolyte in Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.2 For the Synthesis of Bio-resins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.3 As an Adsorbent for Wastewater Treatment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.4 As a Pharmaceutical Excipient . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7.5 Drug Delivery Carrier . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

243 244 246 247 248 248 248 249 249 250 250 251 251 251 252 253 253 255 257 260 260

L. Kumari · T. K. Giri Department of Pharmaceutical Technology, Jadavpur University, Kolkata, India M. Baghel · K. Sakure · H. Badwaik (*) Rungta College of Pharmaceutical Sciences and Research, Kohka, Bhilai, India S. Panda Post-Graduate Department of Zoology, Banwarilal Bhalotia College, Asansol, India © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_10

241

242

L. Kumari et al.

Abstract

Natural gums have gotten a lot of interest because of their low cost, accessibility, outstanding qualities, and structural diversity, as green “bio-based” renewable materials. Natural gum polysaccharides have recently been received a lot of attention for their potential use in the environment, food, biotechnology, and pharmaceutical industries. Moringa oleifera, commonly known as “Moringa or horseradish tree or drumstick tree,” is a plant native to India that thrives in tropical and subtropical climates around the world. Every portion of the tree is suitable for nutritional or economic applications due to its high nutritious contents. Moringa gum has a number of therapeutic properties, including antipyretic, antioxidant, antiasthmatic astringent, and rubefacient properties, and is used to treat syphilis, gastrointestinal problems, and rheumatism. The objective of this chapter is to consolidate information on the collection, isolation, purification, chemistry, physicochemical properties, and various ways for derivatizing moringa gum to improve its surface morphology and physicochemical properties. In addition, we looked at the medicinal potential of moringa gum and derivatized moringa gum in a variety of fields to assess future research opportunities. Keywords

Biopolymers · Biomedical field · Moringa gum · Moringa oleifera · Natural gums Abbreviations

Al-O AMG C16-O-MOG C4-O-MOG C8-O-MOG CCS CRG DPPH DSSCs DW eSf LCM MCG MGAC MG-PUF MOG NaMG NPAMG NVP PAMG

Acetylated oligosaccharides Acryloyl MOG Hexadecyl-MOG Butyl-MOG Octyl-MOG Croscarmellose sodium Carrageenan 1,1-diphenyl-2-picrylhydrazyl Dye-sensitized solar cells Distilled water Ethanol soluble fraction Lannea gum Malachite green MOG activated carbon Moringa gum-polyurethane foam Moringa gum Sodium salt of MOG Nano-polyacryloyl MOG N-vinyl-2-pyrrolidone Polyacryloyl MOG

10

Chemistry, Biological Activities, and Uses of Moringa Gum

RTIL SSG SWF VOS

1

243

Room temperature ionic liquid electrolytes Sodium starch glycolate Simulated wound fluid Volatile organic solvent

Introduction

Natural polymers derived from plants have sparked a lot of interest in recent years due to their wide range of pharmaceutical applications, including diluent, binder, gelling agents, thickeners in oral liquid preparations, disintegrating agents in tablets, colloids in suspensions, and suppository bases [1, 2]. They are also used in the production of textiles, papermaking, paints, and cosmetics [3]. Natural gums and mucilages are favored over synthetic counterparts since they are biocompatible, biodegradable, inexpensive, and readily available. Moreover, natural excipients are often preferred over synthetic and semisynthetic excipients due to their nontoxic and nonirritant nature [4, 5]. Owing to the rising demand for these natural polymers, new sources of these compounds are being created to meet the demand. India has historically been a good source for such products among Asian countries due to its geographical and environmental location [4, 6]. Pharmaceutical companies have long used these natural polymers in the production of new drug delivery technologies that are more targeted in their action to achieve desired therapeutic action [7]. Among them, carbohydrate or polysaccharide-based polymers are one of the most versatile and commercially important biopolymers for the production of drug delivery devices against a variety of pathological conditions [8–10]. They also conform to various post-synthesis alterations that change their physicochemical properties or even prevent them from degrading. Gum polysaccharides, also known as gum hydrocolloids, are popular and flexible materials used in various important fields, such as pharmaceutical, biotechnology, environmental, and food industries. They are composed of sugar salts such as D-galactose, L-arabinose, L-rhamnose, and D-glucuronic acid, as well as traces of sodium, potassium, and magnesium cations. They are generally translucent, amorphous, practically insoluble in most organic solvents; however, they absorb water and get swelled up to produce thick and viscous solutions [11]. Natural gums also possess specialized surface characteristics that allow them to reduce surface tension between solid-liquid, liquid-liquid, and gas-liquid, resulting in stability through electrostatic, steric, and hydration forces. They can be chemically modified to obtain numerous advantages as natural resources or for grafting with other synthetic polymers [12]. Moringa gum (MOG) is a natural polysaccharide derived from the stem exudate of the Moringa oleifera plant, a widespread tree found in the tropical and subtropical regions of the world. Initially, the color of the gum remains white, but when exposed, it turns reddish-brown and finally black. In an aqueous solution, it swells up readily,

244

L. Kumari et al.

yielding a very sticky solution [13]. The pure gum compound comprises L-arabinose, D-galactose, D-glucuronic acid, and L-rhamnose [14]. MOG has been shown to possess antioxidant, antibacterial, antifungal, and anti-inflammatory properties [15]. It possesses several beneficial features, including non-toxicity, biocompatibility, biodegradability, environmental friendliness, and relatively cheap. It is used as a gelling and thickening agent because of its ability to retain water and form hydrogels. It may also be used as a binding, suspending, and stabilizing agent [16, 17]. Physical and chemical modifications of MOG polysaccharides have helped in the production of various formulations for pharmaceutical and biomedical applications such as drug delivery [18, 19], wound dressings [20, 21], polymer electrolytes in cells [22], synthesis of bio-resins [23], etc. In addition, MOG has also been used to produce bioadsorbents for the removal of heavy metals and harmful dyes efficiently and quickly [24, 25]. This chapter concentrates on the collection, isolation, extraction, and purification, as well as chemistry and various modification techniques, with a special focus on its application in various pharmaceutical, biomedical, and other industrial sectors.

2

Source, Collection, Isolation, Extraction, and Purification of Moringa Gum

MOG is derived from the Moringa oleifera plant, which belongs to the Moringaceae family. The plant is also known as a “kelor tree” or “drumstick tree” [26]. India, Arabia, Pakistan, Cambodia, Philippines, America, and Africa are all habitats to the Moringa oleifera [27–29]. The height of the plant ranges between 5 and 10 m, and thrives in a tropical climate and can be found growing along river banks [29, 30]. It can survive in a hot, humid climate and can withstand heavy rain, and needs 250 and 3000 mm of a minimum and maximum annual rainfall, respectively [31]. It has a high nutritional value and is eaten as food in tropical countries. Plant parts with high nutritional value, such as fruits, flowers, immature pods, and leaves are served as a staple food in several countries, including India, Pakistan, Philippines, Hawaii, and Africa [26, 32, 33]. The MOG is collected as exudate from the injured stem site. When the exudate is collected, it appears white; but, when exposed to sunlight, it gradually becomes reddish-brown or brownish-black (Fig. 1). Finally, the dried gum is crushed to create fine particles before being sieved at number 80 sieve [34]. The isolation of MOG was carried out by mixing a weighed amount of dried gum in distilled water (DW) at 37
C for 6–8 h. Subsequently, the supernatant was separated by centrifugation. The residual substance was washed with DW multiple times and the supernatants were carefully mixed. The DW was used to make up the volume of the solution up to 500 mL. Then twice the amount of acetone was added to the solution and stirred vigorously. The resulting precipitate was washed thoroughly with DW

10

Chemistry, Biological Activities, and Uses of Moringa Gum

245

Fig. 1 The collection process of raw MOG. (Reproduced by permission of Badwaik et al. [38])

before being dried under vacuum at 50–60
C [34]. The Bial’s Orcinol test and Aniline acetate test for pentose sugar, and the Tollen’s phloroglucinol test and Cobalt chloride test for hexose sugar may also confirm the existence of hemicelluloses (pentoses and hexoses) in MOG [35]. The isolation of MOG polysaccharides was also performed by Pal and Singh [36]. L-arabinose and D-galactose in a 1:4 molar ratio, with traces of L-fucose, were reported as the obtained watersoluble polysaccharides. Fehling’s solution is not reduced by pure gum polysaccharide, and negative tests were reported for sulfur, halogens, nitrogen, acetyl, and methoxy groups. Raja et al. [37] further isolated the polysaccharide arabinogalactan by extracting and purifying the crude gum. In this study, the water extracted polysaccharide was again dissolved in water, and an anion exchange chromatography was performed on an Amberlite IRA-400 (OH-) column (20 mm  160 mm) at pH 6.5 and yielded water eluted fraction that was known as arabinogalactan.

246

3

L. Kumari et al.

Chemistry of Moringa Gum

Bhattacharya et al. [39] reported the existence of (1 ! 3)-β-type linkages and the extremely branched structure of gum polysaccharides of moringa. L-arabinose, Dgalactose, D-glucuronic acid, L-rhamnose, D-mannose, and D-xylose are all present in the gum obtained from the Moringa oleifera plant in a mole ratio of 14.5:11.3:3:2: 1:1. Methylation of purified gum polysaccharides established the molecular structure of the polysaccharide [40]. Purdie’s [41] and Hakomari’s [42] methods had been used to methylate the polysaccharide of MOG in this analysis. The methylated gum was hydrolyzed with methanolic hydrogen chloride before being saponified. The ether soluble (i.e., methylated polysaccharide) and ether insoluble (i.e., methylated uronic acid) fractions were obtained by extracting the mixture with ether. The presence of different components of methyl sugar in MOG was determined by fractionating the ether soluble fraction using the paper chromatographic technique. Whatman filter paper No. 3 had been used as stationary phase, and the molar ratio of components was found to be 1:1:1:2 for (a) 2,3,4-tri-O-methyl D-galactose, (b) 2,3di-O-methyl-L-arabinose, (c) 2,3,4,6-tetra-O-methyl-D-galactose, and (d) 2,4-di-Omethyl-D-galactose. The 2,3,4-tri-O-methyl-D-glucuronic acid was identified in the ether insoluble fraction [40]. Likewise, Singh [43] used the same methodology as Pal and Singh [40] to investigate the methylation of degraded gum polysaccharides. In the moles’ ratio of 1:2:3:6, it yielded 2,3,6-tri-O-methyl-D-galactose; 2,4-di-Omethyl-D-galactose; 2,3,4-tri-O-methyl-D-glucuronic acid; and 2,3,4-tri-O-methylD-galactose. The periodate oxidation of arabinogalactan established its molecular structure. The backbone of arabinogalactan was discovered to be made up of 1,6-, 1,3-, and 1,3,6-linked galactopyranose units. The ethanol-soluble fraction (eSf) was obtained after Smith degradation, and sugar analysis revealed the presence of galactose and arabinose residues in a 72/28 molar ratio. GC-MS analysis was used by Raja et al. [37] to determine the composition of monosaccharide units and their linkage pattern in MOG. The existence of arabinose, xylose, glycosaminoglycan, rhamnose, and galactose in a molar ratio of 64:4:4:3:25 was reported by GC-MS analysis of acetylated oligosaccharides (A1-O) obtained from the eSf, indicating the presence of arabinogalactan. The MOG linkage pattern revealed a heavily branched arabinogalactan structure comprising nonreducing units of galactopyranose, arabinopyranose, xylopyranose, arabinofuranose, and rhamnopyranose. The galactopyranose units are 1,6-, 1,3-, and 1,3,6-linked (β-linked) based on the above details, whereas, arabinofuranose units are 1,3and 1,3,5-linked (α-linked) [44]. The presence of protein content (7% (w/w)) in MOG was also revealed by GC-MS study, with aspartic acid/asparagine (17.5%), lysine (9.5%), glycine (9.2%), and glutamic acid/glutamine (8.9%) accounting for the majority of the amino acids. The generalized primary structure of MOG was depicted below, based on the findings of various researchers (Fig. 2).

10

Chemistry, Biological Activities, and Uses of Moringa Gum

247

Fig. 2 Generalized primary structure of MOG. (Reproduced by permission of Badwaik et al. [38])

4

Physicochemical Properties of Moringa Gum

MOG was sparingly soluble in cold water, and deacetylation of the aqueous gum extract enhanced its solubility. Sequential extraction with alcohol, water, acid, and alkaline, respectively, at an elevated temperature, yielded the greatest recovery of gum metabolites. The matrix-forming capability of MOG was investigated using soluble and insoluble fractions of deacetylated and water-soluble gum by microscopic analysis [17]. MOG is viscoelastic, which means it behaves like a solid and a liquid at the same time. The rheological qualities of MOG are influenced by a number of parameters, including blend concentration, temperature, and sugar type [45]. Glosh et al. [46] compared the viscosities of MOG blended with PVA to those of the pure components. Phase separation was detected in the MOG/PVA blend solution at room temperature. The phenomenon of phase separation was minimized to a larger extent when the temperature was raised to 50
C. Additionally, pure MOG had a higher viscosity at lower shear rates than both pure PVA and MOG/PVA combinations. In the case of MOG/PVA mix solution, however, the viscosity drops as the concentration of PVA falls (i.e., 5%, 6%, 7%). The physicochemical features of MOG point to its hydrocolloidal character and usefulness as a thickening, suspending, binding agent, and controlled release matrix.

248

5

L. Kumari et al.

Derivatization of Moringa Gum

It has been stated that MOG can be modified to improve their surface morphology and physicochemical properties. Carboxymethylation, grafting, etherification, thiolation, cross-linking, acryloylation, and acid hydrolysis have all been used to derivatize MOG.

5.1

Carboxymethylation

Owing to the reduced cost of chemicals and ease of manufacturing, carboxymethylation is one of the most commonly used modification techniques of natural gums. Carboxymethylated gums are polyelectrolytes with increased water solubility that are used in various drug delivery and biomedical applications [47, 48]. The carboxymethylation process has improved the swelling ability, solubility, micrometric, and rheological properties of arabinoxylan, arabinogalactans, and galactomannans [49]. Williamson’s synthesis was used to perform carboxymethyl functionalization of moringa gum. As compared to native gum, modified gum had a lower viscosity, less swelling, a rougher base, and a higher degree of crystallinity. Using ofloxacin as a model drug, the modified gum was interacted with chitosan to formulate polyelectrolyte complex nanoparticles. Ofloxacin was released continuously in a sustained manner through the polyelectrolyte nanoparticles [50].

5.2

Grafting

The grafting of synthetic polymers onto the natural gums is a novel approach for tailoring their physical and chemical properties. These alteration reactions have a variety of applications in various polymer applications. Because of their adaptability, synthetic polymers are much more efficient than natural ones. However, they have several drawbacks which could be overcome by grafting them with natural polymers. Among various natural polymers, gum polysaccharides are biodegradable, biocompatible, relatively cheap, nontoxic, and reduce flocculation at higher concentrations. The shelf life of natural gums is reduced due to their biodegradable nature, which must be carefully managed. The grafting of various synthetic polymers such as polyacrylamide, polymethylmethacrylate, polyacrylonitrile, N-vinyl imidazole, etc., onto the natural gums have been reported by various researchers in this field. Various techniques are employed to graft synthetic polymers onto the natural gums such as simple grafting method, microwave irradiation, γ-ray irradiation, and by using electron beam [51–53]. The microwave irradiation technique used for grafting is more efficient as compared to the conventional grafting method due to its instant reactions and yield of pure products [54]. Singh and Kumar [55] carried out the grafting of N-vinyl imidazole onto the MOG by implementing a radiation-induced graft copolymerization technique. Briefly, a solution of 10% w/v of MOG and N-vinylimidazole after hydration was agitated for 4 h at 100 rpm to obtain a homogenous mixture. The resulting mixture

10

Chemistry, Biological Activities, and Uses of Moringa Gum

249

was then irradiated in the gamma chamber (60Co-rays) for 24 h at a radiation dose of 0.56 kGy/h. Subsequently, the polymer was thoroughly washed with DW and dried at 45
C in a hot air oven until it reached a constant weight. The concentration of MOG and N-vinylimidazole at 10% (w/v) and 2.19  101 mol l1, respectively, and irradiation dose of 21.69 kGy was considered to be the optimum reaction conditions for copolymer synthesis. FTIR, 13C NMR spectroscopy, AFM and Cryo-SEM, and swelling analyses were used to characterize the polymers. The copolymers were also evaluated for their gel strength, antioxidant function, mucoadhesion, and blood compatibility. The grafted copolymer was mucoadhesive, antioxidant, and nonhemolytic in nature. On the other hand, a microwave-assisted graft copolymerization method was also used to graft N-vinyl-2-pyrrolidone (NVP) onto the MOG. The ideal conditions of the synthesis of graft copolymer were as follows: NVP concentration-2% (w/v), MOG concentration-1% (w/v), and concentration of ammonium persulfate-10 mMol/L, which resulted in a graft copolymer of 24.23% grafting efficiency. FTIR, SEM, and X-ray diffraction studies were used to characterize the obtained graft copolymer. The data showed that grafting NVP on MOG improves surface smoothness and reduces its crystallinity [56].

5.3

Etherification

The modification of gums by etherification technique involves the introduction of nonpolar hydrophobic alkyl groups in the backbone of hydrophilic gum, resulting in amphiphilic character in the skeleton of gum polysaccharide. The modified gum is used for efficient partitioning of dye molecules from their aqueous media at the hydrophobic-hydrophilic interface. The key aspect of this procedure is that it uses a facile synthetic process with minimal chemical usage to produce fast and efficient adsorbents of dyes from bioresources, making it a reliable tool for commercial use. The following technique was used to etherify moringa gum [57]. In brief, the sodium salt of pure MOG was obtained by incubating it in an 18% NaOH solution at 37
C for 2 h with continuous stirring, followed by extraction with isopropanol. Subsequently, butyl bromide was added to the resulting solution and stirred for 6 h at 60
C. Methanol was used to precipitate the butyl-MOG (C4-O-MOG), which was then washed with isopropanol, and then with acetone, and finally evaporated to dryness. Using the corresponding alkyl bromides, a similar procedure was used to obtain different etherified MOG products, namely octyl-MOG (C8-O-MOG) and hexadecyl-MOG (C16-O-MOG).

5.4

Thiolation

The mucoadhesive features of MOG are improved by using the thiolation process. The arabinogalactan moiety is known to be present in the structure of MOG. The hydroxyl groups of arabinogalactan were reacted with the carboxyl group of thioglycolic acid in an acidic milieu to achieve thiol derivatization. MOG was thiolated in acidic conditions by esterification with thioglycolic acid. The reaction

250

L. Kumari et al.

lasted 150 min, and the temperature was raised to 80
C throughout that process. The mixture was then cooled to room temperature, and the resultant was precipitated by gradually adding acetone. The thiolated MOG was then rinsed with acetone before being dried in an oven at 50
C for 1 h. According to Ellman’s approach, the thiol functionalized gum had 0.956 mM of thiol groups/g. It demonstrates that the transformed gum’s surface was smooth and porous, leading to stronger mucus interaction than the native gum [44].

5.5

Cross-Linking

Cross-linking is an effective method for controlling the hydrophilic nature of gum and regulating medication delivery [58]. MOG was modified by using the radiationinduced cross-linking approach [18]. MOG was hydrated by solubilizing it in DW, followed by adding a specific amount of acrylic acid to it and maintained at room temperature. To get a homogeneous solution, the mixture thus obtained was agitated at 100 rpm. The resulting solution was then bombarded with gamma rays for a specified time at a dose of 0.610 kGy/h. The polymer was rinsed with DW after completion of reaction to eliminate any remaining soluble fractions and then processed in a hot air oven at 45
C. The modified gum hydrogel was pH-responsive, antioxidant, mucoadhesive, non-thrombogenic, and nonhemolytic. A similar approach was used by the same research team to cross-link MOG with acrylamide. The tailored polymer was found to be mucoadhesive and antioxidant [19]. The radiation cross-linked hydrogel was observed to be porous in both instances, allowing for sustained and regulated drug encapsulation and release. The superabsorbent hydrogel was also made from MOG and PVA cross-linked with borax. At an elevated temperature, the produced hydrogels showed higher water-holding ability, reswelling characteristics, and salt sensitivity, as well as stimuli-sensitive swelling capacity in physiological saline solutions [59].

5.6

Acryloylation

The MOG was acryloylated by initially synthesizing sodium salt of MOG (NaMG). Isopropanol was used to extract a gum suspension made with 18% w/v NaOH. Subsequently, the extract was rinsed in 2-propanol and evaporated to dryness at 40
C in an oven. After placing the resultant mixture in an ice bath (at 2
C), the acryloyl chloride was added. Acryloyl MOG (AMG) was then precipitated and was repeatedly rinsed with rectified spirit to eliminate unreacted acryloyl chloride and then dried under vacuum at room temperature. Further, the AMG suspension was developed in DW with 1% APS. The suspension was treated to a polymerization procedure at 60
C for 45 min, resulting in polyacryloyl MOG (PAMG), a viscous cross-linked polymer of AMG. PAMG had a porous surface, which could be owing to interactions between polymeric chains following a cross-linking reaction. PAMG had subsequently converted into nano-polyacryloyl MOG (NPAMG) (nanorods) by

10

Chemistry, Biological Activities, and Uses of Moringa Gum

251

mixing it with purified water, centrifuged for 8 h at 5000 rpm, and then sonicated for 24 h at 37
C. Decanting off the water and collecting the settled product yielded NPAMG. NPAMG was then dried in a vacuum at 40–50
C [24].

5.7

Acid Hydrolysis

MOG bio-nanofibers is synthesized via combined acid hydrolysis of purified gum and ultrasonic treatment. Acid hydrolysis of hemicelluloses removes the amorphous part of the gum. Sulfuric acid (20%, 40%, or 60% by weight) is added to the dry powder gum throughout this process. A mechanical stirrer was used to agitate the mixture over a hot plate that was heated to 40
C for 1, 2, or 3 h. The incorporation of DW terminated the process after the accomplishment of hydrolysis. To remove excess sulfuric acid, the resultant suspension was centrifuged for 10 min at speeds of 5000, 7500, and 10,000 rpm. The final product was rinsed in DW until it reached a neutral pH, and suspended in DW. To recover nanofibers, the suspension was sonicated for 15 min in an ice bath with a probe sonicator at 20–25 kHz and 650 W output power. The fibers were comminuted to nano-sized fibers after the sonication procedure. The obtained bio-nanofibers were of 98 nm diameter and 20 μm length. Few glycosidic linkages and intramolecular hydrogen bonds break during acid hydrolysis of MOG. The synthesized nanofibers could be a very promising drug delivery vehicle in the near future [35].

6

Biological Activities of Moringa Gum

MOG was traditionally used as a rubefacient and an astringent, and also to treat dental carries [60, 61]. Gastrointestinal disturbances, fever, headache, rheumatism, syphilis, abortifacient, and asthma were all treated with the gum combined with sesame oil [62]. As per Kushwaha et al. [63], MOG exhibits antifilarial properties. In this study, MOG extract was investigated for antifilarial efficacy against the human lymphatic filarial parasite Brugia malayi. The gum extract was proven to be beneficial both in vitro and in vivo, suggesting that it could be used to generate new antifilarial medicines. The antioxidant activity of MOG was also investigated. The stable DPPH (1,1-diphenyl-2-picrylhydrazyl) radical was used to test the polysaccharide’s free radical scavenging characteristics (i.e., antioxidant activity). Moreover, the MOG polysaccharide formed a stable and water-soluble combination with β-lactoglobulin at pH levels ranging from 4.0 to 7.4 [37].

7

Applications of Moringa Gum in Pharmaceutical, Biomedical, and Other Fields

MOG and its derivatives possess potential applications in diverse fields, as depicted in Fig. 3.

252

L. Kumari et al.

Fig. 3 Applications of MOG

7.1

As Polymer Electrolyte in Cells

Many biopolymer polysaccharide electrolytes, such as chitosan, starch, pectin, cellulose, iota-carrageenan, and kappa carrageenan, have been studied as polymer electrolytes over the last few decades. The utilization of polymer electrolytes in cells provides a number of benefits, including excellent thermal stability, high ionic conductivity, and the avoidance of sealing and solvent leakage issues [38]. Metal salts with low lattice energy are dissolved in polymer matrices such as ester, ether, and amide linkages to form polymer electrolytes. EIS, FTIR, XRD, DSC, and TNM analysis [22] are used to identify eco-friendly bio-based MOG solid proton electrolytes prepared by solution casting technique with ammonium nitrate (NH4NO3). With its low degree of crystallinity values, incorporation of NH4NO3 into the host matrix of MOG confirms the amorphous domain enhancement. At room temperature, the solid polymer electrolyte MOG (1 g) containing 0.5 wt% NH4NO3 had high ionic conductivity of 2.66  103 S cm1 and an ionic transference number of 0.98. Due to its significance in the field of energy conversion, dye-sensitized solar cells (DSSCs) are the subject of extensive research. The semiconductor electrode, the counter electrode, dye sensitizers, and electrolyte are all required components of DSSCs. Because of its ease of fabrication with readily available materials and fair quality, it finds a place in low-cost solar cells. As photoelectrodes; chalcogenides, TiO2, SnO2, and ZnO have been extensively studied. The electrolyte is one of the most important components of a DSSCs because it provides internal electric ion conductivity by diffusing inside the semiconductor electrode’s layer. Various literature is available on types of electrolytes [64], including volatile organic solvent (VOS), polymer electrolytes, room temperature ionic liquid electrolytes (RTIL), and redox pair. VOS has high efficiency, but it has drawbacks such as poor long-term cell stability and the need for a complex scaling mechanism. Synthetic dyes have greater longevity and efficiency as a sensitizer in DSSCs. Despite this, it has a number of drawbacks, including a higher cost, a proclivity for deterioration, and the use of hazardous materials. To address these limits, biocompatible natural sensitizers have been used. Furthermore, the low cost and widespread availability of naturally occurring biocompatible polymer electrolytes can make DSSCs development more feasible on a large scale. The use of gum resin obtained from MOG as a polymer electrolyte for large-scale production of DSSC solar cells was stated by Saehana and

10

Chemistry, Biological Activities, and Uses of Moringa Gum

253

colleagues. They used a solution casting technique to create a polymer electrolyte membrane out of MOG resin. The polymer electrolyte was then used to make DSSCs [65]. The output of DSSCs with MOG resin was found to be superior to that of the other types of solar cells. Metal nanoparticles in the polymer could be responsible for improving conductivity and, as a result, solar cell efficiency. The low performance of other solar cells may be due to the high internal resistance of DSSCs. They also studied the effect of various dye and TiO2 sizes on the efficiency of solar cells. MOG resin was compared to other polymers such as polyvinyl acetate (PVA) and gum obtained from Lannea coromandelica (Houtt.) Merr. (LCM; Lannea gum or Gumpena gum) for its ability as a polymer electrolyte.

7.2

For the Synthesis of Bio-resins

From natural MOG, Koley et al. [23] synthesized an entirely bio-based resin. Four resins were made with different reactant ratios, and their effects on resin properties were investigated. As a source of monosaccharide, the water eluted fraction of MOG polysaccharide was used, and its composition was evaluated employing GC-MS. To synthesize furfural and HMF, the bio-phenols and monosaccharides were condensed using acid catalysts. Time, temperature, and the ratio of reactants were optimized to find the best reaction conditions. The yield of propionate increased as reaction time, temperature, and the ratio of phenol to monosaccharide increased. Higher temperatures resulted in a higher percentage of furfural being converted from carbohydrate; however, removing resin from the reaction vessel at temperatures above 150
C proved difficult. As a result, resins were synthesized at a temperature of 130
C. Because of its high boiling point and higher percentage conversion of monosaccharide to furfural than the other acids studied (oxalic acid, sulfuric acid, and formic acid), sulfuric acid was found to be the most appropriate of the three acids studied (oxalic acid, sulfuric acid, and formic acid). In situ synthesized furfural and HMF are combined with phenol to form resin in a one-pot reaction.

7.3

As an Adsorbent for Wastewater Treatment

Dyes are to blame for the hydrosphere’s decadent state because they are watersoluble and poorly degradable due to their complex structure, poisonous and dangerous nature. Dye-contaminated water has faced a major environmental threat, because it is dumped as effluent into water sources by a variety of industries. Using MOG, Ranote et al. [57] synthesized novel nano-sized malachite green (MCG) dye adsorbents with different alkyl halides having chain length C-4 (butyl bromide), C-8, (octyl bromide), and C-16 (hexadecyl bromide) through an etherification reaction to obtain nano-C4-O-MG, nano-C8-O-MG, and nano-C16-OMG, respectively. Due to the hydrophobic nature of alkyl groups, the amphiphilic property was introduced, and the hydrophilic nature of the polysaccharide backbone was responsible for the rapid and effective removal of MCG dye from water bodies.

254

L. Kumari et al.

At pH 7 and temperature 25
C, the nano-C4-O-MG and nano-C8-O-MG showed quick dye elimination (almost 100%) in 90 min, while the nano-C16-O-MG showed full MCG dye elimination in 120 min. They also described the synthesis of a novel bio-based moringa gum polyurethane foam (MG-PUF), in which MOG acts as a polyol for reaction with 4,40 diphenylmethane diisocyanate via urethane linkages. The experimental data revealed that MG-PUF extracted nearly 100% of MCG dye in 30 min. MG-PUF was utilized an antibacterial agent as well as an adsorbent of MCG dye. The antibacterial assay revealed significant zones of inhibition against E. coli, Enterococcus, S. aureus, and P. aeruginosa, suggesting its antibacterial potential. As a result, MG-PUF could be used to effectively remove synthetic cationic dyes from contaminated wastewater [25]. The same group of authors [24] had used the acryloylation reaction of MOG to make nano-polyacryloyl MOG (NPAMG). The adsorbent property of NPAMG (for Hg2+ ions) was estimated as a function of temperature, pH, the initial Hg2+ ion concentration, and the contact time. With a maximum adsorption power of 840.34 mg/g, NPAMG was found to efficiently adsorb the cations. During the reusability analysis, the high desorption potential of NPAMG was discovered. The reusability of the Hg2+loaded NPAMG was determined by repeating the adsorptiondesorption cycle. For desorption of adsorbed Hg2+ ions, 0.5 N HCl was used, followed by multiple washes with deionized water to extract HCl, and finally drying at 50
C for 24 h for reuse in the next step. This procedure regenerates the NPAMG, which is then reused a total of 20 times. Following the completion of the 20th cycle, the adsorption potential remained at 71.25 mg/g. Furthermore, the same dose of adsorbent adsorbed a total of 1606.25 mg/g of Hg2+ ions. Heavy metal contamination in water has received a lot of attention because of its detrimental effect on the atmosphere and human health [66]. Ravikumar and Udayakumar [67] have reported on the use of MOG in water purification. They developed, characterized, and tested MOG-bentonite clay nanocomposite coagulant for flocculation and adsorption of heavy metals from aqueous solutions. Individual MOG and bentonite had poorer adsorption potential than synthesized nanocomposite. Heavy metal flocculation and adsorption were also rapid, and the pseudo equilibrium condition reached in less than 30 min. As a result, the innovative green composite coagulo-adsorbent can be used to remove heavy metals from aqueous systems used for drinking, potentially contributing to improved water treatment. Manikandan et al. [68] developed a nanocomposite by coating MOG activated carbon (MGAC) with TiO2NPs (titanium dioxide nanoparticles). The loading ratio of TiO2NPs to MGAC was 9:1 w/w. The photocatalytic electron transfer from the phosphate molecule to the TiO2NPs/MGAC is the mechanism of removal. The sol-gel method was used to prepare it, and its efficacy in eliminating phosphate molecules from wastewater was investigated. Pseudo-first-order rate kinetics governs the elimination. As a result, these nanocomposites have been identified as possible wastewater treatment resources. In another study, the sol-gel technique was utilized to develop the nanocomposites based on aluminum oxide nanoparticles (Al2O3 NPs) and MOG activated carbon (MGAC). The photocatalytic removal of

10

Chemistry, Biological Activities, and Uses of Moringa Gum

255

Fig. 4 Applications of MOG as a pharmaceutical excipient

phosphate and nitrate by the nanocomposite was studied under various LED light irradiations. Phosphate and nitrate ions were effectively removed by the nanocomposite and red LED light spectrum. Even after four cycles of phosphate and nitrate reduction, the nanocomposites were found to be stable [69].

7.4

As a Pharmaceutical Excipient

Gums are one of the most understudied plant components. MOG’s physical and pharmacological properties were elucidated by Jarald et al. [70] to develop it as a medicinal excipient. MOG has a lot of potential as a pharmaceutical excipient in a variety of formulations. It has properties similar to tragacanth gum, which is a wellknown pharmaceutical excipient. It has been used as a binder [71], film-forming agent [72], emulsifying agent [73], gelling agent [34], drug delivery carrier [74], and mucoadhesive polymer [75] (Fig. 4).

7.4.1 Gelling Agent The capacity of natural gums obtained from the moringa plant to form gels was investigated and characterized by Panda et al. [34]. To make the gel, they employed different concentrations of drug (diclofenac sodium), preservative (methylparaben), and plasticizer (glycerin). The gels were then tested for viscosity, pH, and in vitro diffusion. The gels made with 8% moringa mucilage were found to be the best for preparing topical drug delivery systems. 7.4.2 Binding Agent MOG can also be used in a number of tablet formulations as a potential binder and release retardant. The effect of diluents such as lactose and calcium sulfate dihydrate on the pattern of drug release was investigated using model drug propranolol hydrochloride. Tablets were produced in a similar way by substituting calcium sulfate dihydrate for lactose. Despite the fact that the two diluents have opposite solubility characteristics, the drug release rates from both tablets were identical. By decreasing the concentration of MOG and increasing the concentrations of the excipients, the drug release rate was enhanced, regardless of the diluent’s solubility properties. The nature of the excipient was found to play a

256

L. Kumari et al.

minor role in controlling drug release, while the MOG played a major role in delaying drug release from the tablet matrix [71]. The drug’s release mechanism was based on Fickian diffusion. MOG’s binding ability was tested in the formulation of chloroquine phosphate tablets. It was tested as a binding agent at concentrations of 4.0, 6.0, and 8.0% w/w, and its binding capacity was compared to that of potato starch. Tapped density, bulk density, angle of repose, Carr’s compressibility index, and Hausner’s ratio were all measured on the MOG. The thickness, weight variance, hardness, friability, disintegration time, and dissolution rate of the prepared tablets were all assessed. The data showed that as the concentration of MOG increased, the tablet’s hardness and disintegration time increased, while the percentage friability and cumulative drug release decreased. As a consequence of the findings, MOG appears to be as strong a binder as potato starch in the preparation of chloroquine phosphate tablets [76]. Another study also looked at the binding properties of MOG in the preparation of paracetamol tablets. It was discovered that as the concentration of the binder (MOG) was increased, the rate of paracetamol release decreased, implying that it could play a role in the formulation of sustained or controlled release formulations [16]. Similarly, copper oxide (CuO) nanoparticles were synthesized using MOG and Acacia nilotica gum as binding agents in a recent study. SEM analysis revealed fine needle-like structures inside the gum system. CuO nanoparticles prepared from both gums had identical antibacterial properties against E.coli and Staphylococcus bacteria [77]. Using paracetamol as a model drug, a comparative release analysis was also conducted between MOG and Terminalia catappa gum. The release rate of Terminalia catappa gum tablets was found to be higher than that of MOG, implying that MOG can be used as a binder for delayed-release GIT drug delivery [78].

7.4.3 Tablet Disintegrating Agent The MOG has the ability to disintegrate. MOG was isolated by Patel and Patel [79], and its disintegrating properties were explored by making an aceclofenac tablet. As the concentration of MOG in the tablet formulation increased, the wetting properties decreased. The disintegration period of MOG (2% w/w, 3% w/w, 4% w/w) tablets was found to be slower than that of tablets formulated with synthetic disintegrating agents such as croscarmellose sodium (CCS) and sodium starch glycolate (SSG). The in vitro dissolution data showed that all of the tablet formulations released the maximum drug. Overall, the isolated MOG could be used as a disintegrating agent in a variety of tablet formulations, according to the findings. Superdisintegrants such as SSG, crospovidone, and CCS and natural disintegrant such as MOG in varying ratios from 1:1 to 1:4 and were used to create a novel directly compressible, fast-dissolving tablet of metoprolol succinate [80]. The formulation F2, which comprises 2% SSG and 4% MOG, was found to be the best of the 12 co-processed formulations, releasing 97% of the drug within 2 min. Patel and Chobey [81] published a similar study to demonstrate the usefulness of MOG as a tablet disintegrating agent.

10

Chemistry, Biological Activities, and Uses of Moringa Gum

257

7.4.4 Film-Forming Agent MOG was also studied as a coating agent and in drug delivery systems due to its ability to build a film. The films were made by combining MOG mucilage with various amounts of plasticizers such as propylene glycol, glycerin, and polyethylene glycol (PEG 400). Films were cast on glass plates and dried using a regulated evaporation process. Tensile capacity, water uptake, folding endurance, and water vapor transmission rate were all tested on the optimized films. Polymeric films made from hydroxypropyl methylcellulose, sodium carboxymethyl guar gum, ethylcellulose, and eudragit produced similar results [72]. 7.4.5 Emulsifying Agent The emulsifying properties of the MOG were also assessed. Castor oil (30% o/w) and MOG (2–4%) emulsions were compared to acacia emulsions with an equivalent concentration of acacia. Various parameters were examined, including coalescence rate, creaming rate, and globule size. The effects of pH, temperature, electrolytes concentration, and centrifugation rate on creaming and globule size had been studied using a 23 factorial design. All of the emulsion formulations were tested for stability at room temperature, and their stability was evaluated at various time intervals for up to 8 weeks. MOG had superior emulsifying properties when compared to gum acacia, according to the data [73].

7.5

Drug Delivery Carrier

MOG and its derivatives had successfully shown their potential as a carrier in various drug delivery systems (Fig. 5). In the preparation of buccal tablets containing propranolol hydrochloride as a model drug, MOG was investigated as a natural mucoadhesive drug delivery carrier. Buccal tablets containing various concentrations of MOG were made and one face was coated with ethyl cellulose (5% w/v). The oral tablet with and without MOG was produced using the direct compression process. The MOG’s mucoadhesive properties were tested using porcine buccal mucosa as a model tissue in simulated buccal conditions. Both tablets were tested in vitro in phosphate buffer at pH 6.8 to determine drug release, and an in vivo bioavailability analysis was performed on healthy human volunteers. The formulation containing 30 and 40 mg of MOG has higher bioavailability, and it also has adequate mucoadhesive properties for buccal drug delivery [82]. Slow and regulated drug release, such as antibiotics, can be achieved by loading it into hydrogel wound dressings that eliminate the need for frequent dressing changes. Singh and Kumar [20] developed a hydrogel dressing for the antibiotic levofloxacin that uses MOG polysaccharides as a slow drug carrier for improved wound healing. By grafting the carbomer onto MOG films, a radiation-induced cross-linking technique was used to construct polymer films. The dressing was porous, absorbing 4.20 g/g of simulated wound fluid (SWF). The non-Fickian diffusion mechanism was used to match the drug release in the Higuchi kinetic model, and there was no

258

L. Kumari et al.

Hydrogel for GI Dr delivery

ug

el

e

siv

es dh oa cc Bu

rig

d Hy

c

Grafting (NVinyl imidazole)

Carboxymethyla tion & Polyelectrolyte complexation

Po

olym esive P

Thiolyation (Thioglycolic acid)

Bucc oadh

Muccoadhesive Hydrigel

Moringa gum

ers

Grafting (NVinyl-2pyrolidone)

Crosslinking (Acrylic acid)

Crosslinking (Acrylamide)

er lym

M

Po

uc

ive

he

d oa

Acid Hydrolysis & Sonication (Sulpuric acid)

lye

lec tr par olyte ticl N es ano

g

ru rs for D no Fibe Bio Na elivery d

Fig. 5 Applications of MOG in drug delivery

burst effect. Grewal et al. [44] developed metronidazole-loaded buccal tablets of thiolated MOG in a related study. The ex vivo bioadhesion period of buccal tablets prepared from modified MOG was 1.5 times more than that of native gum in a comparative study. Furthermore, thiolated MOG promotes the long-term release of metronidazole from buccal tablets. The in vitro release profile of a grafted copolymer loaded with the antibiotic levofloxacin was tested using a hydrogel formulation. The drug was released from the hydrogel formulation in a continuous and sustained fashion, resulting in a consistent drug concentration, shorter dosing times, and few side effects [44]. Similarly, Roy et al. [83] used microwave irradiation to create a pH-sensitive interpenetrating polymeric network made up of MOG and carrageenan (CRG). The water retention capability of the polymeric network improved as the MOG content increased, assisting in the structural integrity of the network. Furthermore, by irradiating gamma rays, a group of researchers had created pH-responsive meropenem-loaded MO/poly-2-hydroxyethyl methacrylate (HEMA) hydrogels to facilitate the treatment of diarrhea and other abdominal infections [84]. The developed matrix could also be used to develop site-specific drug delivery devices for the controlled delivery of antibiotics, such as meropenem. N-vinyl imidazole graft copolymerization onto MOG was investigated for gastrointestinal drug delivery.

10

Chemistry, Biological Activities, and Uses of Moringa Gum

259

Varma et al. [74] prepared diclofenac sodium sustained-release tablets from MOG. According to the in vitro release report, the optimized tablet formulation had 96% drug release and followed zero-order release kinetics, while the marketed tablet “Voltren” had 95.6% drug release and followed first-order release kinetics. As a result, it was concluded that MOG’s sustained release tablet could have better therapeutic effects than a similar traditional formulation. MOG was also used as a carrier for colon-specific drug delivery in another study. MOG curcumin integrated matrix tablets were made using the wet granulation process. MOG was sieved separately (10% of the total harvested Benzoin gum by weight [50]. In 1914, it was found that the major constituent of the Siam balsam is coniferyl benzoate at 75–80% (Fig. 10). Schroeder’s work also shows that the Siam balsam contains p-coumaryl benzoate (10–15%), cinnamyl cinnamate (0.5–6%), benzoic acid (12%), vanillin (0.3%), and siaresinolic acid (6%) [46].

7

The False Balsams

The name “false balsam” seems a little odd at first, even more after knowing balsam history. The first balsam recorded in human history was the Balsam of Judea or Balsam of Gilead. It must be clarified that the term “false” refers to balsams that do not have the characteristic chemical profile of balsam, containing benzoic or cinnamic acid. Thus, several species that were once considered balsams are, in actuality, oleoresins according to the systematic approach based on chemical evidence. Due to their history, false balsams are still referred to as balsams and not as oleoresins (Table 3), a behavior that must be changed by the scientific community.

7.1

Balsam of Judea

The genus Commiphora is one of the 18 genera of the Burseraceae family. There are 190 species within Commiphora, with major geographic distribution in tropical and subtropical regions, such as southern Africa, tropical east Africa, Pakistan, and India. In general, Commiphora species are small shrubs or trees, no higher than 20 m, mostly with a single trunk and branched canopy. The trunk is composed of softwood, which can occur with caudiciform or pachycaul structures in a few species, such as C. wildii [51]. The major attractive feature of Commiphora species is the trunk resinous exudates. Their resin can be presented in several popular forms, such as frankincense (a highly aromatic essential oil), myrrh gum, and the Balsam of Judea. Each form can be related to a distinct Commiphora species. For instance, the aforementioned examples are closely, but not exclusively, related to C. incisa, C. myrrh, and C. gileadensis, respectively [52]. Since ancient times, the Balsam of Judea was extensively used as an incense and perfume in Somalia, Ethiopia, and China and is characterized by a pinaceous, terpenic, and citric fragrance that could resemble a woody lemon essence [2]. In Ancient Egypt, the Balsam of Judea was also used as an embalming ointment. It can even be observed in the name given to the art of dead body preservation, as

17

Chemistry, Biological Activities, and Uses of Balsams

421

Fig. 10 Chemical composition of the volatile extracts of Siam and Sumatra benzoin balsams

“embalming” is derived from the joining of the words “in” and “balsam.” The use of the Balsam of Judea during mummification is due to its pharmacological properties and chemical profile. Despite it not being known in the time of Ancient Egypt, the Balsam of Judea is composed of terpenoid compounds and several hydrophobic compounds. Such composition provided a hydrophobic layer to the dead body, along with antibacterial, antifungal, and antioxidant properties, which thus prevented the proliferation of the microorganisms responsible for human decay [53].

422

A. T. C. Aguiar et al.

Table 3 Species of false balsams Species Copaifera reticulata Ducke; Copaifera multijuga Hayne; Copaifera officinalis L. Commiphora gileadensis(L.) C. Chr. (synonym: Commiphora opobalsamum (L.) Engl.) Abies balsamea (L.) Mill. Dipterocarpus dyeri; species of Dipterocarpus Sedum dendroideum Moc et Sessé ex DC; Sedum praealtum A. DC.

Popular name Copaiba Balsam

Balsam of Judea; Balsam of Gilead; Mecca Balsam; Egyptian Balsam Canada Balsam; Canada Turpentine; Gurjun Balsam Balsam

The Balsam of Judea has many names (Table 3), all of which exist because, at the time of their discovery and during the Great Navigation Era, botanic identification was scarce meaning species were not properly identified. Because of that, the balsam obtain in each location was named after the place. Thus, even though it was extracted from the same species (C. gileadensis), the balsams received different names. It is worth mentioning that for many decades the Balsam of Judea was also misidentified as coming from the species C. opobalsamum. This mistake was due to the absence of a systematic identification system of botanic species before Linnean classification. Only at the end of the sixteenth century, it was discovered that C. opobalsamum was a synonym of C. gileadensis (Fig. 11) [3]. Commiphora gileadensis has several phenotypes, which can range from a small shrub less than 1 m tall, to trees with an average height of 4 m. C. gileadensis is native to the Red Sea area, and traditionally, its exudates were used in wound treatment following Egyptian observation of its antimicrobial proliferation properties. The Greek soldiers used to carry the Balsam of Judea to treat their wounds, burns, and fractures. In addition, the Balsam of Judea was used to treat joint pain, dyspepsia, arthritis, dermatological disorders, liver and stomach diseases, expelling renal calculi and used as an antiseptic [52, 54]. Unfortunately, the outstanding medicinal properties of the Balsam of Judea and its intense application in cultural rituals due to its fragrance have to push C. gileadensis to the brink of extinction. Wild cultivars are extremely rare even in the Red Sea area [54–56]. Due to the scarcity of C. gileadensis, there are few chemical profiles describing the chemical composition of the species itself, so most of the data is related to the essential oil and alcoholic extracts. Extensive chemical profiles are described by Shen et al. using the oleoresin [52]. Briefly, Balsam of Judea is mainly composed of monoterpene hydrocarbons, sesquiterpenes, and oxygenated monoterpenes (>80% of balsam total composition) (Fig. 12). The most abundant compounds are sabinene, α-pinene, myrcene, β-pinene, cymene, and limonene. Such compounds also explain the woody citric scent of this oleoresin. Terpenoids are widely known as remarkable bioactive substances. Studies with isolated terpenoids have already proved such biological properties as antimicrobial, anti-inflammatory, antiherbivore, antiviral, anticancer, and antidiabetic [57]. Most

17

Chemistry, Biological Activities, and Uses of Balsams

423

Fig. 11 Commiphora gileadensis. (Illustration by: Petronella J.M. Pas. Licensed under Public Domain (https://commons.wikimedia.org/wiki/File:Balsamodendron_ehrenbergianum00.jpg))

preparations for intravenous or oral administration of the Balsam of Judea are aqueous. Such preparations have already been described to have hypotensive properties and hepatoprotective activity, inhibit ulcers, and promote cardiovascular protection against strokes [52, 53]. Pharmaceutical studies performed by Bouville et al. [2] also demonstrated that it has the inhibitory activity of 6.50% against l-tyrosine, 47.30% as an antilipoxygenase, 4.30% as an antielastase, 10.8% as an anticollagenase, and 5.70% antioxidant activity in the DPPH test. These biological

424

A. T. C. Aguiar et al.

Fig. 12 Major chemical compounds identified in the Balsam of Judea

properties corroborate the anti-inflammatory and wound-healing properties traditionally attributed to the Balsam of Judea.

7.2

Canada Balsam

The Canada balsam is the exudate obtained from the trunk of Abies balsamea (Pinaceae). This substance is a viscous oleoresin with a translucent yellowish color and resinous appearance. It is commonly used as a mounting media for microscopical procedures, due to its refraction index at 1.5, and it has antimicrobial properties. The Canada balsam was especially important to ethnobotanics in North America.

17

Chemistry, Biological Activities, and Uses of Balsams

425

Due to its medicinal usage by indigenous societies, and further exploitation as a laboratory reagent, the Canada balsam has become an expensive resin [18, 58]. Since the 1920s, the Canada balsam was classified as an oleoresin yet it is still possible to find reports that use this name as the popular name. Other names include Canada turpentine, balsam of Fir, fir balsam, Oregon balsam, Strasbourg turpentine balsam [59]. A. balsamea is a conical tree that can reach 23 m of height and resemble the format of pine trees, with a grey and smooth bark. Culturally, A. balsamea is used as a Christmas tree in North America. The ethnobotanical usage of A. balsamea resin includes as a topical application to treat rashes, as an antiseptic, as an antiinflammatory against insect bites and open wounds, to treat coughs and flu, as a laxative tea, as an infusion for sore throats, and as a raw material for the preparation of medicines for cardioprotection and digestive problems [59, 60]. The chemical composition of the resins of these different fir species is similar in terms of their composition of diterpenes (abietic and pimaric acids) and is characterized by high amounts of cis-abienol, a labdanic alcohol that polymerizes easily and which may be responsible for the particular characteristics of this resin [59].

7.3

Gurjun Balsam

Gurjun balsam, sometimes called “wood oil,” was reported in the Pharmaceutical Journal, as a new kind of Copaiba balsam; it is an oleoresin exuded from species of the genus Dipterocarpus (Dipterocarpaceae), originating from the forest regions of Southeast Asia [16]. In order to obtain this exudate, which consists of 60 to 80% of essential oil, it is necessary to do an incision in the trees of Dipterocarpus. The Gurjun balsam has many applications, including perfumery [61]. Gurjun balsams are very fluid oleoresins, similar to Copaiba balsams, but consisting of triterpenes dissolved in sesquiterpenes, which correspond to a peculiarity of this type of resin. Gurjun balsams are used in the composition of varnishes [59]. According to Salleh et al. [62], the Dipterocarpaceae is a family of sixteen genera and around more than six hundred species of mostly tropical lowland rainforest trees, especially from northern South America to Africa, India, Indochina (Vietnam, Laos, and Cambodia), Indonesia, and Malaysia. In addition, Dipterocarpus is the third largest and most diverse genus among this family, comprising nearly seventy species, which occur in South East Asia and are well recognized for their timber, and less so for their use in traditional herbal medicines. The phytochemical studies of Dipterocarpus produced a bunch of resveratrol oligomers (oligostilbenoids) and triterpenes and contain bicyclic sesquiterpene hydrocarbons, such as humulene and beta-caryophyllene. Furthermore, these plants have been mentioned because of their bioactivities, such as antibacterial, antioxidant, cytotoxic, anti-inflammatory, and antifilarial activities. The remedial properties of this oleoresin are as a diuretic, antifungal, antimicrobial, spasmolytic, antiulcer, stimulant, antirheumatic, and decongestant. The Gurjun essential oil was once reputed to stimulate the heart and increase blood pressure, while other uses included decongesting and relieving respiratory disorders like asthma, chronic cough, and bronchitis. The Gurjun essential oil is regarded as one

426

A. T. C. Aguiar et al.

of the best Ayurvedic remedies (a traditional Indian medicine) for its potential to eliminate the toxic deposits in the joints and the entire system through urine, through its diuretic properties. This essential oil also has the power to reduce Kapha imbalance, which is responsible for excess water deposits, inflammation, and swelling. Apart from medicinal uses, the Gurjun essential oil is best known for its uses in cosmetics, exquisite and expensive perfumes, as well as in the manufacturing of perfumed toiletries. Due to its physical properties (related to the optical rotation of the molecules), as well as its versatile woody scent, the Gurjun essential oil is often used as an adulterant in patchouli, guaiacwood, ylang-ylang, sandalwood, vetiver, and cubeb oils [63].

7.4

Balsam (Sedum)

The genus Sedum is the largest of the Crassulaceae family, with several species of pharmaceutical interest [64]. The balsam Sedum comes from the species Sedum praealtum DC. and has another popular name, “Bálsamo-alemão,” which, translated to English, is “German balsam.” It is usually produced as a syrup or through the crushing of fresh leaves to form a pap, to be used for the intention of healing [65]. The S. praealtum A. DC. species (synonym. Sedum dendroideum and Sedum dendroideum subsp. praealtum A. DC.) is a little bush with yellow flowers, found from Mexico to Guatemala, popularly known as Balsam. The juice of its leaves is said to have healing properties. The spread of S. praealtum is mainly due to the cutting of branches, which must be planted in 0.5  0.5 m pits when plants have five to eight definite leaves. Although little scientific research has been conducted that support the potential therapeutic effects of the aqueous decoction, aqueous extract, or lyophilization of the Balsam juice, they have been investigated for their treatment of ocular symptoms, gastric ulcer, for their anti-inflammatory action, as a contraceptive, in the inhibition of human sperm motility, and their antifertilization activity in mice [27]. In Brazil, S. praealtum is widely adapted, growing spontaneously, and is popularly called Balsam. Within the species S. dendroideum Moc et Sessé ex DC, several specific chemical compounds have been evidenced, such as polysaccharides with anti-inflammatory action, tannins, triterpenoids with hepatoprotective activity, piperidine alkaloids, and pyrrolidines [66]. According to Lorenzi and Souza [67], S. dendroideum occupies the following taxonomic position: Division: Magnoliophyta; Class: Magnoliopside; Subclass: Rosidae; Order: Rosales; Family: Crassulaceae; Genre: Sedum; Species: Sedum dendroideum subsp. praealtum (DC.) The extracts of Sedum species have shown spermicide, antioxidant, anticholinesterase, antibacterial, and anti-inflammatory activities. S. dendroideum is a subshrub succulent plant, originally from semi-desert areas of Africa, and acclimated to various parts of the world. In Brazil, it is popularly known as Balsam and used in folk medicine to treat gastric ulcers, general inflammatory processes, and several other health problems. Some studies have shown that plant polysaccharides may have gastroprotective properties. So that, when S. dendroideum is popularly used in the

17

Chemistry, Biological Activities, and Uses of Balsams

427

form of tea (infusion or decoction) or as a juice made from its leaves, other chemical compounds, such as polysaccharides and secondary metabolites, are also ingested. Some pharmacological properties of the juice of S. dendroideum have been demonstrated. Malvar et al. [68] showed that it acted as an antinociceptive agent, inhibiting abdominal contortions induced by acetic acid in mice. Moreover, DeMelo et al. [69] described it as an anti-inflammatory agent, promoting both antinociceptive and antiedematogenic effects in mice submitted to the acetic acid-induced writhing test, croton oil-induced ear edema formation, and formalin-induced nociception.

8

Harvesting Methods

There are several methods to collect balsam from trees, and the most traditional methods are based on wounding the trunk. Although it seems to be simple, to just cut the trunk and wait, there are some cautions that must be addressed. The first thing to remember is that the tree trunk protects the plant. Inside the trunk, there are several veins to transport nutrients from the roots to the leaves. Injuring the trunk of the tree is similar to making a cut in human skin; without proper care and attention, it can be fatal as the organism (the plant or the human) will be exposed to infectious diseases. The production of balsam is associated with the plant metabolism response to stress conditions, such as wounds and excessive heat. In the case of wounds, the balsam is exudated to close the trunk, like a bandage [70]. Balsam trees only start to produce balsam at a certain age, which is at least 7 years after its first flowering, depending on the species. In addition, the tree must have a minimum diameter at breast height (DBH or trunk thickness). In general, trees with less than 10 cm of DBH are not capable of producing balsam. The DBH is a measure of age, as it tends to increase throughout the plant’s time, but it is also a measure of nutrition. More healthy plants can achieve a larger DBH and be more suitable to produce balsam [20]. The production of balsam by plants requires large amounts of nutrients. Thus, in forest-like farms (cultivation of different wooden trees in the same place), when a balsam tree is chosen for harvesting, other medium to small trees within a 1 m radius is removed to reduce the competition for soil nutrients in the area [9, 29]. Wounding the trunk is a process known as tapping. During tapping, the cut cannot be too deep in the trunk so to avoid unnecessary exposure of the sapwood (Fig. 13). Another caution is to not expose the heartwood, which, in addition to carrying nutrients through the tree, is responsible for its sustentation, like a vertebral spine. Too much damage to the tree can reduce the production of balsam. The extraction of balsam and other exudates is usually in the bark and sapwood. The tapping methods are diverse and differ mainly by the form of the cut (Fig. 13), the height of the cut, and the removal, or not, of the bark. Exudation of balsam after tapping is a relatively slow process. In Styrax species, it can be taken up to 3 months after tapping to harvest. For Myroxylon and Styrax, balsam can usually be harvested 1 to 3 times a year, after leaves change during the winter season. In general, the first harvesting will produce the highest quality and amounts of balsam, from 200 to 500 g [9, 20].

428

A. T. C. Aguiar et al.

Fig. 13 Tapping methods

Other methods to collect balsam involve covering the wounds with a cotton tissue. The tissue absorbs the balsam, which is later separated with boiling water and compression of the tissue. There are records of farmers who physically hit or burn the trunk surrounding the tapping to stimulate balsam production; however, there is not enough data available to scientifically corroborate whether these practices are of any help [20].

9

Conclusions

In the medieval period, the status and high price of balsam are reported in the writings of some Greek authors, such as Dioscorides and Galen, who were trying to identify the active properties of balsam in the Islamic world and medieval Europe. It was believed that there were types of trees, known as “balsam,” that produced this valuable material, but it was later discovered that for the material to be considered balsam, it must contain certain chemical components, thus narrowing the list of tree species. Thus, this chapter illustrates the roles played by historical background, popular legends, and accumulated knowledge in the perception and qualification of balsams.

17

Chemistry, Biological Activities, and Uses of Balsams

429

The medicinal, cosmetic, and toxic properties of many plants discovered and described in the ancient countries of the Middle East, Egypt, China, and India were essential for further studies. The information collected by the aforementioned civilizations was used by scientists from Ancient Greece and Rome, who improved the therapeutic recipes and sought to systematize knowledge regarding ethnobotany. The use of Balsam in ethnobotany began a long time ago, and in folk medicine, it persisted as a nonconventional treatment prepared in several forms, infusions, syrups, and creams, for gastric disorders, wounds, itching, and more. As a chemical definition, balsams were referred to by the elders as an exudate naturally produced by some trees, which contained substances possessing therapeutic properties. As time passed, the definition became a plant exudate that contains a variety of aromatic components, especially cinnamic and benzoic acids, differentiating them from oleoresins and gums. With a formal chemical definition available, we can now identify and separate the true and false “balsams” that have a risen throughout history. Therefore, it may be that genuine balsams are limited to the genera: Styrax (family Styracaceae), Liquidambar (family Hamamelidaceae), and Myroxylon (family Fabaceae). In addition, the others that can now be labeled as false balsams are, for example, the Balsam of Judea or Gilead, Copaifera balsams, and those from Sedum dendroideum. Based on the data in this chapter, it is concluded that to be considered a “true balsam,” it needs to present a considerable concentration of benzoic and cinnamic acid. This means to say that these plants can be considered as having good antimicrobial and antibiotic activity, in addition to other properties, such as a healing effect, as well as been effectively used against gastric disorders. Acknowledgments This study was financed in part by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior – Brasil (CAPES) – Finance Code 001. The authors would like to acknowledge the financial support of Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro – FAPERJ) and the National Council for Scientific and Technological Development (CNPq). The authors also acknowledge the Military Engineering Institute and the Federal University of Amazonas for their academic support.

References 1. Alves LF (2013) Production of phytotherapeutics in Brazil: history, problems and perspectives. Rev Virtual Quim 5:450–513 2. Bouville AS, Erlich G, Azoulay S, Fernandez X (2019) Forgotten perfumery plants – part I: balm of Judea. Chem Biodivers 16:e1900506 3. Baumann BB (1960) The botanical aspects of ancient Egyptian embalming and burial. Econ Bot 14:84–104 4. Courel B, Adam P, Philippe S (2019) The potential of triterpenoids as chemotaxonomic tools to identify and differentiate genuine, adulterated and archaeological balsams. Microchem J 147: 411–421 5. Milwright M (2003) The balsam of Maṭariyya: an exploration of a medieval panacea source. Bull Sch Orient African Stud 66:193–209 6. Makarska-białokoz M (2020) The development of phytotherapy from the middle ages to modern times history and significance of phytotherapy in the human history. Arch Phys Glob Res 24:17–22

430

A. T. C. Aguiar et al.

7. Alfonso-Goldfarb AM, Ferraz MHM, Beltran MHR (2010) Substitutos do “novo” mundo para as antigas plantas raras: um estudo de caso dos bálsamos. Quim Nova 33:1620–1626 8. Grieve M (2015) Modern Herbal. Stone Basin Books, London 9. Mammerler V (2007) Contribution to the analysis and quality control of Peru Balsam. Dissertation, Universitat Wien 10. Lorenzi H, Matos FJA (2008) Plantas Medicinais no Brasil. Nova Odessa, Brasil 11. Pereira R, Souza EB, Fontenelle ROS, Vasconcelos MA, Santos HS, Teixeira EH (2019) Diversidade estrutural e potencial biológico dos metabólitos secundários de espécies do gênero Myroxylon L.f. (Fabaceae): uma revisão da literatura. Hoehnea 46:1–11 12. Schottenhammer A (2020) “Peruvian balsam”: an example of transoceanic transfer of medicinal knowledge. J Ethnobiol Ethnomed 16:69 13. Gurbuz I, Yesilada E, Demirci B, Sezik E, Demirci F, Baser KHC (2013) Characterization of volatiles and anti-ulcerogenic effect of Turkish sweetgum balsam (Styrax liquidus). J Ethnopharmacol 148:332–336 14. Oliveira AF, Luz BB, Werner MFP, Iacomini M, Cordeiro LMC, Cipriani TR (2018) Gastroprotective activity of a pectic polysaccharide fraction obtained from infusion of Sedum dendroideum leaves. Phytomedicine 41:7–12 15. Łyczko J, Pawlak A, Augustyński I, Okińczyc P, Szperlik J, Kulma A, Różański H, ObmińskaMrukowicz B, Szumny A (2020) Chemical profiling and cytotoxic activity of 150-year old original sample of Jerusalem Balsam. Food Chem Toxicol 138:111183 16. Custódio DL, Veiga-Junior VF (2012) True and common balsams. Rev Bras Farmacogn 22: 1372–1383 17. Riesmeier M, Mattonai M, Wong SS, Veall MA, Betts J, Johnston M, Ribechini E, Devièse T (2020) Molecular profiling of Peru Balsam reveals active ingredients responsible for its pharmaceutical properties. Nat Prod Res:1–6 18. Mills AA (1991) Canada balsam. Ann Sci 48:173–185 19. Sartori ÂLB, Lewis GP, Mansano VF, Tozzi AMGA (2015) A revision of the genus Myroxylon (Leguminosae: Papilionoideae). Kew Bull 70:1–12 20. Bedigian D (2003) Monograph on benzoin (balsamic resin from Styrax species). Econ Bot 57: 427–428 21. Aguilar-sandí D (2019) El árbol Myroxylon peruiferum (Fabaceae), nuevo registro en la flora de Costa Rica. UNED Reserach J 11:424–429 22. Merck KGaA (2021) Peru Balsam. https://www.sigmaaldrich.com/BR/en/product/aldrich/ w211613?gclid¼Cj0KCQjwkZiFBhD9ARIsAGxFX8Ax92KWd8FrEEcFHVwOO1xrmrhj Zu32E7SWAoHiMO3J7Ap3GtnQdrMaAlcVEALw_wcB. Accessed 15 June 2021 23. Groot AC (2019) Myroxylon pereirae resin (balsam of Peru) – a critical review of the literature and assessment of the significance of positive patch test reactions and the usefulness of restrictive diets. Contact Dermatitis 80:335–353 24. Marin WA, Flores EM (2008) Myroxylon balsamum (L.) Harms. In: Vozzo JA (ed) Tropical tree seed manual. USDA Forest Service, Washington, DC 25. Seo SM, Park HM, Park IK (2012) Larvicidal activity of ajowan (Trachyspermum ammi) and Peru balsam (Myroxylon pereira) oils and blends of their constituents against mosquito, Aedes aegypti, acute toxicity on water flea, Daphnia magna, and aqueous residue. J Agric Food Chem 60:5909–5914 26. Mammerler V, Kopp V, Canigueral S, Vila R (2007) Contribution to the analysis and quality control of Peru Balsam. Econ Bot 14:343–346 27. Steigenberger G, Herm C (2011) Natural resins and balsams from an eighteenth-century pharmaceutical collection analysed by gas chromatography/mass spectrometry. Anal Bioanal Chem 401:1771–1784 28. Ziegler-Sylakakis K, Fabri J, Graeser U, Simo TA (2019) Toluene. In: ULLMANN’S encyclopedia of industrial chemistry, 40th edn. Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim 29. Coppen JJW (1995) Gums, resins and latexes of plant origin. Food and Agriculture Organization of the United Nations, Rome

17

Chemistry, Biological Activities, and Uses of Balsams

431

30. Bottamedi M, Nascimento MVPS, Fratoni E, Moon YJK, Faqueti L, Tizziani L, Sandjo LP, Siminski A, Dalmarco EM, Mendes BG (2021) Antioxidant and anti-inflammatory action (in vivo and in vitro) from the trunk barks of Cabreúva (Myrocarpus frondosus Allemao, Fabaceae). J Ethnopharmacol 267:113545 31. Costa M, Silva A, Silva A, Lima V, Bezerra-Silva P, Rocha S, Navarro D, Correia M, Napoleão T, Silva M, Paiva P (2017) Essential oils from leaves of medicinal plants of Brazilian Flora: chemical composition and activity against Candida species. Medicines 4:27 32. Maranduba A, Oliveira AB, Oliveira GG, Reis JEP, Gottlieb OR (1979) Isoflavonoids from Myroxylon peruiferum. Phytochemistry 18:815–817 33. Ohsaki A, Takashima J, Chiba N, Kawamura M (1999) Microanalysis of a selective potent antiHelicobacter pylori compound in a Brazilian medicinal plant, Myroxylon peruiferum and the activity of analogues. Bioorganic Med Chem Lett 9:1109–1112 34. Dong J, Sun B, Mao T, Yan D, Liu C, Wang Z, Jin P (2018) Liquidambar (Altingiaceae) and associated insect herbivory from the Miocene of southeastern China. Palaeogeogr Palaeoclimatol Palaeoecol 497:11–24 35. Mancarz GFF, Laba LC, Silva ECP, Prado MRM, Souza LM, Souza D, Nakashima T, Mello RG (2019) Liquidambar styraciflua L.: a new potential source for therapeutic uses. J Pharm Biomed Anal 174:422–431 36. Mancarz GFF, Laba LC, Silva TAM, Pazzim MS, Souza D, Prado MRM, Souza LM, Nakashima T, Mello RG (2019) Chemical composition and biological activity of Liquidambar styraciflua L. leaf essential oil. Ind Crops Prod 138:111446 37. Terzi E, Kartal SN, Ibáñez CM, Köse C, Arango R, Clausen CA, Green F (2012) Biological performance of Liquidambar orientalis Mill. heartwood. Int Biodeterior Biodegrad 75:104–108 38. Lee YS, Kim J, Lee SG, Oh E, Shin SC, Park IK (2009) Effects of plant essential oils and components from oriental sweetgum (Liquidambar orientalis) on growth and morphogenesis of three phytopathogenic fungi. Pestic Biochem Physiol 93:138–143 39. Öztürk M, Çelik A, Güvensen A, Hamzaoǧlu E (2008) Ecology of tertiary relict endemic Liquidambar orientalis Mill. forests. For Ecol Manag 256:510–518 40. Eid HH, Labib RM, Hamid NSA, Hamed MA, Ross SA (2015) Hepatoprotective and antioxidant polyphenols from a standardized methanolic extract of the leaves of Liquidambar styraciflua L. Bull Fac Pharmacy 53:117–127 41. Okmen G, Turkcan O, Ceylan O, Gork G (2014) The antimicrobial activity of Liquidambar orientalis Mill. against food pathogens and antioxidant capacity of leaf extracts. African J Tradit Complement Altern Med 11:28–33 42. Sharif A, Nawaz H, Rafia R, Ayesha M, Rashid U (2016) A review on bioactive potential of benzoin resin. Int J Chem Biochem Sci 10:106–110 43. Fritsch PW (2004) New species and taxonomic changes in Styrax (Styracaceae) from South America. Novon 14:43–57 44. Jaradat N (2020) Phytochemistry, traditional uses and biological effects of the desert plant Styrax officinalis L. J Arid Environ 182:104253 45. Hovaneissian M, Archier P, Mathe C, Vieillescazes C (2006) Contribution de la chimie analytique à l’étude des exsudats végétaux styrax, storax et benjoin. Comptes Rendus Chim 9:1192–1202 46. Fernandez X, Lizzani-Cuvelier L, Loiseau AM, Périchet C, Delbecque C (2003) Volatile constituents of benzoin gums: Siam and Sumatra, part 1. Flavour Fragr J 18:328–333 47. Charehsaz M, Reis R, Helvacioglu S, Sipahi H, Guzelmeric E, Acar ET, Cicek G, Yesilada E, Aydin A (2016) Safety evaluation of styrax liquidus from the viewpoint of genotoxicity and mutagenicity. J Ethnopharmacol 194:506–512 48. Filippi JJ, Castel C, Fernandez X, Rouillard M, Gaysinski M, Lavoine-Hanneguelle S (2009) An unusual acenaphthylene-type sesquiterpene hydrocarbon from Siam and Sumatra benzoin gum. Phytochem Lett 2:216–219 49. Hovaneissian M, Archier P, Mathe C, Culioli G, Vieillescazes C (2008) Analytical investigation of styrax and benzoin balsams by HPLC-PAD-fluorimetry and GC-MS. Phytochem Anal 19: 301–310

432

A. T. C. Aguiar et al.

50. Castel C, Fernandez X, Lizzani-Cuvelier L, Loiseau AM, Perichet C, Delbecque C, Arnaudo JF (2006) Volatile constituents of benzoin gums: Siam and Sumatra, part 2. Study of headspace sampling methods. Flavour Fragr J 21:59–67 51. Khan A, Asaf S, Khan AL, Al-Harrasi A, Al-Sudairy O, AbdulKareem NM, Khan A, Shehzad T, Alsaady N, Al-Lawati A, Al-Rawahi A, Shinwari ZK (2019) First complete chloroplast genomics and comparative phylogenetic analysis of Commiphora gileadensis and C. Foliacea: Myrrh producing trees. PLoS One 14:1–21 52. Shen T, Li GH, Wang XN, Lou HX (2012) The genus Commiphora: a review of its traditional uses, phytochemistry and pharmacology. J Ethnopharmacol 142:319–330 53. Hanus LO, Rezanka T, Dembitsky VM, Moussaieff A (2005) Myrrh-Commiphora chemistry. Biomed Papers 149:3–28 54. Dudai N, Shachter A, Satyal P, Setzer W (2017) Chemical composition and monoterpenoid enantiomeric distribution of the essential oils from Apharsemon (Commiphora gileadensis). Medicines 4:66 55. Al-khulaidi AWA, Studies H (2018) Inventory of most rare and endangered plant species in Albaha region, Saudi Arabia. Int J Biol Pharm Allied Sci 7:443–460 56. Yehoshua SB, Ofir R, Rachmilevitch S, Amiel E, Dudai N, Soloway E (2015) Revival of the extinct balm of gilead in Israel: studying its anti-cancer activity. Acta Hortic 1088:509–514 57. Joshee N, Dhekney SA, Parajuli P (2019) Medicinal plants: from farm to pharmacy. Springer, Cham 58. Ravikumar S, Surekha R, Thavarajah R (2014) Mounting media: an overview. J Dr NTR Univ Heal Sci 3:1 59. Sommer NZ (2004) Thoughts of a young plastic surgeon. Plast Reconstr Surg 113:754 60. Native American Ethnobotany Database (n.d.). http://naeb.brit.org/uses/search/?string¼abies +balsamea. Acessed 27 June 2021 61. Custódio DL, Veiga-Junior VF (2014) Lauraceae alkaloids. RSC Adv 4:21864 62. Salleh WMNHW, Khamis S, Rahman MNA, Nafiah MA (2020) Chemical composition and biological activities of Dipterocarpus cornutus Dyer essential oil. Zeitschrift Für Naturforsch C 75:171–175 63. Murrell W (1890) Gurjun oil as an expectorante.Lecturer on materia medica at the westminster hospital. Lancet:962 64. Boriollo MFG, Marques MB, Silva TA, Silva JJ, Dias RA, Silva Filho THN, Melo ILR, Dias CTS,Bernardo WLC, Oliveira NMS, Peters VM, Höfling JF, Spolidorio DMP (2020) Antimicrobial potential, phytochemical profile, cytotoxic and genotoxic screening of Sedum praealtum a. DC. (balsam). BMC Complement Med Ther 20:1–14 65. Piva MG (2002) O caminho das plantas medicinais: estudo etnobotânico. Mondrian, Curitiba 66. Pacheco TRC, Barata LES, Duarte MCT (2006) Antimicrobial activity of copaiba (Copaifera spp) balsams. Rev Bras Plantas Med 8:123–124 67. Lorenzi H, Souza HM (1995) Plantas ornamentais no Brasil: Arbustivas, herbáceas e trepadeiras. Plantarum, Nova Odessa 68. Malvar DC, Pires PA, Melo GO, Costa SS, Filho PG, Côrtes WS, Vanderlinde FA (2004) Influência do pré-tratamento com o sumo do Sedum dendroideum (bálsamo) sobre a nocicepção de camundongos (Mus musculus). Rev Univ Rural Série Ciências da Vida 24:135–140 69. Melo GO, Malvar DDC, Vanderlinde FA, Pires PA, Côrtes WS, Germano Filho P, Muzitano MF, Kaiser CR, Costa SS (2005) Phytochemical and pharmacological study of Sedum dendroideum leaf juice. J Ethnopharmacol 102:217–220 70. Seyfullah LJ, Beimforde C, Corso JD, Perrichot V, Rikkinen J, Schmidt AR (2018) Production and preservation of resins – past and present. Biol Rev 93:1684

Chemistry, Biological Activities, and Uses of Copal Resin (Bursera spp.) in Mexico

18

Jose´ Blancas, Itzel Abad-Fitz, Leonardo Beltra´n-Rodríguez, Sol Cristians, Selene Rangel-Landa, Alejandro Casas, Ignacio Torres-García, and Jose´ Antonio Sierra-Huelsz

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Botanical Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Bursera copallifera (Moc&. Sessé ex DC.) Bullock . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Bursera bipinnata (Moc. &Sessé ex DC.) Engl . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Past, Present, and Potential Uses of Copal Resin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Documented Past Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Present and Potential Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Chemical Composition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Biological Activities of Copal Resin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

434 436 436 436 437 437 438 440 442 443 444

J. Blancas (*) · I. Abad-Fitz Centro de Investigación en Biodiversidad y Conservación (CIByC) – Universidad Autónoma del Estado de Morelos, Cuernavaca, Morelos, Mexico e-mail: [email protected]; [email protected] L. Beltrán-Rodríguez · S. Cristians Jardín Botánico – Instituto de Biología. Universidad Nacional Autónoma de México, Ciudad de México, Mexico e-mail: [email protected]; [email protected] S. Rangel-Landa · A. Casas Instituto de Investigaciones en Ecosistemas y Sustentabilidad, Universidad Nacional Autónoma de México, Morelia, Michoacán, Mexico e-mail: [email protected]; [email protected] I. Torres-García Escuela Nacional de Estudios Superiores, Unidad Morelia, Universidad Nacional Autónoma de México, Morelia, Michoacán, Mexico e-mail: [email protected] J. A. Sierra-Huelsz People and Plants International, Bristol, VT, USA © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_21

433

434

J. Blancas et al.

Abstract

Copal is an aromatic resin that has been extracted by people from several arboreal species of the Burseraceae family—also known as copal—for at least two thousand years. In Mexico, two species in the genus Bursera (B. copallifera and B. bipinnata) are particularly important for the diversity of their uses, geographical distribution, and trade in commercial networks. At present, the use of copal resin continues to have ritual significance for numerous Mesoamerican peoples. The present chapter summarizes the past, present, and potential uses of copal, its identified chemical compounds, and their known biological activities. Some of the more frequent uses of copal are as an irreplaceable element in ritual ceremonies, in traditional medicine, and as an agglutinant in the elaboration of varnishes, pigments, and fixatives. Among the most abundant compounds in copal resin are the sesquiterpenes germacrene D and β-caryophyllene, the triterpenoids α- and β-amyrin, and the monoterpenes α- and β-pinene, β-phellandrene, and limonene. The chemical components of copal stems, bark, leaves, and resin have antiinflammatory, antioxidative, and antineoplastic properties, because of which developing its application in pharmacology provides a promising opportunity. Keywords

Chemical composition · Medicinal plants · Mesoamerica · Resins · Ritual plants

1

Introduction

Copal is an aromatic resin extracted from some species of the Burseraceae family, mainly of the genera Bursera and Protium, both endemic to the Neotropics [1]. In Mexico, copal has been used by people since pre-Hispanic times, mostly for ritual purposes and, to a lesser extent, as medicine [2]. It is an essential component in multiple propitiatory rituals, religious celebrations, traditional medicine, and it is irreplaceable for the Day of the Dead ceremonies and other festivities [3]. Copal was highly appreciated by several pre-Columbian cultures, and it was part of the exchange and trading networks, including the tributes paid by subject or conquered peoples [4]. The European invasion did not modify this situation substantially since copal was incorporated into the Christian celebrations and continued being important in numerous indigenous communities that adopted this religion. Therefore, copal is one of the components of the traditional peoples’ syncretism that survives until the present. The ritual use of copal is prevailing, and its demand has increased in some regions in the last few years [5]. It is one of the non-timber forest products for rural communities inhabiting tropical deciduous forests (TDF) [6]. In Mexico, the word copal is used to refer to both the aromatic resin and the tree species of the genera Bursera and Protium that produce it, the former genus having a higher production volume and commercial importance [1, 2, 4]. Table 1 lists some of

18

Chemistry, Biological Activities, and Uses of Copal Resin (Bursera. . .

435

Table 1 Main copal resin producing species in the genus Bursera in Mexico (Source: QuirozCarranza and Magaña [7]; CONABIO [4]; De Carlo et al. [8]) Scientific name Bursera bipinnata (Moc. & Sessé ex DC.) Engl. Bursera copallifera (Moc &. Sessé ex DC.) Bullock Bursera cuneata (Schltdl.) Engl.

Common name copal blanco, copal chino, copal cimarrón, copal de la virgen copal de penca, copal de santo, copal manso

Distribution in Mexico Nayarit, Jalisco, Zacatecas, Guanajuato, Colima, Michoacán, Puebla, Morelos, Guerrero, Oaxaca, and Chiapas Nayarit, Jalisco, Guanajuato, Michoacán, Puebla, Morelos, Guerrero, and Oaxaca

copal, copalillo

Bursera glabrifolia (Kunth) Engl. Bursera graveolens (Kunth) Triana & Planch.

copal, copal liso, copal hembra copal, gomilla, incienso, sasafrás, palo de brujo

Bursera laxiflora S. Watson Bursera palmeri S. Watson

torote prieto

Bursera tomentosa (Jacq.) Triana & Planch.

copal

Guanajuato, Michoacán, Estado de México, Ciudad de México, Morelos, and Guerrero Jalisco, Michoacán, Puebla, Estado de México, Morelos, Guerrero, and Oaxaca Nayarit, Jalisco, Colima, Michoacán, Estado de México, Morelos, Puebla, Guerrero, Oaxaca, Veracruz, Chiapas, Tabasco, Yucatán, Campeche, and Quintana Roo Baja California Sur, Sonora, Chihuahua, Sinaloa, and Durango Sinaloa, Durango, Nayarit, Guanajuato, Querétaro, San Luis Potosí, Michoacán, and Ciudad de México Oaxaca, and Chiapas

copal

the most important copal-producing Bursera species, their common names, and their distribution in Mexico. In this chapter, we will refer to the copal blanco produced by Bursera copallifera (Moc&. Sessé ex DC.) Bullock and the copal chino produced by Bursera bipinnata (Moc. &Sessé ex DC.) Engl., the two most important copal-producing species in terms of their distribution, abundance, resin texture, and aromatic qualities, and trade volume in the national and international markets [9]. The copal blanco (B. copallifera) is widely distributed in Mexico, and for this reason, its resin is the most used and more frequently found in markets [10]. In contrast, the distribution of the copal chino (B. bipinnata) is less extended, and its populations are scarcer and less dense than those of the copal blanco [11]. Copal is an important source of income for the communities that extract it, in some of which households depend on it for covering their needs [6]. Both products are mainly interchanged in local and regional trading networks [12], the demand in markets frequently exerting a strong pressure to increase the product’s availability, which in turn has originated some cases of unsustainable harvesting practices causing reduction of the trees’ wild populations [6]. Fortunately, valuable efforts for the conservation of copal trees exist in some communities, which are driven by the interaction of diverse actors and sectors, all of which agreed to

436

J. Blancas et al.

carry out interdisciplinary research and actions to reach a comprehensive understanding of the consequences of extracting copal and ways to mitigate its effects on tree populations [13, 14]. These efforts have enhanced growing interest in studying copal-producing species, their population’s ecology, and traditional management, all of them considered to be the bases to contribute to the conservation of the forests where the copal trees occur (tropical dry forest, TDF) as well as to maintain or improve the livelihoods of households dedicated to its extraction. The research efforts have adopted different approaches, for instance, some have focused on the trees’ traditional management [4, 6], ethnobotany [2], uses [15], or the consequences of management [5]. However, despite the diversity of copal types and uses, aspects like the phytochemistry and biological activity of the resins remain little studied, and the available information is fragmented [16]. This chapter is an attempt to systematize information on historical and present uses of copal and their relationships with the chemistry and active principles of the resins.

2

Botanical Description

2.1

Bursera copallifera (Moc&. Sesse´ ex DC.) Bullock

Trees or shrubs, 3 to 6 m tall; dioecious. External bark not exfoliating, grayish with aromatic resin. Leaves, imparipinnate, laminae 9 to 19 cm in length, rachis villous or lanose, narrowly winged; leaflets 13 to 19, sessile, elliptic to oblong, margin irregularly indented, upper surface dark green, pubescent, bottom surface yellowish green, densely to sparingly lanose, with prominent primary, secondary, and tertiary venation. Inflorescences in panicles, 3 to 5 cm in length, with numerous flowers, densely lanose. Flowers greenish-white; male flowers tetramerous, calyx lobes 1.5 to 3.0 mm in length, petals 2 to 3 mm in length, with a vestigial gynoecium; female flowers with petals shorter than calyx lobes; flowers, tetramerous, yellow, orangishyellow, or greenish-white. Fruits up to 3 cm in length, yellowish, lanose; pedicels 1 to 2 mm in length, spherical to ellipsoid. Seeds 5 to 7 mm in diameter, spherical to ellipsoid, total or partially covered with a yellow or red pseudaril (Fig. 1). Endemic to Mexico distributed in the states of Colima, Guerrero, Jalisco, Mexico, Michoacan, Morelos, Nayarit, Oaxaca, Puebla, and Zacatecas [17, 18].

2.2

Bursera bipinnata (Moc. &Sesse´ ex DC.) Engl

Trees or shrubs 8 to 12 m in height; dioecious or polygamodioecious. Stem 35 to 50 cm in diameter; external bark not exfoliating, generally smooth, greyish, with abundant aromatic resin. Leaves, fasciculated at the apex or alternate on new branches, similar to fern fronds, bipinnate to tripinnate, occasionally, pinnate; petioles 1.5 to 2 cm in length; laminae 2.5 to 10 cm in length, 1 to 6.5 cm in width, ovate to oblong; rachis and rachilla narrowly winged, margin entire; leaflets sessile or subsessile, upper surface shiny and glabrescent, a bottom surface,

18

Chemistry, Biological Activities, and Uses of Copal Resin (Bursera. . .

437

Fig. 1 “Copal blanco”(Bursera copallifera). (a) General appearance of the tree; (b) Detail of the trunk; (c) Detail of leaves and fruit (Photos: Francisco Javier Rendón)

puberulous, villose to glabrescent, with prominent venation. Inflorescences, racemose, or paniculate, 2 to 6 cm in length, puberulous; flowers whitish to yellowish or greenish, male flowers, tetramerous, calyx lobes 1.5 to 2.5 cm in length, petals 1.8 to 2.5 cm in length, stamens 8, anthers 0.4 to 0.5 mm in length, with an inconspicuous vestigial gynoecium; female flowers tetramerous, similar to male flowers in form and size, ovary bilocular, glabrous, with two stigmas. Fruits in up to 6 cm in length peduncles 6 to 8 mm in length, bivalved, 6 to 8 mm in length, obovoid, glabrous; seeds 5 to 6 mm in length, 3 to 4 mm in width, slightly compressed, almost completely covered by a red pseudaril, the exposed portion, black (Fig. 2). Distributed in Mexico and Central America. In Mexico, in the states of Aguascalientes, Chiapas, Colima, Durango, Guanajuato, Guerrero, Jalisco, Mexico, Michoacan, Morelos, Nayarit, Oaxaca, Puebla, Veracruz, and Zacatecas [17, 18].

3

Past, Present, and Potential Uses of Copal Resin

3.1

Documented Past Uses

Some pre-Hispanic and Colonial codices, and post-Conquest chronicles highlight the cultural significance of copal among Mesoamerican peoples (Maya, Mixtec, and Aztec) [2]. The importance of copal was recorded by the authors of the Matrícula de Tributos [19], Codex Mendoza [20], and Natural History of the New Spain [21], and

438

J. Blancas et al.

Fig. 2 “Copal chino” (Bursera bipinnata). (a) General appearance of the tree; (b) Detail of the trunk with the incisions to extract the copal resin; (c) Detail of leaves and fruits (Photos A and C: José Blancas; B: Luis Sánchez Méndez)

it is underlined by its representation with a glyph in the Codex Mendoza [20] (Fig. 3), which was reserved to plants with high cultural value like cacao or maize. These Colonial documents describe the uses of copal, mainly as an offering to deities or in rituals as rain-propitiatory ceremonies, harvest thanksgiving festivals, and for pre-Hispanic medicinal use [2]. Pre-Hispanic accounts of artists also used copal—probably from B. bipinnata—as an agglutinating agent in the preparation of varnishes applied on jade and pigments used for mural paintings [16, 22], to adhere stone, seashell, or other materials incrustations in masks and objects found by archaeologists in ritual contexts [15]. Sahagún mentioned the pre-Hispanic use of copal mixed with wax produced by Meliponini bees, used for casting of gold and silver objects by the “lost wax” technique, in which the resin-wax mixture was lined on clay molds into which the molten metal was poured [4, 23].

3.2

Present and Potential Uses

Among the present uses of copal resin, its role in ritual ceremonies is undoubtedly the most important. The aromatic resin’s smoke is used by practitioners of religious

18

Chemistry, Biological Activities, and Uses of Copal Resin (Bursera. . .

439

Fig. 3 Representation of the glyph for copal in the Codex Mendoza [20]

ceremonials and traditional medicine, mostly for therapeutic rituals called limpias (cleansings) to treat culture-specific syndromes like, among others, mal de aire (air), levantamiento de la sombra or deasombro—a fright in which the spirit (sombra) abandons the body, and mal de ojo (evil eye) [24, 25]. The Nahua people prepare an infusion with copal powder to treat diarrhea and other stomach disorders [5, 9, 10, 26, 27]. The Maya and Nahua use copal resin to plug tooth cavities [7, 28]. In Morelos and Guerrero, copal is used as an antiinflammatory poultice for treating strains and muscle pain, for which the resin is heated until melt, and rubbed on the affected part before it solidifies, then covered with cotton bandages [6, 9]. A copal poultice is also used in Oaxaca to treat boils and cysts. Parsons [29] documented the use of copal resin mixed with milk and egg yolk rubbed on the back to treat pneumonia, and the resin is also frequently used to alleviate the common cold symptoms [27]. The chewing gum and ointment made with B. copallifera resin are being used to treat uterine disorders, and the resin’s smoke is inhaled to treat headaches [25, 30]. In Sinaloa and other regions in Mexico, B. bipinnata resin is used to treat wounds due to its antiseptic and antibacterial properties [9, 30]. The ointment prepared with copal resin is used to treat scorpion stings because of its analgesic and antiseptic activities [27] and as an insect repellent [10]. The copal resin has potential applications in medicine, art, and industry. Sharma et al. [31] proposed, for instance, using copal resin as a coating film for colontargeted drug delivery. Renowned painters representing the Mexican muralist movement–reaching its apex after the twentieth century Mexican Revolution– like Diego Rivera and Gerardo Murillo (Dr. Atl) used copal resin in their refined mural and canvas painting techniques [16]. Copal resins are currently used for the elaboration

440

J. Blancas et al.

of varnishes, pigments, fixatives, for caulking boats [7], and as an agglutinating agent in industrial processes like textile stamping [10]. Other less common uses of copal are as a general purpose adhesive. For example, the resin is used to glue the wood with which they are manufactured traditional Mesoamerican drums (teponaztli), tun drums, and other musical instruments like violins and guitars, for adhering leather straps on tool handles, and to repair leakages in pottery or metal containers exposed to fire [10].

4

Chemical Composition

Copal resins are fragrant exudates secreted by specialized gummy cells located in the vascular bundles [5, 32]. Resin secretion has a protective function against herbivores, pathogenic fungi, and other organisms [8]. Although copal resins are classified as hard resins, they initially flow from trees in a liquid state, eventually solidifying as their chemical components become polymerized and oxidized, a process throughout which the resin changes in appearance—from crystalline to amber or whitish—and hardens [10, 33]. The chemical components of copal resins include a mixture of volatile liposoluble mono- and sesquiterpenes (essential oils), and nonvolatile long-chain triterpenoids [5, 9]. These essential oils are often lost through the polymerization and oxidation processes. Among the most common essential oils in plant, resins are heptane, α- and β-pinene, ß-phellandrene, and limonene, but the most common sesquiterpenes in resins produced by Bursera species are ß-caryophyllene and germacrene D [33]. Copal resin is soluble in alcohol and other organic solvents and is characterized by having a high melting temperature [7, 32]. It contains monoterpenes—important components of essential oils—that confer fluidity and density to the resin, triterpenoids that provide copal its consistency—of which α- and β-amyrin are the dominant compounds, and flavonoids that protect plants from UV light and give durability and stability to the wood [7, 16, 34]. Copal resin extraction is carried out through an incision made in the copal bark’s tree and then recollect in different ways. The people that extract it in Mexico classifies it according to its extraction process into a) Copal de penca, in Spanish, derived from the name given to the leaves of Agave angustifolia, which are used to collect the resin and allow it solidifying; b) Copal de lágrima, in Spanish meaning “tears copal,” alluding to the elongated secretions that dripped from the incisions made in trees to the collecting agave leaf; c) Mirra, in Spanish meaning myrrh, mainly consisting in the secretion that accumulates in the bark surrounding the incision; and d) Goma, meaning gum in Spanish, which is the resin naturally exuding from trees, in particular when attacked by herbivores, mainly larvae of some lepidopterans [5]. B. bipinnata is considered to have a higher variation in its chemical composition than other species of the genus, but according to Gigliarelli et al. [9], the most important volatile compound present in its fresh resin is α-pinene. However, AbadFitz et al. [5] reported that in populations of this species from the state of Morelos,

18

Chemistry, Biological Activities, and Uses of Copal Resin (Bursera. . .

441

Table 2 Volatile and semivolatile compounds present in the resin of Bursera bipinnata (Source: Abad-Fitz et al. [5]) Compound β-amyrin α-phellandrene betulin α-amyrin terpinolene caryophyllene lupeol acetate β-phellandrene δ-cadinol α-pinene α-humulene δ-cadinene verbenol sabinene α-thujene β-myrcene calemene caryophyllene oxide β-pinene sabinyl acetate

Characteristic conferred to resin by the compound Consistency Scent Consistency Consistency Scent Scent Consistency Scent Scent Scent Scent Scent Scent Scent Scent Scent Scent Scent Scent Scent

ß-amyrin, α-phellandrene, and betulin were the volatile compounds with the highest concentration in the resin, and these authors found a total of 20 volatile compounds, 16 of which provide its characteristic scent, the other four being responsible for its consistency (Table 2). But interestingly, Abad-Fitz et al. [5] found significant differences in the quantity and concentration of chemical components between the resin of wild trees and trees managed in agroforestry systems, living fences, or incipient plantations of B. bipinnata. This result could mean that management practices may favor the reproduction and propagation of trees having the desired characteristics according to the notion of quality of the people that extract the resin, in this case, higher production, scent, and consistency. According to Noge and Becerra [35], Gigliarelli et al. [9], Murthy et al. [36], and Lucero-Gómez et al. [37], the resin of B. copallifera is composed mainly of germacrene D, α-humulene, lupeol, and lupenone, and in lesser concentrations, by ß-caryophyllene and bicyclogermacrene. Romero et al. [38] in the same species found high concentrations of 3-epilupeol (59.75%) and α-amyrin (21.1%), and Case et al. [10] identified a total of 27 compounds, the most abundant of which was α-copaene and germacrene. Table 3 shows the 14 compounds found in the resin of B. bipinnata having the highest retention index (RI) values (RI >1). At least four sources of variation in the determination of the chemical composition of resins from B. bipinnata and B. copallifera might explain this apparent

442

J. Blancas et al.

Table 3 Main compounds present in the resin of Bursera copallifera (Source: Case et al. [10]) Compound α-copaene germacrene D β-caryophyllene β-elemene β-bourbonene spathulenol bicyclogermacrene δ-cadinene β-ylangene α-humulene caryophyllene oxide α-amorphene β-cubebene α-cubebene

RI† (Mean
SD%) 14.52
1.28 13.75
1.06 8.54
0.54 8.50
0.35 6.07
0.75 5.14
1.07 3.77
0.37 2.66
0.26 2.29
0.11 2.18
0.38 2.18
0.16 1.67
0.16 1.56
0.63 1.39
0.61

Note: †Retention index

discrepancy in the reports referred to. The first may be related to differences in sample preparation and compound identification. The techniques usually applied for molecules identification are chromatography and spectrophotometry, but in each case, samples are differently processed before being analyzed. The second source of discrepancy in the chemical composition of the resins is the samples’ origin and storage period. Researchers often analyze copal samples acquired in local marketplaces or obtain them from archaeological contexts—both commonly leading to samples losing part of their chemical components, more so of the volatile ones—but some studies used fresh resin samples taken directly from trees and processed in a short period of time. The third probable cause of disagreement in reports of resin chemical composition is the confusion of the taxonomic identity of the sampled trees, in part due to different species sharing common names. Finally, the fourth cause of variations in the reported chemical composition might be due to differences in the part of the tree used to obtain the samples, that is, the leaves, resin, or bark.

5

Biological Activities of Copal Resin

Little is known about the biological activity of compounds in the resins of Mexican species of Bursera. In a review about the use of South American species of Burseraceae in traditional medicine and pharmacological properties, Rüdiger et al. [39] concluded that the resin of species of the Burseraceae family lowers water permeability and has an antioxidative effect, suggesting its potential for industrial applications in the drug and food products as packaging material [7]. Quiroz-Carranza and Magaña [7] reviewed the literature about Mexican natural resins produced by plants from several families, mentioning the bactericidal,

18

Chemistry, Biological Activities, and Uses of Copal Resin (Bursera. . .

443

antimicrobial, disinfectant, and antiviral activities of copal resin reported by Orta [40]. In their reviews about the scientific knowledge of the composition and biological properties of resin from Mexican species of Bursera available in the market, Gigliarelli et al. [9] and Zúñiga et al. [41] mention their anti-inflammatory activity, which was evaluated by Carrera-Martínez et al. [42] for the resin of B. morelensis. Guevara et al. [43] evaluated the anti-inflammatory activity of the flavonoids in the resin of B. morelensis and referred to reports by Bah et al. [44] about the anti-inflammatory activity of B. simaruba bark and those by ColumbaPalomares et al. [45] about antioxidative and cytotoxic activities of B. copallifera stem, bark, and leaf extracts. In addition, Guevara et al. [43] refer to the study by Parrales et al. [46], who assessed the anti-inflammatory, analgesic, and antioxidant properties of B. morelensis bark. Sánchez-Monroy et al. [47] studied the cytotoxicity of nine species of Bursera [8]. Through clinical assays in mice, Romero-Estrada et al. [38] demonstrated significant anti-inflammatory activity of B. copallifera resin, specifically identifying 3epilupeol formiate, α-amyrin acetate, 3-epilupeol acetate, lupenone, 3-epilupeol, and α-amyrin as the most promising components, which gives scientific support to the traditional use of copal resin for treating rheumatism, asthma, and other inflammatory diseases. Domínguez et al. [48] studied the activity of the phenolic compounds of B. copallifera leaf extracts on breast cancer cell lines, finding a therapeutic potential of the extract as an antineoplastic drug, which the authors suggest is due to hydroxycinnamic acid and flavonol derivatives present in the extracts.

6

Conclusions

The resins from several species in the genus Bursera have been used by pre-Columbian peoples, probably for millennia; many of its uses persist until the present. The most frequent uses of copal are the burning of the resin to produce aromatic smoke in religious and other ritual ceremonies, and in traditional medicine for treating several diseases, and, of culture-specific syndromes. Regardless of being a widely used resource, the research about its chemical components and their biological activities is still incipient. The results of the identification of chemical compounds present in copal resin show an apparent discrepancy which might be due to the techniques used, sample origin, storage time or age of the analyzed samples, the precision of the taxonomic identification of the sampled plants, and the plant parts being analyzed. Therefore, for the future chemical characterizations of copal resins, it will be necessary to standardize the methodology applied for extraction and processing of samples and the accurate identification of the plants. Regarding the therapeutic potential of the plants, clinical assays are yet scarce, but the antineoplastic activity of B. copallifera leaf extracts seems promising. Recognizing the high value of the traditional knowledge of rural communities about characteristics and properties of copal is basic for making significant

444

J. Blancas et al.

advancements to identify biologically active agents in the resin and other parts of the copal trees.

References 1. Cházaro M, Mostul B, García F (2010) Los copales mexicanos (Bursera spp.). Bouteloua 7: 57–70 2. Linares E, Bye R (2008) El copal en México. Biodiversitas 78:8–11 3. Montúfar A (2016) Copal de Bursera bipinnata. Una resina mesoamericana de uso ritual. Trace 70:45–77 4. Purata SE (ed) (2008) Uso y manejo de los copales aromáticos: resinas y aceites. CONABIO/ RAISES, México 5. Abad-Fitz I, Maldonado-Almanza B, Aguilar-Dorantes KM, Sánchez-Méndez L, GómezCaudillo L, Casas A, Blancas J, García-Rodríguez YM, Beltrán-Rodríguez L, Sierra-Huelsz JA, Cristians S, Moreno-Calles AI, Torres-García I, Espinosa-García FJ (2020) Consequences of traditional management in the production and quality of copal resin (Bursera bipinnata (Moc. & Sessé ex DC.) Engl.) in Mexico. Forests 11(9):991. https://doi.org/10.3390/f11090991 6. Mena F (2018) Estrategias ecológicas y culturales para garantizar la disponibilidad de productos forestales no maderables: árboles medicinales en la selva baja del sur de Morelos. Dissertation, Universidad Autónoma del Estado de Morelos 7. Quiroz-Carranza JA, Magaña MA (2015) Resinas naturales de especies vegetales mexicanas: usos actuales y potenciales. Madera y Bosques 21(3):171–183 8. De Carlo A, Dosoky NS, Satyal P, Sorensen A, Setzer WN (2019) The essential oils of the Burseraceae. In: Malik S (ed) Essential Oil Research. Trends in Biosynthesis, Analytics, Industrial Applications and Biotechnological Production. Springer, Cham. https://doi.org/10. 1007/978-3-030-16546-8_4 9. Gigliarelli G, Becerra JX, Curini M, Marcotullio MC (2015) Chemical composition and biological activities of fragrant mexican copal (Bursera spp.). Molecules 20(12):22383– 22394. https://doi.org/10.3390/molecules201219849 10. Case RJ, Tucker AO, Maciarello MJ, Wheeler KA (2003) Chemistry and ethnobotany of commercial incense copals copal blanco, copal oro, and copal negro, of North America. Econ Bot 57(2):189–202. https://doi.org/10.1663/0013-0001(2003)057[0189:CAEOCI]2.0.CO;2 11. Rzedowski J, Guevara-Féfer F (1992) Burseraceae. Flora del Bajío y de regiones adyacentes. Fascículo 3:1–46 12. Hersch P (2009) Plantas medicinales silvestres del suroccidente poblano y su colindancia en Guerrero, México: rutas de comercialización, antecedentes y dinámica actual. In: Long J, Attolini A (eds) Caminos y mercados de México. Universidad Nacional Autónoma de México, Ciudad de México 13. Castellanos-Castro C, Bonfil Sanders C (2010) Field establishment and initial growth of cuttings of three species of Bursera Jacq. ex. L Rev Mex Cienc Forestales 1(2):93–108 14. Castellanos-Castro C, Bonfil C (2013) Propagation of three Bursera species from cuttings. Bot Sci 91(2):217–224 15. Montúfar A (2007) Los copales mexicanos y la resina sagrada del Templo Mayor de Tenochtitlan. Instituto Nacional de Antropología e Historia, Ciudad de México 16. De la Cruz-Cañizares J, Doménech-Carbó MT, Gimeno-Adelantado JV, Mateo-Castro R, BoschReig F (2005) Study of Burseraceae resins used in binding media and varnishes from artworks by gas chromatography-mass spectrometry and pyrolysis-gas chromatography-mass spectrometry. J Chromatogr A 1093(1-2):177–194. https://doi.org/10.1016/j.chroma.2005.07.058 17. Rzedowski J, Kruse H (1979) Algunas tendencias evolutiv as en Bursera (Burseraceae). Taxon 28(1–3):103–116

18

Chemistry, Biological Activities, and Uses of Copal Resin (Bursera. . .

445

18. Medina-Lemos R (2008) Flora del Valle de Tehuacán – Cuicatlán. Fascículo 66. BURSERACEAE. Universidad Nacional Autónoma de México, Ciudad de México 19. Matrícula de Tributos (1997) Edición facsímil. Introducción y explicación Luis Reyes García, con una contribución de Remco Jansen sobre los glifos toponímicos. Akademische Druck- und Verlagsanstalt, Fondo de Cultura Económica, Ciudad de México 20. Codex Mendoza (1992) University of California Press, Berkeley, CA 21. Hernández F (1959) Historia natural de Nueva España, Obras completas, T. II-III. Universidad Nacional Autónoma de México, Ciudad de México 22. Stross B (1997) Mesoamerican copal resins. U-Mut Maya 6:177–186 23. Pitses E (2018) An assessment of stingless beeswax as a pattern material in ancient Mesoamerican lost-wax casting. Dissertation, Massachusetts Institute of Technology 24. Kelli IT (1965) Folk practices in north Mexico. Birth costumes, folk medicine, and spiritualism in La Laguna zone. The University of Texas Press, Austin 25. Biblioteca Digital de la Medicina Tradicional Mexicana (2009) Atlas de las Plantas de la Medicina Tradicional Mexicana. BURSERACEAE. http://www.medicinatradicionalmexicana. unam.mx/apmtm/termino.php?l¼3&t¼bursera-bipinnata. Accessed 14 May 2021 26. Vogel VJ (1977) American Indian medicine. University of Oklahoma Press, Norman, OK 27. Peters CM, Purata SE, Chibnik M, Brosi BJ, Lopez AM, Ambrosio M (2003) The life and times of Bursera glabrifolia (H.B.K.) Engl. in Mexico: a parable for ethnobotany. Econ Bot 57(4):431–441 28. Savinelli A (1997) Plants of power. Alfred Savinelli, Taos, NM 29. Parsons EC (1936) Mitla: Town of the souls and other Zapoteco-speaking pueblos of Oaxaca, Mexico. University of Chicago Press, Chicago, IL 30. Standley P (1926) Trees and shrubs of Mexico. Contributions from the United States National Herbarium, vol 23. Smithsonian Institution, Washington 31. Sharma J, Kaur L, Kanuja N, Nagpal M, Bala R (2013) Natural polymers-promising potential in drug delivery. Int J PharmTechnol 5(2):684–699 32. Nussinovitch A (2010) Plant gum exudates of the world. Sources, distribution, properties, and applications. CRC Press Taylor & Francis Group, Boca Raton, FL 33. Marcotullio MC, Curini M, Becerra JX (2018) An Ethnopharmacological, phytochemical and pharmacological review on lignans from Mexican Bursera spp. Molecules 23(8):1976. https:// doi.org/10.3390/molecules23081976 34. Stacey RJ, Cartwright CR, McEwan C (2006) Chemical characterization of ancient mesoamerican “copal” resins: preliminary results. Archaeometry 48(2):323–340. https://doi.org/10.1111/ j.1475-4754.2006.00259.x 35. Noge K, Becerra JX (2009) Germacrene D, a common sesquiterpene in the genus Bursera (Burseraceae). Molecules 14:5289–5297. https://doi.org/10.3390/molecules14125289 36. Murthy K, Reddy MC, Rani SS, Pullaiah T (2016) Bioactive principles and biological properties of essential oils of Burseraceae: A review. J Pharmacogn Phytochem 5(2):247–258 37. Lucero-Gómez P, Mathe C, Vieillescazes C, Bucio L, Belio I, Vega R (2014) Analysis of Mexican reference standards for Bursera spp. resins by gas chromatography-mass spectrometry and application to archaeological objects. J Archeol Sci 41:679–690 38. Romero-Estrada A, Maldonado-Magaña A, González-Christen J, Bahena SM, Garduño-Ramírez ML, Rodríguez-López V, Alvarez L (2016) Anti-inflammatory and antioxidative effects of six pentacyclic triterpenes isolated from the Mexican copal resin of Bursera copallifera. BMC Complement Altern Med 16(1):1–10. https://doi.org/10.1186/s12906-016-1397-1 39. Rüdiger AL, Siani AC, Veiga VF (2007) The chemistry and pharmacology of the South American genus Protium Burm f. (Burseraceae) Pharmacogn Rev 1(1):93–104 40. Orta MN (2007) Copal: microestructura, composición y algunas propiedades relevantes. Dissertation, Instituto Politécnico Nacional 41. Zúñiga B, Guevara-Fefer P, Herrera J, Contreras JL, Velasco L, Pérez FJ, Esquivel B (2005) Chemical composition and anti-inflammatory activity of the volatile fractions from the bark of eight Mexican Bursera species. Planta Med 71(9):825–828. https://doi.org/10.1055/s2005-871293

446

J. Blancas et al.

42. Carrera-Martínez CA, Rosas-López R, Rodríguez-Monroy MA, Canales-Martínez MM, Román-Guerrero A, Jiménez-Alvarado R (2014) Chemical composition and in vivo antiinflammatory activity of Bursera morelensis Ramírez Essential Oil. J Essent Oil Bear Plants 17:758–768 43. Guevara P, Muñoz V, Llanos RE, Zúñiga B, Cárdenas RJ, Contreras JL, Ocampo F (2017) Flavonoides de trece especies del género Bursera con potencial antioxidante. Polibotánica 44: 185–193 44. Bah M, Gutiérrez-Avella DM, Mendoza S, Rodríguez-López V, Castañeda-Moreno R (2014) Chemical constituents and antioxidant activity of extracts obtained from branch bark of Bursera simaruba. Bol Latinoam Caribe Plant Med Aromat 13(6):527–536 45. Columba-Palomares MF, Villareal ML, Acevedo Quiroz ME, MarquinaBahena S, Álvarez Berber LP, Rodríguez-López V (2015) Anti-inflammatory and cytotoxic activities of Bursera copallifera. Pharmacogn Mag 11(suppl 2):S322–S328 46. Parrales RS, Cruz BV, Cobos DS, Anaya-Lang AL, Jimenez-Estrada M, Canales- Martínez M (2012) Anti-inflammatory, analgesic and antioxidant properties of Bursera morelensis bark from San Rafael, Coxcatlán, Puebla (México): Implications for cutaneous wound healing. J Med Plants Res 6(44):5609–5615 47. Sánchez-Monroy MB, León-Rivera I, Llanos-Romero RE, García-Bores AM, Guevara-Fefer P (2020) Cytotoxic activity and triterpenes content of nine Mexican species of Bursera. Nat Prod Res 16:1–5. https://doi.org/10.1080/14786419.2020.1739680 48. Domínguez F, Maycotte P, Acosta-Casique A, Rodríguez-Rodríguez S, Moreno DA, Ferreres F, Flores-Alonso JC, Delgado-López MG, Pérez-Santos M, Anaya-Ruiz M (2018) Bursera copallifera extracts have cytotoxic and migration-inhibitory effects in breast cancer cell lines. Integr Cancer Ther 17(3):654–664. https://doi.org/10.1177/1534735418766416

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of Commiphora wightii

19

Prerna Sarup, Sonia Pahuja, and Jai Malik

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Chemistry of C. wightii . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Volatile Oil and Its Terpenoidal Constituents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Steroids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Flavonoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Guggultetrols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Lignans . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6 Sugars . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.7 Amino Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Biological Activities of Guggulu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Hypolipidemic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Anti-Inflammatory and Anti-Arthritic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Anti-atherosclerotic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Anti-hyperglycemic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5 Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6 Anticancer Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7 Antimicrobial Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8 Cardioprotective Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9 Cytotoxic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10 Effect on Platelet Aggregation and Fibrinolytic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11 Thyroid Stimulatory Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.12 Miscellaneous Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Uses of Guggulu . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Traditional . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Spiritual . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Formulations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Safety and Toxicity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

448 449 450 450 450 456 456 456 456 456 456 461 462 462 462 463 463 463 464 464 464 465 466 466 466 466 471

P. Sarup (*) · S. Pahuja Swami Vivekanand College of Pharmacy, Patiala, Punjab, India J. Malik University Institute of Pharmaceutical Sciences, Panjab University, Chandigarh, India © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_22

447

448

P. Sarup et al.

6 C. Wightii: An Endangered Plant of Conservational Concern . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472 7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 472 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 473

Abstract

Guggul is a pathological oleo-gum resin obtained after inflicting injury to the stem bark of Commiphora wightii (Arnott) Bhandari [syn. “Commiphora mukul (Hook. Ex Stocks) Engl; Balsamodendron mukul (Hook. Ex Stocks)”; Family – Burseraceae]. It grows naturally in the warm and dry regions of Rajasthan and Gujarat in India and the bordering regions of Pakistan. It has been employed since antiquity in the Ayurvedic system of medicines for the treatment of multifarious ailments including bone fractures, arthritis, obesity, gout, inflammation, rheumatism, and lipid disorders. Guggul resin is composed mainly of volatile oil (rich in terpenoidal constituents monoterpenoids and sesquiterpenoids), other terpenoids (di- and triterpenoids), steroids, lignans, flavonoids, sugars, guggultetrols, and amino acids. This compilation entails a comprehensive account of chemical constituents, therapeutic activities, and uses of this oleo-gum resin. Guggul has been declared as a Critically Endangered species and is on the IUCN red list of threatened species. Commercial exploitation, nonscientific methods of tapping and collection of resin, and poor regeneration of the plant are some of the major reasons for its current status. Consequently, there is an imperative need for stringent measures for its conservation before this vital healing plant is lost entirely. Keywords

Anti-arthritic · Anti-inflammatory · Balsamodendron mukul · Commiphora mukul · Commiphora wightii · E-guggulsterone · Endangered · Guggulu · Oleo-gum resin · Z-guggulsterone

1

Introduction

Guggulu or guggul or Indian Bdellium is an oleo-gum resin obtained by tapping the stem and branches of Commiphora wightii (Arnott) Bhandari [syn. Balsamodendron mukul (Hook. Ex Stocks); Commiphora mukul(Hook. Ex Stocks) Engl.] Family Burseraceae. It grows naturally in warm, dry, and arid areas of India, Pakistan, and Bangladesh. Gujarat, Rajasthan, Madhya Pradesh, Assam, and Karnataka are the main areas that act as their natural habitat. C. wightii is a small, thorny tree that produces a yellowish oleo-gum resin in small ducts located through its bark which oozes out upon tapping. It is interesting to note that gum tapping is mainly done by the tribals. They make incisions on the stem and then apply a paste containing guggul along with urine of horse or wild ass and copper sulfate [1, 2]. This method is known to produce 3–4 times more gum compared to normal tapping, but it leads to tree death. Soni [3] explained that the death of the tree is due to copper toxicity from

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

449

the paste applied after stem incision. Also, the deep incision made by the local communities is thought to be harmful to the guggul tree [3]. An improved tapping method was developed by Bhatt et al. using the “Mitchie Golledge knife” and application of ethephon. They claimed that by this method the oleo-gum resin production increased by 22 times as compared to the conventional one. Also, the plants remained healthy by this method. There are variable reports on the optimum time for tapping [4]. Atal et al. reported that the tapping season for guggul was between November and December (cold season) and collection should be done till May to June (hot season) whereas Bhatt et al. reported that the favorable period to obtain guggul in high yield is April to May. On average, 250–500 g of dry oleo-gum resin is produced by a guggul tree in each season [5, 6]. In the Ayurvedic system of medicine, guggulu has been used since ages against lipid metabolic disorders, rheumatism, inflammation, arthritis, gout, and obesity [7]. Besides therapeutic indications, guggulu has also been used as an incense in meditation and religious rituals, in the dyeing and perfumery industry, and also as firewood [8, 9]. The quality of guggul varies, in terms of both appearance and content of active constituents, with the samples collected from different regions, making its analysis important to check adulteration and to validate its quality. A good quality guggul sample should have volatile oil (
1%), guggulsterone (1.0–1.5%), and total and acid insoluble ash not more than 5% and 1%, respectively [6, 7]. Guggulu Shodhana: According to Ayurveda, usage of raw guggul may lead to certain side effects such as nausea, diarrhea, headache, skin rashes, and sometimes even hepatotoxicity [10]. Therefore, it must be purified before it is incorporated into formulations. The purification process, known as Shodhanvidhi in Ayurveda, involves the usage of different fluids (dravyas), namely, cow milk, cow urine, decoction, and/or aqueous extract of vasaka leaves, a decoction of triphala, etc. These dravyas not only mitigate the toxicity but also augment its biological activity [5]. In the process of purification, raw guggul is broken into small pieces which are then packed in a muslin cloth (potli) and is hanged into a container having any one of the dravayas [7]. The potli with guggul is immersed in dravya and is boiled till all the soluble matter of guggul is dissolved. The insoluble portion is discarded and the soluble portion is then heated to dryness in ghee smeared wooden trays. The final product is known as purified guggul. Besides wide usage of guggul in herbal formulations, the effect of purification on its therapeutic efficacy has still not been explored [11, 12]. Though some reports have shown reduced gastric irritancy and increased anti-inflammatory, antioxidant, and antinociceptive activity of purified guggul, but still it warrants detailed investigations [13, 14].

2

Chemistry of C. wightii

The steam distillation of gum resin of C. wightii yields essential oil (0.4%), the chief components of which include monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids. Besides these, steroids, long-chain aliphatic tetrols, aliphatic esters,

450

P. Sarup et al.

ferulates, lignans, carbohydrates, a variety of inorganic ions, minor amounts of sesamin, and other unidentified constituents have been found in guggulu [7].

2.1

Volatile Oil and Its Terpenoidal Constituents

The monoterpenoids such as myrcene, dimyrcene, and polymyrcene along with the other constituents (1–10) [15, 16], a bicyclic sesquiterpenoid, cadinene11, and diterpenoids including cembrenoids and representative compounds 12–14 [17] have been isolated from volatile oil (Fig. 1a). The diterpenoid, Cembrene-A (13) derived from geranylgeranyl pyrophosphate by C-1 to C-14 cyclization is an elementary tetraene. The structure of a new class of cembrane alcohol (15) isolated from the aerial parts and the resin of guggulu [18, 19] was established by spectral analysis and mild dehydration which yielded cembrene (Fig. 1a). The bioassayguided isolation from a hexane-soluble portion of methanolic extract of guggulu revealed the occurrence of other cembrane-type (16–20) diterpenes (Fig. 1b) [20]. Furthermore, the polypodane-type triterpenes (21–25), myrrhanone A acetate (26), commipherol (27), commipherin (28), octanordammarane-type triperpenoid (29) [21– 23], and triterpenoidal components namely mansumbinone (30) and mansumbinoic acid (31) have been reported from gum resin [24]. The absolute stereostructure of the myrrhanol A (21) was determined to be (3S,5S,8R,9R,10S)-3,8,30-trihydroxypolypoda-13E,17E,21E-triene. Further, the triterpenoid 22, is 30-oic acid of myrrhanol A with altered stereostructure at C-5 (5R in contrast to 5S in myrrhanol A). Myrrhanone A and B are 3-keto analogs of myrrhanol A and B, respectively [22]. A myrrhanone derivative (32) and a myrrhanol derivative (33) have also been isolated (Fig. 1b) [20].

2.2

Steroids

The hypolipidemic and anti-inflammatory activities can be ascribed to the presence of several steroidal compounds in the oleo-gum resin [25–27]. The major constituents include E-guggulsterone (34), Z-guggulsterone (35), and a series (I–VI) of guggulsterol (36–41) (Fig. 2a). Other steroids (42–48) along with cholesterol (49) have also been isolated [23, 24]. Three novel isolated steroids are guggulsterone-M, dihydro guggulsterone-M (50), and guggulsterol-Y (51) [24] (Fig. 2b).

2.3

Flavonoids

Flavones (52–53) have been isolated from ethanolic extract of the trunk of C. wightii. The microbial sensitive assay has revealed the activity of muscanone (52), a novel flavone against Candida albicans [28]. Additionally, major flavonoid components (55–59) have also been reported from flowers of C. mukul (Fig. 3) [29].

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

Fig. 1 (continued)

451

452

Fig. 1 (a and b) Terpenoidal constituents isolated from C. wightii

P. Sarup et al.

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

Fig. 2 (continued)

453

454

Fig. 2 (a and b) Steroids isolated from C. wightii

P. Sarup et al.

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

Fig. 3 Flavonoids isolated from C. wightii

455

456

2.4

P. Sarup et al.

Guggultetrols

The saponified gum resin has been reported to yield a crystalline material that comprises components termed guggultetrols and constitute a new class of naturally occurring lipids. They are long-chain linear aliphatic tetrols with hydroxyl functions at C-1, C-2, C-3, and C-4 positions and include a mixture of lower (C-16, C-17) and higher (C-21, C-22) homologous tetrols (in small amounts) along with octadecan-1,2,3,4-tetrol (60), nonadecan-1,2,3,4-tetrol (61), and eicosan-1,2,3,4-tetrol (62). The guggultetrol-18 (63) and guggultetrol-20 (64) were obtained in pure form by derivatization and preparative GLC (Fig. 4) [30]. A mixture of two ferulates (n ¼ 16, n ¼ 17) (65) with an unusual skeleton was found in a cytotoxic fraction of ethyl acetate extract of guggulu. It was identified as a mixture of esters based on homologous long-chain tetrols and acid [31].

2.5

Lignans

Two lignans, sesamin (66) [25] and diayangambin (67) [32], have been reported from guggulu. Also, 5,50 -tetrahydro-1H,3H-furo[3,4-c]furan-1,4-diylbis[7-(methoxy)-1,3benzodioxole] (68) has been reported from methanolic extract of guggulu (Fig. 4) [20].

2.6

Sugars

Complete hydrolysis of gum revealed the presence of sugars (69–72). Graded hydrolysis of the gum furnished an aldobiouronic acid [6-O-(4-O-methyl-β-Dglucopyranosyluronic acid)-D-galactose] (73) [33]. Additionally, sugars (74–78) in the ratio of 1:1:1:2:1 were furnished upon hydrolysis of methylated gum. The provisional structure showed the gum to be a highly branched polysaccharide containing 1–6, 1–3, and 1–5 types of linkage (Fig. 5) [34].

2.7

Amino Acids

The chromatographed aqueous fraction obtained from the alcoholic extract of C. mukul revealed the presence of various amino acids (79–92) and isoleucine (Fig. 6) [35].

3

Biological Activities of Guggulu

3.1

Hypolipidemic Activity

In the year 1966, a doctorate proposition was presented to the Banaras Hindu University (BHU) wherein the lipid-lowering effect of guggulu in context to atherosclerosis and obesity was cited for the first time [36]. A group of researchers

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

Fig. 4 Guggultetrols and lignans isolated from C. wightii

457

458

Fig. 5 Sugars isolated from C. wightii

P. Sarup et al.

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

459

Fig. 6 Amino acids isolated from C. wightii

accomplished pioneering studies on rabbits wherein hyperlipidemia was induced by feeding them cholesterol (in trans fat). The serum cholesterol in hypercholesterolemic rabbits and body weight was significantly lowered with crude guggulu, and

460

P. Sarup et al.

also protected these animals, against cholesterol-induced atherosclerosis, at the fatty streak stage. Clinical studies in obese and hypercholesterolemic patients with crude guggulu revealed a substantial reduction in the serum cholesterol levels [36]. A hypolipidemic preparation being marketed in India, since 1988 comprising of standardized ethyl acetate extract of gugulipid, owes its action chiefly due to the presence of Z and E-guggulsterones [37, 38]. Guggulsterone is present in a concentration of 4.0–6.0%, comprising of a mixture of E and Z stereoisomers, with Zisomer being potent antilipidemic. Primarily, the commercial basis coupled with the probability of synergism exhibited by other components of this extract led to preferring standardized extract over two guggulsterone [39]. The hypolipidemic activity of gugulipid has been validated through scores of clinical studies remarkable being the findings of multicentric clinical trials in India executed in association with CDRI [39, 40]. Early studies reported that crude guggulu has promising hypolipidemic activity in rabbits [41] which was further substantiated in other animals such as an albino rat, domestic pig, presbytis monkey, and white leghorn chicks [5]. The serum cholesterol level lowering effect was studied on white leghorn chicks (atherogenic diet-fed hypercholesterolemic models) employing three fractions, namely petroleum ether (A), alkali washed neutral portion (B), and a petrol-insoluble fraction (C). The most and least potent fractions were A and B, respectively. However, none of the studied fractions were good enough to prevent the induction of hypercholesterolemia in test models [41]. A literature report demonstrated its hypolipidemic activity, wherein a significant decrease in average serum cholesterol and triglyceride levels was cited in animals that received a high-fat diet for a continuous period of 1 month along with guggulu. Furthermore, atherosclerosis in the aorta was partially reversed with the administration of guggulu [42]. Another study revealed the lowering of cholesterol with alcoholic extract (by 59.2%) and terpenoidal compound (by 54.3%) isolated from petroleum ether extract [41]. The alteration in lipid profile and a significant decrease in total cholesterol and LDL cholesterol after treatment with guggulu were revealed in a clinical report [43]. The triton (WR-1339) or cholesterol-induced hyperlipidemia in rats was improved significantly as evident from lowering of serum lipid levels upon administration of guggulsterone (E and Z ) isomers [44]. Several mechanisms have been ascribed to the hypolipidemic action of guggulu. The increase in plasma LDL cholesterol catabolism may be credited to decreased hepatic steroid production eventually due to guggulu. Alternatively, an increase in hepatic binding sites for LDL cholesterol, thus accelerating LDL clearance by active components of guggulu, guggulsterones (E and Z ), may be anticipated [7]. However, the latest developments have proposed that the highly efficacious antagonism of farnesoid X receptor (FXR) by guggulsterone isomers allows increased cholesterol catabolism and excretion from the body [45, 46]. Guggulsterone and cembrenoids present in stem bark resin of C. mukul have been found to specifically modulate two independent sites which are also modulated by bile salts to control cholesterol absorption and catabolism. Guggulsterone

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

461

antagonized the chenodeoxycholic acid-activated nuclear farnesoid X receptor (FXR), which regulates cholesterol metabolism in the liver. The cembrenoids, instead of exerting any noticeable effect on FXR, were found to lower the cholateactivated rate of human pancreatic IB phospholipase A2 (hPLA2), which in turn controlled gastrointestinal absorption of fat and cholesterol [47]. Ayurveda considers fresh guggulu for bṛhmaṇa (body mass increasing) effect; while lekhana (scarificant) effect is attributed to the old one [25]. This highlights that the therapeutic effects of new and old guggulu are different which may be due to various chemical or physical changes that occur with time. Lipid-lowering and weight-reducing effect of guggulu get altered as guggulu ages which means that old guggulu is comparatively better than new in the management of hyperlipidemia (Medoroga). The active principles behind this specific activity may be further evaluated through well-designed experimental trials [48]. The mechanism of the antihyperlipidemic activity of guggulu is well explained by various scientists in their recent publications [49].

3.2

Anti-Inflammatory and Anti-Arthritic Activity

Numerous literature citations have endorsed anti-inflammatory and anti-arthritic activities of guggulu [7, 13, 20, 32, 50–52]. The 50% aqueous methanolic extract illustrated an anti-inflammatory effect on adjuvant-induced air pouch granuloma in mice by inhibiting nitric oxide production in lipopolysaccharide activated mouse peritoneal macrophages [7]. An anti-inflammatory response of a crystalline steroid isolated from the pet ether extract was determined wherein inflammation in rats was induced with Freund’s adjuvant. The development of primary lesions in adjuvant arthritis was inhibited entirely, and there was a substantial decrease in the severity of secondary lesions vis-à-vis the untreated control group [53]. Few research works have provided a succinct account of the formulation of guggulosome wherein the guggul lipid is being used as a carrier for antiinflammatory drugs and also exert synergism with the latter. Anti-inflammatory activity of guggulosomes of guggul with ibuprofen prepared by bath sonication and trituration methods unambiguously revealed enhanced efficacy of guggulosomes than ibuprofen. Additionally, both guggul and ibuprofen exhibited synergism corroborating that gugulipid could be used as a carrier for entrapping and sustained release action of drugs [54]. A literature report entailed the formulation of guggulosome carrier by trituration method and then incorporating it into carbopol gel, with rationale for achieving synergism with phenylbutazone and achieving enhanced the topical drug delivery [55]. A similar report described the formulation of diclofenac sodium loaded solid lipid nanoparticles by melt-emulsion sonication/low temperature-solidification method using guggul lipid as major lipid component and subsequent formulation into a gel. These particulate systems were stable with optimum physical parameters with a controlled drug release profile. The guggul lipid nanoparticle gel showed a

462

P. Sarup et al.

promising permeation profile vis-à-vis commercial emulgel and plain carbopol gel containing drug and optimum anti-inflammatory activity [56]. Several animal and clinical investigations involving standard osteoarthritis models have demonstrated the effectiveness of guggulu extract for alleviation of symptoms associated with disease including pain and stiffness [57].

3.3

Anti-atherosclerotic Activity

The accumulation of cholesterol in human foam cells occurs due to LDL deposition in atherosclerotic lesions. Since LDL oxidation is necessary for atherogenesis, so antioxidants may either slow down or prevent atherogenesis. The in vitro LDL oxidation is effectively inhibited by guggulsterones, the lipid-lowering components of guggulu. Thus antioxidant property coupled with lipid-lowering action of guggulu renders it valuable against atherogenesis [58].

3.4

Anti-hyperglycemic Activity

A study showed the hypoglycemic effects of pure guggulsterone in diabetic rats fed on a high-fat diet to induce the disease. The determination of different biochemical parameters including in vivo insulin release, glucose homeostatic enzymes (glucose6-phosphatase and hexokinase), glycogen content, and expression profiles of various genes involved in carbohydrate and lipid metabolism unambiguously indicated that guggulsterone has both hypoglycemic (type II diabetes) and hypolipidemic effect [59]. Also, it has been proved that the administration of alcoholic extract of C. mukul at 200 mg/kg dose for 2 months continuously decreased plasma glucose levels in streptozotocin-induced diabetic rats [60]. There is another study that emphasizes the effectiveness of the ethanolic extract of gum resin as an adjuvant in the prevention and management of the prediabetic state of insulin resistance for people who require to increase their insulin sensitivity [61]. Furthermore, data from another literature report indicated the preventive role of C. mukul against streptozotocin-induced diabetic oxidative stress. It is noteworthy that the ethanolic extract of guggulu has potential antihyperglycemic activity in correlation with antioxidant activity without any toxicity induction [62].

3.5

Antioxidant Activity

The guggulu prevented cholesterol oxidation and subsequent hardening of arteries lessened platelet stickiness and also reduced the likelihood of coronary artery disease [63]. Additionally, it augmented thyroxin and triiodothyronine production, which in turn increased carbohydrates metabolism and protein synthesis and thus helped in lowering the lipid [64].

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

463

In an investigation, guggulsterone were tested in vitro against the formation of oxygen free radicals. The oxidation of human LDL induced by rat peritoneal macrophages or Fe2+ caused the marked formation of lipid peroxidation products. Guggulsterone prevented lipid hydroperoxidation of low-density lipoprotein and generation of thiobarbituric acid reactive substances in the above system. However, it did not protect lipids against the formation of conjugated dienes, which is the preliminary step of the lipid peroxidation cascade. Guggulsterone significantly inhibited the reaction of lipid peroxidation in liver microsomes challenged with Fe2+ and sodium ascorbate. Thus, the free radical scavenging and metal chelating ability of guggulsterone might support its protective role and hence antioxidant activity [65]. The alcoholic extract of C. mukul also exhibited antioxidant property [60].

3.6

Anticancer Activity

Guggulsterone has anti-proliferative capabilities against a wide range of cancer cells, rendering it a potential candidate for complementary or preventive cancer treatment [66]. Direct modification of signaling molecules such as Nrf2, NF-kB, STAT3, and AP-1, kinases, and P-glycoprotein by guggulsterones represents an important mechanism underlying its cancer chemopreventive functions [67].

3.7

Antimicrobial Activity

The effectiveness of the essential oil of C. mukul against Rhyzopertha dominica indicated its possible role as a fumigant. The ethanolic extract (5 mg/mL) of the plant exhibited the best antibacterial activity against multidrug-resistant Klebsiella pneumonia [68]. A phytoconstituent, 5-(1-methyl, 1-aminoethyl)-5-methyl-2-octanone, present in methanolic extract of oleo-gum resin possessed substantial and moderate antibacterial activity against Gram-positive and Gram-negative bacteria, respectively [69–71].

3.8

Cardioprotective Action

In an investigation, isoproterenol-induced myocardial necrosis in rats caused a marked increase in serum creatine phosphokinase and glutamate pyruvate transaminase. The level of enzymes namely phospholipase, xanthine oxidase, and lipid peroxides was simultaneously augmented in the ischemic heart followed by depletion of glycogen, phospholipids, and cholesterol. Significant cardioprotection of ischemic rats against cardiac damage was evident by reversal of blood and heart biochemical parameters upon treatment with guggulsterone [72].

464

3.9

P. Sarup et al.

Cytotoxic Activity

Ferulates, vital bioactive constituents present in guggulu gum, were reported to exhibit significant in vitro cytotoxicity by decreasing the cell viability in MCF-7 (breast) tumor cells, PC-3 (prostate) tumor cells, and in parental and transfected P 388 cells [50]. Thus, ferulate compounds are utilized in the prevention and treatment of neoplasia, abnormal cell growth and proliferation of inflammation, and cardiovascular disease. Significant in vitro cytotoxicity was exhibited by ethyl acetate extract. A fraction comprising a mixture of two ferulates exhibited marked cytotoxic activity and moderate scavenging effect against 2,2-diphenyl-1-picryl hydrazyl (DPPH) radicals [73]. The potential of gugulipid to reduce the viability of human prostate cancer cell lines LNCaP (androgen-dependent) and LNCaP (androgen-independent) has been indicated in apoptosis and cancer prevention (C-81) [74]. Further, it is interesting to note that guggulsterone induces apoptosis and inhibits proliferation of cultured PC-3 cells. But the normal prostate epithelial cell line (PrEC) was relatively more resistant to Gugulipid-mediated cellular responses in comparison to prostate cancer cells. Therefore, these findings justified more preclinical and clinical screening of guggulsterone for its effectiveness against prostate cancer [75].

3.10

Effect on Platelet Aggregation and Fibrinolytic Activity

The ADP, adrenaline, and serotonin-mediated platelet aggregation were effectively prevented by the pure steroid blend from the oleo-resin. The effectiveness of the steroidal mixture compared to purified guggulsterone isomer (E or Z ) was shown to be insignificant which in turn had similar inhibitory action as that of clofibrate. This revelation has therapeutic implications in the treatment of myocardial infarction and thromboembolism [63]. Another literature recount assessed the effect of guggulu on fibrinolysis and platelet adhesiveness in coronary heart disease wherein guggulu fraction A (pet ether extract) was administered to healthy individuals and patients with coronary artery disease (CAD) for a month. It indicated a statistically significant decrease in platelet adhesive index and an increase in serum fibrinolytic activity in both healthy individuals and CAD patients. Consequently, guggulu fraction A may be effective in CAD treatment [76].

3.11

Thyroid Stimulatory Activity

The ethanolic extract of guggulu augmented the triiodothyronine (T3) concentration and T3/T4 ratio in female albino mice; however, insignificant change in serum thyroxine (T4) concentrations was reported [64]. The thyroid stimulatory effect was discerned upon Z-guggulsterone administration to rats and significant elevation in all thyroid function parameters, including iodine uptake, enzymes involved in thyroid hormones synthesis, and tissue oxygen uptake was noticed [77].

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

3.12

465

Miscellaneous Activities

3.12.1 Antidepressant Activity Literature findings revealed that Z-guggulsterone, isolated from the gum resin of C. mukul, protects against neuroinflammation-induced behavioral abnormalities and scopolamine-induced memory impairment by attenuating the malfunction of the CREB-BDNF signaling pathway, and thus exert antidepressant-like effects. This has provided an approach to investigate the role of Z-guggulsterone involvement in the central nervous system, paving the way for the development of novel antidepressants [78]. 3.12.2 Anti-Hemorrhoids The resin of C. mukul was used in this randomized controlled clinical trial which demonstrated a significant reduction in symptoms of hemorrhoids such as associated GI symptoms including flatulence, GE-reflux, colonoscopic stage, and significant improvement in most of hemorrhoids symptoms [79]. 3.12.3 Anti-Urolithiatic Activity Struvite is a mineral, also known as triple phosphate, and is present in urine as crystallites and constitutes 30% of kidney stones worldwide. The growth of struvite crystals in vitro was inhibited with C. wightii extract [80, 81]. 3.12.4 Proandrogenic Activity Various literature reports reveal that men with diabetes mellitus have a higher proportion of spermatozoa with nuclear DNA damage which results in alterations of male fertility. Since oxidative stress damages spermatozoa, antioxidants present in various herbs play a vital role in the maintenance and restoration of sperms motility and their DNA integrity in the face of oxidative damage. Rezaei et al. found that C. mukul has antioxidant and proandrogenic properties, allowing it to have a positive impact on spermatogenesis and improve sperm parameters in rats [82]. Contrary to this activity in male rats, there is a report that suggested the usefulness of guggulu as an antifertility agent. Guggulu lowered the weight of the uterus, ovaries, and cervix in female rats, whereas glycogen and sialic acid levels in these organs increased [83]. 3.12.5 Skin Diseases Gugulipid administration was reportedly effective for the treatment of nodulocystic acne which affects the face, chest, and back in males. It is marked by multiple inflamed and uninflamed nodules (firm lumps) and cysts (fluid-filled cavities lined by epithelium). A trial involving 21 patients found gugulipid to be equally effective as tetracycline in the treatment of nodulocystic acne with better response in patients with oily faces [84]. Various literature reports connote the potential of guggulu in the treatment of chronic diseases such as dermatitis and psoriasis which can be attributed to its well-established anti-inflammatory and antioxidant effects mediated via targeting multiple signaling pathways [85].

466

P. Sarup et al.

3.12.6 Wound Healing The exudate of C. mukul has been mentioned in TPM books as an effective treatment for various types of wounds. A clinical study demonstrated the effectiveness of a mouthwash prepared from the exudate in the treatment of intra-oral mucosal wounds [86].

4

Uses of Guggulu

4.1

Traditional

Guggulu has been used in Ayurveda for ages. The Atharvaveda is perhaps the oldest record where different biological properties of guggul have been recorded [87]. Besides Atharvaveda, other Ayurvedic treatise namely Charak, Sushrutasamhitas, and Vagbhata also have detailed descriptions of guggul, its varieties, and its therapeutic activities [88]. It has been mentioned for numerous disorders such as inflammatory, metabolic, lipidemic, hepatic, kidney, and other nephrological disorders. It has also been used for facial paralysis, kidney stone, sciatica, anemia, arthritis, gout, and as an antiseptic, bitter and carminative [89, 90]. Guggulu has also been used as a diuretic, emmenagogue, uterine stimulant, ulceroprotective, gargles in dental caries, pyorrhea, and throat infections. Fumes of burnt guggul were inhaled for treatment of hay fever, nasal infection, laryngitis, bronchitis, and phthisis [6].

4.2

Spiritual

In the Vedic period, guggulu has been used as incense during the workship of God in Yagnas on various rituals with a belief that it would ward off evil spirits. The dhoop powder is placed on charcoal coals and its vapors are offered to God in puja. It is strongly believed that wherever there is the smell of this drug, the people will not be suffering from any disease. Also, it has been mentioned that the fragrance of guggulu does not even permit the curses to work and it purifies the environment leaving a positive impact on the body, soul, and mind [91].

4.3

Formulations

See Table 1.

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

467

Table 1 Marketed polyherbal Ayurvedic formulations of C. wightii [92–99] Guggulu formulations Abha Guggulu

Abhyadi Guggulu

Amrita Guggulu

Amrita Guggulu Dvitya

Amritadi Guggulu

Chandraprabha vati

Dashang Guggulu Gokshuradi Guggulu

Herbal ingredients Babool, Haritaki, Bibhitaki, Amalaki, Shunthi, Maricha, Pippali, Shuddha Guggulu Haritaki, Amalaki, Munakka, Shatahwa, Bharangi, Shvet Sariva, Krishana Sariva, Majith, Haridra, Daruharidra, Vach, Shuddha Guggulu, Musli, Mulethi, Muramansi, Dalchini, Sukshamaila, Tejpatra, Nagkeshar, Vidanga, Lvang, Durlabha, Trivrit, Trayamana, Sunthi, Maricha, Pippali Guduchi, Shuddha Guggulu, Haritaki, Bibhitaki, Amalaki, Dantimula, Pippali, Shunthi, Twak, Vidanga, Trivritmula Guduchi, Guggulu, Haritaki, Bibhitaki, Amalaki, Dantimula, Pippali, Shunthi, Maricha, Dalchini, Vidanga, Trivritmula Guduchi, Shuddha Guggulu, Haritaki, Bibhitaki, Amalaki, Varshambu, Danti, Chitrakmula, Pippali, Shunthi, Tvak, Vidanga, Trivrit Chandraprabha, Karpura, VachaMusta, Bhunimb, Amruta, Daruka, Haridra, Ativisha, Darvi, Pippalimoola, Chitraka, Dhanyaka, Haritaki, Vibhitaki, Amalaki, Chavya, Vidanga, Gajapippali, Shunti, Maricha, Pippali, Makshika Dhatu Bhasma, Swarjika Kshara, Saindhava Lavana, Sauvarchala Lavana, Vida Lavana, Trivrit, Danti, Patra, Twak, Ela, Vamshalochana, Loha Bhasma, Sita, Shilajatu, Guggulu Shunthi, Maricha, Pippali, Haritaki, Bibhitaki, Amalaki, Musta, Vidanga, Suddha Guggulu Gokshura panchaag, Shuddha Guggulu, Shunthi, Maricha, Pippali, Haritaki, Bibhitaki, Amalaki, Mustaka

Indications Bone-related disorders such as osteoporosis Brain disorders, constipation, indigestion, gout

Leprosy, malignant jaundice, urticaria, loss of appetite, spleen enlargement, abdominal diseases Leprosy, malignant jaundice, urticaria, loss of appetite, spleen enlargement, abdominal diseases Piles, gout, skin diseases, rheumatoid arthritis, fistula, decreased digestive power

Cures urinary infections and retention, relieves joint and muscle pains, used as an aphrodisiac and as a tonic

Useful in pain with swelling and joint pains and improves digestion and basic metabolic rate, obesity Effective in renal colic and urinary disorders, dysuria, useful in calculus, gout, leucorrhoea, and spermatic disorders (continued)

468

P. Sarup et al.

Table 1 (continued) Guggulu formulations Hritkyadi Guggulu Kaishor Guggulu

Kanchnar Guggulu

Laksha Guggulu

Lauh Guggulu

Mahayograj Guggulu

Navak Guggulu

Panchamrit Lauha Guggulu

Panchtiktghrit Guggulu

Herbal ingredients Haritaki, Sunthi, Vidharamula, Shuddha Guggulu, Erand taila Shuddha Guggulu, Haritaki, Bibhitaki, Amalaki, Guduchi, Pippali, Shunthi, Maricha, Vidanga, Trivrit mula, Dantimula, Go ghrita Kanchnar, Haritaki, Bibhitaki, Amalaki, Shunthi, Maricha, Pippali, Varun Chaal, Tejpatra, Sukshamaila, Dalchini, Shuddha Guggulu Laksha, Asthi samhrita, Arjun, Aswagandha, Nagbala, Shuddha Guggulu Shuddha Lauh bhasma, Shuddha Guggulu, Shunthi, Maricha, Pippali, Haritaki, Bibhitaki, Amalaki Shunthi, Pippali mula, Pippali, Chitrak, Chavya, Maricha, Bhrisht Hingu, Ajmoda, Sarshap, Krishan jirak, Shwet jirak, Indrayav, Renuka, Patha, Vidang, Gajpippali, Kutaki, Ativisha, Bharangi, Vach, Murva, Tejpatra, Devdaru, Kustha, Rasna, Mustaka, Saindhav lavana, Gokshur, Haritaki, Bibhitaki, Amalaki, Shuddha Guggulu,Vanga bhasma, Rajat bhasma, Naga bhasma, Loha bhasma, Abhrak bhasma, Mandura bhasma, Rasa sindura Pippali, Shunthi, Maricha, Haritaki, Bibhitaki, Amalaki, Chitrakmula, Musta, Vidang, Shuddha Guggulu Shuddha parada, Shuddha gandhaka, Rajat bhasma, Abhrak bhasma, Svarnmakshik bhasama, Lauh bhasma, Shuddha Guggulu, Katu taila Nimbchaal, Guduchi, Adusapanchang, Patolpatra, Kantkarimula, Shuddha Guggulu, Goghrita, Patha, Vidanga,

Indications Neuromuscular conditions, rheumatoid arthritis, backache, constipation Diabetes, skin diseases, gout, arthritis, constipation, obesity, cold, and cough

Cures kidney stones and ulcers, treats urinary infections, tonic

Osteoporosis, osteopenia, and fractured bones Anemia, general debility, loss of appetite, abdominal colic, jaundice, liver diseases, peptic ulcers Arthritis, gout, rheumatism, reduces joint pain, treats dysmenorrhea and obesity

Weight loss, diabetes, rheumatoid arthritis, and improves digestion

Treatment of mental disorders, neuralgia, neuritis, myalgia, myositis, sciatica, frozen shoulder (adhesive capsulitis), lumbar pain (a low backache), osteoarthritis, rheumatoid arthritis Treatment of sinus, asthma, rhinitis, cough, and cold, gout, cardiac diseases, psoriasis, arthritis (continued)

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

469

Table 1 (continued) Guggulu formulations

PathyadiGuggulu

Punarvava Guggulu

Punarnavadi Guggulu

RasabhrGuggulu

Rasanadi Gutika

Saptang Guggulu

Saptvinshtika Guggulu

Herbal ingredients Devdaru, Gajpippal, Swarjikakshar, Yavakshara, Shunthi, Haridra, Shatahva, Chavya, Kushtha, Tejowati, Maricha, Indrayava, Jirak, Chitrak chaal, Kutaki, Shuddha bhallatak, Vach, Pipplamula, Manjishtha, Ativisha, Haritaki, Bibhitaki, Amalaki, Yavani Haritaki, Bibhitaki, Amalaki, Guggulu, Vidanga, Danti, Guduchi, Pippali, Trivrit, Shunthi, Maricha

Punarnava mula, Erand mula, Shunthi, Shuddha Guggulu, Trivritmula, Dantimula, Guduchi, Pippali, Shunthi, Maricha, Haritaki, Bibhitaki, Amalaki, Chitrakmula, Saindhav lavana, Shuddha Bhallatak, Vidanga, Swarnmakshik Punarnava, Devdaru, Haritaki, Guduchi, Gomutra, Shuddha Guggulu, Ghrita

Shuddha parad, Lauha bhasma, Shuddha gandhaka, Abhrak bhasma, Guggulu, Guduchi svarasa, Pippali, Shunthi, Maricha, Haritaki, Bibhitaki, Amalaki Dantimool, Indrayanmula, Vidanga, Nagkesar, Trivritmula Rasna, Shuddha Guggulu, Ghrit

Shuddha Guggulu, Haritaki, Bibhitaki, Amalaki, Shunthi, Marich, Pippali, Go Ghrita Pippali, Shunthi, Maricha, Haritaki, Bibhitaki, Amalaki, Mustaka, Vidanga, Guduchi, Chitraka, Shati, Sukhamaila, Pippalimula, Hapusha, Devdaru, Tumbru, Pushkarmula, Chavya,

Indications

Headache, migraine, vascular headache, earache, toothache, night blindness, eye pain, eye disorders related to inflammation, and vision disturbances Rheumatoid arthritis, gout, hernia, sciatica, frozen shoulder, backache, urinary bladder pain, tail bone pain, neck pain, spondylitis

Gout, abdominal diseases, anemia, obesity, sciatica, spondylitis, rheumatoid arthritis, other skeletomuscular and joint disorders, inflammation and swelling Rheumatoid arthritis, skin diseases, fistula, vitiligo, eczema, and lymphadenitis

Tinnitus, headache, migraine, rheumatoid arthritis, fistula, flatulence, intestinal gas, abdominal pain, sciatica Sinus, ulcers, and anal fissures Anal fissures, sinuses, skin infections, anorectal pain, abdominal pain, bloating, diabetic foot ulcer, kidney stones, hernia, asthma (continued)

470

P. Sarup et al.

Table 1 (continued) Guggulu formulations

Shatavari Guggulu

Shiva Guggulu

Singhnaad Guggulu

Dvitya Singhnaad Guggulu

Svayambhuv Guggulu

Triphala Guggulu

Herbal ingredients Vishala, Haridra, Daruharidra, Vid lavana, Sauvarchal lavana, Yavakshara, Saindhav lavana, Gajpippali, Shuddha Guggulu Shatavari, Guduchi, Gandhprasarini, Gokshura, Pippali, Shatahva, Yavani, Rasna, Ashwagandha, Sanghyak, Karchur, Shunthi, Mahishaksh Guggulu, Triphala kvath (shodhanarth),Go Ghrit Haritaki, Bibhitaki, Amalaki, Erand taila, Shuddha Guggulu, Shuddha Gandhaka, Rasna, Vidanga, Maricha, Pippali, Dantimula, Jatamansi, Shunthi, Devdaru Ghrit Kuttit Guggulu, Sarshap taila, Haritaki, Bibhitaki, Amalaki, Sunthi, Maricha, Pippali, Mustaka, Vidanga, Devdaru, Guduchi, Chitrakmula, Trivrit, Dantimula, Chavya, Shuddha Surankanda, Shuddha Parad, Shuddha Gandhaka, Jaipal beej churna Shuddha Guggulu, Haritaki, Bibhitaki, Amalaki, Danti, Trivrit, Shunthi, Maricha, Pippali, Bhumyamalaki, Vidanga, Mustaka, Guduchi, Kutaki, Vach, Aaluk, Mankand, Gandhaka, Parad, Shuddha dhatur phal churna Bakuchi, Shilajit, Guggulu, Swarnmakshik, Lauh bhasma, Mundi, Haritaki, Amalaki, Karanj patra, Kher, Guduchi, Trivrit, Jamalghota, Mustaka, Vidanga, Haridra, Kutaj chaal, Madhu Haritaki, Bibhitaki, Amalaki, Pippali Shuddha Guggulu

Vatari Guggulu

Erand taila, Shuddha Gandhak, Shuddha Guggulu, Haritaki, Bibhitaki, Amalaki

Vidangadi Guggulu

Vidang, Haritaki, Bibhitaki, Amalaki, Shunthi, Maricha,

Indications

Muscles strengthening, nerve tonic, vata disorders, treatment of hemiplegia and paralysis

Rheumatoid arthritis, low backache, and sciatica

Soothe joints, improves digestion, removes toxins from plants and excess fluid from the body

Chronic rheumatism, paralysis stroke, arthritis, treat menstrual disorders, diuretics, mucilage secretory agent, worm destroyer

Treatment of abdominal and liver disorders, skin infections, gout, arthritis

Beneficial in hemorrhoids, fistula, renal stones, vata related pains, paralysis, sciatica, diabetes, acne, blood purifier Treatment of rheumatoid arthritis, hip pain, sciatica, gout, joint pain, burning sensation. It is used even in chronic degenerative diseases Sinus, skin disorders, urinary disorders, diabetes, healing of wounds and ulcers (continued)

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

471

Table 1 (continued) Guggulu formulations

Vyoshadi Guggulu

Yograj Guggulu

5

Herbal ingredients Pippali, Shuddha Guggulu, Go Ghrita Shunthi, Maricha, Pippali, Chitraka, Mustaka, Haritaki, Bibhitaki, Amalaki, Vidanga, Shuddha Guggulu Chitraka, Pippali, Ajmoda, Krishan Jirak, Vidang, Yavani, Shwet Jirak, Devdaru, Chavya, Shuksham aila, Saindhava lavana, Kushta, Rasna, Gokshura, Dhanyaka, Haritaki, Bibhitaki, Amalaki, Mustaka, Shunthi, Marich, Pippli, Twak, Ushir, Yavakshar, Talispatra, Tejpatra, Ghrita, Shuddha Guggulu

Indications

Treatment of arthritis, hypercholesterolemia, rheumatoid arthritis, swelling, gout, bloating, congestion, fatty liver Treatment for arthritis and diseases affecting bone, joints, and bone marrow, increases digestion power, complexion, strength, and immunity

Safety and Toxicity

Numerous Ayurvedic texts have mentioned that administration of raw guggul may occasionally lead to diarrhea, skin rashes, irregular menstruation, mild nausea, headache, and liver toxicity at very high doses [7, 10]. A number of purification processes (shodhanvidhi) have been described in Ayurveda to surmount the side effects of raw guggulu, in different “dravyas,” that is, fluids. The purification prevents the propensity of adverse effects but also improves the therapeutic activity [6]. Additionally, Ayurvedic manuscripts have emphasized the relevance of guggulu purification before incorporating it into herbal formulations. A myriad of polyherbal anti-inflammatory formulations with guggulu as the main ingredient is available commercially [13]. The clinical trials of standardized gum guggul extracts revealed transient side effects including skin rashes, diarrhea, and irregular menstruations [7, 36]. According to a report carried on 22 individuals administered with guggulu (2160 mg daily for 12 weeks), ten persons experienced one or the other side effect including gastrointestinal distress, fatigue, and skin rash [7, 100]. Other trials on guggulipid (ethyl acetate fraction, 1–2 g daily for a month) have revealed the occurrence of skin rashes though it did not report any intestinal distress [7, 101]. Although generally accepted as a safe drug, consumption of guggul may be warranted with caution. As per a comprehensive toxicity report under the condition of 3-month gavage studies, administration of the selected GGE formulation in animals resulted in increased globulin concentrations and decreased bile acid, cholesterol, and phospholipid concentrations in rats, whereas increased cholesterol and phospholipid concentrations were observed in mice. Reduction in an average number of homogenization-resistant spermatids in mice suggested that the testes

472

P. Sarup et al.

might be a target organ of GGE toxicity (lowest-observed-effect level ¼ 62.5 mg/kg/ day). Significantly increased absolute and relative liver weights in male and female rats were related to the GGE formulation dose administered. Furthermore, improved hepatic activity (CYP3A and CYP2B) was observed in both species with altered metabolic potential in human in vitro assays which suggested an improved potential for dietary supplement-drug pharmacokinetic interactions [102].

6

C. Wightii: An Endangered Plant of Conservational Concern

The resin owes its high commercial value specifically in international trade due to its multifaceted medicinal utility. Since the majority of guggul is collected through wild harvesting methods like destructive tapping, application of ethephon or sulfuric acid on tapping cuts, etc. [103, 104], there has been a significant decrease in the population of guggul trees growing naturally. Besides poor harvesting methods, the poor regeneration ability of the guggul trees has also added to its decreasing population. Consequently, UNDP has listed this species as “critically endangered” [105]. The Government of India has also included guggul under RET (Rare, Endangered, Threatened) category [106]. Due to this wild collection/tapping and export of guggul has been completely banned in India [107–109]. Collection of guggul from cultivated sources and only using sustainable methods is now allowed. Due to over-exploitation, C. wightii is one of the top 40 conservation priority species in India [110, 111]. According to an estimate, if such exploitation continues without sustainable and appropriate management of the genetic resources, the diversity and natural abundance of this species will be eroded [112]. Ample work is going on to conserve this commercially important plant. Measures including a ban on wild tapping to community-based conservation methods to more formal in situ and ex situ conservation initiatives are being employed [8] to save this plant. Measuring the extent and distribution of genetic variation of guggul trees is a must to frame an effective conservation strategy [113].

7

Conclusions

Guggul is a revered Ayurvedic product, used since antiquity. It enjoys elite status, primarily being used for anti-inflammatory and hypolipidemic actions. However, side effects such as rashes, nausea, headache, GIT problems, and hepatotoxicity have been reported upon the usage of raw guggul. So to circumvent these toxic effects, Ayurveda recommends purification of guggul prior to its use. Although diverse literature reports have mentioned numerous purification processes, pertinent investigation(s) are still awaited which could cite the probable effect of purification on the therapeutic efficacy of guggul. Thus, a vigilant investigation needs to ponder upon transformations that take place during the purification of raw guggul. Additionally, the natural variability in the composition of the oleo-gum resin due to geographic location, climate, soil nutrition, and genetic variation renders this task

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

473

more challenging. Furthermore, due to the imbalance between demand and supply of guggul, adulteration of guggul with some morphologically similar cheap gums has become an attractive proposition for the guggul suppliers. Therefore, rapid, specific, and selective analytical methods to check the adulteration and quality of guggul are required to be developed and validated. Further, authors are of the view that rationale approaches to investigate purification processes and standardization of guggul need to be embarked upon the active markers, the guggulsterone which is credited with a myriad of pharmacological activities including anti-inflammatory, anti-proliferative, analgesic, anti-diabetic, hypotensive, hepatoprotective, hypolipidemic, and many more. Furthermore, the government should render necessary support to local people and tribes to cultivate guggul on large scale to help in preventing the extinction of this promising medicinal plant. It would not be hyperbole, if we conclude by saying guggul the magical herb serves as a gold mine for the treatment of multiple disorders. Acknowledgements The corresponding author feels indebted toward her Alma mater and supervisors for their motivation and unconditional support during her doctoral research project on Commiphora wightii.

References 1. Atal CK, Gupta OP, Afaq SH (1975) Commiphora mukul: source of guggal in Indian systems of medicine. Econ Bot 29:208–218 2. Dalal KC, Sriram S (1995) Guggal. In: Chadha KL, Gupta R (eds) Advances in horticulture, Vol- Medicinal and aromatic plants. Malhotra Publishing House, New Delhi 3. Soni V (2008) Final Project Report of In-situ conservation of Commiphora wightii a red-listed medicinal plant species of Rajasthan state, India. http://www.cropwildrelatives.org. Accessed 20 July 2021 4. Bhatt JR, Nair MNB, Mohan Ram HY (1989) Enhancement of oleo-gum resin production in Commiphora wightii by improved tapping technique. Curr Sci 58:349–357 5. Anonymous (2007) The Ayurvedic pharmacopoeia of India (Formulations), 1st edn. Department of Indian Systems of Medicine and Homeopathy, Ministry of Health and Family Welfare, Government of India, New Delhi 6. Anonymous (2001) The Ayurvedic pharmacopoeia of India, 1st edn. Department of Indian Systems of medicine and homeopathy, Ministry of Health and Family Welfare, Government of India, New Delhi 7. Sarup P, Bala S, Kamboj S (2015) Pharmacology and phytochemistry of oleo-gum resin of Commiphora wightii (Guggulu). Scientifica 2015:138039 8. Cunningham AB, Brinckmann JA, Kulloli RN, Schippmann U (2018) Rising trade, declining stocks: the global gugul (Commiphora wightii) trade. J Ethnopharmacol 223:22–32 9. Anonymous (1996) Indian pharmacopoeia. The Controller of Publications, New Delhi 10. Masten SA (2005) Gum guggul and some of its steroidal constituents: review of toxicological literature. Document prepared for National Toxicology Program (NTP), National Institute of Environmental Health Sciences (NIEHS), National Institutes of Health, U.S Department of Health and Human Services, North Carolina, USA 11. Karan M, Kumar V, Suneja V, Vasisht K (2009) Commercial herbal anti-inflammatory formulations- a survey. Pharmacos 36:14–25

474

P. Sarup et al.

12. Sangle VD, Nadkarni SD, Vahalia MK, Darp MS (2004) The study of effect of Ayurvedic processing of Commiphora wightii on gastric irritancy index in experimental animals. Indian Drugs 41:268–271 13. Karan M, Sarup P, Suneja V, Vasisht K (2012) Effect of traditional Ayurvedic purification processes (Sodhanvidhi) of Guggulu on carrageenan-induced paw oedema in rats. J Pharm Biomed Sci 21:1–5 14. Karan M, Sarup P, Vasisht K (2013) Evaluation of antioxidant and antinociceptive potential of raw and purified guggulu. J Pharm Biomed Sci 31:1150–1158 15. Bhati A (1950) Essential oil from the resin of Commiphora mukul, Hook. Ex. Stocks. J Indian Chem Soc 27:436–440 16. Saxena VK, Sharma RN (1998) Constituents of the essential oil from Commiphora mukul gum resin. J Med Aromat Plant Sci 20:55–56 17. Ruecker G (1972) Monocyclic diterpenes from Indian guggul resin (Commiphora mukul). Arch Pharm 305:486–493 18. Prasad RS, Dev S (1976) Chemistry of Ayurvedic crude drugs-IV. Absolute stereochemistry of mukulol. Tetrahedron 32:1437–1441 19. Patil VD, Nayak UR, Dev S (1973) Chemistry of Ayurvedic crude drugs-II, Guggulu (resin from Commiphora mukul)- 2: diterpenoid constituents. Tetrahedron 29:341–348 20. Francis AJ, Raja NS, Nair GM (2004) Bioactive terpenoids and guggulusteroids from Commiphora mukul gum resin of potential anti-inflammatory interest. Chem Biodivers 1: 1842–1852 21. Matsuda H, Morikawa T, Ando S, Oominami H, Murakami T, Kimura I, Yoshikawa M (2004) Absolute stereostructures of polypodane-type triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resin (the resin of Balsamodendron mukul). Chem Pharm Bull 52:1200–1203 22. Kimura I, Yoshikawa M, Kobayashi S, Sugihara Y, Suzuki M, Oominami H, Murakami T, Matsuda H, Doiphode VV (2001) New triterpenes, myrrhanol A and myrrhanone A, from guggul-gum resins, and their potent anti-inflammatory effect on adjuvant-induced air-pouch granuloma of mice. Bioorg Med Chem Lett 11:985–989 23. Xu J, Guo Y, Li Y, Zhao P, Xie C, Jin DQ, Hou W, Zhang T (2011) Neuroprotective cadinane sesquiterpenes from the resinous exudates of Commiphora myrrha. Fitoterapia 82:1198–1201 24. Hanus LO, Rezankab T, Dembitskya VM, Moussaieffa A (2005) Myrrh-Commiphora chemistry. Biomed Papers 149:3–28 25. Patil VD, Nayak UR, Dev S (1972) Chemistry of Ayurvedic crude drugs-I, Guggulu (resin from Commiphora mukul)- 1: steroidal constituents. Tetrahedron 28:2341–2352 26. Purushothaman KK, Chandrasekharan S (1976) Guggulsterols from Commiphora mukul (Burseraceae). Indian J Chem 14B:802–804 27. Bajaj AG, Dev S (1982) Chemistry of Ayurvedic crude drugs- V, Guggulu (resin from Commiphora mukul )- 5: some new steroidal components and stereochemistry of guggulsterol-I at C-20 and C-22. Tetrahedron 38:2949–2954 28. Fatope MO, Al-Burtomani SKS, Ochei JO, Abdulnour AO, Al-Kindy SMZ, Takeda Y (2003) Muscanone: a 3-O-(100 ,800 ,1400 -trimethylhexadecanyl) naringenin from Commiphora wightii. Phytochemistry 62:1251–1255 29. Kakrani HK (1981) Flavonoids from the flowers of Commiphora mukul. Fitoterapia 52: 221–223 30. Kumar V, Dev S (1987) Chemistry of Ayurvedic crude drugs-VII, absolute stereochemistry of guggultetrols. Tetrahedron 43:5933–5948 31. Su SL, Duan JA, Tang YP, Zhang X, Yu L, Jiang FR, Zhou W, Luo D, Ding AW (2009) Isolation and biological activities of neomyrrhaol and other terpenes from the resin of Commiphora myrrha. Planta Med 75:351–355 32. Matsuda H, Morikawa T, Ando S, Oominami H, Murakami T, Kimura I, Yoshikawa M (2004) Absolute stereostructures of polypodane- and octanordammarene- type triterpenes with nitric oxide production inhibitory activity from guggul-gum resins. Bioorg Med Chem 12: 3037–3046

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

475

33. Bose S, Gupta KC (1966) Structure of Commiphora mukul gum I: nature of sugars present and the structure of aldobiouronic acid. Indian J Chem 2:57–60 34. Ali MA, Hasan M (1967) Chemical investigation of Commiphora mukul Engl. (Burseraceae). Pak J Ind Res 10:21–23 35. Satyavati GV (1991) Guggulipid: a promising hypolipidemic agent from gum guggul (Commiphora wightii). Econ Med Plant Res 5:47 36. Satyavadi GV (1988) Gum guggul (Commiphora mukul)- the success story of an ancient insight leading to a modern discovery. Indian J Med Res 87:327–335 37. Morais SMD, Facundo VA, Bertini LM, Cavalcanti ESB, Junior JFDA, Ferreira SA, De Brito ES, De Souza Neto MA (2007) Chemical composition and larvicidal activity of essential oils from piper species. Biochem Syst Ecol 35:670–675 38. Sahni S, Hepfinger C, Saucer K (2000) Guggulipd use in hyperlipidaemia: case report and review of the literature. Am J Health-Syst Pharm 62:1690–1692 39. Nityanand S, Srivastava JS, Asthana OP (1989) Clinical trials with gugulipid- a new hypolipidaemic agent. J Assoc Physicians India 37:323–328 40. Verma SK, Bordia A (1988) Effect of Commiphora mukul (gum guggulu) in patients of hyperlipidemia with special reference to HDL- cholesterol. Indian J Med Res 87:356–360 41. Satyavadi GV, Dwarakanath C, Tripathi SN (1969) Experimental studies on the hypocholesterolemic effect of Commiphora mukul. Indian J Med Res 57:1950–1962 42. Baldwa V, Bhasin V, Ranka P, Mathur K (1981) Effects of Commiphora mukul (guggulu) in experimentally induced hyperlipidemia and atherosclerosis. J Assoc Physicians India 29: 13–17 43. Hasani RS, Nayabi N, Moradi L, Mehri A, Larijani B, Abdollahi M (2010) The efficacy and safety of herbal medicines used in the treatment of hyperlipidemia; a systematic review. Curr Pharm Des 16:2935–2947 44. Chander R, Khanna AK, Kapoor NK (1996) Lipid lowering activity of guggulsterone from Commiphora mukul in hyperlipidaemic rats. Phytother Res 10:508–511 45. Wu J, Xia C, Meier J, Li S, Hu X, Lala DS (2002) The hypolipidemic natural product guggulsterone acts an antagonist of the bile acid receptor. Mol Endocrinol 16:1590–1597 46. Urizar NL, Liverman AB, Dodds DT, Silva FV, Ordentlich P, Yan Y, Gonzalez FJ, Heyman RA, Mangelsdorf DJ, Moore DD (2002) A natural product that lowers cholesterol as an antagonist ligand for FXR. Science 296:1703–1706 47. Yu BZ, Kaimal R, Bai S, El Sayed KA, Tatulian SA, Apitz RJ, Jain MK, Deng R, Berg OG (2009) Effect of guggulsterone and cembranoids of Commiphora mukul on pancreatic phospholipase A(2): role in hypocholesterolemia. J Nat Prod 72:24–28 48. Vyas KY, Bedarkar P, Galib R, Prajapati PK (2015) Comparative anti-hyperlipidaemic activity of Navīna (fresh) and Purāṇa (old) Guggulu. Anc Sci Life 35:101–109 49. Azhar Y, Parmar A, Miller CN, Samuels JS, Rayalam S (2016) Phytochemicals as novel agents for the induction of browning in white adipose tissue. Nutr Metab (Lond) 13:89 50. Chaudhary G (2012) Pharmacological properties of Commiphora wightii Arn. Bhandari – an overview. Int J Pharm Pharm Sci 4:73–75 51. Gujral ML, Sareen K, Tangri KK, Amma MK, Roy AK (1960) Antiarthritic and antiinflammatory activity of gum guggul (Balsamodendron mukul Hook). Indian J Physiol Pharmacol 4:267–273 52. Khanna D, Sethi G, Ahn KS, Pandey MK, Kunnumakkara AB, Sung B, Aggarwal A, Aggarwal BB (2007) Natural products as a gold mine for arthritis treatment. Curr Opin Pharmacol 7:344–351 53. Arora RB, Taneja V, Sharma RC, Gupta SK (1972) Anti-inflammatory studies on a crystalline steroid isolated from Commiphora mukul. Indian J Med Res 60:929–931 54. Verma S, Jain A, Gupta VB (2010) Synergistic and sustained anti-inflammatory activity of guguul with the ibuprofen: a preliminary study. Int J Pharm Bio Sci 1:1–7 55. Dave V, Yadav R, Gupta S, Sharma S (2017) Guggulosomes: a herbal approach for enhanced topical delivery of phenylbutazone. Fut J Pharm Sci 3:23–32

476

P. Sarup et al.

56. Gaur PK, Mishra S, Purohit S (2013) Solid lipid nanoparticles of guggul lipid as drug carrier for transdermal drug delivery. Biomed Res Int 2013:750690 57. Singh BB, Mishra LC, Vinjamury SP, Aquilina N, Singh VJ, Shepard N (2003) The effectiveness of Commiphora mukul for osteoarthritis of the knee: an outcome study. Altern Ther Health Med 9:74–79 58. Wang X, Greilberger J, Ledinski G, Kager G, Paigen B, Jurgens G (2004) The hypolipidemic natural product Commiphora mukul and its component guggulsterone inhibit oxidative modification of LDL. Atherosclerosis 172:239–246 59. Sharma B, Salunke R, Srivastava S, Majumder C, Roy P (2009) Effects of guggulsterone isolated from Commiphora mukul in high fat diet induced diabetic rats. Food Chem Toxicol 47:2631–2639 60. Bellamkonda R, Rasineni K, Singareddy SR, Kasetti RB, Pasurla R, Chippada AR, Desireddy S (2011) Antihyperglycemic and antioxidant activities of alcoholic extract of Commiphora mukul gum resin in streptozotocin induced diabetic rats. Pathophysiology 18:255–261 61. Bellamkonda R, Karuna R, Sasi Bhusana Rao B, Haritha K, Manjunatha B, Silpa S, Saralakumari D (2017) Beneficiary effect of Commiphora mukul ethanolic extract against high fructose diet induced abnormalities in carbohydrate and lipid metabolism in Wistar rats. J Tradit Complement Med 8:203–211 62. Ramesh B, Karuna R, Sreenivasa RS, Haritha K, Sai MD, Sasi BR, Saralakumari D (2012) Effect of Commiphora mukul gum resin on hepatic marker enzymes, lipid peroxidation and antioxidants status in pancreas and heart of streptozotocin induced diabetic rats. Asian Pac J Trop Biomed 2:895–900 63. Mester L, Mester M, Nityanand S (1979) Inhibition of platelet aggregation by guggulu steroids. Planta Med 37:367–369 64. Panda S, Kar A (1999) Guggulu (Commiphora mukul) induces triiodothyronine production: possible involvement of lipid peroxidation. Life Sci 65:137–141 65. Chander R, Khanna AK, Pratap R (2002) Antioxidant activity of guggulsterone, the active principle of guggulipid from Commiphora mukul. J Med Aromat Plant Sci 24:371–375 66. Macha MA, Rachagani S, Gupta S, Pai P, Ponnusamy MP, Batra SK, Jain M (2013) Guggulsterone decreases proliferation and metastatic behavior of pancreatic cancer cells by modulating JAK/STAT and Src/FAK signaling. Cancer Lett 341:166–177 67. Almazari I, Surh YJ (2013) Cancer chemopreventive and therapeutic potential of guggulsterone. Top Curr Chem 329:35–60 68. Sharma A, Patel VK, Rawat S, Ramteke P, Verma R (2010) Identification of the antibacterial component of some Indian medicinal plants against Klebsiella pneumoniae. Int J Pharm Pharm Sci 2:123–127 69. Goyal P, Chauhan A, Kaushik P (2010) Assessment of Commiphora wightii (Arn.) Bhandari (Guggul) as potential source for antibacterial agent. J Med Sci 3:71–75 70. Ishnava BK, Mahida YN, Mohan JSS (2010) In vitro assessments of antibacterial potential of Commiphora wightii (Arn.) Bhandari. gum extract. J Pharmacogn Phytother 2:91–96 71. Romero CD, Chopin SF, Buck G, Martinez E, Garcia M, Bixby L (2005) Antibacterial properties of common herbal remedies of the southwest. J Ethnopharmacol 99:253–257 72. Chander R, Rizvi F, Khanna AK, Pratap R (2003) Cardioprotective activity of synthetic guggulsterone (E- and Z- isomers) in isoproterenol induced myocardial ischemia in rats: a comparative study. Indian J Clin Biochem 18:71–79 73. Zhu N, Rafi MM, Dipaola RS, Xin J, Chin CK, Badmaev V, Ghai G, Rosen RT, Ho CT (2001) Bioactive constituents from gum guggul (Commiphora wightii). Phytochemistry 56:723–727 74. Singh SV, Zeng Y, Xiao D, Vogel VG, Nelson JB, Dhir R, Tripathi YB (2005) Caspasedependent apoptosis induction by guggulsterone, a constituent of Ayurvedic medicinal plant Commiphora mukul, in PC-3 human prostate cancer cells is mediated by Bax and Bak. Mol Cancer Ther 4:1747–1754 75. Xiao D, Zeng Y, Prakash L, Badmaev V, Majeed M, Singh SV (2011) Reactive oxygen species-dependent apoptosis by gugulipid extract of Ayurvedic medicine plant Commiphora

19

Chemistry, Biological Activities, and Uses of Oleo-Gum Resin of. . .

477

mukul in human prostate cancer cells is regulated by c-Jun N-terminal kinase. Mol Pharm 79: 499–507 76. Bordia A, Chuttani SK (1979) Effect of gum guggulu on fibrinolysis and platelet adhesiveness in coronary heart disease. Indian Med Res 70:992–996 77. Tripathi YB, Malhotra OP, Tripathi SN (1984) Thyroid stimulating action of Z- Guggulsterone obtained from Commiphora mukul. Planta Med 1:78–80 78. Liu FG, Hu WF, Wang JL, Wang P, Gong Y, Tong LJ, Jiang B, Zhang W, Qin YB, Chen Z, Yang RR, Huang C (2017) Z-Guggulsterone produces antidepressant-like effects in mice through activation of the BDNF signaling pathway. Int J Neuropsychopharmacol 20:485–497 79. Yousefi M, Mahdavi MR, Hosseini SM, Bahrami A, Davati A, Kamalinejad M, Faghihzadeh S (2013) Clinical evaluation of Commiphora Mukul, a botanical resin, in the management of hemorrhoids: a randomized controlled trial. Pharmacogn Mag 36:350–356 80. Chauhan CK, Joshi MJ, Vaidya ADB (2009) Growth inhibition of Struvite crystals in the presence of herbal extract Commiphora wightii. J Mater Sci Mater Med 20:S85–S92 81. Kaleeswaran B, Ramadevi S, Murugesan R, Srigopalram S, Suman T, Balasubramanian T (2019) Evaluation of anti-urolithiatic potential of ethyl acetate extract of Pedalium murex L. on struvite crystal (kidney stone). J Tradit Complement Med 9:24–37 82. Rezaei AA, Salehi I, Karimi SA, Rahnama M (2020) The effects of Commiphora mukul extract on spermatogenesis and testosterone levels in male diabetic rats. Clin Exp Reprod Med 47:34–41 83. Amma MKP, Malhotra N, Suri RK, Arya OP, Dani HM, Sareen K (1978) Effect of oleoresin of gum guggul on the reproductive organs of female rat. Indian J Exp Biol 16:1021–1023 84. Thappa DM, Dogra J (1994) Nodulocystic acne: oral guggulipid versus tetracycline. J Dermatol 21:729–731 85. Kunnumakkara AB, Banik K, Bordoloi D, Harsha C, Sailo BL, Padmavathi G, Roy NK, Gupta SC, Aggarwal BB (2018) Googling the Guggul (Commiphora and Boswellia) for prevention of chronic diseases. Front Pharmacol 9:686 86. Hosseinkhani A, Falahatzadeh M, Raoofi E, Zarshenas MM (2017) An evidence-based review on wound healing herbal remedies from reports of traditional Persian medicine. J Evid Based Complement Altern Med 22:334–343 87. Anonymous (1954) Sushruta Samhita Chapter 15 verse 37–38. Chowkamba Sanskrit Sirija, Varanasi 88. Pandey G (2004) Dravyaguna Vijnana. Chaukhambla Orientalia, Varanasi 89. Dev S (1987) A modern look at an age old Ayurvedic drug guggulu. Sci Age 5:13–18 90. Anurekha J, Gupta VB (2006) Chemistry and pharmacological profile of guggulu- a review. Indian J Tradit Knowl 5:478–483 91. Sastry VVS (1976) History of Guggulu-based on Ayurvedic literature. Bull Indian Inst Hist Med 6:102–116 92. Tomar R, Kaur G, Sannd R, Singh H, Sarkar B (2014) A review on guggulu formulations used in Ayurveda. Ann Ayurvedic Med 3:96–113 93. Shastri A (2005) Bhaganrog Chikitsa (49:15); Mashtishk Chikitsa (101:18–22); Vatarakta (27: 91–97, 114–121); Shoth chikitsa (42: 135); Amavata chikitsa (29: 162–189, 196–199). In: Bhaishajya Ratnavali, Govindadasa, Vidyotini Hindi Commentary, Chaukhamba Prakashan, Varanasi 94. Anonymous (2011) The Ayurvedic formulary of India Part III, 1st edn. Department of AYUSH, Ministry of Health and Family Welfare, Government of India, New Delhi 95. Mishra BS (2005) Utrardh, Vatraktadhikar (29:46, 170–176, 177–181, 229–246); Sthoulyadhikar (39:30–31); Rasaynadhikar (73:14); Vatvyadhadhikar (24:145–150); Kusthrogadhikar (54:64–67). Bhavaprakasha, Bhavmishra, Vidyotini Hindi Commentary, Chaukhambha Sanskrit Sansthan, Varanasi 96. Anonymous (2003) The Ayurvedic formulary of India Part I, 2nd edn. Department of AYUSH, Ministry of Health and Family Welfare, Government of India, New Delhi 97. Anonymous (2004) Guggulu Adhyaya. In: Ayurved Sara Samgraha. Baidyanath Ayurved Bhavan Private Limited, Nagpur

478

P. Sarup et al.

98. Anonymous (2000) The Ayurvedic formulary of India Part II, 1st edn. Department of AYUSH, Ministry of Health and Family Welfare, Government of India, New Delhi 99. Shastri A (1970) Ekangvatachikitsa (21:129–131, 147). Ras Ratan Samuchhya, Vagbhatacharya, Suratnojjvala Hindi Commentary. Chaukhamba Sanskrit Series Office, Varanasi 100. Nohr LA, Rasmussen LB, Straand J (2009) Resin from the mukul myrrh tree, guggul, can it be used for treating hypercholesterolemia? A randomized, controlled study. Complement Ther Med 17:16–22 101. Szapary PO, Wolfe ML, Bloedon LT, Cucchiara AJ, Der Marderosian AH, Cirigliano MD, Rader DJ (2003) Guggulipid for the treatment of hypercholesterolemia: a randomized controlled trial. J Am Med Assoc 290:765–772 102. National Toxicology Program (2020) Toxicity studies of a gum guggul extract formulation administered by gavage to Sprague Dawley (Hsd:Sprague Dawley SD) rats and B6C3F1/N mice. Toxic Rep Ser 99:NTP-TOX-99 103. Soni V (2010) Conservation of Commiphora wightii an endangered medicinal shrub, through propagation planting, and education awareness program in the Aravali Hills of Rajasthan, India. Conserv Evid 7:27–31 104. Khan TI, Frost S (2001) Floral biodiversity: a question of survival in the Indian Thar Desert. Environmentalist 21:231–236 105. UNDP (2008) Rajasthan Red Listed Medicinal Plants. http://envis.frlht.org/documents/ rajasthan-medicinal-plantsconservation.pdf 106. Ved D, Saha D, Ravikumar K, Haridasan K (2015) Commiphora wightii. The IUCN red list of threatened species 2015: e.T31231A50131117 107. Reddy CS, Meena SL, Krishna PH, Charan PD, Sharma KC (2012) Conservation threat assessment of Commiphora wightii (Arn.) Bhandari – an economically important species. Taiwania 57:288–293 108. Sabins SD, Rao KSS (1983) Rare and endangered endemics of South Eastern Kutch. Assessment of threatened plants of India, proceedings of seminar, Dehra Dun 109. Billore KV (1989) Some threatened medicinal plants of Rajasthan and their conservation. Indian Forester 115:595–599 110. Bhattacharyya R, Bhattacharya S, Chaudhuri S (2006) Conservation and documentation of the medicinal plant resources of India. Biodivers Conserv 5:2705–2717 111. Jain N, Nadgauda R (2013) Commiphora wightii (Arnott) Bhandari – a natural source of guggulsterone: facing a high risk of extinction in its natural habitat. Am J Plant Sci 4:57–68 112. Haque I, Bandopadhyay R, Mukhopadhyay K (2010) Population genetic structure of the endangered and endemic medicinal plant Commiphora wightii. Mol Biol Rep 37:847–854 113. Milligan BG, Leebens-Mack J, Strand AE (1994) Conservation genetics: beyond the maintenance of marker diversity. Mol Ecol Notes 3:423–435

Chemistry and Biological Activities of Garcinia Resin

20

Hosakatte Niranjana Murthy and Guggalada Govardhana Yadav

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Phytochemicals Isolated from Garcinia Resin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Xanthones . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Terpenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Flavonoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Biological Activities of Chemical Compounds Isolated from Garcinia Resin . . . . . . . . . . . . 3.1 Antioxidant Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Antimicrobial Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Anticancer Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Antidiabetic Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5 Anti-inflammatory Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

480 481 481 488 489 490 490 490 509 510 511 512 512

Abstract

Resins obtained from Garcinia spp. are referred to as “gamboges.” Phytochemical studies have shown that resins of Garcinia hanburyi, G. cowa, G. kola, G. mangostana, G. morella, G. parvifolia, and G. scortechinii contained several secondary metabolites such as xanthones, terpenoids, and flavonoids. Evidence from different studies has demonstrated that phytochemicals isolated from gamboge possess antioxidant, antibacterial, anti-HIV, and, anti-inflammatory activities. Majority of xanthones isolated from gamboge exhibited cytotoxic, antiproliferative, and antiangiogenic activities on different cancer cell lines. Xanthones such as 10-methoxygambogenic acid, desoxymorellin, gambogenic acid, gambogic acid, gambogoic acid, morellic acid, and moreollic acid have exhibited both alpha-glucosidase inhibitor and tyrosine phosphatase 1B inhibitor activities so that these compounds could be used as antidiabetic drugs against type-2 diabetes. Therefore, bioactive compounds from the resin of Garcinia spp. H. N. Murthy (*) · G. G. Yadav Department of Botany, Karnatak University, Dharwad, Karnataka, India © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_24

479

480

H. N. Murthy and G. G. Yadav

could be used in the preparation of pharmaceuticals. This review summarizes the information on phytochemicals of resins of Garcinia spp. and their biological activities. Keywords

Biological activities · Flavonoids · Gamboge · Garcinia · Phytochemicals · Resin · Terpenoids · Xanthones

1

Introduction

Gamboge is a resin or sap obtained from various Garcinia species which belongs to the family Clusiaceae or Guttiferae. Gamboge is commonly obtained from Garcinia hanburyi Hook. f. which is naturally distributed in Cambodia, Thailand, and Southern China, and G. morella (Gaertn.) Desr. (syn. G. elliptica Wall.) which is common in India, Sri Lanka, Myanmar, and Southern China [1, 2]. Other Garcinia species which yield resin are G. cowa Roxb., G. gummi-gutta (L.) N. Robson (syn. G. cambogia (Gaertn.) Desr.,), G. indica Choisy, G. kola Heckel, G. livingstonei T. Anderson, G. mangostana L., G. parvifolia (Miq.) Miq.,G. scortechinii King, and G. xanthochymus Hook. f. ex T. Anderson. The trees that are more than 10 years old are useful for tapping the resin. The resin is extracted by making incisions in the bark and by breaking off leaves or shoot letting the milky yellow resinous gum dropout (Fig. 1a). The resulting resin is normally collected in hollow bamboo canes, after the resin is congealed; the bamboo is broken to obtain gamboge [3]. The raw fruits and seeds of the Garcinia species also yield yellow resin (Fig. 1b). Gamboge was well known as a natural fresh orange-yellow pigment both in East Asia and Europe in the arts since the middle ages [4]. The resin is valued for the production of varnishes and adhesives [5]. Gamboge has been used in traditional medicine as a potent purgative and for infected wounds. Gamboge is also internally applied for the treatment of

Fig. 1 Resin from stem (a) and fruit (b) of Garcinia morella

20

Chemistry and Biological Activities of Garcinia Resin

481

chronic dermatitis, tapeworm, bedsore, and hemorrhoid [6]. Gamboge has also demonstrated larvicidal activity against Culex quinquefasciatus third instar larvae [7]. It had been developed as an antitumor drug for clinical testing via intravenous injection in China in the 1970s [6]. In recent years, many pharmaceutical studies focused on antitumor activities of its chemical constituents [6, 8].

2

Phytochemicals Isolated from Garcinia Resin

Varied secondary metabolites have been reported from gamboge and they include xanthones, triterpenoids, and flavonoids (Table 1) [9–46].

2.1

Xanthones

Xanthones are a class of heterocyclic compounds containing oxygen which are derived from dibenzo-g-pyrone as the basic skeleton [47]. Xanthones are generally classified into six major groups: simple xanthones, xanthone glycosides, prenylated xanthones, xantholignoids, bis-xanthones, and miscellaneous xanthones. These main groups are further subdivided into non-, mono-, di-, tri-, tetra-, penta-, and hexa-oxygenated according to the degree of oxygenation. Simple xanthones consists of substituents that are simple groups such as hydroxyl, methoxy, or methyl [47]. About 127 xanthones have been reported from gamboge of Garcinia species (Table 1, Figs. 2, 3, 4, 5, and 6). Xanthones that were isolated from G. cowa are 1,3,6-trihydroxy-7-methoxy-2,5-bis (3-methyl-2- butenyl)xanthone (1); 3-O-methylcowaxanthone; 7-O-methylgarcinone; 7-O-methylgarcinone E; cowagarcinone A (2); cowagarcinone B; cowagarcinone C; cowagarcinone D; cowagarcinone E (3); cowanin (4); cowanol (5); cowaxanthone (6); fucaxanthone A (7); fuscaxanthone A; mangostinone; norcowanin; rubraxanthone; α-mangostin; γ-mangostin [10–14]. Majority of xanthones are isolated from gamboge of Garcinia hanburyi; they include 10-ethoxygambogic acid (8); 10methoxygambogenicacid (9); 10-methoxygambogic acid (10); 10-methoxygambogin (11); 10α-Butoxy gambogic acid; 10α-ethoxy-9,10-dihyrogambogenic acid (12); 10αethoxy-9,10-dihydromorellic acid (13); 10α-hydroxygambogic acid (14); 12-hydroxygambogefic acid A (15); 16,17-dihydroxygambogenic acid (16); 22,23-dihydroxydihydrogambogenic acid (17); 2-isoprenylforbesione (18); 30-hydroxyepigambogic acid (19); 30-hydroxygambogic acid (20); 3-O-geranylforbesione (21); 7-methoxydesoxymorellin (22); 7-methoxyepigambogeic acid (23); 7-methoxygambogellic acid (24); 7-methoxygambogic acid (25); 7-methoxyisomorellinol (26); 8,8a-dihydro-8-hydroxygambogenic acid (27); 8,8a-dihydro-8-hydroxygabmogic acid (28); 8,8a-dihydro-8-hydroxygambogic acid isomer; 8,8a-dihydro-8hydroxymorellic acid (29); 8,8a-epoxymorellic acid (30); deoxygaudichaudione A (31); desoxygambogenin (32); desoxymorellin (33); desoxymorellinin (34); dihydroisomorellin (35); epiformoxanthone J (36); epigambogic acid; epigambogic acid A (37); epigambogic acid B (38); epigambogic acid C; epiisogambogic acid; forbesione (39); formoxanthone J (40); gambogefic acid (41); gambogefic acid A (42);

482

H. N. Murthy and G. G. Yadav

Table 1 Compounds isolated from the resin of Garcinia spp. Chemical group Xanthones

Species G. cambogia G. cowa

G. hanburyi

Compound Cambogin Camboginol 1,3,6-Trihydroxy-7-methoxy-2,5-bis (3-methyl-2- butenyl)xanthone 3-O-Methylcowaxanthone 7-O-Methylgarcinone 7-O-Methylgarcinone E Cowagarcinone A Cowagarcinone B Cowagarcinone C Cowagarcinone D Cowagarcinone E Cowanin Cowanol Cowaxanthone Fucaxanthone A Fuscaxanthone A Mangostinone Norcowanin Rubraxanthone α-Mangostin γ-Mangostin 10-Ethoxygambogic acid 10-Methoxygambogenic acid 10-Methoxygambogic acid 10-Methoxygambogin 10α-Butoxy gambogic acid 10α-Ethoxy-9,10-dihydrogambogenic acid 10α-Ethoxy-9,10-dihydromorellic acid 10α-Hydroxygambogic acid 12-Hydroxygambogefic acid A 16,17-Dihydroxygambogenic acid 22,23-Dihydroxydihydrogambogenic acid 2-Isoprenylforbesione 30-Hydroxyepigambogic acid 30-Hydroxygambogic acid 3-O-Geranylforbesione 7-Methoxydesoxymorellin 7-Methoxyepigambogic acid 7-Methoxygambogellic acid 7-Methoxygambogic acid 7-Methoxyisomorellinol

Reference [9] [9] [10, 11] [12] [12] [13] [10, 13] [10] [10] [10] [10] [10, 11, 13] [10, 11, 13] [10–13] [10] [13] [10] [11] [13, 14] [12] [12] [15] [15–17] [15] [17] [18] [18, 19] [19] [18] [20] [20] [20] [24] [20–22] [20–22, 25] [23] [24] [23] [23] [23] [23] (continued)

20

Chemistry and Biological Activities of Garcinia Resin

483

Table 1 (continued) Chemical group

Species

Compound 8,8a-Dihydro-8-hydroxygambogenic acid 8,8a-Dihydro-8-hydroxygambogic acid 8,8a-Dihydro-8-hydroxygambogic acid isomer 8,8a-Dihydro-8-hydroxymorellic acid 8,8a-Epoxymorellic acid Deoxygaudichaudione A Desoxygambogenin

Desoxymorellin

Desoxymorellinin Dihydroisomorellin Epiformoxanthone J Epigambogic acid Epigambogic acid A Epigambogic acid B Epigambogic acid C Epiisogambogic acid Forbesione Formoxanthone J Gambogefic acid Gambogefic acid A Gambogellic acid Gambogellic acid A Gambogenic acid Gambogenific acid Gambogenin Gambogenin dimethyl acetal Gambogic acid

Gambogic acid A Gambogic acid B Gambogic acid C Gambogic aldehyde Gambogin Gambogoic acid A

Reference [20, 23] [23] [23] [23] [24] [19, 26] [15, 18, 19, 24, 26, 28, 46] [15, 17–19, 24, 26, 28, 46] [15] [20, 24] [20] [21] [18] [18] [18] [21] [24, 25] [20] [23] [22] [15, 18, 20, 25, 28] [22] [17–19, 21, 25–29, 46] [23, 46] [20, 28, 46] [28] [15–17, 19, 24–29, 32, 46, 68] [18] [18, 20] [18] [43] [15, 18, 28] [16, 17, 26, 27] (continued)

484

H. N. Murthy and G. G. Yadav

Table 1 (continued) Chemical group

Species

Compound Gambogoic acid B Gamboketanol Gambospiroene Garcinolic acid Gaudichaudic acid Hanburin Hanburixanthone Isogambogenic acid Isogambogenin Isogambogic acid Isomorellic acid Isomorellin Isomorellinol Isomoreollin B Methyl 8,8a-dihydromorellate Morellic acid

G. mangostana

Morellin dimethyl acetal Morellin Morellinol Moreollic acid Oxygambogic acid β-Morellic acid 1,7-Dihydroxy-3-methoxy-2-(3-methylbut2 enyl)xanthone 3-Hydroxy-4-geranyl-5-methoxybiphenyl 8-Desoxygartanin 9-Hydroxycalabaxanthone Cowaxanthone D Cratoxylone Garcinone B Garcinone D Garcinone E Gartanin Mangostanin Mangostin α-Mangostin β-Mangostin

Reference [26] [22] [23] [19] [26] [15, 19, 24, 28] [20] [28, 46] [20, 21, 25– 27, 33, 46] [20, 25, 26] [24, 28] [24, 26, 68] [28] [23] [15, 17, 18, 24–26, 28, 46] [28] [46] [17] [15–18, 28] [23] [29] [30] [31] [30] [30] [30] [30] [30] [30] [30, 31] [30, 33] [30] [34] [30, 31, 33, 35, 36] [30, 31, 33, 34] (continued)

20

Chemistry and Biological Activities of Garcinia Resin

485

Table 1 (continued) Chemical group

Species G. morella

G. parvifolia G. scortechinii

Flavonoids

G. kola

Triterpenoids

G. hanburyi

Compound γ-Mangostin Gambogic acid Isomorellic acid Isomorellin Morellic acid Rubraxanthone Scortechinone A Scortechinone B Scortechinone D Scortechinone E Scortechinone F Scortechinone G Scortechinone H Scortechinone I Scortechinone J Scortechinone K Garcinoic acid Garcinia biflavonoid 1 Garcinia biflavonoid 1a Garcinia biflavonoid 2 Hydrogenated Garcinoic acid Hydroxylated Garcinoic acid Isomer of Garcinoic acid Isomer of Garcinia biflavonoid 1 Kolaflavanone Methylated Garcinoic acid 2-O-Acetyl-3-O-(30 ,40 -O-diacetyl)-α-L arabinopyranosylmaslinic acid 2-O-Acetyl-3-O-(30 -O-acetyl)-α-Larabinopyranosylmaslinic acid 2-O-Acetyl-3-O-(40 -O-acetyl)-α-Larabinopyranosylmaslinic acid 2-O-Acetylmaslinic acid 2α-Acetoxy-3β-hydroxy-19β-hydrogenlup-20(29)-en-28-oic acid (2-acetoxyalphitolic acid) 2α-Hydroxy-3β-O-acetylbetulinic acid 3-O-(30 -O-Acetyl)- α-Larabinopyranosyloleanolic acid 3-O-(40 -O-Acetyl)-α-Larabinopyranosyloleanolic acid 3-O-Acetylmaslinic acid

Reference [37] [37] [38] [37] [45] [39] [39] [39] [39] [39] [39] [39] [39] [39] [39] [40] [40] [40] [40] [40] [40] [40] [40] [40] [40] [41] [41] [41] [41] [44]

[41] [41] [41, 42] [41] (continued)

486

H. N. Murthy and G. G. Yadav

Table 1 (continued) Chemical group

Species

Compound 2α-Hydroxy-3β-Acetoxy-19β-hydrogenlup-20(29)-en-28-oic acid (3acetoxyalphitolic acid) Betulinic acid Maslinic acid Messagenic acid

Reference [42, 44]

[41, 42, 44] [41] [42]

Fig. 2 Biologically active xanthones isolated from the resin of Garcinia kowa

gambogellic acid (43); gambogellic acid A (44); gambogenic acid (45); gambogenific acid (46); gambogenin (47); gambogenin dimethyl acetal (48); gambogic acid (49); gambogic acid A (50); gambogic acid B (51); gambogic acid C; gambogic aldehyde (52); gambogin (53); gambogoic acid; gambogoic acid A (54); gambogoic acid B; gamboketanol (55); gambospiroene (56); garcinolic acid (57); gaudichaudic acid (58); hanburin (59); hanburixanthone (60); isogambogenic acid (61); isogambogenin (62); isogambogic acid (63); isomorellic acid (64); isomorellin (65); isomorellinol (66); isomoreollin B (67); methyl 8,8a-dihydromorellate (68); morellic acid (69); methyl dimethyl acetal (70); morellin (71); morellinol (72); moreollic acid (73); oxygambogic acid (74); β-morellic acid [15–29, 32, 43, 46, 68]. Xanthones extracted from gamboge of Garcinia mangostana are 1,7-dihydroxy-3-methoxy-2-(3-methylbut-2 enyl)xanthone;3-hydroxy-4-geranyl-5-methoxybiphenyl; 8-desoxygartanin; 9-hydroxycalabaxanthone; cowaxanthone D; cratoxylone; garcinone B; garcinone D; garcinone E; gartanin (75); mangostanin; mangostin; α-mangostin (76); ß-mangostin (77); γ-mangostin (78) [30, 31, 33–36]. Garcinia morella gamboge xanthones are gambogic acid, isomorellic acid, isomorellin, and morellic acid [37, 38]. Rubraxanthone (79) was extracted from gamboge of Garcinia parvifolia [45]. Major xanthones that were isolated from Garcinia scortechinii are scortechinone A; scortechinone B;

20

Chemistry and Biological Activities of Garcinia Resin

487

Fig. 3 Biologically active xanthones isolated from the resin of Garcinia hanburyi

scortechinone D; scortechinone E; scortechinone F; scortechinone G; scortechinone H; scortechinone I, scortechinone J; scortechinone K [39]. Cambogin and camboginol were isolated from gamboge Garcinia cambogia [9].

488

H. N. Murthy and G. G. Yadav

Fig. 4 Biologically active xanthones isolated from the resin of Garcinia hanburyi

2.2

Terpenoids

Terpenoids are organic compounds derived from five-carbon isoprene units, and more than 25,000 terpenoids have been recognized from natural sources which have potential applications in the pharmaceutical, and chemical industries [48]. Based on structures, terpenoids are composed of several subclasses, including monoterpenes, sesquiterpenes, diterpenes, triterpenes, and tetraterpenes [48]. Several triterpenes were

20

Chemistry and Biological Activities of Garcinia Resin

489

Fig. 5 Biologically active xanthones isolated from the resin of Garcinia hanburyi

Fig. 6 Biologically active xanthones isolated from the resin of Garcinia mangostana and G. parvifolia

isolated from gamboge of Garcinia hanburyi including 2α-acetoxy-3β-hydroxy-19β-hydrogen-lup-20(29)-en-28-oic acid (2-acetoxyalphitolic acid) (80); 2α-hydroxy3β-acetoxy-19β-hydrogen-lup-20(29)-en-28-oic acid (3-acetoxyalphitolic acid) (81); 2α-hydroxy-3β-O-acetyllup-20(29)-en-28-oic acid; 3-O-(40 -O-acetyl)-α-L-arabinopyranosyloleanolic acid (82); betulinic acid (83) (Table 1, Fig. 7) [41, 42, 44].

2.3

Flavonoids

Flavonoids are polyphenolic compounds having a benzo-γ-pyrone structure and are ubiquitously present in plants. They are synthesized by the phenylpropanoid pathway and are responsible for varied pharmaceutical activities [49]. Several

490

H. N. Murthy and G. G. Yadav

Fig. 7 Biologically active triterpenoids isolated from the resin of Garcinia hanburyi

flavonoids have been reported from the gamboge of Garcinia kola including garcinoic acid, garcinia biflavonoid-1, garcinia biflavonoid-1a, garcinia biflavonoid-2, hydrogenated garcinoic acid, hydroxylated garcinoic acid, isomer of garcinoic acid, isomer of garcinia biflavonoid-1, kolaflavanone, and methylated garcinoic acid (Table 1) [40].

3

Biological Activities of Chemical Compounds Isolated from Garcinia Resin

3.1

Antioxidant Activities

Antioxidants are the compounds that inhibit the oxidation of biological molecules at low concentrations and thus play diverse physiological roles in humans. Varied natural compounds such as carotenoids, vitamins, phenolics, flavonoids, glutathione, and endogenous metabolites are considered as antioxidants that convert reactive radicals into less reactive species. These compounds showed activity as singlet and triplet oxygen quenchers, free radical scavengers, peroxide decomposers, enzyme inhibitors, and synergists [50]. Xanthones are reported to be good scavengers for various oxidizing species such as superoxide anions, hydroxyl, and peroxyl radicals [51]. Seven xanthones isolated from G. cowa, namely, 1,3,6-trihydroxy-7-methoxy2,5-bis(3 methyl-2-butenyl) xanthone (1), cowagarcinone A (2), cowagarcinone E (3), cowanin (4), cowanol (5), cowaxanthone (6), and fucaxanthone A (7), have shown free-radical scavenging activity on α-diphenyl-ß-picrylhydrazyl (DPPH) [10]. α-Mangostin (76) and γ-mangostin (78) showed higher DPPH radical scavenging activity and ferric reducing antioxidant potential (FRAP) (Table 2) [36].

3.2

Antimicrobial Activities

Antibiotic resistance is a major problem in the field of medicine and other allied fields because multidrug-resistant microbial strains are increasing enormously [52, 53]. Plants are a rich source of a wide variety of secondary metabolites which possess antimicrobial properties and plant-based antimicrobial compounds have

Chemical group Xanthones

G. hanburyi

Species G. cowa DPPH radical scavenging activity DPPH radical scavenging activity Staphylococcus aureus (ATCC 25923 and penicillin-resistant strains) DPPH radical scavenging activity Staphylococcus aureus (ATCC 25923 and penicillin-resistant strains) DPPH radical scavenging activity DPPH radical scavenging activity DPPH radical scavenging activity In vitro cytotoxic activity against HL-60, SMMC-7721, and BGC-83 cell lines In vitro cytotoxic activity against HL-60, SMMC-7721, and BGC-83 cell lines In vitro enzyme activity assay using p-nitrophenyl phosphate as substrate

Antioxidant Antioxidant Antibacterial Antioxidant Antibacterial Antioxidant Antioxidant Antioxidant Cytotoxic Cytotoxic Tyrosine phosphatase 1B inhibitor α-Glucosidase inhibitor Cytotoxic

Cowanol (5)

Cowaxanthone (6) Fucaxanthone A (7) 10-Ethoxygambogic acid (8)

10-Methoxygambogenic acid (9)

10-Methoxygambogic acid (10)

In vitro cytotoxic activity against HL-60, SMMC-7721, and BGC-83 cell lines

In vitro enzyme inhibition assay

Model/method DPPH radical scavenging activity

Activity Antioxidant

Compound 1,3,6-Trihydroxy-7-methoxy-2,5-bis (3 methyl-2-butenyl) xanthone (1) Cowagarcinone A (2) Cowagarcinone E (3) Cowanin (4)

Table 2 Biological activities of compounds isolated from the resin of Garcinia spp.

Chemistry and Biological Activities of Garcinia Resin (continued)

[15]

[16]

[17]

[15]

[10] [10] [10] [15]

[10] [11]

[10] [10] [11]

Reference [10]

20 491

Chemical group

Species

Table 2 (continued)

Cytotoxic

Cytotoxic

30-Hydroxyepigambogic acid (19)

Cytotoxic

Cytotoxic

α-Glucosidase inhibitor Cytotoxic

Cytotoxic

Activity Tyrosine phosphatase 1B inhibitor Cytotoxic

16,17-Dihydroxygambogenic acid (16) 22,23Dihydroxydihydrogambogenic acid (17) 2-Isoprenylforbesione (18)

12-Hydroxygambogefic acid A (15)

10α-Ethoxy-9,10dihydrogambogenic acid (12) 10α-Ethoxy-9,10-dihydromorellic acid (13) 10α-Hydroxygambogic acid (14)

Compound 10-Methoxygambogin (11)

In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines In vitro cytotoxic activity against A549, HCT116, andMDA-MB-231 cell lines

In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines

In vitro cytotoxic activity against A549, HCT116, SK-BR-3, and HepG2 cell lines In vitro cytotoxic activity against A549, HCT116, SK-BR-3, and HepG2 cell lines In vitro enzyme inhibition assay

Model/method In vitro enzyme activity assay using p-nitrophenyl phosphate as substrate

[20]

[24]

[20]

[20]

[20]

[18]

[19]

[19]

Reference [17]

492 H. N. Murthy and G. G. Yadav

Cytotoxic Cytotoxic

Cytotoxic Cytotoxic Cytotoxic Cytotoxic Cytotoxic

Cytotoxic

3-O-Geranylforbesione (21)

7-Methoxydesoxymorellin (22)

7-Methoxyepigambogic acid (23)

7-Methoxygambogellic acid (24)

7-Methoxygambogic acid (25)

7-Methoxyisomorellinol (26)

8,8a-Dihydro-8-hydroxygambogenic acid (27)

8,8a-Dihydro-8-hydroxygambogic acid (28) 8,8a-Dihydro-8-hydroxymorellic acid (29)

Cytotoxic

Cytotoxic

30-Hydroxygambogic acid (20)

In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro cytotoxic activity against HeLa cell line In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines In vitro cytotoxic activity against HeLa cell line In vitro cytotoxic activity against HeLa cell line In vitro cytotoxic activity against HeLa cell line In vitro cytotoxic activity against HeLa cell line In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro cytotoxic activity against HeLa cellcell line In vitro cytotoxic activity against HeLa cell line In vitro cytotoxic activity against HeLa cellcell line (continued)

[23]

[23]

[23]

[20]

[23]

[23]

[23]

[23]

[24]

[23]

[20]

20 Chemistry and Biological Activities of Garcinia Resin 493

Chemical group

Species

Table 2 (continued)

Cytotoxic

Anti-HIV Antiproliferative

Deoxygaudichaudione A (31)

Desoxygambogenin (32)

Cytotoxic

Activity Anti-HIV Cytotoxic

Compound 8,8a-Epoxymorellic acid (30)

Model/method Anti-HIV-1 RT assay and syncytium assay In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines In vitro cytotoxic activity against A549, HCT116, SK-BR-3, and HepG2 cell lines In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines Anti-HIV-1 RT assay and syncytium assay In vitro antiproliferative activity against HUVEC cell lines In vitro cytotoxic activity against HeLa and HEL cell lines In vitro cytotoxic activity against A549, HCT116, SK-BR-3, and HepG2 cell lines In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines

[26]

[19]

[28]

[24] [46]

[26]

[19]

Reference [24] [24]

494 H. N. Murthy and G. G. Yadav

Desoxymorellin (33)

Cytotoxic

α-Glucosidase inhibitor Anti-HIV Antiproliferative

Anti-HIV-1 RT assay and syncytium assay In vitro antiproliferative activity against HUVEC cell lines In vitro cytotoxic activity against HeLa and HEL cell lines In vitro cytotoxic activity against A549, HCT116, SK-BR-3, and HepG2 cell lines In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines

In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116 and HepG-2) In vitro enzyme inhibition assay

(continued)

[24]

[26]

[19]

[28]

[24] [46]

[18]

[46]

[24]

20 Chemistry and Biological Activities of Garcinia Resin 495

Chemical group

Species

Table 2 (continued)

Cytotoxic α-Glucosidase inhibitor

Epiformoxanthone J (36)

Epigambogic acid A (37)

Desoxymorellinin (34) Anti-HIV Cytotoxic

Tyrosine phosphatase 1B inhibitor α-Glucosidase inhibitor Cytotoxic

Dihydroisomorellin (35)

Activity

Compound

In vitro cytotoxic activity against HL-60, SMMC-7721, and BGC-83 cell lines Anti-HIV-1 RT assay and syncytium assay In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro enzyme inhibition assay

In vitro enzyme inhibition assay

Model/method In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116 and HepG-2) In vitro enzyme activity assay using p-nitrophenylphosphate as substrate

[18]

[20]

[24]

[24] [20]

[15]

[18]

[17]

Reference [46]

496 H. N. Murthy and G. G. Yadav

Anti-HIV Cytotoxic Cytotoxic Cytotoxic Cytotoxic

α-Glucosidase inhibitor Cytotoxic

Gambogefic acid (41)

Gambogefic acid A (42)

Gambogellic acid (43)

Gambogellic acid A (44)

α-Glucosidase inhibitor Cytotoxic

Formoxanthone J (40)

Forbesione (39)

Epigambogic acid B (38)

In vitro cytotoxic activity against HeLa cell line

In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines Anti-HIV-1 RT assay and syncytium assay In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro cytotoxic activity against HeLa cell line In vitro cytotoxic activity against HeLa cellcell line In vitro cytotoxic activity against HeLa and HEL cell lines In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro enzyme inhibition assay

In vitro enzyme inhibition assay

(continued)

[22]

[18]

[20]

[28]

[22]

[23]

[24] [20]

[24]

[18]

20 Chemistry and Biological Activities of Garcinia Resin 497

Chemical group

Species

Table 2 (continued)

Gambogenin (47)

Gambogenific acid (46)

Compound Gambogenic acid (45)

Antiangiogenic Antiproliferative

Cytotoxic

Tyrosine phosphatase 1B inhibitor α-Glucosidase inhibitor Antiproliferative

Cytotoxic

Activity Antiproliferative

In vitro antiproliferative activity against HUVEC cell lines In vitro cytotoxic activity against HeLa cellcell line In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) In vivo antiangiogenic activity in zebrafish In vitro antiproliferative activity against HUVEC cell lines

In vitro enzyme inhibition assay

Model/method In vitro antiproliferative activity against HUVEC cell lines In vitro cytotoxic activity against HeLa and HEL cell lines In vitro cytotoxic activity against A549, HCT116, SK-BR-3, and HepG2 cell lines In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116 and HepG-2) In vitro enzyme activity assay using p-nitrophenyl phosphate as substrate

[46] [46]

[46]

[23]

[46]

[18]

[17]

[46]

[26]

[19]

[28]

Reference [46]

498 H. N. Murthy and G. G. Yadav

Angiostatic

Gambogic acid (49)

Cytotoxic

Antiangiogenic Anti-HIV Antiproliferative

Cytotoxic

Gambogenin dimethyl acetal (48)

Cytotoxic

In vitro cytotoxic activity against HeLa and HEL cell lines In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) In vitro cytotoxic activity against HeLa and HEL cell lines MTT cell viability/proliferation assay on human retinal pigment epithelial cells (ARPE19) and effects on vascular endothelial growth factor (VEGF)-induced endothelial cell proliferation and migration were investigated by the scratch-wound model using human umbilical vein endothelial cells (HUVECs) In vivo antiangiogenic activity in zebrafish Anti-HIV-1 RT assay and syncytium assay In vitro antiproliferative activity against HUVEC cell lines In vitro cytotoxic activity against HeLa and HEL cell lines In vitro cytotoxic activity against A549, HCT116, SK-BR-3, and HepG2 cell lines In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines In vitro cytotoxic activity against KB and drug-resistant KB-V1 cell lines

Chemistry and Biological Activities of Garcinia Resin (continued)

[33]

[26]

[19]

[28]

[46] [24] [46]

[32]

[28]

[46]

[20]

[28]

20 499

Chemical group

Species

Table 2 (continued)

Cytotoxic

Gambogic aldehyde (52)

Gambogin (53)

Tyrosine phosphatase 1B inhibitor α-Glucosidase inhibitor α-Glucosidase inhibitor Cytotoxic

Activity

α-Glucosidase inhibitor Antiproliferative

Gambogic acid B (51)

Gambogic acid A (50)

Compound

In vitro antiproliferative assay against mouse leukemia P388 and P388/ADR cell lines

In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro enzyme inhibition assay

In vitro enzyme inhibition assay

In vitro enzyme inhibition assay

Model/method In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) In vitro enzyme activity assay using p-nitrophenylphosphate as substrate

[28]

[43]

[18]

[20]

[18]

[16]

[17]

[46]

Reference [24]

500 H. N. Murthy and G. G. Yadav

α-Glucosidase inhibitor Cytotoxic

Tyrosine phosphatase 1B inhibitor α-Glucosidase inhibitor Cytotoxic Cytotoxic Cytotoxic Cytotoxic

Gambogoic acid A (54)

Gamboketanol (55)

Gambospiroene (56)

Garcinolic acid (57)

Gaudichaudic acid (58)

In vitro cytotoxic activity against HeLa cell line In vitro cytotoxic activity against HeLa cell line In vitro cytotoxic activity against A549, HCT116, SK-BR-3, and HepG2 cell lines In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines

In vitro enzyme inhibition assay

In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines In vitro enzyme activity assay using p-nitrophenylphosphate as substrate

In vitro cytotoxic activity against HeLa and HEL cell lines In vitro enzyme inhibition assay

(continued)

[26]

[19]

[23]

[22]

[16]

[17]

[26]

[18]

20 Chemistry and Biological Activities of Garcinia Resin 501

Chemical group

Species

Table 2 (continued)

Cytotoxic Antiangiogenic Antiproliferative

Hanburixanthone (60)

Isogambogenic acid (61)

Cytotoxic

Activity Anti-HIV Cytotoxic

Compound Hanburin (59)

Model/method Anti-HIV-1 RT assay and syncytium assay In vitro cytotoxic activity against HeLaand HEL cell lines In vitro cytotoxic activity against A549, HCT116, SK-BR-3, and HepG2 cell lines In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vivo antiangiogenic activity in zebrafish In vitro antiproliferative activity against HUVEC cell lines In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro cytotoxic activity against HL-60, SMMC-7721, and BGC-83 cell lines In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) [46]

[26]

[15]

[20]

[46] [46]

[20]

[24]

[19]

Reference [24] [28]

502 H. N. Murthy and G. G. Yadav

Cytotoxic

Cytotoxic

Isomorellin (65)

Cytotoxic

Antiproliferative

Cytotoxic

Antiproliferative

Isomorellic acid (64)

Isogambogic acid (63)

Isogambogenin (62)

In vitro antiproliferative activity against HUVEC cell lines In vitro cytotoxic activity against HeLa and HEL cell lines In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) In vitro antiproliferative activity against HUVEC cell lines In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro cytotoxic activity against KB and drug-resistant KB-V1 cell lines In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116, and HepG-2) In vitro cytotoxic activity against A549, HCT116, and MDA-MB-231 cell lines In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines In vitro cytotoxic activity against HeLa and HEL cell lines In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines

Chemistry and Biological Activities of Garcinia Resin (continued)

[24]

[28]

[26]

[20]

[46]

[33]

[20]

[46]

[46]

[28]

[46]

20 503

Chemical group

Species

Table 2 (continued) Activity Cytotoxic

Cytotoxic Cytotoxic Antiangiogenic Anti-HIV Antiproliferative

Compound Isomorellinol (66)

Isomoreollin B (67)

Methyl 8,8a-dihydromorellate (68)

Morellic acid (69)

Model/method In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines In vitro cytotoxic activity against KB and drug-resistant KB-V1 cell lines In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines In vitro cytotoxic activity against HeLa and HEL cell lines In vitro cytotoxic activity against HeLa cellcell line In vivo antiangiogenic activity in zebrafish Anti-HIV-1 RT assay and syncytium assay In vitro antiproliferative activity against HUVEC cell lines

[46] [24] [46]

[23]

[28]

[24]

[33]

Reference [26]

504 H. N. Murthy and G. G. Yadav

Morellin (71)

Morellinol (72)

Antiproliferative

Morellin dimethyl acetal (70)

Tyrosine phosphatase 1B inhibitor

Cytotoxic

Tyrosine phosphatase 1B inhibitor α-Glucosidase inhibitor Cytotoxic

Cytotoxic

In vitro cytotoxic activity against HeLa and HEL cell lines In vitro antiproliferative activity against HUVEC cell lines In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116 and HepG-2) In vitro enzyme activity assay using p-nitrophenylphosphate as substrate

In vitro enzyme inhibition assay

In vitro cytotoxic activity against HeLaand HEL cell lines In vitro cytotoxic activity against human leukemia K562 (K562/S) and doxorubicinresistant K562 (K562/R) cell lines In vitro cytotoxic activity using sulforhodamine B assay against P-388 (mouse lymphoid neoplasma), ASK (rat glioma), KB (human epidermoid carcinoma in mouth), COL-2 (human colon cancer), BCA-1 (human breast cancer), and LU-1 (human lung cancer) cell lines In vitro cytotoxic activity against human cancer cell lines (HeLa, A549, HCT-116 and HepG-2) In vitro enzyme activity assay using p-nitrophenyl phosphate as substrate

Chemistry and Biological Activities of Garcinia Resin (continued)

[17]

[46]

[46]

[28]

[18]

[17]

[46]

[24]

[26]

[28]

20 505

Chemical group

G. mangostana

Species

Table 2 (continued)

β-Mangostin (77)

Antibacterial

Antioxidant

Antibacterial

α-Mangostin (76)

Oxygambogic acid (74) Antibacterial

Tyrosine phosphatase 1B inhibitor α-Glucosidase inhibitor Cytotoxic

Gartanin (75)

Activity Cytotoxic

Compound Moreollic acid (73)

In vitro cytotoxic activity against HeLa cellcell line Bacillus subtilis (ATCC 6633), Enterococcus faecalis(ATCC 29212),Micrococcus luteus (ATCC 10240), Salmonella typhi (NCTC 786), Staphylococcus epidermidis (ATCC 12228), Streptococcus mutans (ATCC 25175), and Vibrio cholera (Inaba) Bacillus subtilis (ATCC 6633), Enterococcus faecalis (ATCC 29212), Micrococcus luteus (ATCC 10240), Salmonella typhi (NCTC 786), Staphylococcus epidermidis (ATCC 12228), Streptococcus mutans (ATCC 25175), and Vibrio cholera (Inaba) DPPH radical scavenging activity and FRAP assay Bacillus subtilis (ATCC 6633), Enterococcus faecalis (ATCC 29212), Micrococcus luteus (ATCC 10240), Salmonella typhi (NCTC 786), Staphylococcus epidermidis (ATCC

In vitro enzyme inhibition assay

Model/method In vitro cytotoxic activity against HeLa and HEL cell lines In vitro enzyme activity assay using p-nitrophenylphosphate as substrate

[33]

[36]

[33]

[33]

[23]

[16, 18]

[17]

Reference [28]

506 H. N. Murthy and G. G. Yadav

Triterpenoids

G. hanburyi

G. parvifolia

Betulinic acid (83)

3-O-(40 -O-Acetyl)-α-Larabinopyranosyloleanolic acid (82)

2α-Hydroxy-3β-acetoxy19β-hydrogen-lup-20(29)-en-28-oic acid (81)

2α-Acetoxy-3β-hydroxy19β-hydrogen-lup 20(29)-en-28-oic acid (80)

Rubraxanthone (79)

γ-Mangostin (78)

Anti-HIV Antiinflammatory

Antiproliferative

Anti-HIV Antiinflammatory Anti-HIV Antiinflammatory Antiproliferative

Antimicrobial

Antioxidant

12228), Streptococcus mutans (ATCC 25175), and Vibrio cholerae (Inaba) DPPH radical scavenging activity and FRAP assay Staphylococcus aureus (ATCC 25923 and penicillin-resistant strains), Microsporum gypseum, and Trichophyton mentagrophytes Anti-HIV-1 RT assay and syncytium assay Ethyl phenylpropiolate -induced ear edema in male Sprague-Dawley rats Anti-HIV-1 RT assay and syncytium assay Ethyl phenylpropiolate-induced ear edema in male Sprague-Dawley rats In vitro antiproliferative activity against human leukemia cell lines (HL-60, U937, K562, and NB4) In vitro antiproliferative activity against human leukemia cell lines (HL-60, U937, K562, and NB4) Anti-HIV-1 RT assay and syncytium assay Ethyl phenylpropiolate-induced ear edema in male Sprague-Dawley rats [44] [44]

[42]

[42]

[44] [44]

[44] [44]

[45]

[36]

20 Chemistry and Biological Activities of Garcinia Resin 507

508

H. N. Murthy and G. G. Yadav

great therapeutic potential. Phenolics, terpenoids, and alkaloids have demonstrated potent antimicrobial potentialities including antibacterial, antiviral, and antifungal activities.

3.2.1 Antibacterial Activities Na Pattalung et al. [11] isolated five xanthones from resin of Garcinia cowa, namely, cowanin, cowanol, cowaxanthone, 1,3,6-trihydroxy-7-methoxy-2,5-bis(3-methyl-2butenyl) xanthone, norcowanin, and among them two xanthones cowanin (4) and cowanol (5) showed inhibitory activity against Staphylococcus aureus (ATTCC 25923 and penicillin-resistant strain) (Table 2). Anggia et al. [33] tested the effect of gartanin (75), α-mangostin (76), and ß-mangostin (77) which were extracted from the resin of Garcinia mangostana against Bacillus subtilis (ATCC 6633), Enterococcus faecalis (ATCC 29212), Micrococcus luteus (ATCC 10240), Salmonella typhi (NCTC 786), Streptococcus epidermidis (ATCC 12228), Streptococcus mutans (ATCC 25175), and Vibrio cholerae and their results showed gartanin (75), α-mangostin (76), and ß-mangostin (77) inhibited the growth of V. cholera significantly, while α-mangostein (76) and ß-mangostin (77) were active against B. subtilis, E. faecalis (Table 2). The mechanism of antibacterial activity of specific agent is mainly due to the interference of agent with the synthesis or function vital components of bacteria [54]. To decipher the role of α-mangostin on Staphylococcus epidermidis RP62A, Sivaranjini et al. [55] carried out transcriptomic and proteomic studies. They challenged Staphylococcus epidermidis with subminimum inhibitory concentration (8.75 μg/ml) of α-mangostin at various time points and analyzed the differential expression pattern of genes/proteins using RNA sequencing and liquid chromatography-mass spectroscopy experiments. Their studies revealed that α-mangostin treated cells showed a reduction in the expression of genes confirming cytoplasmic membrane integrity, cell division, teichoic acid biosynthesis, fatty acid biosynthesis, and DNA replication and repair machinery. Further, they observed increased expression of oxidative and cellular stress response genes. These results suggest that α-mangostin is involved in suppression of cytoplasmic membrane integrity of Staphylococcus epidermidis which leads to the onset of bactericidal activity. 3.2.2 Anti-HIV Activities Human Immunodeficiency Virus (HIV)/Acquired Immunodeficiency Syndrome (AIDS) is a great threat to mankind; highly active antiretroviral therapy and preventive measures are the only solution for this deadly disease. Recently, natural products especially plant-based chemical compounds are the alternatives for the treatment of HIV and management of AIDS [56]. Varied natural products such as calanolides (coumarins), betulinic acid (a triterpene), baicalin (a flavonoid), polycitone A (an alkaloid), lithospermic acid (a polyphenol) have been recognized as promising anti-HIV agents [56]. Several terpenoid and xanthone compounds that are isolated from the resin of Garcinia species are reported to possess anti-HIV activity (Table 2). Reutrakul et al. [44] isolated lupanes (terpenoid compounds) from the resin of Garcinia hanburyi, namely, 2α-acetoxy-3β-hydroxy-19β-hydrogen-lup 20(29)-en-

20

Chemistry and Biological Activities of Garcinia Resin

509

28-oic acid (80), 2α-hydroxy-3β-acetoxy-19β-hydrogen-lup-20(29)-en-28-oic acid (81), and betulinic acid (83) which have displayed anti-HIV-1 activities in the antiHIV-1 reverse transcriptase (RT) (IC50 values 16.3–116.9 μg/ml) and syncytium assays (EC50 5.6–73.6 μg/ml). Xanthones such as 8,8a-epoxymorellic acid (30), desoxygambogenin (32), desoxymorellin (33), dihydroisomorellin (35), forbesione (39), gambogic acid (49), hanburin (59), morellic acid (69) which were isolated from gamboge of Garcinia hanburyi were reported to have anti-HIV-1 activities [24]. Dihydroisomorellin (35), gambogic acid (49), and morellic acid (69) showed potent HIV-1 RT inhibitory activity (IC50 < 50 μg/ml), while compounds 8,8aepoxymorellic acid (30) and forbesione (39) were moderately active (IC50 between 50 and 150 μg/ml), and desoxymorellin (33) and hanburin (59) were weakly active (IC50 between 150 and 200 μg/ml) in reverse transcriptase assay [24].

3.3

Anticancer Activities

A plethora of different malignancies in humans can be considered cancer. Cancer is a major health problem in the world and the number of people who are suffering from cancer is increasing year by year [57]. Current cancer treatments are not only aiming at the elimination of cancer cells by induction apoptosis but also include targeting the tumor microenvironment, avoiding angiogenesis, and modulation of immune response by using new therapeutic strategies. Plant-based phytochemicals are promising options in this direction [58]. Phytochemicals obtained from the resin of Garcinia species have demonstrated cytotoxic, antiproliferative, and antiangiogenic activities (Table 2). Terpenoids extracted from the resin of Garcinia hanburyi such as 2α-hydroxy-3β-acetoxy-19β-hydrogen-lup-20(29)-en-28-oic acid (81) and 3-O(40 -O-acetyl)-α-L-arabinopyranosyloleanolic acid (82) showed in vitro antiproliferative activity against human leukemia cell lines HL-60, U937, K562, and NB4 [42]. Several xanthones that were isolated from the resin of Garcinia hanburyi also demonstrated cytotoxic activities against several types of cancers (Table 2). Feng et al. [15] reported in vitro cytotoxic activity of 10-ethoxygambogic acid (8), 10-methoxygambogenic acid (9), 10-methoxygambogic acid (10), isogambogenic acid (61) against peripheral blood leukocytes (HL-60), human hepatoma cells (SMCC-7721), and human gastric carcinoma cells (BGC-83). 10α-Ethoxy-9,10dihydrogambogenic acid (12), 10α-ethoxy-9,10-dihydromorellic acid (13), 12-hydroxygambogefic acid A (15), 16,17-dihydroxygambogenic acid (16), 22,23dihydroxydihydrogambogenic acid (17), 30-hydroxyepigambogic acid (19), 30-hydroxygambogic acid (20), 3-O-geranylforbesione (21), 8,8a-dihydro-8hydroxygambogenic acid (27), deoxygaudichaudione A (31), desoxygambogenin (32), desoxymorellin (33), dihydroisomorellin (35), epiformoxanthone J (36), formoxanthone J (40), gambogellic acid (43), gambogenic acid (45), gambogenin (47), gambogic acid (49), gambogic acid B (51), garcinolic acid (57), hanburin (59), hanburixanthone (60), isogambogenic acid (61), isogambogic acid (63), isomorellic acid (64) have shown cytotoxic effects against human lung carcinoma (A549), human colon carcinoma (HCT116), and human breast adenocarcinoma (MB-231)

510

H. N. Murthy and G. G. Yadav

cell lines [20]. Reutrakul et al. [24] showed in vitro cytotoxic activities of 2-isoprenylforbesione (18), 7-methoxydesoxymorellin (22), 8,8a-epoxymorellic acid (30), desoxygambogenin (32), desoxymorellin (33), dihydroisomorellin (35), forbesione (39), gambogic acid (49), hanburin (59), isomorellin (65), isomorellinol (66), morellic acid (69) against mouse lymphoid neoplasma (P-388), rat glioma (ASK), human mouth epidermoid carcinoma (KB), human colon cancer (COL-2), and human breast cancer (BCA-1), human lung cancer (LU-1) cell lines. Xanthones such as 3-O-geranylforbesione (21), 7-methoxyepigambogic acid (23), 7-methoxygambogellic acid (24), 7-methoxygambogic acid (25), 8,8a-dihydro-8hydroxygambogenic acid (27), 8,8a-dihydro-8-hydroxygambogic acid (28), 8,8adihydro-8-hydroxymorellic acid (29), gambogefic acid (41), gambogefic acid A (42), gambogellic acid A (44), gambogenific acid (46), gamboketanol (74), gambospiroene (56), methyl 8,8a-dihydromorellate (68), oxygambogic acid (74) were cytotoxic to HeLA cells as shown by Tao et al. [23] through in vitro studies. Han et al. [26] displayed cytotoxic activities of deoxygaudichaudione A (35), desoxygambogenin (32), desoxymorellin (33), gambogenic acid (45), gambogic acid (49), gaudichaudic acid (58), isogambogenic acid (61), isomorellic acid (64), isomorellinol (66), morellic acid (69) against human leukemia cell lines K562/S and doxorubicin-resistant K562/R. Yang et al. [46] revealed cytotoxic activity of isogambogenin (62) against human lung carcinoma (A549), human colon carcinoma (HCT-116), and human hepatocyte carcinoma (Hep G2) cell lines. Several xanthone compounds desoxygambogenin (32), desoxymorellin (33), gambogenic acid (45), gambogenific acid (46), gambogenin (47), gambogic acid (49), isogambogenic acid (61), isogambogic acid (63), morellin (71) exhibited in vitro antiproliferative activity against human umbilical vein endothelial cells (HUVEC) cells [46]. Gambogic aldehyde (52) showed antiproliferative against mouse leukemia P388 and P388/ADR cell line [43]. The antiangiogenic activity of gambogic acid (49) has been demonstrated using human umbilical vein endothelial cells and zebra-fish models by Cao et al. [32] and Yang et al. [46].

3.4

Antidiabetic Activities

Diabetes mellitus, commonly called diabetes, is a metabolic disorder that causes high blood sugar. Insulin is the pancreatic hormone responsible for regulating blood glucose levels as part of energy metabolism. Diabetes is caused due to deficiencies in insulin secretion, action, or both. Hyperglycemia condition in the body leads to progressive metabolic complications in the body such as neuropathy, retinopathy, nephropathy, and cardiovascular diseases [59]. There are three main types of diabetes, namely, type-1 diabetes, type-2 diabetes, and gestational diabetes. Type-1 diabetes results from the failure of the pancreas to produce enough insulin due to loss of beta cells which is caused by the autoimmune response. Type-2 diabetes occurs when the body cannot properly use insulin, decreasing the ability to regulate glucose metabolism, and this mechanism is called insulin resistance. Gestational diabetes occurs in pregnant women and this is due to pregnancy hormones which

20

Chemistry and Biological Activities of Garcinia Resin

511

blocks the action of insulin. Among these types, type-2 diabetes is most common (>80%) of all the cases [60]. Several medications are currently in use for the treatment of type-2 diabetes. Protein tyrosine phosphatase 1B is a negative regulator of insulin receptor signal transduction, and protein tyrosine phosphatase 1B inhibitors are used as drugs for the treatment of type-2 diabetes [61]. Αlpha-glucosidase inhibitors are also used in the treatment of type-2 diabetes since they delay the absorption of carbohydrates from the small intestine and thus have a lowering effect on postprandial blood glucose and insulin levels [62]. Several xanthones of plant origin are potent protein tyrosine phosphatase 1B inhibitors as well as alphaglucosidase inhibitors and these could be used for the treatment of diabetes, obesity, and other related complications [17, 63]. Tan et al. [17] showed in vitro protein tyrosine phosphatase 1B inhibitor activity of several prenylated caged xanthones obtained from Garcinia hanburyi resin by using p-nitrophenyl phosphate as substrate (Table 2). Compounds 10-methoxygambogenic acid (9), 10-methoxygambogin (11), desoxymorellin (33), gambogenic acid (45), gambogic acid (49), gambogoic acid A (54), morellic acid (69), morellinol (72), and moreollic acid (73) inhibited p-nitrophenyl phosphate in a dose-dependent manner. Among these compounds, Tan et al. [17] showed that gambogic acid is the most potent inhibitor (IC50 ¼ 0.47 μM). Jin et al. [16] demonstrated alpha-glucosidase inhibitory activity of 10-methoxygambogenic acid (9), 10α-hydroxygambogic acid (14), moreollic acid (73), gambogic acid (49), and gambogoic acid (58) through spectroscopic data. Chen et al. [18] also showed alpha-glucosidase inhibitory activity of 10α-hydroxygambogic acid (14), desoxygambogenin (32), desoxymorellin (33), epigambogic acid A (37), epigambogic acid B (38), gambogellic acid (43), gambogenic acid (45), gambogic acid A (50), gambogic acid B (51), gambogin (53), morellic acid (69), and moreollic acid (73), and these compounds could be used for the treatment of type-2 diabetes.

3.5

Anti-inflammatory Activities

Inflammation is part of the human body’s defense mechanism and is caused by a variety of stimuli including physical damage, ultraviolet radiation, and microbial invasion. Major symptoms of inflammation are redness, heat, swelling, and pain. Prolonged inflammation may lead to chronic diseases such as cancer, diabetes, asthma, heart disease, and Alzheimer’s disease. During inflammation, the plasma and leukocytes from the blood are transported into injured tissues. Further, monocytes that locally differentiate into macrophages, which lead to the production of various pro- and anti-inflammatory mediators, that is, cytokines, such as tumor necrosis factors (TNF-α), interleukins (IL-1ß, IL-6), and inducible enzymes, namely, cyclooxygenase (COX-2), and all of these will play in mediating inflammatory process [64]. Several classes of anti-inflammatory drugs such as glucocorticoids and nonsteroidal anti-inflammatory agents such as ketoprofen, aspirin, meloxicam, and nimesulide are in usage; however, such drugs have adverse effects on cardiovascular, renal, and gastrointestinal systems [65, 66]. Therefore, researchers are

512

H. N. Murthy and G. G. Yadav

exploring natural plant products that could be used as anti-inflammatory agents [67]. Plant-derived phytochemicals such as flavonoids, terpenoids, and alkaloids are known to act as anti-inflammatory agents. Terpenoids that are isolated from the resin of Garcinia hanburyi such as 2α-acetoxy-3β-hydroxy-19β-hydrogen-lup 20 (29)-en-28-oic acid (80), 2αßhydroxy-3ββ-acetoxy-19β-hydrogen-lup-20(29)-en28-oic acid (81), betulinic acid (83) are reported to possess anti-inflammatory activity in an ethyl phenylpropiolate-induced ear edema in Sprague-Dawley rat model (Table 2) [44].

4

Conclusions

The resin of Garcinia spp. is rich in varied phytochemicals such as xanthones, terpenoids, and flavonoids. Several xanthones have exhibited antioxidant, antibacterial, anti-HIV, cytotoxic, antiproliferative, and antiangiogenic activities. Xanthones have also depicted alpha-glucosidase inhibitor and tyrosine phosphatase 1B inhibitor activities; thus, they could be used as drugs for curing type-2 diabetis. Certain triterpenoids obtained from Garcinia hanburyi are proved to be anti-inflammatory agents. Thus, resin/gamboge of Garcinia spp. are a good source of biologically active compounds. Extensive analysis of resin of Garcinia hanburyi has been carried out; however, chemical constituents of resin of Garcinia gummi-gutta, G. indica, G. mangostana, G. livingstonei, G. morella, G. parvifolia, and G. xanthochymus has not been carried out. Future studies should be focused on analyzing chemical constituents’ of resins of the above-mentioned species and their bio-prospecting.

References 1. Eastaugh N, Walsh V, Chaplin T, Siddall R (2004) The pigment compendium: a dictionary of historical pigments. Elsevier Butterworth-Heinemann, Burlington 2. Murthy HN, Dalawai D, Dewir YH, Ibrahim A (2020) Phytochemicals and biological activities of Garcinia morella (Gaertn.) Desr.: a review. Molecules 25:5690 3. Kassia SC (2016) The secret lives of colour. John Murray, London 4. Chantarasriwong O, Batova A, Chavasiri W, Theodorakis EA (2010) Chemistry and biology of caged Garcinia xanthones. Chemistry 16:9944–9962 5. Abraham Z, Malik S, Rao GE, Subramaian LN (2006) Collection and charactrization of Malabar tamarind (Garcinia cambogia (Gaertn.) Desr.). Genet Resour Crop Evol 53:401–406 6. Han QB, Wang YL, Yang L, Tso TF, Qiao CF, Song JZ, Xu LJ, Chen SL, Yang DJ, Xu HX (2006) Cytotoxic polyprenylated xanthones form the resin of Garcinia hanburyi. Chem Pham Bull 54:265–267 7. Murthy HN, Joseph KS, Payamalle, Dalawai D, Ganapumane V (2017) Chemical composition, larvicidal and antioxidant activities of latex from Garcinia morella (Gaertn.) Desr. J Parist Dis 41:666–670 8. Asano J, Chiba K, Tada M, Yoshii T (1995) Cytotoxic xanthones from Garcinia hanburyi. Phytochemistry 41:815–820 9. Rao AVR, Venktakswamy G, Pendse AD (1978) Camboginol and cambogin. Tetrahedron Lett 21:1975–1970

20

Chemistry and Biological Activities of Garcinia Resin

513

10. Mahabusarakam W, Chairerk P, Taylor WC (2005) Xanthones from Garcinia cowa Roxb. latex. Phytochemistry 66:1148–1153 11. Na Pattalung P, Thongtheeraparp W, Wiriyachitra P, Taylor WC (1994) Xanthones of Garcinia cowa. Planta Med 60:365–368 12. Na Z, Song Q, Hu H (2013) A new prenylated xanthone from latex of Garcinia cowa Roxb. Rec Nat Prod 7:220–224 13. An NTK, Ha DT, Long PQ, Thuy TT (2018) Tetraoxygenated xanthones from the latex of Garcinia cowa growing in Vietnam. Vietnam J Sci Technol 56:560–566 14. Dachriyanus ANS, Susanti M (2017) Determination of rubraxanthone in the latex of Asam Kandis (Garcinia cowa Roxb.) by reverse phase high performance liquid chromatography. Pharm J 9:288–291 15. Feng F, Liu WY, Chen YS, Guo QL, You QD (2014) Five novel prenylated xanthones from Resina Garciniae. J Asian Nat Prod Res 9:735–741 16. Jin YM, Kim JY, Lee SM, Tan XF, Park KH (2019) α-Glucosidase inhibitory caged xanthones from the resin of Garcinia hanburyi. J Appl Biol Chem 62:81–86 17. Tan XF, Uddin Z, Park C, Song YH, Son M, Lee KW, Park KH (2017) Competative protein tyrosine phosphotase 1B (PTP1b) inhibitors, prenylated caged xanthones from Garcinia hanburyi and their inhibitory mechanism. Bioorg Med Chem 25:2498–2506 18. Chen Y, He S, Tang C, Li J, Yang G (2016) Caged polyprenylated xanthones from the resin of Garcinia hanburyi. Fitoterapia 109:108–112 19. Deng YX, Pan SL, Zhao SY, Wu MQ, Sun ZQ, Chen XH, Shao ZY (2012) Cytotoxic alkoxylated xanthones from the resin of Garcinia hanburyi. Fitoterapia 83:1548–1552 20. Deng YX, Guo T, Shao ZY, Xie H, Pan SL (2013) Three new xanthones from the resin of Garcinia hanburyi. Planta Med 79:792–796 21. Song JZ, Yip YK, Han QB, Qiao CF, Xu HX (2007) Rapid determination of polyprenylated xanthones in gamboges resin of Garcinia hanburyi by HPLC. J Sep Sci 30:304–309 22. Tao SJ, Guan SH, Li XN, Guo DA (2010) A highly rearranged pentaprenylxanthonoid from the resin of Garcinia hanburyi. Helv Chim Acta 93:1395–1400 23. Tao SJ, Guan SH, Wang W, Lu ZQ, Chen GT, Sha N, Yue QX, Liu X, Guo DA (2009) Cytotoxic polyprenylated xanthones from the resin of Garcinia hanburyi. J Nat Prod 72:117–124 24. Reutrakul V, Anantachoke N, Jaipetch T, Sophasan S, Yoosook C, Kasisit J, Napaswat C, Santisuk T, Tuchinda P (2007) Cytotoxic and anti-HIV-1 caged xanthones from the resin and fruits of Garcinia hanburyi. Planta Med 73:33–40 25. Li SL, Song JZ, Han QB, Qiao CF, Xu HX (2008) Improved high-performance liquid chromatographic method for simultaneous determination of 12 cytotoxic caged xanthones in gamboges, a potential anticancer resin from Garcinia hanburyi. Biomed Chromatogr 22:637–644 26. Han QB, Wang YL, Yan L, Tso TF, Qiao CF, Song JZ, Xu LJ, Chen SL, Yang DJ, Xu HX (2006) Cytotoxic polyprenylated xanthones form the resin of Garcinia hanburyi. Chem Pharm Bull 54:265–267 27. Han QB, Zhou Y, Feng C, Xu G, Hunag SX, Huang SX, Li SL, Qiao CF, Song JZ, Song JZ, Chang DC, Luo KQ, Xu HX (2009) Bioassay guided discovery of apoptosis inducers form gamboges by high-speed counter-current chromatography and high-pressure liquid chromatography/electrospray ionization quadrupole time-of-flight mass spectrometry. J Chromagtogr B 877:401–407 28. Asano J, Chiba K, Tada M, Yoshii T (1996) Cytotoxic xanthones from Garcinia hanburyi. Phytochemistry 41:815–820 29. Pan LY, Wang YS, Liu XH, Wang N, Xu W, Xiu YF (2019) Pharmacokinetic comparison of five xanthones in rat plasma after oral administration of crude and processed Garcinia hanburyi extract. J Chromagtogr B 1126-1127:121737 30. Jaratrungtawee A, Suksamran S (2012) Xanthones of the Garcinia mangostana fruit latex. SWU Sci J 28:48–57 31. Dharmaratne HRW, Piyasena KGNP, Tennakoon SB (2005) A gernylated biphenyl derivative from Garcinia mangostana. Nat Prod Res 19:239–243

514

H. N. Murthy and G. G. Yadav

32. Cao L, Liu H, DSC L, GHF Y, Pang CP (2010) In vitro screening for agniostatic potential of herbal chemicals. Invest Opthalmol Vis Sci 51:6658–6664 33. Anggia V, Bakhtiar A, Arbain D (2015) The isolation of xanthones form trunk latex of Garcinia mangostana Linn. and their antimicrobial activities. Indones J Chem 15:187–193 34. Govindachari TR, Kalyanaraman PS, Muthukumaraswamy N, Pai BR (1971) Xanthones of Garcinia mangostana Linn. Tetrahedron 27:3919–3926 35. Rasyid R, Susanti M, Gusmiwalti I (2016) Development of analytical method of α-mangostin in dichloromethane extract of green fruit latex Garcinia mangostanta L. using high performance liquid chromatography. Der Pharm Chem 8:52–57 36. Sukatta U, Takenaka M, Ono H, Okadome H, Sotome I, Nanayama K, Thanapase W, Isobe S (2013) Distribution of major xanthones in the pericarp, aril, and yellow gum of mangosteen (Garcinia mangostana Linn.) fruit and their contribution to antioxidant activity. Biosci Biotechnol Biochem 77:984–987 37. Karanjgaonkar CG, Madhavan Nair P, Venkataraman K (1966) Morellic, isomorellic and gambogic acids. Tetrahedron Lett 7:687–691 38. Nair PM, Venkataraman K (1964) The colouring matters of Garcinia morella. Part IV. Isomorellin. Indian J Chem 2:402–404 39. Rukachaisirikul V, Painuphong P, Sukpondma Y, Koysomboon S, Sawangchote P, Taylor WC (2003) Caged-triprenylated and tetraprenylated xanthones from the latex of Garcinia scortechinii. J Nat Prod 66:933–938 40. Wang X, Li R, Liu X, Huang S, Li B, Wang H, Chai X, Wang Y (2020) Study on characteristics of biflavanones distribution in Garcinia kola seeds and identification of compounds in gum resin exuded from fresh slices. J Pharm Biomed Anal 190:113512 41. Wang HM, Liu QF, Zhao YW, Liu SZ, Chen ZH, Zhang RJ, Wang ZZ, Xiao W, Zhao WM (2014) Four new triterpenoids isolated from resin of Garcinia hanburyi. J Asian Nat Prod Res 16:20–28 42. Wamg LL, Li ZL, Song DD, Sun L, Pei YH, Jing YK, Kua HM (2008) Two novel triterpenoids with antiproliferative and apoptotic activities in human leukemia cells isolated from the resin of Garcinia hanburyi. Planta Med 74:1735–1740 43. Wang LL, Li ZL, Xu YP, Liu XQ, Pei YH, Jing YK, Hua HM (2008) A new cytotoxic caged polyprenylated xanthone from the resin of Garcinia hanburyi. Chin Chem Lett 19:1221–1223 44. Reutrakul V, Anantachoke N, Pohamakotr M, Jaipetch T, Yoosook C, Kasisit J, Napaswa C, Pathong A, Santisuk T, Prabpai S, Kongsaeree P, Tuchinda P (2009) Anti-HIV-1 and antiinflammatroy lupanes from the leaves, twigs, and resin of Garcinia hanburyi. Planta Med 76: 368–371 45. Na Pattalung P, Wiriyachitra P, Ongsakul M (1988) The antimicrobial activities of rubraxanthone isolated form Garcinia parviflolia (Miq.) Miq. J Sci Soc Thail 14:67–71 46. Yang J, He S, Li S, Zhang R, Peng A, Chen L (2013) In vitro and in vivo antiangiogenic activity of caged polyprenylated xanthones isolated from Garcinia hanburyi Hook. f. Molecules 18: 15305–15313 47. Vieira LMM, Kijjoa A (2005) Naturally-occurring xanthones: recent developments. Curr Med Chem 12:2413–2446 48. Gershenzon J, Dudareva N (2007) The function of terpene natural products in the natural world. Nat Chem Biol 3:408–414 49. Kumar S, Pandey AK (2013) Chemistry and biological activities of flavonoids: an overview. Sci World J 2013:162750 50. Larson RA (1988) The antioxidants of higher plants. Phytochemistry 27:969–978 51. Panda SS, Chang M, Sakhuja R, Jain SC (2013) Xanthones as potential antioxidants. Curr Med Chem 20:4481–4507 52. Cowan MM (1999) Plant products as antimicrobial agents. Clin Microbiol Rev 12:564–582 53. Gyawali R, Ibrahim SA (2014) Natural products as antimicrobial agents. Food Control 46: 412–429

20

Chemistry and Biological Activities of Garcinia Resin

515

54. Khameneh B, Iranshahy M, Soheili V, Bazzaz BSF (2019) Review on plant antimicrobials: a mechanistic viewpoint. Antimicrob Resist Infect Control 8:118 55. Sivaranjani M, Leskinen K, Aravindraja C, Saavalainen P, Pandian SK, Skurnik M, Ravi AV (2019) Deciphering the antimicrobial mode of action of alpha-mangostein on Staphylococcus epidermidis RP62A through an integrated transcriptomic and proteomic approach. Front Microbiol 10:150 56. Kurapati KRV, Atluri VS, Samikkannu T, Gracia G, Nair MPN (2016) Natural products as antiHIV agents and role in HIV-associated neurocognitive disorders (HAND): a brief overview. Front Microbiol 6:1444 57. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A (2018) Global cancer statistics: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424 58. Choudhari AS, Mandave PG, Deshpande M, Ranjekar P, Prakash O (2020) Phytochemicals in cancer treatment: from preclinical studies to clinical practice. Front Pharmacol 10:1614 59. American Diabetes Association (2014) Diagnosis and classification of diabetes mellitus. Diabetes Care 37:S81–S90 60. Baynes HW (2015) Classification, pothophysiology, diagnosis and management of diabetes mellitus. J Diabetes Metabol 6:541 61. Johnson TO, Ermolieff J, Jirousek MR (2002) Protein tyrosine phosphatase 1B inhibitors for diabetes. Nat Rev Drug Discov 1:696–709 62. Van de Larr FA (2008) Alpha-glucosidase inhibitors in the early treatment of type 2 diabetes. Vasc Health Risk Manag 4:1189–1195 63. Santos CMM, Freitas M, Fernandes E (2018) A comprehensive review on xanthone derivatives as α-glucosidase inhibitors. Eur J Med Chem 157:1460–1479 64. Recio MC, Andujar I, Rios JL (2012) Anti-inflammatory agents from plants: progress and potential. Curr Med Chem 19:2088–2103 65. Harirforoosh S, Asghar W, Jamali F (2019) Adverse effect of nonsteroidal anti-inflammatory drugs: an update of gastrointestinal, cardiovascular and renal complications. J Pharm Pharm Sci 16:821–847 66. Oliveira MMC, Silva MM, Moreira TIM, Couto VF, Coelho YN, Nunes CP (2019) The chronic use of non-steroid anti-inflammatory and their adverse effects. Rev Cad Med 2:90–100 67. Gautam R, Jachak SM (2009) Recent developments in anti-inflammatory natural products. Med Res Rev 29:767–820 68. Lin LJ, Lin LZ, Pezzuto JM, Cordell GA (1993) Isogambogic acid and isomorellinol from Garcinia hanburyi. Magn Reson Chem 31:340–347

Chemistry, Biological Activities, and Uses of Resin of Boswellia serrata Roxb.

21

Tanveer Alam, Shah Alam Khan, and Lubna Najam

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Botanical Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Taxonomy of Boswellia serrata Roxb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Common Vernacular Names of Boswellia serrata Roxb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Phytochemistry of Boswellia serrata Roxb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Chemical Constituents of Boswellia serrata Roxb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Constituents of Volatile/Essential Oil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Pharmacological Activities of Boswellia serrata Roxb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Analgesic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Antimicrobial Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Antihyperlipidemic and Antidiabetic Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5 Antiasthmatic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6 Antidiarrheal Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7 Anticancer Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8 Anticomplementary Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9 Clastogenic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10 Antidepressant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11 Neuroprotective and Anti-Alzheimer’s Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.12 Anti-arthritic and Anti-inflammatory Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.13 Hepatoprotective Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.14 Immunomodulatory Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.15 Useful Actions on Psoriasis and Other Skin Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.16 Activities in Crohn’s Disease and Ulcerative Colitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

519 520 521 521 522 523 523 528 533 533 535 536 536 537 537 537 537 537 539 540 540 540 544 544

T. Alam (*) Natural & Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman e-mail: [email protected] S. A. Khan National University of Science and Technology, Muscat, Sultanate of Oman e-mail: [email protected] L. Najam DAV(PG) College Muzaffarnagar, CCS University, Meerut, India © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_25

517

518

T. Alam et al.

3.17 Diuretic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.18 Antiplasmodial Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Toxicity Studies of Boswellia serrata Roxb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Traditional Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Branded Formulations Containing Boswellia serrata Roxb. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

545 546 546 546 548 548 549

Abstract

The plant Boswellia serrata Roxb., often known as “Salai-guggal” is a member of the Burseraceae family. This plant can be found in dry highland woods throughout India, including Assam, Bihar, Gujarat, Madhya Pradesh, Orissa, Rajasthan, and the central peninsular districts of Andhra Pradesh. The fundamental concern of public health in most developing nations is still the great need for basic health care, which is unfortunately insufficient even at the most basic level. This is true in both fast-growing urban and rural areas. A report published by the World Health Organization (WHO) pointed out that a major proportion of the world’s population either do not have access to adequate primary health care facilities or due to financial constraints cannot afford current health care services. As a result, novel alternative ways are required to address this issue. Medicinal plants provide alternative treatments with a lot of potentials. Many traditional healing herbs and plant parts, especially in rural areas, have been proven to have medicinal potential and can be used to prevent, mitigate, or cure a variety of human ailments like asthma, blood problems, boils, bronchitis, cardiovascular disorders, cough, diarrhea, dysentery, fever (antipyretic), mouth sores, ringworm, skin disease, and vaginal discharges. Boswellia serrata is an example of such a miraculous medicinal plant that has been used by mankind since time immemorial to treat various acute and chronic diseases. It is a traditional medicinal plant that is used in many indigenous systems of medicine including Ayurveda, Chinese, Siddha, and Unani. The resin of this plant is of particular importance which has been shown to exhibit useful biological activities. The traditional applications, phytochemistry, and pharmacology of Boswellia serrata have been highlighted in this chapter. Keywords

Boswellic acids · Boswellia serrata · Edible · Phytochemistry · Traditional uses Abbreviations

AA AD AKBA Aβ B.C bw

Acetic Acid Alzheimer’s Disease Acetyl-11-keto-β-boswellic Acid Amyloid beta-peptide Before Christ Body Weight

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

BAs BS BSE CHIKV COX-2 DNA DOX EO GC GC-MS 1 H-NMR HbA1c HFD i.c.v injection IBD IC50 IgE IL-6 iNOS KBA LD50 5-LOX LPS MAPK MLD-STZ NAFLD NF-kB Nrf2/HO-1 p.o. SPME TNBS TNF-α USFDA WHO

1

519

Boswellic Acids Boswellia serrata Boswellia serrata Extract Chikungunya Virus Cyclooxygenase-2 Deoxyribonucleic Acid Doxorubicin Essential Oils Gas Chromatography Gas Chromatography-Mass Spectrometry Proton Nuclear Magnetic Resonance Hemoglobin A1c High-Fat Diet Intracerebroventricular injection Inflammatory Bowel Disease Inhibitory Concentration in 50% of Population Immunoglobulin E Interleukin 6 Inducible Nitric Oxide Synthase 11-keto-β-boswellic Acid Lethal dose is the amount of an ingested substance that kills 50% of a test sample 5-Lipoxygenase Lipopolysaccharide Extraction Mitogen-Activated Protein Kinase Multiple Low-Dose Streptozotocin Nonalcoholic Fatty Liver Disease Nuclear factor-kappa B The nuclear factor erythroid-2-related factor 2 /heme oxygenase-1 per oral Solid-Phase MicroExtraction 2,4,6-TrinitroBenzene Sulfonic Acid Tumor Necrosis Factor-alpha United States Food and Drug Administration World Health Organization

Introduction

Boswellia genus consists of more than 30 species belonging to the order Sapindales and the family Burseraceae. Although all trees of the Boswellia genus are famous for the fragrant resin, true frankincense is obtained from only four or five main species. Boswellia comprises medium-sized flowering plants that are mainly found in Africa and the tropical regions of Asia.

520

T. Alam et al.

Frankincense or olibanum is an important oleo-gum resin product obtained from a variety of plants in the Boswellia genus. The term “frankincense” comes from the old French word “frankincense” which means “pure incense”. In Arabic, frankincense is called “luban” which means “white” or “cream”; in Greek, “libanos”; and in Ethiopia, “etan.” Since ancient times, olibanum has been popularly used as incense throughout the world [1]. It has become a major constituent in the manufacture of cosmetics and perfumes in recent years. Olibanum is also used as antibacterial, antihyperlipidemic, anti-inflammatory, and sedative in Chinese and Unani (Greek) systems of medicine [2, 3]. Historical evidence suggests that olibanum has been a major trading commodity for civilizations in North Africa and the Arabian Peninsula for over 5000 years. Early kings and queens, like the Queen of Saba, used it as far back as 700 B.C., making it a valuable economic item even before Christian times. With the advent of Christianity, it was listed in the Bible as one of the gifts presented to the Jesus by wise men on the night of his birth. In the Episcopal, Eastern Orthodox, and Roman Catholic churches, this resin is still widely used as an incense ingredient in religious rites. As a result, countries such as Ethiopia, India, Sultanate of Oman, Saudi Arabia, and Somalia give due importance to olibanum production and export. Olibanum, due to its oriental aroma, has found a place as a cosmeceutical agent in the cosmetic and perfumery industry in the manufacture of fragrances, soaps, creams, lotions, detergents, perfume, and other cosmetic products. The involvement of the pharmaceutical sector has led to the creation of the third market for olibanum. Since old age, olibanum in various forms has been used by mankind as a folkloric medicine to treat acute and chronic ailments especially infections, joint pain, and various inflammatory diseases. It has been studied more closely over the past 20 years in an attempt to understand the underlying mechanism and to identify chemical constituents responsible for its beneficial medical effects [4]. Frankincense is primarily obtained from five species of Boswellia native to various regions, including East Africa’s Boswellia carteri, Boswellia frereana (Somalia), Boswellia papyrifera (Sudan), Boswellia sacra (Middle East), and India’s Boswellia serrata. Sultanate of Oman, Republic of Yemen, and the Federal Republic of Somalia produce the most traded frankincense in the world [5, 6]. Indian frankincense is produced by the shrub Boswellia serrata. It is commonly called Indian olibanum, Salai-guggul [7]. A large part of India, as well as Pakistan’s Punjab region, is home to the plant producing two varieties, namely, serrata and glabra [8]. It is synonymous with B. glabra Roxb., because of the glabrous leaves. Indian olibanum is produced by both varieties (serrata & glabra) of Boswellia.

1.1

Botanical Description

Boswellia serrata with serrated and pubescent leaves is a deciduous, balsamiferous tree medium to big. It appears to have a light, spreading crown along with drooping branches. Generally, it grows to a girth of 2.4 m and a height of 18 m [9].

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

521

Bark The bark is thin and can be easily peeled off. Its color is greenish-gray when young and then with age changes to yellow, or reddish and to ash color upon aging. Peeling or incision of the papery bark produces translucent lumps, rips, or drops of white to yellow sticky oleoresin. The gummy resin has a bitter flavor and a balsamic aroma. Leaves Leaves are compound and leaflets are odd in number. Leaves are pinnate and 30–45 cm long, exstipulate, and variable in shape. They grow opposite (alternate) to each other along with their branches. The fresh leaves have a delicate down covering. Flowers Flowers are tiny, bell-shaped, yellowish-white, and gathered in axillary racemes or panicles. The calyx is 5–7-toothed and deltoid. Petals are 5–7 erect and 0.5 cm long and ovate. Stamens are 10 in number and a cup with 5 teeth [10]. Fruits Fruits are small around 1.3 cm long, trigonous, drupe, or capsule with three valves and three heart-shaped ridges. When they reach maturity, they break open to release small brown winged and heart-shaped seeds.

1.2

Taxonomy of Boswellia serrata Roxb.

For the genus Boswellia, there are 40 scientific plant names of species rank. There are 30 approved species among them. The genus Boswellia was named after Johann Boswell (1719–1780), who documented 25 Boswellia species (Tables 1 and 2).

1.3

Common Vernacular Names of Boswellia serrata Roxb.

Arabic, Unani: Kundur, kuurdur, luban Bengali: Luban, salai English: Indian frankincense or olibanum tree Gujarati: Dhup, gugal, saleda Hindi: Madi, salai, saler, salga, salhe, sali Kannada: Adimar, chilakdhupa, chitta, dhupa, guggula, maddi, shallaki, tallaki Persian: Kundur Sanskrit: Ashwamuthri, kunduru Tamil: Gugulu, kundrikam, kungli, morada Telugu: Anduga, kondagugi, parang, phirangisambrani; sambrani, tamu Urdu: Kundur

522

T. Alam et al.

Table 1 Taxonomic hierarchy of B. serrata Roxb. [11] Taxonomic hierarchy Rank Scientific name and common name Kingdom Plantae-plants Subkingdom Viridiplantae Infrakingdom Streptophyta-land plants Superdivision Embryophyta-seed plants Division Tracheophyta Subdivision Spermatophytina Class Magnoliopsida Subclass Rosidae Order Sapindales Family Burseraceae Genus Boswellia Species serrata Binomial Name: Boswellia serrata Roxb. (Indian Frankincense), Boswellia glabra Roxb.

Table 2 List of Boswellia species B. ameero Balf. f. B. bullata Thulin B. dalzielii Hutch. B. elongata Balf. f. B. hildebrandtii Engl.

B. boranensis Engl. B. carteri B. dioscoridis Thulin B. frereana Birdw. B. holstii Engl.

B. microphylla Chiov. B. neglecta S. Moore B. ovalifoliolata N.P. Balakr. & A.N. Henry B. popoviana Hepper B. sacra Flueck.

B. multifoliolata Engl. B. odorata Hutch. B. papyrifera (Del.) Hochst. B. rivae Engl. B. serrata Roxb. ex Colebr.

2

B. bricchettii Chiov. B. chariensis Guillaumin B. elegans Engl. B. globosa Thulin B. madagascariensis Capuron B. nana Hepper B. ogadensis Vollesen B. pirottae Chiov. B. ruspoliana Engl. B. socotrana Balf. f

Phytochemistry of Boswellia serrata Roxb.

The phytochemistry and related aspects of Boswellia serrata (BS) plant have been extensively studied and many different phytochemicals occurring in the leaf, resin, bark, and seeds of Boswellia serrata plant were identified (Fig. 1). The chemical structures of some selected naturally occurring phytoconstituents from the different parts of BS are presented in Fig. 2. BS is reported to contain, triterpenic acids, tannins, volatile oils, fatty acids, etc. However, the maximum number of compounds that have been isolated from the BS resin are triterpenes. The plant’s gum is made up of mainly two pentose and hexose monosaccharides. It also contains oxidizing and

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

523

Fig. 1 Boswellia serrata Roxb.: (a) Boswellia serrata tree (b) Frankincense oozing out from the trunk of Boswellia tree (c) Frankincense tears (resin)

digesting enzymes. Oleo-gum resin primarily contains pentacyclic triterpene acid with boswellic acid as the main and active moiety [12]. According to available data, olibanum contains 60–85% resins (terpene mixtures), 20–30% gums (polysaccharide mixtures), and 5–9% volatile oil [13, 14].

2.1

Chemical Constituents of Boswellia serrata Roxb.

The chemical constituents isolated from different parts of Boswellia serrata Roxb. are presented in Table 3 and their structures are presented in Fig. 2. Several scientists have investigated the phytochemicals in various parts of BS and isolated a number of triterpenoids. Details of the isolated triterpenoids from BS are given in Table 4. The triterpenoid composition of frankincense derived from various Boswellia species is summarized in Table 5. In general, the triterpenoids obtained from the frankincense can be classified into the following types: (i) cemberene-type triterpenes (C type), (ii) ursane-type triterpenes (U type), (iii) oleanane-type triterpenes (O type), (iv) lupane-type triterpenes (L type), (v) tirucallane-type triterpenes (T type), and Euphane-type triterpene (type E). The chemical structures of triterpenoids and related compounds are shown in Fig 2.

2.2

Constituents of Volatile/Essential Oil

Several studies have demonstrated that the chemical composition of BS oil (frankincense) depends on the geographical conditions including climate, harvesting time, origin, soil, and thus varies considerably between species [55]. Chemical analysis of commercial brands of Boswellia confirmed the presence of various chemical constituents belonging to monoterpenes, sesquiterpenes, and diterpenes in the volatile oil [56]. Bornyl acetate and α-terpineol are among the major terpenoids present in the

524

T. Alam et al.

BS fresh leaves essential oil [16, 57]. Another study reported α- and β-pinene as the key components of the volatile oil [36]. Simonson and Ross investigated the oil’s low boiling fractions and detected minor amounts of α-thujene, as well as substantial amounts of α-pinene and β-phellandrene. High boiling fractions showed terpenol, methyl chavicol, and some other

Fig. 2 (continued)

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

525

sesquiterpenes to be the major constituents [58]. According to study results, the primary ingredients of the essential oil are α-thujene (50%), p-cymene (14%), and α-pinene (6.2%). Other constituents present in the smaller quantities include d-limonene, cadinene, geraniol, and elemol [58]. Some other studies also identified

Fig. 2 (continued)

526

T. Alam et al.

Fig. 2 Chemical structures of various phytochemicals present in Boswellia serrata Roxb.

α-thujene as the main component in BS oil. However, its content ranged from 22.7% to 61.4% [59–61]. Hamm following an SPME method identified α-thujene (11.7 %) as the dominating chemical constituent in the BS extract. However, Basar provided just qualitative data for the SPME analyses to show the varied composition of BS oil [4, 62]. A combination of gas chromatography with or without mass spectrometry and 1 H-NMR analytical techniques are routinely used to analyze the chemical composition of volatile oils. A study used these techniques to analyze olibanum oil produced from the resin of Indian species. A total of 40 components were detected in the oil but only 26 could be identified with α-thujene as the major component (Table 6) [60, 63, 64].

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

527

Table 3 Chemical constituents of Boswellia serrata Roxb. S. No. Name of compounds 1. Boswellic acids, pentacyclic triterpenoids; α- and β-amyrin 2. β-sitosterol, holocellulose – 48.7%, lignin – 28.8%, pentosans – 18.3%, and tannin – 9.1% 3. β-sitosterol 4. Crude protein – 8.0; moisture – 9.0, pentosans – 29.3, and water sol mucilage 5. Incensole acetate, acetyl-lupeolic acid, lupeolic acid, incensole oxide, and isoincensole oxide 6. Diterpenes (macrocyclic diterpenoids) – incensole, incensole oxide, iso-incensole oxide Diterpene alcohol – serratol Triterpenes – α- and β-amyrins Pentacyclic triterpenic acids – boswellic acids Tetracyclic triterpenic acids – Tirucall-8, 24-dien 21-oic acids 7. Tirucallic acids – β-boswellic acid, acetyl-β-boswellic acid, 11-keto-β-boswellic acid, and acetyl-11-keto-β-boswellic acid Methyl chavicol, α- and β-amyrins, serratol, 3-α-acetoxytirucall-8, 24-dien-2l-oic acid, 3-ketotirucall-8, 24-dien-21-oic acid, 3-α-hydroxytirucall-8, 24-dien-21-oic acid, 3-β-hydroxytirucall-8, 24-dien-21-oic acid, β-boswellic acid, acetyl-β-boswellic acid, acetyl-11-keto-β-boswellic acid and 11-keto-β-boswellic acid 8. New triterpenoids: 2α, 3α-dihydroxy-urs-12-ene-4-β-oic acid and urs-12-ene-3α, 24-diol 3α-hydroxy-urs-9,12-diene-4β-oic acid 9. 3α-hydroxy-lup-20(29) ene-24-oic acid 10. 9,11-dehydro-α- and β-boswellic acids lupeolic acid, acetyl lupeolic acid 3α-hydroxy-lup-20(29)-en-24 oic acid, Tetracyclic triterpene acids E, F, G, and H 24-noroleana-3, 12-diene, 24-norursa-3, 12-diene 24-norlupa-3, 20 (29)-diene 11. 3α-acetyl-α-Boswellic acid, 3α-Acetyl-βboswellic acid, 3α-acetyl-9,11-dehydro-β-boswellic acid, 3α-acetyl-9,11-dehydro-α-boswellic acid, 3α-acetyl-11-keto-β-boswellic acid 12. α-amyin, 3-isopropyl-4-methyl-5-oxo-heptan-1-ol and β-sitosterol 13. Tirucallane nucleus: 3-keto-8,24-diene-21-β-oic acid (3-oxotirucallic acid), 3-β-hydroxy-tirucall-8,24-diene-21-β-oic acid (3-hydroxytirucallic acid), 3-β-acetoxy-tirucall-8,24-diene-21-β-oic acid (3-acetoxytirucallic acid)

Plant parts Resin Bark

References [15] [16, 17]

Bark [18] Seeds [16] Plant

[19–24]

Resin

[25]

Resin

[26, 27] [27, 28] [29–31]

Resin

[32]

Resin Resin

[33] [34]

Resin

[35]

Resin Resin

[36] [37]

(continued)

528

T. Alam et al.

Table 3 (continued) S. No. Name of compounds 14. Gum nitrogen (0.16%) Sugars – arabinose, xylose, and galactose 15. 4-O-methyl-glucurono-arabinogalactan Sugars- Pentose and hexose, oxidizing and digestive enzymes 16. Diterpenes: (1S,3E,7E,11R)-verticilla-3,7,12 (18)-triene Cembrene A Serratol 1S,3E,7R,8R,11E-7,8-epoxy-cembra-3,11-dien-1-ol Incensole oxide Rel (1S,3R,7E,11S,12R)-1,12-epoxy-4-methylenecembr-7-ene-3, 11-diol Isoincensole oxide Isodecaryiol Triterpenes: Oleanolic acid 11-keto-β-boswellic acid 3-epi-neoilexonol Uvaol β-boswellic aldehyde 5α-tirucalla-8,24-dien-3α-ol Isoflindissone lactone Isoflindissol lactone Rel (8R,9S,20R)-tirucall-24-ene-3β,20-diol Rel (3α,8R, 9S,20R,24S)-20,24-epoxytirucalla-3,25-diol Sesquiterpene: β-bourbonene Monoterpene: Carvacrol, Phenylpropanoids, methyleugenol p-methoxycinnamaldehyde

Plant parts Gum resin Gum resin Gum resin

References [38, 39] [40] [41] [42]

Eight monoterpenes and three sesquiterpenes were reported to be present in the volatile oil of Boswellia (Table 7) [65]. The volatile oil extracted from BS oleo-gum resin harvested from natural habitat in the Jabalpur area of Madhya Pradesh, India, was found to contain 35 volatile compounds with α-thujene as a major constituent [59]. Analysis of essential oil obtained from the oleo-gum-resin of BS from Shivpuri Forest, Madhya Pradesh, India, showed it to be rich in monoterpene hydrocarbons (81.9–88.1%). The resin was identified as α-thujene (61.4–69.8%) chemotype [66] (Table 8).

3

Pharmacological Activities of Boswellia serrata Roxb.

The exploration of the therapeutic potential of BS has revealed it to possess antimicrobial, antiviral, anticancer, antidiabetic, anti-arthritic, and hepatoprotective effects, etc. Different extracts and individual phytoconstituent isolated from the BS plant

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

529

Table 4 Details of the isolated triterpenoids from Boswellia serrata Roxb. S. No. Common name Pentacyclic triterpenes Ursane-type triterpenes (type U) 1. β-boswellic acid (β-BA) 2. 3-acetyl-β-BA (Aβ-BA) 3. 11-keto-β-BA (Kβ-BA) 4. 5. 6. 7. 8. 9. 10. 11.

3-acetyl-11-keto-β-BA (AKβ-BA) 12-ursene-2-diketone – urs-12-en-3α,24-diol α-amyrenone 3-epi-α-amyrin α-amyrin 3-acetyl-11-hydroxy-BA

Oleanane-type triterpenes (type O) 12. α-boswellic acid (α-BA) 13. 3-acetyl α-BA (Aα-BA) 14. β-amyrenone 15. 3-epi-β-amyrin 16. β-amyrin 17. 18. 9,11-dehydro-α-BA 19.

3-acetyl-9,11-dehydro-α-BA

20.

3-acetyl-11-keto-α-BA

Lupane-type triterpenes (type L) 21. Lupeolic acid 22. Acetyl lupeolic acid Tetracyclic triterpenes Tirucallane-type triterpenes (type T) 23. α-elemolic acid 24. Elemonic acid (3-oxo-tirucallic acid) 25. β-elemolic acid 26. 3α-acetoxy-tirucallic acid Euphane-type triterpenes (type E) 27. –

IUPAC name

References

3α-hydroxy-urs-12-en-24-oic acid 3α-O-acetyl-urs-12-en-24-oic acid 3α-hydroxy-11-oxo-urs-12-en-24-oic acid 3α-O-acetyl-11-oxo-urs-12-en-24-oic acid urs-12-en-3,11-diketone 2α,3α-dihydroxy-urs-12-en-24-oic acid 3α, 24-dihydroxy-urs-12-ene urs-12-en-3-one 3α-urs-12-en-3-ol 3β-urs-12-en-3-ol 3α-O-acetyl-11-hydroxy-urs-12-en-24oic acid

[43] [44] [45]

3α-hydroxy-olean-12-en-24-oic acid 3α-O-acetyl-olean-12-en-24-oic acid olean-12-en-3-one 3α-olean-12-en-3-ol 3β-olean-12-en-3-ol 3α,24-dihydroxy-olean-12-ene 3α-hydroxy-9,11-dehydro-olean-12-en24-oic acid 3α-O-acetyl-9,11-dehydro-olean-12-en24-oic acid 3α-O-acetyl-11-oxo-olean-12-en-24-oic acid

[50] [35] [50] [50] [50] [22, 48] [51]

3α-hydroxy-lup-20(29)-en-24-oic acid 3α-O-acetyl-lup-20(29)-en-24-oic acid

[34] [34]

3α-hydroxy-tir-8,24-dien-21-oic acid 3-oxo-tir-8,24-dien-21-oic acid

[27] [27]

3β-hydroxy-tir-8,24-dien-21-oic acid 3α-O-acetyl-tir-8,24-dien-21-oic acid

[27] [27, 37]

20,22-epoxyeupha-24-ene-3-one

[53]

[45, 46] [47] [32] [32, 48] [49] [49] [49] [31]

[35] [52]

were found to exhibit distinct biological actions. The pharmacological properties of BS investigated by the researchers’ using experimental pharmacological methods are summarized in Fig. 3. Furthermore, an extensive literature review reviewed that

Compound class/ type Diterpenoids (C type) (C type) (C type) (C type) (C type) (C type) (C type) (C type) (C type) (C type) Triterpenoids (O type) (U type) (L type) (T type) (O type) (O type) (U type) (U type) (L type) 3.6 10.0 3.8 0.2 0.5 ce 1.0 2.6 0.4

olean-12-en-3α-ol urs-12-en-3α-ol lup-20(29)-en-3α-ol tirucalla-8,24-dien-3-ol olean-12-en-3-one olean-12-en-3β-ol urs-12-en-3-one urs-12-en-3β-ol lup-20(29)-en-3β-ol

epi-β-amyrin epi-α-amyrin epi-lupeol Tirucallol β-amyrenone β-amyrin α-amyrenone α-amyrin lupeol

B. carterii 1.0 0.2 0.2 0.3 – 2.3 17.7 7.0 – –

IUPAC name

Cembrene A Cembrene isomer Serratol isomer Cembrene C Verticilla-4(20),7,11-triene Unknown (?) Incensol Serratol Incensol acetate Incensol oxide acetate

Compound name

Table 5 Triterpenoid composition of frankincense derived from various Boswellia species [54]

2.9 5.0 4.5 0.4 3.8 ce 10.8 3.0 1.0

2.1 1.4 1.8 1.7 – 1.0 tr 13.7 – –

B. sacra

0.9 3.0 0.7 0.6 0.5 ce 1.1 1.8 ce

1.7 0.8 0.9 0.5 – 0.7 tr 14.3 – –

B. serrata

0.1 0.3 0.3 0.4 Ce ce 0.5 0.6 ce

1.8 – – 0.2 6.6 0.2 6.9 – 11.8 0.1

B. papyrifera

530 T. Alam et al.

α-boswellic acid β-boswellic acid lupeolic acid 11-hydroxy-β-boswellic acid

3α-hydroxy-olean-12-en-24-oic acid 3α-hydroxy-urs-12-en-24-oic acid 3α-hydroxy-lup-20(29)-en-24-oic acid 3α,11α-dihydroxy-urs-12-en-24-oic acid (T type) β-elemonic acid 3-oxo-tirucalla-8,24-dien-21-oic acid (T type) β-elemolic acid 3-hydroxy-tirucalla-8,24-dien-21-oic acid (T type) 3-O-acetyl-β-elemolic acid 3-acetoxy-tirucalla-8,24-dien-21-oic acid (O type) 3-O-acetyl-α-boswellic acid 3α-acetoxy-olean-12-en-24-oic acid (U type) 3-O-acetyl-β-boswellic acid 3α-acetoxy-urs-12-en-24-oic acid (L type) 3-O-acetyl-lupeolic acid 3α-acetoxy-lup-20(29)-en-24-oic acid (U type) 3-O-acetyl-113α-acetoxy-11α-hydroxy-urs-12-en-24hydroxy-β-boswellic acid oic acid (U type) 11-keto-β-boswellic acid 3α-hydroxy-11-oxo-urs-12-en-24-oic acid (U type) 3-O-acetyl-11-keto-β-boswellic 3α-acetoxy-11-oxo-urs-12-en-24-oic acid acid Total amyrins: epi-amyrins (3α-OH), amyrenones (3-oxo), and amyrins (3β-OH) Total boswellic acids: boswellic acids, hydroxy/keto boswellic acids, and their acetates Total lupanes (L): epi-lupeol, lupeol, lupeolic acid and its acetate Total tirucallanes (T): β-elemonic acid, β-elemolic acid and its acetate

(O type) (U type) (L type) (U type)

4.6 14.8 1.5 – tr tr tr 6.3 14.5 2.1 tr 0.4 2.7 25.4 43.3 9.1 0.4

7.6 13.5 1.1 0.7 2.9 1.5 0.4 3.9 9.3 1.0 0.6 0.8 5.6 17.9 42.0 6.3 5.0

7.3 60.0 1.1 12.7

1.6

1.5

5.5 18.3 0.1 0.2

5.9

6.0 0.3

9.3 23.2 0.3 0.4

1.5 47.8 0.9 22.1

8.3

2.0

7.1 11.2 0.5 2.2

5.5

13.9 2.2

4.8 11.3 0.1 0.9

21 Chemistry, Biological Activities, and Uses of Resin of Boswellia. . . 531

532 Table 6 Composition of volatile oil from Boswellia serrata Roxb. resin

T. Alam et al.

S. No. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40.

Compounds Tricyclene α-Pinene α-Thujene Camphene β-Pinene Sabinene 3-Carene α-Phellandrene α-Terpinene Unidentified Limonene β-Phellandrene γ-Terpinene Unidentified p-Cymene Unidentified Fenchone α-Thujone β-Thujone Menthone Unidentified Isomenthone β-Bourbonene Camphor Linalol Terpinen-4-ol Unidentified Zingiberene Unidentified Sesquiterpene (MW 204) Estragol α-Terpineol Unidentified Unidentified Citronellol Unidentified (MW 202) Unidentified Methyleugenol Elemicin or asarone Sesquiterpene (MW 218)

Percentage (%) 0.02 7.73 61.36 1.04 0.21 5.07 1.15 2.22 0.41 0.33 1.55 0.03 0.15 0.36 4.28 0.08 Traces 1.76 1.40 Traces 0.71 Traces 1.49 0.04 0.19 0.45 0.48 1.01 0.09 0.22 2.74 0.55 0.26 0.08 0.01 2.17 0.05 0.33 0.37 0.60

triterpenic phytoconstituents such as β-boswellic acid (BA) and acetyl-11keto-β-boswellic acid (AKBA) possess promising activities including anticancer, antibacterial, antifungal, anti-inflammatory, anti-arthritic, and antiasthma properties.

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

533

Table 7 Chemical composition of the volatile oils of B. serrata oleo-gum resin analyzed by GC-MS S. No. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11.

Retention time 6.74 9.13 13.52 16.2 16.9 18 22.37 24.1 31.2 31.43 37.13

Compound α-Thujene Sabinene Terpinen-4-ol cis-Carveol Chavicol Linalool Terpinyl acetate β-Caryophyllene Elemicin β-Copaen-4-α-ol Germacrene D Total unidentified Total identified

Composition (%) 1.29 19.11 14.64 6.26 4.75 1.02 13.01 3.03 7.05 10.24 12.6 7 93%

In this chapter, the experimental evidence of animal and human studies reported in the literature for the BS is described with the cynosure that the plant has been traditionally used to treat various diseases as mentioned in Fig. 3. In vitro and in vivo pharmacological activities of the BS studied for the treatment of different ailments and disorders are summarized in the following sections.

3.1

Analgesic Activity

In several indigenous systems of medicine, BS is used in many preparations as an analgesic to alleviate muscular and joint pain [67]. The analgesic and calming effect was exhibited by the non-phenolic fraction of BS. Menon and Kar demonstrated that Boswellia treatment could lead to a substantial decrease in spontaneous locomotor activity [68]. Sharma et al. evaluated the analgesic efficacy of different polar extracts of BS [67]. In comparison to the gum (54.88%) and oil (20.70%) fractions, the oleo-gum resin fraction was the most potent. It was showed significant inhibition (60.54%). AKBA has been reported to exhibit a dose-dependent elevation in antinociceptive activity in the acetic acid-induced writhing technique in mice and was noted to be potent than nimesulide. A dose of 100 mg of AKBA had a comparable reaction to 200 mg in the tail-flick method [69].

3.2

Antimicrobial Activity

According to several investigations, the crude extract of Boswellia species contains an antibacterial ingredient that inhibits microorganism growth. Kora et al. refer to silver nanoparticles made from aqueous Boswellia extract that functions as an antibacterial agent against both Gram-positive and Gram-negative bacteria [70]. Ismail et al. revealed

534

T. Alam et al.

Table 8 Various chemical constituents identified in the essential oil of Boswellia serrata from its natural habitat S. No. 1. 2. 3. 4 5 6. 6 7 8 9 10 11 1 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27

Compounds Tricyclene α-Thujene α-Pinene Dehydrosabinene Sabinene β-Pinene Myrcene δ-3-Carene o-Cymene p-Cymene Limonene γ-Terpinene (E)-Sabinene hydrate p-1,3,8-Menthatriene Menth-2-en-1-ol (E)-Sabinol p-Mentha-1,5-diene-8-ol Terpin-4-ol p-Cymen-8-ol α-Terpineol (Z )-anethole Thymol β-Bourbonene (Z )-Methyl eugenol Terpinylisobutyrate (E)-Nerolidol 10-Epi-γ-eudesmol Eudesmol Monoterpene hydrocarbons Oxygenated monoterpenoids /benzenoids Sesquiterpenes Total

KI 926 931 939 957 976 980 991 1022 1026 1028 1031 1062 1097 1111 1121 1140 1166 1177 1183 1189 1251 1290 1384 1401 1471 1584 1619 1630

Composition (%) 0.1 61.4 3.5 0.5 5.5 0.3 0.4 3.8 0.1 3.0 2.4 0.4 0.4 0.5 1.4 0.6 1.1 0.8 0.1 3.4 0.1 0.1 0.9 0.5 0.1 0.1 0.1 0.7 81.9 8.1 2.3 92.3

that frankincense had antibacterial action against Staphylococcus aureus, Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, Proteus mirabilis, and Bacillus subtilis [71]. Furthermore, De Rapper et al. found that BS essential oil (EO) exhibits antimicrobial and antifungal activities. The activity could be attributed to the high content of pinene and myrcene [72]. Vahabi et al. have demonstrated antibacterial activity of BS extract [73]. Patel and Patel evaluated the antimicrobial activity of BS extracts of varying polarities against Gram-negative urinary tract infection pathogens. Acetone extract exerted the most powerful activity against K. pneumonia and E. coli in comparison to the polar (aqueous, alcohol) and nonpolar extract (pet ether) [74]. Baratta

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

21

535

Analgesic Activity

Antimicrobial Activity

Antihyperlipidemic and Antidiabetic Activities

Antioxidant Activity

Antiasthmatic Activity

Antidiarrheal Activity

Anticancer Activity

Anticomplementary Activity

Clastogenic Activity

Neuroprotective & Anti-Alzheimer’s Activities

Pharmacological Activities

Antidepressant Activity Anti-arthritic & Anti-inflammatory Activities

Hepatoprotective Activity

Immunomodulatory Activity

Useful Actions on Psoriasis and other Skin Diseases

Activities in Crohn's Disease & Ulcerative Colitis

Diuretic Activity

Antiplasmodial Activity

Fig. 3 Pharmacological activities of Boswellia serrata Roxb.

et al. found that the essential oil of BS possesses good antibacterial activity and antioxidant activity [75]. Raja et al. showed that the antibacterial component of BS is AKBA [76]. The antibacterial properties of boswellic acids (BAs) against microbial infections of the oral cavity were investigated. AKBA produced a dose-dependent bactericidal action. It also inhibited the Streptococcus mutans and Actinomyces viscosus developed biofilms. AKBA seems to be a promising antibacterial agent against oral pathogens and thus it could be developed as a mouthwash to prevent and cure oral infections [77]. BS ethanolic extract contains some chemical compounds that could inhibit the growth of a plant pathogenic fungus Colletotrichum falcatum and thereby prevent the plants from red rot disease [78]. However, the BS oil is moderately active against human pathogens in comparison to plant pathogens [79]. Arora et al. reported the antiviral activity of frankincense against chikungunya virus (CHIKV), i.e., arthropod-borne alpha-virus. Both (BA and AKBA) blocked the entry of lentiviral vectors and prevented in vitro infection with CHIKV [80].

3.3

Antihyperlipidemic and Antidiabetic Activities

Several experimental studies in rats revealed that BS extract of olibanum gum resin possesses hypolipidemic and hepatoprotective properties. It was also shown to decrease elevated total cholesterol levels [81–83]. A double-blinded interventional study compared olibanum resin to placebo for the treatment of type 2 diabetes in 71 subjects. Findings showed that olibanum gum resin improved glycemic management and reduced glucose, HbA1c, insulin, total cholesterol, and triglyceride levels in the blood [84]. The hypoglycemic effect of BS gum resin could be due to its effect on hepatic gluconeogenesis and phosphoenolpyruvate carboxykinase. BS organic extracts prepared using gum resin have the potential to inhibit islet breakdown and subsequent hyperglycemia in type 1 diabetes induced in experimental animals [85].

536

T. Alam et al.

11-keto-β-boswellic acids and Acetyl-11-keto-β-boswellic acids (KBA and AKBA) are effective in controlling the multiple low-dose streptozotocin (MLD-STZ) induced diabetes in rodents. The BA derivatives in a dose of 7.5 and 15 mg/kg were able to inhibit the initiation of autoimmune reactions, insulitis, and elevation of serum glucose levels. Both KBA and AKBA significantly reduced STZ-induced hyperglycemia in animals [86]. BS alcoholic extract at different doses (25–50 mg/kg p.o.) showed antihyperlipidemic action in hypercholesterolemic rats and was able to reduce elevated levels of cholesterol (30–50%) and triglycerides (20–60%) [83]. In experimental mice, the hydrophilic component of BS extract increased high-density lipoprotein and decreased total cholesterol concentrations by 38–48%. Experimental evidence indicates that Salai-guggal is rich in compounds that have the potential to be used in atherosclerosis. Treatment of rats fed high cholesterol, a saturated fat-rich diet, with the BS extract did not increase the blood cholesterol and triglyceride levels. The study concluded that BS extract can be used to control and maintain optimal levels of cholesterol and triglycerides in obese people [83]. AKBA is recognized to have anti-adipocyte properties since it promotes lipolysis in mature human adipocytes [87]. In atherosclerosis, AKBA has been found to suppress nuclear factor kappa B (NF-kB) activity [88]. BS oleo-gum-resin herbal formulation has been shown to provide considerable hypoglycemic action [89]. A clinical study demonstrated that supplementing BS to type 2 DM patients for 6 weeks could cause a reduction in fasting blood glucose probably by increasing insulin levels [90, 91]. The antidiabetic efficacy of BS aqueous extract was tested at three different doses (200, 400, and 600 mg/kg) in experimental animals. After 17 days, BS extract-treated rats had significantly lower blood glucose and HbA1c levels (P
0.01) [92]. Topical application of BS cream (2.5%) on the wound of diabetic Wistar rats and supplementation with BS extract (400 mg/kg, p.o.) for 3 weeks was associated with a decrease in the levels of blood glucose, liver enzymes, and enhanced wound healing [93].

3.4

Antioxidant Activity

Beghelli et al. compared the AKBA content and in vitro free radical scavenging activity of BS extracts. The extract, which had the greatest AKBA concentration, had the highest antioxidant activity and phenolic content [94]. Essential oil of BS isolated using supercritical fluid carbon dioxide extraction method has been demonstrated to exert excellent in vitro antioxidant and antimicrobial activity [95].

3.5

Antiasthmatic Activity

BS resins have the ability to decrease leukotriene production and thereby produce a positive effect on respiratory problems. Gupta et al. observed that BS alcoholic extract had a significant impact on asthma. They examined the promising antiasthmatic activity of alcoholic extract of Salai-guggal in a double-blind placebocontrolled clinical study. Around two-thirds of the participants experienced an

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

537

improvement in bronchitis and dyspnea. There was also intracellular Ca2+ mobilization and MAPK activation [96, 97]. Liu et al. evaluated the antiasthmatic potential of BA and examined its effect in a mouse asthma model. They discovered that BA was able to reduce allergic inflammation, hyper-responsiveness, Th2 cytokine production, and ovalbumin-specific IgE [98]. In an experimental model of pulmonary fibrosis employing bleomycin, BA was found to decrease cell infiltration, diminish lung structure destruction, and attenuate fibrotic lungs by inhibiting 5-LO [99].

3.6

Antidiarrheal Activity

In individuals with inflammatory bowel syndrome, BAs from BS helped to reduce diarrhea without inducing constipation. BAs reduced cholinergic and barium chloride (BaCl2)-induced diarrhea by reducing the spasm of intestinal smooth muscles [100].

3.7

Anticancer Activity

Antitumor chemicals occur in abundance in many plants. Triterpenoids having anticancer effects are detected in oleo-gum resins from several Boswellia species [101]. Numerous research studies have shown that Boswellia extract, its triterpenoids mainly BA derivatives possess potent anticancer properties. Anticancer activities of BS and its constituents are summarized in Table 9.

3.8

Anticomplementary Activity

BAs were shown to prevent immune hemolysis at a dose of 100 μg in the conventional complement pathway. BA has also been shown to have a detrimental impact on guinea pig serum in an in vivo study [115]. BAs showed anticomplementary activity by inhibiting the C3-convertase enzyme [116, 117].

3.9

Clastogenic Activity

BS has the ability to enhance memory, learning, performance, and cognitive ability. Pregnant women are encouraged to consume BS to boost their children’s intellect and memory [118]. Mixed extracts of BS and M. officinalis (200, 400 mg/kg body weight) improved the scopolamine-induced memory impairments [119].

3.10

Antidepressant Activity

In an acute model of depression, BS has been shown to exhibit antidepressant efficacy in acute forms of depression at a dosage of 100 mg/kg. In a forced swim experiment, it decreased the time immobility [120].

538

T. Alam et al.

Table 9 Anticancer activities of Boswellia serrata Roxb. plant and its constituents S. No. 1.

Extracts/phytochemicals AKBA

2.

Boswellic and lupeolic acid

3.

Boswellic acid

4.

Boswellic acid

5.

BS extract (60% of BAs)

6.

Boswellic acids

7.

BS methylene chloride extract

8.

BA nanoparticle formulation

9.

Boswellic acids

10.

Boswellin (BE), a methanol extract of BS gum resin (triterpenoids – β-boswellic acid and structurally similar derivatives)

Finding of the study Prevent proliferation of colorectal cancer cells by regulating certain microRNA pathways Exhibited cytotoxicity against the human triple-negative breast cancer cell lines MDA-MB-231, MDA-MB-453, and CAL-51. They also showed suppression of TNF-α, IL-1β, IL-6, IL-8, and IL-10 Effectively suppressed the ascetic and solid Ehrlich tumor models BA therapy at 25 mg/kg reduced the levels of vascular endothelial growth factor and TNF-α, while increased the levels of IL-12 Antiangiogenic capability was revealed by the reduction in peritoneal angiogenesis and microvessel density AKBA produced an inhibitory impact on NF-kB, as well as potentiated apoptosis in addition to inhibition of angiogenesis in neoplastic cells through the signaling transducer pathway and activation of transcription 3-related pathways in neoplastic cells BAs block basic fibroblast growth factor-induced angiogenesis in an in vivo Matrigel plug test Therapy groups had a significant decline in cyclin D1 and COX-2 expression in the colon cancer cells BA nanoparticles produced DNA fragmentation, a hallmark of apoptosis BAs reduced tumor cell invasiveness and motility, moderated tumor growth, and reduced tumor angiogenesis Topical administration of BE to the backs of mice significantly reduced TPA-induced increases in skin inflammation, epidermal proliferation, epidermal cell layers, and tumor promotion in 7,12dimethylbenz[a]anthracene (DMBA)-initiated animals

References [102]

[103]

[104]

[105, 106]

[107–109]

[110]

[111]

[107]

[112]

[113]

(continued)

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

539

Table 9 (continued) S. No. 11.

Extracts/phytochemicals BS extracts and volatile oil

12.

BS extract (AKBA and KBA)

3.11

Finding of the study Extracts induced the most prominent cytotoxic activity in the HepG2 cell line, with IC50 values of 1.58 and 5.82 μg/mL at 48 h, respectively, which were comparable to doxorubicin (IC50 of 4.68 μg/mL) Radiation and BS/placebo treatment, 60% of patients receiving BS and 26% of patients receiving placebo had a reduction of cerebral edema of >75%

References [65]

[114]

Neuroprotective and Anti-Alzheimer’s Activities

Neuro-inflammation is implicated in the progression of Alzheimer’s disease (AD) and numerous other neurodegenerative diseases, such as cognitive, behavioral, and functional impairment. The active components of Boswellia species, BAs have undergone a rigorous investigation, because of their powerful anti-inflammatory properties, they’re being examined for a possible role in neuroprotection [121]. Chronic injection of frankincense aqueous extract for 21 days did not affect learning parameters, whereas treatment for 42 days significantly increased stepthrough latency (p < 0.05) [122]. AKBA and KBA were tested for their neuroprotective effects against ischemic brain injury [123]. The findings of the study confirmed that both BAs (KBA and AKBA) protects neuronal cells from oxidative stress-induced ischemia injury. The neuroprotective effect of BAs was attributed to activation of the nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway [123]. Syed and Sayed investigated the effect of the combination therapy comprising a 5-lipoxygenase (5-LO) and selective COX-2 inhibitors with respect to the individual treatment. They combined AKBA and celecoxib and evaluated the combination as dual enzyme inhibitors of 5-LO and COX-2 in comparison to individual monotherapies, i.e., celecoxib and AKBA alone. Lipopolysaccharide (LPS, i.p.) was used to induce cognitive dysfunction in mice. Glutamate, tumor necrosis factor-alpha (TNF-α), and amyloid beta-peptide (Aβ) were estimated following the LPS and BS treatment. The findings revealed that combination/dual therapy of AKBA and celecoxib rectified the behavioral and biochemical abnormalities induced by the LPS in mice. The dual therapy produced beneficial ameliorating effects in cognitive dysfunction by virtue of their antiinflammatory, anti-glutamatergic, and anti-amyloidogenic actions [124]. BS/BAs seem to be a promising remedy for halting the progression of AD. They can be used to develop disease-modifying lead compounds effective in the treatment of AD [125]. Aqueous infusions of BS (45 and 90 mg/kg/day, respectively) significantly ameliorated the AD symptoms in rats. Boswellia has the potential to treat the AlCl3-induced Alzheimer’s by improving ACh level by inhibiting AChE activity in

540

T. Alam et al.

brain homogenates [126, 127]. Beheshti et al. reported that frankincense (50 mg/kg) can treat dementia type of AD produced by i.c.v injection of streptozotocin (STZ) [122].

3.12

Anti-arthritic and Anti-inflammatory Activities

Numerous studies have proved that BS possesses excellent anti-arthritic and antiinflammatory activities. BS herbal extracts are available commercially and used as a popular herbal supplement in various inflammatory conditions. The antiinflammatory actions of BS are mainly due to the inhibition of 5-LO. The reported anti-arthritic and anti-inflammatory activities of B. serrata Roxb. along with the mechanism of action are consolidated in Table 10.

3.13

Hepatoprotective Activity

In an experimental setup, BAs were found to possess hepatoprotective action in dietinduced nonalcoholic fatty liver disease (NAFLD) in rats. Rats were given a high-fat diet (HFD) for 3 months to develop hepatic steatosis and inflammation (NFLD) which was confirmed by the deviations in the levels of key liver biomarkers during the assessment. When compared to the control group, rats given BAs (125 or 250 mg/kg) or pioglitazone had enhanced insulin sensitivity and lowered the liver index, activity of liver enzymes, serum TNF-α and IL-6, and hepatic iNOS expression. BAs (250 mg/kg) also improved the expression of thermogene sis-related mitochondrial uncoupling protein-1 and carnitine palmitoyl transferase-1 in white adipose tissues at the cellular level. The outcome of this study suggested that BAs have clinical potential in the treatment of NAFLD [148]. Another research study demonstrated that prophylactic oral therapy with BS extracts is associated with a better prognosis of hepatic fibrosis [149]. The hepatoprotective efficacy of the BA-rich fraction of BS extract was tested at two different concentrations of 250–500 mg/kg/day alone and with doxorubicin (DOX). Interestingly, BS extract inhibited the growth of HepG2 (IC50 value of 21.21  0.92 μg/mL) and HepG2 (IC50 value of 18.65  0.71 μg/mL). DOX inhibited growth in HepG2 and Hep3B cells with an IC50 of 1.06  0.04 μg/mL and 1.92  0.09 μg/mL. With DOX (1 μM) and BS extract (20 μg/mL), BS extract generated a dose-dependent rise in caspase-3 activity, TNF-α level, and increased IL-6 level ( p < 0.001) [150].

3.14

Immunomodulatory Activity

Many research looked into the immune system’s cell-mediated and humoral components, as well as the immune-toxicological characteristics of BAs [151]. AcetylBA derivative binds with human topoisomerases via a high-affinity binding site. The BA derivative gave KD values of 70.6 nM for topoisomerase I and 7.6 nM for

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

541

Table 10 Anti-arthritic and anti-inflammatory activities of Boswellia serrata Roxb. S. No. 1.

Extracts/phytochemicals BS alcoholic extract

2.

Mixture of boswellic acid

3.

Alcoholic extract

4.

Gastro-resistant formulation with a mixture of Boswellia and bromelain supplements

5.

BS gum resin preparations

6.

BA with a combination of Myrrha

7.

Herbal gel containing Boswellia extract

8.

Boswellia extract containing 10% AKBA

9.

Incensole acetate

10.

BS oleo-gum extract and AKBA

11.

Dry distillates of BS

12.

Ethanolic extracts of the gum resin BS

13.

BHUx (a polyherbal formulation containing BS)

Finding of the study Anti-inflammatory activity in carrageenan-induced oedema in rats and mice and dextran oedema in rats Showed anti-arthritic activity (45–67%) Beneficial in both adjuvant arthritis (35–59%) and established arthritis (54–84%) A useful non-pharmacological approach for enhancing the quality of life (QoL) of patients with various types of osteoarthritis As a folk medicine to treat a variety of chronic inflammatory disorders The combination showed antiinflammatory activity as well as analgesic effect Topical application of gel was effective in the treatment of arthritis. BA suppressed the synthesis of 5-LO products in in vitro models Inhibited tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), NO, and mitogen-activated protein kinases (NAPK) Inhibition of nuclear factor-kappa B activation (NF-κB) Pretreatment with the combination significantly prevented functional and morphological alterations and also the NF-κB phosphorylation induced by the inflammatory stimuli at 0.1–10 μg/mL and 0.027 μg/mL, respectively A substantial anti-inflammatory effect was observed in acute inflammation induced by 1% carrageenan Inhibit the formation of 5-LO products in polymorphonuclear neutrophil leukocytes (PMNL) in a dose-dependent manner BHUx exhibited significant antiinflammatory properties through inhibition of COX-2 and LO-15

References [128]

[28] [128]

[129]

[130]

[131]

[132]

[133]

[133] [134]

[135]

[136]

[137]

(continued)

542

T. Alam et al.

Table 10 (continued) S. No. 14.

Extracts/phytochemicals Aflapin ®, a novel synergistic composition derived from BS gum

15.

BS gum resin extract

16.

A mixture of boswellic acids

17.

Boswellic acid

18.

BS fractions, viz., essential oil (10 mL/kg) and oleo-gum resin (100 mg/kg)

19.

BAs

20.

Alcoholic extract of BS’s oleogum resin

21.

Boswellia combination with Curcuma longa, Zingiber officinale, and Withania somnifera

22.

Crude methanolic extract and the pure compound

Finding of the study Aflapin is more efficacious as an anti-inflammatory agent, and it is a safe, fast-acting, and effective alternative intervention in the management of OA Treatment with 100 and 200 mg/ kg body weight once daily for 21 days resulted in significantly reduced levels of inflammatory mediators (IL-1β, IL-6, TNF-α, IFN-γ, and PGE2), an increased level of IL-10 Mixture of boswellic acids decreased paw oedema in rats by 25–46% Boswellic acid from BS demonstrated substantial efficacy, inhibiting inflammation by 35% (new model) in papaya latex model. Essential oil (10 mL/kg) and oleogum resin (100 mg/kg) reduced carrageenan-induced inflammation in rats and showed analgesic activity in acetic acidinduced writhing response, formalin induced pain, hot plate and tail flick methods BAs from BS are specific, non-redox inhibitors of leukotriene synthesis. Act as potent anti-inflammatory agents either by interacting immediately with 5-LO or restricting its translocation Inhibition of carrageenan-induced edema in rats and mice, as well as dextran-induced edema in rats Treatment with the combination of Boswellia serrata, Curcuma longa, Zingiber officinale, and Withania somnifera resulted in a substantial reduction in disability and pain severity A pure compound from BS extract exhibited anti-inflammatory properties in human PBMCs and mouse macrophages through inhibition of TNFα, IL-1β, NO,

References [138]

[139]

[140]

[21]

[67]

[141]

[128]

[142, 143]

[47]

(continued)

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

543

Table 10 (continued) S. No.

Extracts/phytochemicals

23.

Boswellia extract

24.

BS extracts (dry extract (extract A) and a hydroenzymatic extract (extract G)

25.

LI13019F1 (also known as Serratrin ®), a unique composition containing the acidic and nonacidic fractions of BS gum resin

26.

A new synergistic formulation, Aflapin ®-containing BS extract enriched with 20% AKBA and BS nonvolatile oil

Finding of the study and MAP kinases. All three cytokines are down regulated when PBMCs are cultured in the presence of crude extract or the pure compound at various time points Boswellia extract might help to reduce periodontal inflammation associated with plaque-induced gingivitis Extract A was toxic at higher doses and restored pAEC viability after LPS challenge only at lower doses. Extract A showed proangiogenic properties at the lowest dose, and the same result was observed using pure AKBA at the corresponding concentration, whereas extract G did not show any effect on the migration capacity of endothelial cells LI13019F1 strongly inhibited 5-LOX activity with the halfmaximal inhibitory concentration (IC50) of 43.35  4.90 μg/mL. Also, LI13019F1 strongly inhibited the leukotriene B4 (IC50, 7.80  2.40 μg/mL) and prostaglandin E2 (IC50, 6.19  0.52 μg/mL) productions in human blood-derived cells. Besides, LI13019F1 reduced TNF-α production with the IC50 of 12.38  0.423 μg/mL. LI13019F1, a new composition of BS gum resin extracts, reduced pain and protected articular cartilage from the damaging action of MIA in a rodent model BS extract-derived BAs are specific, non-redox inhibitors of 5-LOX. Among BAs, AKBA exerted the most powerful inhibitory action. Aflapin® is a patented, selective, and most potent 5-LOX inhibitor, that dramatically lowers joint pain, inflammation, stiffness, and improves physical function compared to placebo

References

[144]

[145]

[146]

[147]

544

T. Alam et al.

topoisomerase IIα, indicating a firm interaction between the ligand and receptor. The plausible mechanism of inhibition of topoisomerases I and IIα by AKBA could be through competition with DNA for binding to the enzyme. It was suggested that acetyl-BA belongs to a unique class of dual catalytic inhibitors of human topoisomerases I and IIα and therefore might play an important role in anticancer activity [152]. BS has been contemplated and tested for its anti-anaphylactic and mast cell stabilizing activity. Oral administration of gum resin extract of BS containing a mixture of BAs (60% AKBA and other BAs) has been shown to inhibit the passive paw anaphylaxis reaction in rats at 20, 40, and 80 mg/kg [153]. Oily (nonpolar) extracts of gum resins of Boswellia species are employed in traditional medicine to treat various inflammatory disorders and infections. [154]. Gum resin extracts of BS and some of its pure isolated constituents including BAs may affect the immune system by acting at different pathways. BAs primarily interfere with the release and or production of cytokines and thus affect the cellular defense system. BAs inhibit the activation of NFkB, a product of neutrophile granulocytes. These events result in the downregulation of TNF-α along with a marked reduction in the levels of pro-inflammatory cytokines such as IL-1, IL-2, IL-4, IL-6, and IFN-γ. Studies showed that suppressions of the classic complement pathway by BAs could be due to the inhibition of the conversion of C3 into C3a and C3b [155].

3.15

Useful Actions on Psoriasis and Other Skin Diseases

BS extract has been found in studies to reduce skin redness and irritation and also restoring an even skin tone. Chinese people have used olibanum since ancient times to heal bruised skin and infected wounds. Furthermore, AKBA is touted to be a wonderful topical treatment for softening facial wrinkles and relaxing the skin [156]. In a double-blind clinical trial, the effectiveness of a BA formulation, Bosexil( ®) (lecithin, BS resin extract), was compared to Vaccinium myrillus seed oil therapy and placebo in the local treatment of psoriasis and erythematous eczema in human beings. Bosexil( ®) formulation treatment improved erythema (50%), itch (60%), and scales (70%) with no deterioration [157]. Wang et al. developed a transdermal patch to treat psoriasis. The transdermal patch mainly consisted of a mixture of BAs and their derivatives [158]. Kim showed that various BA fraction (α-BA and β-BA) compositions at a concentration of about 60% w/w and polysaccharide fraction (galactose, arabinose, D-glucuronic acid, and 4-O-methyl-glucuronoarabino-galactan) at a concentration of about 40% w/w could have potent activities toward melanin synthesis collagenase [159].

3.16

Activities in Crohn’s Disease and Ulcerative Colitis

The oleo-gum resin of BS and B. carteri are used in the traditional Iranian system of medicine to reduce inflammation. It is considered as one of the most effective

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

545

treatments for inflammatory bowel disease (IBD). The BS gum resin has been proven to be of value in treating chronic colitis, with just moderate adverse effects [36]. A study compared the efficacy of a BS extract and the mesalazine molecule in the treatment of Crohn’s disease. Surprisingly, BS outperformed mesalazine in terms of both efficacy and safety [160]. Oral therapy with BS extract at doses of 17.1 and 34.2 mg/kg and its component AKBA (3.4 and 5.1 mg/kg) significantly decreased the leukocyte-endothelial cell contacts and tissue injury in indomethacin-induced ileitis in rats. This activity is produced by blocking 5-LO activity [44]. Prophylactic treatment with a mixture of Boswellia extracts (50 mg/kg) and Scutellaria extracts (150 mg/kg) has been reported to inhibit colonic fibrosis in TNBS colitis. The plausible mechanism was attributed to the inhibition of the TGG-β1/Smad3 pathway [161]. Hartmann et al. screened the anti-inflammatory and antioxidant properties of BS extract in acute ulcerative colitis induced by acetic acid (AA) in rats. The extract given orally at a dose of 34.2 mg/kg/day, 2 days before and after the induction of colitis revealed a significant reduction in inflammation (p < 0.001) in comparison to the control groups. Similarly, BS extract was able to lower lipid peroxidation, nitric oxide, and iNOS levels after pretreatment and during treatment [162]. In patients with ulcerative colitis grade II and III, the effects of BS gum resin preparation (350 mg thrice daily for 6 weeks) on stool properties, histopathology and scan microscopy of rectal biopsies, blood parameters including Hb, serum iron, calcium, phosphorus, proteins, total leukocytes, and eosinophils were studied. Sulfasalazine (1 g twice a day) was given to patients as a control. Treatment with BS gum resin improved all the examined parameters, and the obtained results were similar to the control group. Remission was achieved in 82% of treated individuals versus 75% achieved with sulfasalazine [163]. Twenty patients received a BS gum resin preparation (900 mg daily given into three doses for 6 weeks) and ten patients received sulfasalazine (3 gm daily given into three doses for 6 weeks). Eighteen of the 20 patients treated with Boswellia gum resin exhibited an improvement in one or more of the criteria, including stool characteristics, histology, and scanning electron microscopy (SEM), in addition to hemoglobin, serum iron, calcium, phosphorus, proteins, total leukocytes, and eosinophils. Six out of ten patients in the control group had similar findings using the same parameters. Four out of ten patients treated with sulfasalazine went into remission, whereas 14 out of 20 patients treated with Boswellia gum resin went into remission. In conclusion, findings suggest that a gum resin product derived from BS may be beneficial in the treatment of chronic colitis while having few adverse effects [164]. BS hexane and methanol extracts containing six BAs (29.9% and 34.4%, respectively) were tested for their potential to reduce tissue damage in chemically induced colitis [165].

3.17

Diuretic Activity

In normal albino rats, the effects of a crude aqueous extract of olibanum resin on pH, urine electrolytes, and diuretic activity were studied. Based on Lipschitz values,

546

T. Alam et al.

when compared to the reference medication, the crude extract showed 44% diuretic action at a dose of 50 mg/kg. Even at the higher dose of 3000 mg/kg, albino mice showed no signs of death. The aqueous extract of olibanum gum resin, at a dose of 50 mg/kg, was found to have significant effects on urine volume and urinary electrolyte concentration with no symptoms of toxicity [166].

3.18

Antiplasmodial Activity

Greve et al. isolated 22 compounds, namely, (1S,3E,7E,11R)-verticilla-3,7,12 (18)triene (1), cembrene-A (2), serratol (3), 1S,3E,7R,8R,11E7,8-epoxy-cembra-3,11-dien1-ol (4), incensole oxide (5), rel (1S,3R,7E,11S,12R)-1,12-epoxy-4-methylenecembr-7ene-3, 11-diol (6), isoincensole oxide (7), isodecaryiol (8); oleanolic acid (9), 11-keto-β-boswellic acid (10), 3-epi-neoilexonol (11), uvaol (12), β-boswellic aldehyde (13), 5α-tirucalla-8,24-dien-3α-ol (14), isoflindissone lactone (15), isoflindissol lactone (16), rel (8R,9S,20R)-tirucall-24-ene-3β,20-diol (17), rel (3α,8R, 9S,20R,24S)-20,24epoxytirucalla-3,25-diol (18), β-bourbonene (19), carvacrol (20), phenyl propanoidsmethyleugenol (21), and p-methoxycinnamaldehyde (22) from the resin of BS and screened for their in vitro activity against Plasmodium falciparum. In L6 rat skeletal myoblasts, antiplasmodial IC50 values and cytotoxicity were assessed. The most active molecule was isoflindissone lactone (15), which had an IC50 of 2.2 μM and a selectivity index of 18 against P. falciparum [42] (Table 11).

4

Toxicity Studies of Boswellia serrata Roxb.

BS toxicity investigations in rats and primates revealed no pathological alterations in biochemical, hematological, or histological parameters at dosages up to 1000 mg/kg, and the LD50 was found to be >2 g/kg [169]. In acute, subacute, and chronic models, BAs have been proven to be safe. Toxicity and serious adverse effects are uncommon with BS (LD50 > 2 g/kg). Mild gastrointestinal distress (diarrhea), nausea, skin rashes, and urticaria are among the adverse effects. Topical use of BS extract can cause contact dermatitis [170–172]. The USFDA has approved the use of Boswellia gum resin as a food additive, and it is on the list of safe medications [76].

5

Traditional Uses

Fodder: It is utilized as a substitute feed for buffaloes in India, even though it is not readily grazed by cattle. Fuel: The wood of Boswellia is a good source of energy. It is particularly well-suited to the production of charcoal for smelting iron.

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

547

Table 11 Active components of Boswellia and their medicinal properties [167, 168] S. No. 1. 2. 3. 4. 5. 6. 7. 8.

Active components of Boswellia serrata Roxb. E-β-Ocimene Cembrene α-Cubebene Sabinene β-Elemene Allo-aromadendrene α-Thujene α-Pinene

9. 10. 11.

Lupeolic acid Acetyl lupeolic acid 11-keto-β-boswellic acid

12.

α-Boswellic acid

13.

3-O-Acetyl-α-boswellic acid Acetyl-β-boswellic acid

14. 15.

Acetyl-11-keto-β-boswellic acid

Medicinal properties Antimicrobial and antioxidant Antimicrobial and antioxidant Antimicrobial Antimicrobial, antioxidant, antitumor, and larvicidal Anticancer, and wound healing Antibacterial, and antifungal Antimicrobial, and antioxidant Anticancer, antidiabetic, antioxidant, antimicrobial, and analgesic Anticancer, and anti-inflammatory Anticancer, antioxidant, and antimicrobial Anticancer, antibacterial, antifungal, anti-inflammatory, and immunostimulator Antibacterial, anticancer, antifungal, anti-inflammatory, immunostimulator, and anti-arthritic Antibacterial, anticancer, antifungal, anti-inflammatory, immunostimulator, and anti-arthritic Antibacterial, anticancer, antifungal, anti-inflammatory, immunostimulator, and anti-arthritic Antibacterial, anticancer, antifungal, anti-inflammatory, immunostimulator, anti-arthritic, and antiasthma

Fiber: BS has recently gained popularity as a source of pulp paper and newspaper. Experiments have shown that blending 25–40% long-fibered bamboo pulp in the finish can generate strong writing and printing papers. Cordage can also be made from the bark of B. serrata. Timber: It was found that BS timber can be used in inexpensive house furniture, mica boxes, ammunition boxes, packing containers, well construction, water pipes, cement barrels, matches boxes, plywood, and veneers, among other things. Gum or Resin: Salai-guggal is a yellowish-green gum-oleoresin produced by wounds in the tree’s bark. When this gum is burned, it emits a pleasant aroma. Each year, a mature tree produces roughly 1–1.5 kg of gum resin. It has been discovered that it is a good substitute for imported Canadian balsam. It is also tapped for “lobal” resin, which is used to make incense. Medicine: The olibanum resin is used as a diaphoretic and astringent. It has been used for diabetes in Indian traditional medicine [173]. Ornamental: In India, it is often used for avenue planting. Other Applications: In West Bengal, BS has been found as a new lac host. Many Christian denominations, including the Eastern Orthodox, Oriental Orthodox, and Catholic churches, use frankincense.

548

T. Alam et al.

BS gum-resin extracts have long been considered as a pillar of Ayurvedic medicine, especially for their well-known effects in the treatment of rheumatoid arthritis and inflammatory diseases.

6

Branded Formulations Containing Boswellia serrata Roxb.

Apart from its usage in spiritual rites, Boswellia has long been used as an essential adhesive in lotions, creams, fragrances, and detergents, and its scent has an oriental note, making it a popular ingredient in perfume and cosmetic products. Many preparations containing BS are available in the market, and they are described in detail below: • Sabinsa Corporation’s approved trademark, Boswellin ®, became popular in the USA and European markets. It comes in tablet or pill form, as well as a relaxing pain-relieving cream containing capsaicin. BAs ranging from 150 to 250 mg per capsule or tablet are included in the product, which should be taken orally twice to three times per day: Boswellin ® (The anti-inflammatory phytonutrient) (Table 12). • Dr. Reddy’s Laboratories Limited, Hyderabad, manufactures Niltan®, a cream formulation for external usage. It is a blend of active botanical extracts (arbutin, boswellin, coriander seed oil, and liquorice extract in a semisolid base). It produces the action by lowering the level of the enzyme tyrosinase in the skin, as well as the level of melanin, which is responsible for skin darkening. • Himalayan Company, Makali, Bengaluru, produces Shallaki ®, a capsule containing 125 mg BS. It possesses anti-inflammatory and analgesic properties that are beneficial in the relief of joint problems. • Sunrise Herbals, Banaras (U.P., India), produces Rheumatic-X ®, which contains 20 mg “Shallaki” and many other ingredients and is used to treat osteoarthritis, gout, rheumatoid arthritis, and pain (Fig. 4).

7

Conclusions

The present chapter provides an updated and structured compilation of various studies on Boswellia serrata Roxb. Extensive literature survey revealed that Boswellia serrata is an important medicinal plant with a diverse pharmacological spectrum. The plant has been extensively studied in terms of the pharmacological activity of its major components, and the results indicate potent antimicrobial and antioxidant, antiasthmatic, anticancer, anti-arthritic, and anti-inflammatory activities. In recent years, the emphasis of research has been on utilizing traditional medicines that have a long and proven history of treating various ailments. The review renders elaborate data on the range of chemical constituents present in various parts of the plant. It is obvious from this chapter that Boswellia serrata can be regarded as an important traditionally used medicinal plant harboring a panoply of bioactive

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

549

Table 12 Marketed preparations containing Boswellia extract

Total boswellic acid β-boswellic acid AKBA Gum acacia Polysal

Boswellin ® Forte 75.0–85.0% w/w 40.0–45.0% w/w 10.0% w/w (min.) -

Boswellin ® HBD 70.0–85.0% w/w 20.0–30.0% w/w 2.0% w/w (min.) -

Boswellin ® HBD (D.C) 70.0–80.0% w/w

Boswellin ® PS 35.0–50.0% w/w

20.0–30.0% w/w

20.0–30.0% w/w

2.0% w/w (min.)

10.0–12.0% w/w (min.) 35.0–45.0% w/w

3%

Fig. 4 Branded formulations containing Boswellia serrata Roxb.

compounds, pharmacological properties, and modern applications in emerging fields of interest. In this regard, further evaluation needs to be carried out on Boswellia serrata to explore the concealed areas and their practical clinical applications, which can be used for the welfare of mankind.

References 1. Safayhi H, Sailer ER (1997) Anti-inflammatory actions of pentacyclic triterpenes. Planta Med 63(06):487–493 2. Fan A, Lao L, Zhang R, Zhou A, Wang L, Moudgil K, Lee D, Ma Z, Zhang W, Berman B (2005) Effects of an acetone extract of Boswellia carteri Birdw.(Burseraceae) gum resin on adjuvant-induced arthritis in lewis rats. J Ethnopharmacol 101(1–3):104–109

550

T. Alam et al.

3. Akihisa T, Tabata K, Banno N, Tokuda H, Nishihara R, Nakamura Y, Kimura Y, Yasukawa K, Suzuki T (2006) Cancer chemopreventive effects and cytotoxic activities of the triterpene acids from the resin of Boswellia carteri. Biol Pharma Bull 29(9):1976–1979 4. Basar S (2005) Phytochemical investigations on Boswellia species. Staats-und Universitätsbibliothek Hamburg Carl von Ossietzky 5. Guenther E (1972) The essential oils, vol IV. Krieger Publication Company, New York 6. Lawrence GHM (1969) Taxonomy of vascular plants. IBH Publishing, New Delhi 7. Pole S (2006) Ayurvedic medicine: The principles of traditional practice. Elsevier Health Sciences, Edinburgh 8. Pant C, Mishra A, Tomar H, Singhal M, Shaheen G, Kumar A, Gaurav N Some potential and effective important medicinal plants for cancer treatment. Int J Sci Eng 12(5):975–984 9. Saxena HO, Brahman M (1994) The flora of Orissa. Regional Research Laboratory (Council of Scientific & Industrial Research), Bhubaneswar, India 10. Dymock W, Warden CJH, Hooper D (1976) Pharmacographia Indica: a history of the principal drugs of vegetable origin met with in British India, vol III. M/S Bishen Singh Mahendra Pal Singh, Dehra Dun 11. Murthy TK, Shiva M (1977) Salai guggul from Boswellia serrata Roxb.-its exploitation and utilization. Indian For 103(7):466–474 12. Kokate C, Purohit A, Gokhale S (1999) Resin and resin combinations. Pharmacognosy Nirali Prakashan, Pune 13. WC E (1996) Trease and Evans’ pharmacognosy. 14 [sup] th ed. Bailiere Tindall WB Saunders Company Ltd, London, pp 224–228 14. Khalid SA (1983) Chemistry of the Burseraceae. Chem Chem Taxon Rutales 22:281 15. Winterstein A, Stein G (1932) Search in Sapninreihe. X. Mitteilung. Zur Kenntnis der Monooxy-triterpensauren. Hoppe Seyler’s Z. Physiol Chem 208:9–25 16. Chatterjee A, Pakrashi S (2003) Treaties on Indian medicinal plants, vol 3. National Institute of Science Communication and Information Resources, New Delhi, pp 146–147 17. Chopra RN, Chopra IC, Varma BS (1998) Supplement to glossary of Indian Medicinal Plants. National Institute of Science Communication, New Delhi 18. Beri R, Karnik M (1964) Chemistry of Boswellia serrata bark. Indian Forest Leaflet 175:1–7 19. Wang C, Xia L, Song Z, Li Q, Zeng L, Liu Z (2011) Determination of five boswellic acids in Boswellia serrata. Zhongguo Zhong yao za zhi¼ ¼ China J Chinese Mat Med 36 (10):1330–1333 20. Moussaieff A, Gross M, Nesher E, Tikhonov T, Yadid G, Pinhasov A (2012) Incensole acetate reduces depressive-like behavior and modulates hippocampal BDNF and CRF expression of submissive animals. J Psychopharmacol 26(12):1584–1593 21. Paul M, Jauch J (2012) Efficient preparation of incensole and incensole acetate, and quantification of these bioactive diterpenes in Boswellia papyrifera by a RP-DAD-HPLC method. Nat Prod Commun 7(3) 1934578X1200700303 22. Bhushan S, Malik F, Kumar A, Isher HK, Kaur IP, Taneja SC, Singh J (2009) Activation of p53/p21/PUMA alliance and disruption of PI-3/Akt in multimodal targeting of apoptotic signaling cascades in cervical cancer cells by a pentacyclic triterpenediol from Boswellia serrata. Mol Carcinog: Published in cooperation with the University of Texas MD Anderson Cancer Center 48(12):1093–1108 23. Schmidt TJ, Kaiser M, Brun R (2011) Complete structural assignment of serratol, a cembranetype diterpene from Boswellia serrata, and evaluation of its antiprotozoal activity. Planta Med 77(08):849–850 24. Song Z, Xia L, Wei Z, Cao Y, Zhang L, Liu Z (2012) Determination of alpha-pinene and octyl acetate contents in Boswellia serrata. Zhongguo Zhong yao za zhi ¼ China J Chinese Mat Med 37(10):1431–1433 25. Siddiqui M (2011) Boswellia serrata, a potential antiinflammatory agent: an overview. Indian J Pharm Sci 3 (3):255 26. Pardhy R, Bhattacharyya S (1978) Structure of serratol, a new diterpene cembranoid alcohol from Boswellia serrata Roxb. Indian J Chem B 16(3):171–173

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

551

27. Pardhy R, Bhattacharyya S (1978) Tetracyclic triterpene acids from the resin of Boswellia serrata Roxb. Indian J Chem 16(3):174–175 28. Pardhy R, Bhattacharyya S (1978) Beta-boswellic acid, acetyl-beta-boswellic acid, acetyl-11keto-beta-boswellic acid & 11-keto-beta-boswellic acid, four pentacyclic triterpene acids from the resin of Boswellia serrata Roxb. Indian J Chem B 16(3):176–178 29. Ganzera M, Khan IA (2001) A reversed phase high performance liquid chromatography method for the analysis of boswellic acids in Boswellia serrata. Planta Med 67(08):778–780 30. Tawab MA, Kaunzinger A, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M (2001) Development of a high-performance liquid chromatographic method for the determination of 11-keto-β-boswellic acid in human plasma. J Chromatogr B: Biomed Sci Appl 761(2):221– 227 31. Schweizer S, von Brocke AF, Boden SE, Bayer E, Ammon HP, Safayhi H (2000) Workupdependent formation of 5-lipoxygenase inhibitory boswellic acid analogues. J Nat Prod 63(8): 1058–1061 32. Mahajan B, Taneja S, Sethi V, Dhar K (1995) Two triterpenoids from Boswellia serrata gum resin. Phytochemistry 39(2):453–455 33. Culioli G, Mathe C, Archier P, Vieillescazes C (2003) A lupane triterpene from frankincense (Boswellia sp., Burseraceae). Phytochemistry 62(4):537–541 34. Büchele B, Zugmaier W, Simmet T (2003) Analysis of pentacyclic triterpenic acids from frankincense gum resins and related phytopharmaceuticals by high-performance liquid chromatography. Identification of lupeolic acid, a novel pentacyclic triterpene. J Chromatogr B 791 (1–2):21–30 35. Belsner K, Büchele B, Werz U, Syrovets T, Simmet T (2003) Structural analysis of pentacyclic triterpenes from the gum resin of Boswellia serrata by NMR spectroscopy. Magn Reson Chem 41(2):115–122 36. Alam M, Khan H, Samiullah L, Siddique K (2012) A review on phytochemical and pharmacological studies of Kundur (Boswellia serrata Roxb ex Colebr.)-A Unani drug. J Appl Pharm Sci 2(3):148–156 37. Boden SE, Schweizer S, Bertsche T, Düfer M, Drews G, Safayhi H (2001) Stimulation of leukotriene synthesis in intact polymorphonuclear cells by the 5-lipoxygenase inhibitor 3-oxo-tirucallic acid. Mol Pharmacol 60(2):267–273 38. Fowler GJ, Malandkar MA (1921) A Suggested method for the extraction of turpentine, resin and gum from the gum-oleo-resin of Boswellia serrata without the use of solvents. J Indian Inst Sci 4:27–42 39. Malandkar M (1925) II. Chemical constitution of the gum from Boswellia serrata. J Indian Inst Sci 8(Part A):221–244 40. Malandkar M (1925) Chemical constitution of the gum from Boswellla serrata. J Indian Inst Sci 8:240 41. Sen AK Sr, Das AK, Banerji N, Vignon MR (1992) Isolation and structure of a 4-O-methylglucuronoarabino-galactan from Boswellia serrata. Carbohydr Res 223:321–327 42. Greve HL, Kaiser M, Brun R, Schmidt TJ (2017) Terpenoids from the oleo-gum-resin of Boswellia serrata and their antiplasmodial effects in vitro. Planta Med 83(14/15):1214–1226 43. Hairfield E, Hairfield H, McNair H (1989) GC, GC/MS, and TLC of β-Boswellic Acid and O-Acetyl-β-Boswellic Acid from B. serrate, B. carteii, and B. papyrifera. J Chromatogr Sci 27 (3):127–133 44. Krieglstein CF, Anthoni C, Rijcken EJ, Laukötter M, Spiegel H-U, Boden SE, Schweizer S, Safayhi H, Senninger N, Schürmann G (2001) Acetyl-11-keto-β-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin, attenuates experimental ileitis. Int J Colorectal Dis 16(2):88–95 45. Shen T, Lou HX (2008) Bioactive constituents of myrrh and frankincense, two simultaneously prescribed gum resins in Chinese traditional medicine. Chem Biodivers 5(4):540–553 46. Safayhi H, Mack T, Sabieraj J, Anazodo MI, Subramanian LR, Ammon H (1992) Boswellic acids: novel, specific, nonredox inhibitors of 5-lipoxygenase. J Pharmacol Exp Ther 261(3): 1143–1146

552

T. Alam et al.

47. Gayathri B, Manjula N, Vinaykumar K, Lakshmi B, Balakrishnan A (2007) Pure compound from Boswellia serrata extract exhibits anti-inflammatory property in human PBMCs and mouse macrophages through inhibition of TNFα, IL-1β, NO and MAP kinases. Int Immunopharmacol 7(4):473–482 48. Bhushan S, Kumar A, Malik F, Andotra SS, Sethi VK, Kaur IP, Taneja SC, Qazi GN, Singh J (2007) A triterpenediol from Boswellia serrata induces apoptosis through both the intrinsic and extrinsic apoptotic pathways in human leukemia HL-60 cells. Apoptosis 12(10):1911–1926 49. Mathe C, Connan J, Archier P, Mouton M, Vieillescazes C (2007) Analysis of frankincense in archaeological samples by gas chromatography-mass spectrometry. Annali di Chimica: J Anal Environ Cult Herit Chem 97(7):433–445 50. Mathe C, Culioli G, Archier P, Vieillescazes C (2004) Characterization of archaeological frankincense by gas chromatography–mass spectrometry. J Chromatogr A 1023(2):277–285 51. Büchele B, Simmet T (2003) Analysis of 12 different pentacyclic triterpenic acids from frankincense in human plasma by high-performance liquid chromatography and photodiode array detection. J Chromatogr B 795(2):355–362 52. Büchele B, Zugmaier W, Estrada A, Genze F, Syrovets T, Paetz C, Schneider B, Simmet T (2006) Characterization of 3α-acetyl-11-keto-α-boswellic acid, a pentacyclic triterpenoid inducing apoptosis in vitro and in vivo. Planta Med 72(14):1285–1289 53. Singh T, Bhakuni R (2006) A new euphane triterpene and a lipid diester from oleo-gum resin of Boswellia serrata. Indian J Chem B 45B(4):976–979 54. Baeten J, Deforce K, Challe S, De Vos D, Degryse P (2014) Holy smoke in medieval funerary rites: chemical fingerprints of frankincense in southern Belgian incense burners. PloS One 9 (11):e113142 55. Tucker AO (1986) Frankincense and myrrh. Econ Bot 40(4):425–433 56. Yates RL, Wenninger JA (1970) Constituents of olibanum oil: Sesquiterpene hydrocarbons. JAOAC 53(5):941–948 57. Kumar A, Saxena V (1979) TLC and GLC studies of the essential oil from Boswellia serrata leaves. Indian Drugs 16:80–83 58. Simonsen J, Ross W (1957) The Terpenes, vol 5. Cambridge University Press, New York 59. Singh B, Kumar R, Bhandari S, Pathania S, Lal B (2007) Volatile constituents of natural Boswellia serrata oleo-gum-resin and commercial samples. Flavour Fragr J 22(2):145–147 60. Verghese J (1988) Olibanum in focus. Perfum flavor 13(1):1–12 61. Camarda L, Dayton T, Di Stefano V, Pitonzo R, Schillaci D (2007) Chemical composition and antimicrobial activity of some oleogum resin essential oils from Boswellia spp.(Burseraceae). Annali di Chimica: J Anal, Environ Cult Herit Chem 97(9):837–844 62. Hamm S, Bleton J, Connan J, Tchapla A (2005) A chemical investigation by headspace SPME and GC–MS of volatile and semi-volatile terpenes in various olibanum samples. Phytochemistry 66(12):1499–1514 63. Hayashi S, Amemori H, Kameoka H, Hanafusa M, Furukawa K (1998) Comparison of volatile compounds from olibanum from various countries. J Essent Oil Res 10(1):25–30 64. Verghese J, Joy M, Retamar J, Malinskas GG, Catalan C, Gros E (1987) A fresh look at the constituents of Indian olibanum oil. Flavour Fragr J 2(3):99–102 65. Ahmed HH, Abd-Rabou AA, Hassan AZ, Kotob SE (2015) Phytochemical analysis and anticancer investigation of Boswellia serrata bioactive constituents in vitro. Asian Pac J Cancer Prev 16(16):7179–7188 66. Gupta M, Rout P, Misra L, Gupta P, Singh N, Darokar M, Saikia D, Singh S, Bhakuni R (2017) Chemical composition and bioactivity of Boswellia serrata Roxb. essential oil in relation to geographical variation. Plant Biosyst 151(4):623–629 67. Sharma A, Bhatia S, Kharya M, Gajbhiye V, Ganesh N, Namdeo A, Mahadik K (2010) Antiinflammatory and analgesic activity of different fractions of Boswellia serrata. Int J Phytomedicine 2(1):94–96 68. Menon M, Kar A (1971) Analgesic and psychopharmacological effects of the gum resin of Boswellia serrata. Planta Med 19(02):333–341

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

553

69. Bishnoi M, Patil C, Kumar A, Kulkarni S (2005) Analgesic activity of acetyl-11-keto-betaboswellic acid, a 5-lipoxygenase-enzyme inhibitor. Indian J Pharmacol 37(4):255 70. Kora AJ, Sashidhar R, Arunachalam J (2012) Aqueous extract of gum olibanum (Boswellia serrata): a reductant and stabilizer for the biosynthesis of antibacterial silver nanoparticles. Process Biochem 47(10):1516–1520 71. Ismail SM, Aluru S, Sambasivarao K, Matcha B (2014) Antimicrobial activity of frankincense of Boswellia serrata. Int J Curr Microbiol App Sci 3(10):1095–1101 72. De Rapper S, Van Vuuren S, Kamatou G, Viljoen A, Dagne E (2012) The additive and synergistic antimicrobial effects of select frankincense and myrrh oils–a combination from the pharaonic pharmacopoeia. Lett Appl Microbiol 54(4):352–358 73. Vahabi S, Hakemi-Vala M, Gholami S (2019) In vitro antibacterial effect of hydroalcoholic extract of Lawsonia inermis, Malva sylvestris, and Boswellia serrata on aggregatibacter actinomycetemcomitans. Adv Biomed Res 8:22 74. Patel NB, Patel KC (2014) Antibacterial Activity of Boswellia serrata Roxb. ex Colebr. Ethnomedicinal Plant against Gram Positive UTI Pathogens. Life Sci Leaflets 53:79–88 75. Baratta MT, Dorman HD, Deans SG, Figueiredo AC, Barroso JG, Ruberto G (1998) Antimicrobial and antioxidant properties of some commercial essential oils. Flavour Fragr J 13(4): 235–244 76. Raja AF, Ali F, Khan IA, Shawl AS, Arora DS, Shah BA, Taneja SC (2011) Antistaphylococcal and biofilm inhibitory activities of acetyl-11-keto-β-boswellic acid from Boswellia serrata. BMC Microbiol 11(1):1–9 77. Raja AF, Ali F, Khan IA, Shawl AS, Arora DS (2011) Acetyl-11-keto-β-boswellic acid (AKBA); targeting oral cavity pathogens. BMC Res Notes 4(1):1–8 78. Chaurasia A, Gharia A (2017) Antifungal activity of medicinal plant Boswellia Serrata. JUC 13(4):88–90 79. Ray AB, Sarma BK, Singh UP (2004) Medicinal properties of plants: Antifungal, antibacterial and antiviral activities. International Book Distributing Co, Lucknow 80. Arora K, Tomar PC, Kumari P, Kumari A (2020) Medicinal alternative for chikungunya cure: a herbal approach. J Microbiol Biotech Food Sci 9(5):970–978 81. Zutshi U, Rao P, Kaur S, Singh G, Surjeet S, Atal C (1986) Mechanism of cholesterol lowering effect of Salai guggal ex. Boswellia serrata roxb. Indian J Pharmacol 18(3):182–183 82. Lang G, Michal G (1974) Methods of enzymatic analysis, vol III, 2nd English Edition, ed. by HU Bergmeyer. Academic Press Inc, New York/London, p 1238 83. Zutshi U, Siddiqui M, Singh GB, Atal CK (1980) Mechanism of action of Salai guggul as antilipidmic, agent Souvenier, 13th Indian Pharmacological Society, Conference, India 84. Azadmehr A, Ziaee A, Ghanei L, Huseini HF, Hajiaghaee R, Tavakoli-Far B, Kordafshari G (2014) A randomized clinical trial study: anti-oxidant, anti-hyperglycemic and antihyperlipidemic effects of olibanum gum in type 2 diabetic patients. Iran J Pharm Res 13(3): 1003 85. Shehata AM, Quintanilla-Fend L, Bettio S, Singh C, Ammon H (2011) Prevention of multiple low-dose streptozotocin (MLD-STZ) diabetes in mice by an extract from gum resin of Boswellia serrata (BE). Phytomedicine 18(12):1037–1044 86. Shehata A, Quintanilla-Fend L, Bettio S, Jauch J, Scior T, Scherbaum W, Ammon H (2015) 11-Keto-β-boswellic acids prevent development of autoimmune reactions, insulitis and reduce hyperglycemia during induction of multiple low-dose streptozotocin (MLD-STZ) diabetes in mice. Horm Metab Res 47(06):463–469 87. Liu J-J, Toy WC, Liu S, Cheng A, Lim BK, Subramaniam T, Sum CF, Lim SC (2013) Acetylketo-β-boswellic acid induces lipolysis in mature adipocytes. Biochem Biophys Res Commun 431(2):192–196 88. Cuaz-Pérolin C, Billiet L, Baugé E, Copin C, Scott-Algara D, Genze F, Büchele B, Syrovets T, Simmet T, Rouis M (2008) Antiinflammatory and antiatherogenic effects of the NF-κB inhibitor acetyl-11-keto-β-boswellic acid in LPS-challenged ApoE/ mice. Arterioscler Thromb Vasc Biol 28(2):272–277 I

554

T. Alam et al.

89. Al-Awadi F, Fatania H, Shamte U (1991) The effect of a plants mixture extract on liver gluconeogenesis in streptozotocin induced diabetic rats. Diabetes Res (Edinburgh, Scotland) 18(4):163–168 90. Ahangarpour A, Heidari H, Fatemeh RAA, Pakmehr M, Shahbazian H, Ahmadi I, Mombeini Z, Mehrangiz BH (2014) Effect of Boswellia serrata supplementation on blood lipid, hepatic enzymes and fructosamine levels in type2 diabetic patients. J Diabetes Metab Disord 13(1):1–5 91. Ahangarpour A, Ramezani AAF, Heidari H, Pakmehr M, Shahbazian H, Ahmadi I, Mombeini Z, Babadi HM (2012) The effect of Boswellia serrata on blood glucose, insulin level and insulin resistance in type 2 diabetic patients. Daneshvar Med 103:1–10 92. Azemi ME, Namjoyan F, Khodayar MJ, Ahmadpour F, Padok AD, Panahi M (2012) The antioxidant capacity and anti-diabetic effect of Boswellia serrata triana and planch aqueous extract in fertile female diabetic rats and the possible effects on reproduction and histological changes in the liver and kidneys. Jundishapur J Nat Pharm Prod 7(4):168 93. Namjou A, Rouhi-Broujeni H (2020) Antihyperglycemic, antihyperlipidemic and wound healing of Boswellia serrata on experimentally induced diabetic rats. Abanico Vet 10:1–17 94. Beghelli D, Isani G, Roncada P, Andreani G, Bistoni O, Bertocchi M, Lupidi G, Alunno A (2017) Antioxidant and ex vivo immune system regulatory properties of Boswellia serrata extracts. Oxid Med Cell Longev 2017:7468064 95. Ayub MA, Hanif MA, Sarfraz RA, Shahid M (2018) Biological activity of Boswellia serrata Roxb. oleo gum resin essential oil: effects of extraction by supercritical carbon dioxide and traditional methods. Int J Food Prop 21(1):808–820 96. Gupta I, Gupta V, Parihar A, Gupta S, Lüdtke R, Safayhi H, Ammon H (1998) Effects of Boswellia serrata gum resin in patients with bronchial asthma: results of a double-blind, placebo-controlled, 6-week clinical study. Eur J Med Res 3(11):511–514 97. Miller A (2001) Effects of Boswellia serrata on asthma. Altern Med Rev 6(1):20–47 98. Liu Z, Liu X, Sang L, Liu H, Xu Q, Liu Z (2015) Boswellic acid attenuates asthma phenotypes by downregulation of GATA3 via pSTAT6 inhibition in a murine model of asthma. Int J Clin Exp Patho 8(1):236 99. Ali EN, Mansour SZ (2011) Boswellic acids extract attenuates pulmonary fibrosis induced by bleomycin and oxidative stress from gamma irradiation in rats. Chin Med 6(1):1–14 100. Borrelli F, Capasso F, Capasso R, Ascione V, Aviello G, Longo R, Izzo AA (2006) Effect of Boswellia serrata on intestinal motility in rodents: inhibition of diarrhoea without constipation. Br J Pharmacol 148(4):553–560 101. Estrada AC, Syrovets T, Pitterle K, Lunov O, Büchele B, Schimana-Pfeifer J, Schmidt T, Morad SA, Simmet T (2010) Tirucallic acids are novel pleckstrin homology domaindependent Akt inhibitors inducing apoptosis in prostate cancer cells. Mol Pharmacol 77(3): 378–387 102. Takahashi M, Sung B, Shen Y, Hur K, Link A, Boland CR, Aggarwal BB, Goel A (2012) Boswellic acid exerts antitumor effects in colorectal cancer cells by modulating expression of the let-7 and miR-200 microRNA family. Carcinogenesis 33(12):2441–2449 103. Schmiech M, Lang SJ, Ulrich J, Werner K, Rashan LJ, Syrovets T, Simmet T (2019) Comparative investigation of frankincense nutraceuticals: Correlation of boswellic and lupeolic acid contents with cytokine release inhibition and toxicity against triple-negative breast cancer cells. Nutrients 11(10):2341 104. Khan MA, Ali R, Parveen R, Najmi AK, Ahmad S (2016) Pharmacological evidences for cytotoxic and antitumor properties of Boswellic acids from Boswellia serrata. J Ethnopharmacol 191:315–323 105. Csuk R, Niesen-Barthel A, Barthel A, Kluge R, Ströhl D (2010) Synthesis of an antitumor active endoperoxide from 11-keto-β-boswellic acid. Eur J Med Chem 45(9):3840–3843 106. Yadav VR, Prasad S, Sung B, Gelovani JG, Guha S, Krishnan S, Aggarwal BB (2012) Boswellic acid inhibits growth and metastasis of human colorectal cancer in orthotopic mouse model by downregulating inflammatory, proliferative, invasive and angiogenic biomarkers. Int J Cancer 130(9):2176–2184

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

555

107. Pang X, Yi Z, Zhang X, Sung B, Qu W, Lian X, Aggarwal BB, Liu M (2009) Acetyl-11keto-β-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2–mediated angiogenesis. Cancer Res 69(14):5893–5900 108. Liu JJ, Huang B, Hooi SC (2006) Acetyl-keto-β-boswellic acid inhibits cellular proliferation through a p21-dependent pathway in colon cancer cells. Br J Pharmacol 148(8):1099–1107 109. Lu M, Xia L, Hua H, Jing Y (2008) Acetyl-keto-β-Boswellic acid induces apoptosis through a death receptor 5–mediated pathway in prostate cancer cells. Cancer Res 68(4):1180–1186 110. Sinha V, Singh A, Singh S, Bhinge J (2007) Compression coated systems for colonic delivery of 5-fluorouracil. J Pharm Pharmacol 59(3):359–365 111. Ahmed HH, Abdel-Rahman M, Salem F, Shalby AB, Lokman MS (2013) Antitumor efficacy of Boswellia serrata extract in management of colon cancer induced in experimental animal. Int J Pharm Pharm Sci 5:379–389 112. McCarty MF (2004) Targeting multiple signaling pathways as a strategy for managing prostate cancer: multifocal signal modulation therapy. Integr Cancer Ther 3(4):349–380 113. Huang MT, Badmaev V, Ding Y, Liu Y, Xie JG, Ho CT (2000) Anti-tumor and anticarcinogenic activities of triterpenoid, β-boswellic acid. Biofactors 13(1-4):225–230 114. Kirste S, Treier M, Wehrle SJ, Becker G, Abdel-Tawab M, Gerbeth K, Hug MJ, Lubrich B, Grosu AL, Momm F (2011) Boswellia serrata acts on cerebral edema in patients irradiated for brain tumors: A prospective, randomized, placebo-controlled, double-blind pilot trial. Cancer 117(16):3788–3795 115. Kapil A, Moza N (1992) Anticomplementary activity of boswellic acids—an inhibitor of C3-convertase of the classical complement pathway. Int J Immunopharmacol 14(7):1139– 1143 116. Knaus U, Wagner H (1996) Effects of boswellic acid of Boswellia serrata and other triterpenic acids on the complement system. Phytomedicine 3(1):77–80 117. Sharma M, Khajuria A, Kaul A, Singh S, Singh G, Atal C (1988) Effect of salai guggal ex-Boswellia serrata on cellular and humoral immune responses and leucocyte migration. Agents Act 24(1):161–164 118. Hosseini M, Hadjzadeh MA-R, Derakhshan M, Havakhah S, Rassouli FB, Rakhshandeh H, Saffarzadeh F (2010) The beneficial effects of olibanum on memory deficit induced by hypothyroidism in adult rats tested in Morris water maze. Arch Pharm Res 33(3):463–468 119. Mahboubi M, Taghizadeh M, Talaei SA, Firozeh SMT, Rashidi AA, Tamtaji OR (2016) Combined administration of Melissa officinalis and Boswellia serrata extracts in an animal model of memory. Iranian J Psychiatry Behav Sci 10(3):e681 120. Prabhakar A, Chandrashekar R, Rao S (2013) Evaluation of antidepressant activity of Boswellia serrata in Swiss albino mice by forced swim test. Int J Univ Pharm Bio Sci 2:417–424 121. Zaker SR, Beheshti S, Aghaie R, Noorbakhshnia M (2015) Effect of olibanum on a rat model of Alzheimer’s disease induced by intracerebroventricular injection of streptozotocin. Physiol Pharmacol 18(4):477–489 122. Beheshti S, Aghaie R (2016) Therapeutic effect of frankincense in a rat model of Alzheimer’s disease. Avicenna J Phytomed 6(4):468 123. Ding Y, Chen M, Wang M, Li Y, Wen A (2015) Posttreatment with 11-keto-β-boswellic acid ameliorates cerebral ischemia–reperfusion injury: Nrf2/HO-1 pathway as a potential mechanism. Mol Neurobiol 52(3):1430–1439 124. Sayed AS, El Sayed NSED (2016) Co-administration of 3-acetyl-11-keto-beta-boswellic acid potentiates the protective effect of celecoxib in lipopolysaccharide-induced cognitive impairment in mice: possible implication of anti-inflammatory and antiglutamatergic pathways. J Mol Neurosci 59(1):58–67 125. Haghaei H, Soltani S, Arefhosseini S, Rashidi M-R, Karima S (2021) Boswellic acids as promising leads in drug development against Alzheimer’s disease. Pharm Sci 27(1):14–31 126. Yassin N, El-Shenawy S, Mahdy KA, Gouda N, Marrie A, Farrag A, Ibrahim B (2013) Effect of Boswellia serrata on Alzheimer’s disease induced in rats. J Arab Soc Med Res 8:1–11 127. Ibrahim BMM (2012) Experimental study of the effects of Boswellia serrata and ginger (Zingiber officinale) on Alzheimer’s disease induced in rats. CU Theses, Calcutta

556

T. Alam et al.

128. Singh G, Atal C (1984) Pharmacology of an extract of salai guggul ex-Boswellia serrata. Indian J Pharmacol 16:51 129. Italiano G, Raimondo M, Giannetti G, Gargiulo A (2020) Benefits of a food supplement containing Boswellia serrata and bromelain for improving the quality of life in patients with osteoarthritis: A pilot study. J Altern Complement Med 26(2):123–129 130. Asante-Kwatia E, Yeboah Mensah A, Frimpong Baidoo M (2020) Analgesic and antiinflammatory effect of Ghanaian medicinal plants. Med Plants Use Prev Treat Dis. Intechopen. https://doi.org/10.5772/intechopen.90154 131. Su S, Hua Y, Wang Y, Gu W, Zhou W, J-a D, Jiang H, Chen T, Tang Y (2012) Evaluation of the anti-inflammatory and analgesic properties of individual and combined extracts from Commiphora myrrha, and Boswellia carteri. J Ethnopharmacol 139(2):649–656 132. Agrawal P, Baajpayee M, Singh SP (2013) Formulation and evaluation of herbal gel containing Boswellia serrata, curcuma longa extract and oil of wintergreen for rheumatoid arthritis. Int Bull Drug Res (IBDR) 2(3):31–40 133. Andor BC, Cerbu S, Barattini DF, Dogaru DE, Dulgheru O, Guadagna S, Rosu S (2013) Pilot, open and non-controlled trial to assess the objective parameters which correlate knee mobility with pain reduction in patients affected by knee osteoarthritis and treated with oral hyaluronic acid. Rev Chim 70:3364–3371 134. Catanzaro D, Rancan S, Orso G, Dall’Acqua S, Brun P, Giron MC, Carrara M, Castagliuolo I, Ragazzi E, Caparrotta L (2015) Boswellia serrata preserves intestinal epithelial barrier from oxidative and inflammatory damage. PloS One 10 (5):e0125375 135. Sara BB, Sailaja AK (2019) A review on polyherbal formulations used in the treatment of autoimmune disease like rheumatoid arthritis. Res Rev 8:11–16 136. Ammon H, Mack T, Singh G, Safayhi H (1991) Inhibition of leukotriene B4 formation in rat peritoneal neutrophils by an ethanolic extract of the gum resin exudate of Boswellia serrata. Planta Med 57(03):203–207 137. Tripathi YB, Reddy MM, Pandey R, Subhashini J, Tiwari O, Singh B, Reddanna P (2004) Anti-inflammatory properties of BHUx, a polyherbal formulation to prevent atherosclerosis. Inflammopharmacol 12(2):131–152 138. Vishal AA, Mishra A, Raychaudhuri SP (2011) A double blind, randomized, placebo controlled clinical study evaluates the early efficacy of Aflapin ® in subjects with osteoarthritis of knee. Int J Med Sci 8(7):615–622 139. Umar S, Umar K, Sarwar AHMG, Khan A, Ahmad N, Ahmad S, Katiyar CK, Husain SA, Khan HA (2014) Boswellia serrata extract attenuates inflammatory mediators and oxidative stress in collagen induced arthritis. Phytomedicine 21 (6):847–856 140. Siddiqui M (2011) Boswellia serrata, a potential antiinflammatory agent: an overview. Indian J Pharm Sci 73 (3):255–261 141. Poeckel D, Werz O (2006) Boswellic acids: biological actions and molecular targets. Curr Med Chem 13(28):3359–3369 142. Chopra A, Lavin P, Patwardhan B, Chitre D (2000) Randomized double blind trial of an ayurvedic plant derived formulation for treatment of rheumatoid arthritis. J Rheumatol 27(6): 1365–1372 143. Kulkarni R, Patki P, Jog V, Gandage S, Patwardhan B (1991) Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 33(1–2):91–95 144. Khosravi SM, Mahmoodian H, Moghadamnia A, Poorsattar BMA, Chitsazan M (2011) The effect of Frankincense in the treatment of moderate plaque-induced gingivitis: a double blinded randomized clinical trial. Daru 19(4):288–294 145. Bertocchi M, Isani G, Medici F, Andreani G, Tubon Usca I, Roncada P, Forni M, Bernardini C (2018) Anti-inflammatory activity of Boswellia serrata extracts: an in vitro study on porcine aortic endothelial cells. Oxid Med Cell Longev. 2018:2504305 146. Alluri VK, Kundimi S, Sengupta K, Golakoti T, Kilari EK (2020) An anti-inflammatory composition of Boswellia serrata resin extracts alleviates pain and protects cartilage in

21

Chemistry, Biological Activities, and Uses of Resin of Boswellia. . .

557

monoiodoacetate-induced osteoarthritis in rats. Evid Based Complement Alternat Med 2020: 7381625 147. Suva MA, Kheni DB, Sureja VP (2018) Aflapin ®: A novel and selective 5-lipoxygenase inhibitor for arthritis management. Indian J Pain 32(1):16–23 148. Zaitone SA, Barakat BM, Bilasy SE, Fawzy MS, Abdelaziz EZ, Farag NE (2015) Protective effect of boswellic acids versus pioglitazone in a rat model of diet-induced non-alcoholic fatty liver disease: influence on insulin resistance and energy expenditure. Naunyn Schmiedebergs Arch Pharmacol 388(6):587–600 149. Sferra R, Vetuschi A, Catitti V, Ammanniti S, Pompili S, Melideo D, Frieri G, Gaudio E, Latella G (2012) Boswellia serrata and Salvia miltiorrhiza extracts reduce DMN-induced hepatic fibrosis in mice by TGF-beta1 downregulation. Eur Rev Med Pharmacol Sci 16 (11): 1484–1498 150. Khan MA, Singh M, Khan MS, Najmi AK, Ahmad S (2014) Caspase mediated synergistic effect of Boswellia serrata extract in combination with doxorubicin against human hepatocellular carcinoma. Biomed Res Int 2014:294143 151. Gupta A, Khajuria A, Singh J, Singh S, Suri K, Qazi G (2011) Immunological adjuvant effect of Boswellia serrata (BOS 2000) on specific antibody and cellular response to ovalbumin in mice. Int Immunopharmacol 11(8):968–975 152. Syrovets T, Büchele B, Gedig E, Slupsky JR, Simmet T (2000) Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and IIα. Mol Pharmacol 58(1):71–81 153. Pungle P, Banavalikar M, Suthar A, Biyani M, Mengi S (2003) Immunomodulatory activity of boswellic acids of Boswellia serrata Roxb. Indian J Exp Biol 41(12):1460–1462 154. Henkel A, Tausch L, Pillong M, Jauch J, Karas M, Schneider G, Werz O (2015) Boswellic acids target the human immune system-modulating antimicrobial peptide LL-37. Pharmacol Res 102:53–60 155. Ammon H (2010) Modulation of the immune system by Boswellia serrata extracts and boswellic acids. Phytomedicine 17(11):862–867 156. Qurishi Y, Hamid A, Zargar M, Singh SK, Saxena AK (2010) Potential role of natural molecules in health and disease: Importance of boswellic acid. J Med Plants Res 4(25): 2778–2786 157. Togni S, Maramaldi G, Di Pierro F, Biondi M (2014) A cosmeceutical formulation based on boswellic acids for the treatment of erythematous eczema and psoriasis. Clin Cosmet Investig Dermatol 7:321–327 158. Wang H, Ren T, Li J, Zhao L, Wang X, Fang L (2012) Transdermal patch containing natural medicine for treating psoriasis. CN102670565 159. Kim C (2014) Composition comprising α-boswellic acid and/or β-boswellic acid, having melanin synthesis inhibitory activity and collagenase inhibitory activity, useful for skin whitening or reducing wrinkle. KR2014029654 160. Somani SJ, Modi KP, Majumdar AS, Sadarani BN (2015) Phytochemicals and their potential usefulness in inflammatory bowel disease. Phytother Research 29(3):339–350 161. Latella G, Sferra R, Vetuschi A, Zanninelli G, D’angelo A, Catitti V, Caprilli R, Gaudio E (2008) Prevention of colonic fibrosis by Boswellia and Scutellaria extracts in rats with colitis induced by 2, 4, 5-trinitrobenzene sulphonic acid. Eur J Clin Invest 38(6):410–420 162. Hartmann RM, Fillmann HS, Morgan Martins MI, Meurer L, Marroni NP (2014) Boswellia serrata has beneficial anti-inflammatory and antioxidant properties in a model of experimental colitis. Phytother Res 28 (9):1392–1398 163. Gupta I, Parihar A, Malhotra P, Singh G, Lüdtke R, Safayhi H, Ammon H (1997) Effects of Boswellia serrata gum resin in patients with ulcerative colitis. Eur J Med Res 2(1):37–43 164. Gupta I, Parihar A, Malhotra P, Gupta S, Lüdtke R, Safayhi H, Ammon HP (2001) Effects of gum resin of Boswellia serrata in patients with chronic colitis. Planta Med 67(05):391–395 165. Kiela PR, Midura AJ, Kuscuoglu N, Jolad SD, Sólyom AM, Besselsen DG, Timmermann BN, Ghishan FK (2005) Effects of Boswellia serrata in mouse models of chemically induced colitis. Am J Physiol Gastrointest Liver Physiol 288(4):G798–G808

558

T. Alam et al.

166. Asif M, Jabeen Q, Abdul-Majid A, Atif M (2014) Diuretic activity of Boswellia serrata Roxb. oleo gum extract in albino rats. Pak J Pharm Sci 27(6):1811–1817 167. Rashan L, Hakkim FL, Idrees M, Essa MM, Velusamy T, Al-Baloshi M, Al-Balushi BS, Al Jabri A, Al-Rizeiqi MH, Guillemin GJ (2019) Boswellia gum resin and essential oils: Potential health benefits an evidence based review. Int J Nutr Pharmacol Neurol Dis (IJNPND) 9 (2): 53–71 168. Rashan L, White A, Haulet M, Favelin N, Das P, Cock IE (2021) Chemical composition, antibacterial activity, and antibiotic potentiation of Boswellia sacra flueck. Oleoresin extracts from the Dhofar region of Oman. Evid Based Complement Alternat Med 2021:9918935 169. Singh G, Atal C (1986) Pharmacology of an extract of salai guggal ex-Boswellia serrata, a new non-steroidal anti-inflammatory agent. Agents Act 18(3):407–412 170. Singh P, Chacko KM, Aggarwal M, Bhat B, Khandal R, Sultana S, Kuruvilla BT (2012) A-90 day gavage safety assessment of Boswellia serrata in rats. Toxicol Int 19(3):273–278 171. Mantle D, Gok MA, Lennard T (2001) Adverse and beneficial effects of plant extracts on skin and skin disorders. Adverse Drug React Toxicol Rev 20(2):89–103 172. Lampl C, Haider B, Schweiger C (2012) Long-term efficacy of Boswellia serrata in four patients with chronic cluster headache. Cephalalgia 32(9):719–722 173. Mehrzadi S, Tavakolifar B, Huseini HF, Mosavat SH, Heydari M (2018) The effects of Boswellia serrata gum resin on the blood glucose and lipid profile of diabetic patients: A double-blind randomized placebo-controlled clinical trial. Evid Based Integr Med 23: 2515690X18772728

Chemistry, Biological Activities, and Uses of Benzoin Resin

22

Mohammad Sohail Akhtar and Tanveer Alam

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.1 Botanical Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.2 Taxonomical Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1.3 Common Vernacular Names . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Phytochemistry of Benzoin Resin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Chemical Constituents of Benzoin Resin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Chemical Constituents of Volatile Oil/Essential Oil . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Biological Activities of Benzoin Resin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Antiasthmatic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Beneficial Action in Skincare . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Gastrointestinal Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Diuretic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5 Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6 Hepatoprotective Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7 Antimicrobial Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8 Memory Enhancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9 Topical Adhesive and Antiseptic Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10 Sedative and Anticonvulsive Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11 Anti-Inflammatory Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.12 Anti-Allergic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Toxicity Profile for Benzoin Resin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Traditional Uses of Benzoin Resin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

560 561 562 562 563 563 563 565 565 566 568 572 573 573 573 573 574 574 574 574 574 574 576 576

M. Sohail Akhtar (*) School of Pharmacy, College of Pharmacy & Nursing, University of Nizwa, Nizwa, Oman e-mail: [email protected] T. Alam Natural & Medical Sciences Research Center, University of Nizwa, Nizwa, Sultanate of Oman e-mail: [email protected] © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_26

559

560

M. Sohail Akhtar and T. Alam

Abstract

Styrax benzoin belonging to the family Styracaceae is an indefinitely long-lasting tree. Benzoin is a natural complex balsamic resin available in the sap of trees. This benzoin resin containing trees are cultivated in many Asian countries such as Laos, Thailand, Vietnam, and Indonesia. In Indonesia, this plant is cultivated especially in the islands of Java, Kalimantan, and Sumatra. Styrax benzoin generally contains cinnamic acid, benzoic acid, benzaldehyde, vanillin, and benzyl benzoate. The chemical constituents of this plant are influenced by the place of its geography, origin, and climatic conditions. Romans and Egyptians are using these plants widely since long ago for the treatment of respiratory infections. Nowadays, the use of benzoin resin has not only been used as incense and fragrances because of its fixative effects but also used as flavor enhancers in the food industry and an antioxidant in the cosmetics industry. The phytotherapeutic effects of benzoin resins are also used in the pharmaceutical industry. In reality, benzoin resin in the Asian region has been used in erythema, wound healing, and cough. This chapter highlights the traditional uses, phytochemistry, and pharmacology of benzoin resin. Keywords

Benzaldehyde · Phytochemistry · Styrax benzoin · Styrax tonkinensis · Traditional uses

1

Introduction

Benzoin is a natural complex balsamic resin available in the sap of trees. This benzoin resin containing trees are cultivated in many Asian countries such as Thailand, Laos, Indonesia, and Vietnam. Approximately 150 species of Styrax are available and aromatic resins are produced from them. Styrax is divided into two types, Sumatran Benzoin and Siam Benzoin [1–3]. Presently, both types of benzoin are available in the market, and although both are extracted in the same way while they have different chemical properties [4]. Under normal conditions, the plant will not produce the resin. Resins are produced and come out due to pathological incisions made on the stems of the plant [5]. Styrax benzoin has several names all around the world. The vernacular names of the Styrax benzoin are Sumatra benzoin, benzoin trees, and benzoin resins. Styrax is known as benzoin in Sweden. In Germany, it is known as benzoebaum. In Spain, it is called as bálsamo de Benjuí and in France as arbre à benjoin. In China, it is called xi Xiang. The Styrax species is divided into two groups “Siam Benzoin” and “Sumatra Benzoin.” Styrax tonkinensis is called “Benzoin Siam,” and Styrax parallelonerus and Styrax benzoin are known as “Benzoin Sumatra” [2]. Siam benzoin is collected from the species Styrax tonkinensis. Sumatra benzoin is obtained from two species: Styrax parallelonerus Perkins and Styrax benzoin

22

Chemistry, Biological Activities, and Uses of Benzoin Resin

561

Dryand. Nowadays, the use of benzoin resin has not only been used as incense and fragrances because of its fixative effects but also used as flavor enhancers in the food industry and as an antioxidant in the cosmetics industry [6]. Because of its phytotherapeutic effects, benzoin resins are used in the pharmaceutical industry. Mostly, benzoin resin in the Asian region has been used in erythema, cough, and wound healing [5]. The name of this plant is divided into two parts, Styrax, which is derived from the Greek language, and the word benzoin is an Arabic word meaning dry incense. This plant began to be used 2000 years ago for many purposes, and this plant is spread a lot in Indonesia, especially on the island of Sumatra, so this plant is called by the name Sumatran Benzoin [7]. Romans and Egyptians are using these plants widely since long ago for the treatment of respiratory infections [8]. This plant is also widely used as a disinfectant [9]. In Asian countries, the smoke produced from burning benzoin resin is used to cure negative effects of evil spirits and diseases, and also it is used in various religious ritual ceremonies [10]. Styrax is cross- or self-pollinated and changeability is available in blossoms, organic products shape and colors and stem wood, or synthetic organization of pitches because of cross-fertilization [11]. Styrax benzoin is bitter, stunningly sweet-smelling, and has a solid vanilla-like smell. It has been used in incense and pharmaceutical formulations for thousands of years in various parts of the world [12].

1.1

Botanical Description

Benzoin is a shrubby, aromatic, deciduous tree growing from 8 to 34 m tall with a slightly buttressed bole that can be from 10 to 100 cm in diameter. The tree has a shallow root system, and Styrax benzoin also has tap roots that vanish laterally. The benzoin plant has simple leaves, gray bark, and short racemes of fragrant, small, bellshaped white flowers. Benzoin tree produces balsamic resin of yellowish color called gum benzoin or gum benjamin (Fig. 1) [13]. Bark The tree has grey, wine-reddish brown bark. Leaves Leaves are ovate and are arranged alternately as a crown around the stem with smooth upper surface having 3–5 cm wide and length in the range of 6–10 cm with hairy underside. Flowers Flowers are white in color, bisexual, bell-shaped at the time of bloom in spring, and have five petals that are arranged in the form of a cluster along the branches.

562

M. Sohail Akhtar and T. Alam

Fig. 1 (a) Benzoin tree (b) Leaves (c) Flowers (d) Resin

Fruits Fruits are depressed 2
2.5 cm. and blue in colors that are eaten by birds and thus distributed by them. The blue color of the fruit is caused not by a pigment but by the structure of the cuticle which reflects blue light. Seeds Edge of the hilum is smooth, subglobose, ca. 15
19 mm hilum 3–6 mm.

1.2

Taxonomical Classification [14] (Table 1)

1.3

Common Vernacular Names [15]

Common name Hindi Kannada Telugu Urdu

Loban Kundar, Makund Lobana, Chilakadupa Kunduruvu Kundur, Loban (continued)

22

Chemistry, Biological Activities, and Uses of Benzoin Resin

Common name Bengali Tamil Table 1 Taxonomical classification

563

Loban Dhuna Sambrani

Taxonomic hierarchy Rank Kingdom Subkingdom Infrakingdom Superdivision Division Subdivision Class Subclass Superorder Order Family Genus Species

Scientific name and common name Plantae Viridiplantae Streptophyta Embryophyta Tracheophyta Spermatophytina Magnoliopsida Dilleniidae Asteranae Ericales Styracaceae Styrax benzoin

Binomial name: Styrax tonkinensis Pierre (Benzoin Siam) and Styrax benzoin Dryand (Benzoin Sumatra)

2

Phytochemistry of Benzoin Resin

2.1

Chemical Constituents of Benzoin Resin

Styrax benzoin is aromatic, acrid, and has a strong vanilla-like smell. The main active constituents of Styrax benzoin are cinnamic acid, benzoic acid, benzaldehyde, benzyl benzoate, and vanillin. Different chemical compounds were isolated from Styrax plants like saponins, aryl propanoids, lignans, and triterpenoids [16–23]. The isolated compounds from the benzoin resin are summarized in Table 2 and the structures of the main components are presented in Fig. 2.

2.2

Chemical Constituents of Volatile Oil/Essential Oil

Volatile compounds of oils from benzoin isolated by using solid-phase microextraction (SPME). The volatile oil composition of two different benzoin gum resins, Sumatra and Siam, were analyzed by GC–MS. Twenty-nine components representing more than 97.4% of the oil from Sumatra and 20 components representing more than 99.1% of the oil from Siam benzoin were analyzed [1, 2].

564

M. Sohail Akhtar and T. Alam

Table 2 Chemical constituents of the Benzoin resin S. No. 1.

Plant part Resin

2.

Resin

3. 4.

Resin Resin

5. 6.

Resin Resin

7.

Resin

8.

Resin

9.

Resin

10.

Resin

11.

Resin

12.

Resin

Name of compounds Benzaldehyde, benzyl benzoate, benzoic acid, vanillin, cinnamic acid cinnamyl cinnamate, methyl cinnamate, benzyl cinnamate, and phenyl propylic alcohol Cinnamic acid and cinnamic acid esters (cinnamyl cinnamate, coniferyl cinnamate) and pinoresinol Vanillin Benzaldehyde, styrene, cinnamic acid, and cinnamic acid derivatives Egonol, oleanolic acid Benzoic acid, coniferyl benzoate, benzyl benzoate, vanillin, 1-(4-hydroxy-3-methoxyphenyl)-2-propanone, and 2-hydroxy-1- phenylethanone Benzyl, coniferyl, and p-coumaryl benzoates, benzoic acid, cinnamyl cinnamate (styracin), coniferyl alcohol (lubanol), siaresinolic (3β,19α-dihydroxyolean12-en-28-oic) acid, and vanillin 3-epi-oleanolic (3α-hydroxyolean-12-en-28-oic) acid and free or esterified oleanolic (3β-hydroxyolean-12-en-28-oic) acid Vanillin, lubanol, cinnamic acid, benzoic acid, p-coumaryl cinnamate, ethyl cinnamate, benzyl benzoate, coniferyl benzoate, benzyl cinnamate Styrene, TMS vanillin, TMS benzoic acid, TMS isovanillin, TMS cinnamic acid, Ethyl cinnamate, benzyl benzoate, TMS lubanol, TMS p-coumaryl benzoate, TMS coniferyl benzoate, TMS lupeol, TMS p-coumaryl cinnamate, TMS oleanolic acid, TMS oleanonic acid, unidentified triterpene Pinoresinol, sumaresinolic acid, siaresinolic acid, benzoic acid, vanillin, p-hydroxy benzaldehyde, vanillic acid, cinnamic acid, p-coumaryl alcohol, cinnamyl benzoate, pcoumaryl benzoate, coniferyl benzoate, benzyl cinnamate, cinnamyl cinnamate, p-coumaryl cinnamate, and coniferyl cinnamate Benzyl benzoate, 3-(4-hydroxy-3-methoxyphenyl)-2oxopropyl benzoate 6β-hydroxy-3-oxo-11α,12α-epoxyolean-28,13β-olide, 3β-hydroxy-12-oxo-13Hα-olean-28,19β-olide, 3β,6β-dihydroxy-11α,12α-epoxyolean-28,13β-olide, 3β,6β-dihydroxy-11-oxo-olean-12-en-28-oic acid, 6β-hydroxy-3-oxo-olean-12-en-28-oic acid, 19α-hydroxy-3oxo-olean-12-en-28-oic acid, oleanolic acid, sumaresinolic acid, siaresinolic acid 4-(E)-3-ethoxyprop-1-enyl)-2-methoxy phenol, Trans(tetrahydro-2-(4-hydroxy-3- methoxyphenyl)-5-oxofuran-3yl) methyl benzoate, 3-(4-hydroxy-3-methoxyphenyl)-2oxopropyl benzoate

References [7]

[24] [25] [26] [27] [28]

[1, 29–34]

[35]

[36]

[29, 30, 32, 37–39]

[22, 23] [22, 23, 29, 30, 38–41]

(continued)

22

Chemistry, Biological Activities, and Uses of Benzoin Resin

565

Table 2 (continued) S. No. 13. 14.

Plant part Resin Gum resin

Name of compounds Benzoic acid-(4-hydroxy-3-methoxy-trans-cinnamyl ester) and the benzoate of trans-p-coumaryl alcohol Triterpenes, epilupeol, dipterocarpol, dammarandiol-II, dammarenolic acid, eichlerianic acid, and asiatic acid

References [42] [43]

Volatile oils were analyzed from Siam benzoin and Sumatra benzoin. Around 58 compounds were identified by GC-RI and GC-MS: 40 of them were characterized in Sumatra and 42 of them were in Siam benzoin resin [6]. The mixture of resin and bark obtained after size-grading of Siam benzoin resin was evaluated and analyzed its essential oil active constituents using static headspace and SPME led to the identification of 26 and 50 compounds, respectively (Tables 3, 4, and 5; Figure 2) [32].

3

Biological Activities of Benzoin Resin

3.1

Antiasthmatic Activity

Chest infections, influenza, asthma, loud breathing, sleep apnea, and pneumonia are all common respiratory issues. Congestion, cough, and some other breathing disorders are treated with benzoin essential oils. Benzoin is a powerful disinfectant with antiseptic properties that help to clear mucus and improve breathing. Its sedative effects will help pave the way for a decent night’s sleep along with cleaning up the respiratory system. Benzoin essential oil can help with gastrointestinal problems such as cramping and flatulence. This essential oil has carminative effects and the ability to alleviate gas and abdominal inflammation or discomfort. It relieves gas pressure by calming the abdominal muscles and allowing excess gas to pass naturally. There are a lot of respiratory issues, for example, chest diseases, pneumonia, asthma, uproarious relaxing, obstructive rest apnea, and aspiration. Benzoin essential oil is utilized to treat clog, hacking, and other respiratory issues. Benzoin is an excellent sanitizer and furthermore has expectorant characteristics which help free body fluids and ease relaxing. Its calming action can help make room for a great night’s rest. Styrax benzoin is used in drug formulations for the treatment of bronchitis, laryngitis, and also used as a germicide to forestall the diseases [44]. Coughing, congestion, and other breathing issues are treated with benzoin essential oil. Benzoin is having a powerful disinfectant activity and used as expectorant that helps to clear mucus and improve breathing. Its relaxing effects could help pave the way for decent sleep at night as well as clear the respiratory tract. In the pharmacy industry, Styrax benzoin is used to cure cough laryngitis, bronchitis, and as an antiseptic to avoid infections [45].

566

3.2

M. Sohail Akhtar and T. Alam

Beneficial Action in Skincare

In skincare, benzoin is used to shape the skin and also to harden it. Additionally, benzoin oils benefit the conditioning of the epidermis, resulting in having the epidermis more youthful and radiant. Additionally, it is capable of recuperating

Fig. 2 (continued)

22

Chemistry, Biological Activities, and Uses of Benzoin Resin

567

Fig. 2 (continued)

scars and injuries. While benzoic acid, benzyl benzoate, and benzaldehyde may have restorative characteristics, benzoin oil works by replacing benzyl benzoate in the skin. Benzoin as well as cinnamates are used to harden the skin; however, they are hazardous and causes skin irritation [46].

568

M. Sohail Akhtar and T. Alam

Fig. 2 (continued)

3.3

Gastrointestinal Activity

Benzoin essential oil is helpful in digestive problems such as cramping and flatulence. Carminative characteristics are found in the essential oil of benzoin resin as well as the ability to alleviate gas and gastrointestinal inflammation. It relaxes the

22

Chemistry, Biological Activities, and Uses of Benzoin Resin

Fig. 2 Chemical structures of various phytoconstituents present in Benzoin resin

569

570

M. Sohail Akhtar and T. Alam

Table 3 Chemical composition of the volatile extracts of Siam and Sumatra benzoin gums S. No. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35.

Compounds Styrene Benzaldehyde 6-Methyl-5-hepten-2-one Phenyl acetaldehyde 1,8-Cineole Acetophenone Methyl benzoate Benzoic acid Ethyl benzoate Allyl benzoate (E)-Cinnamaldehyde Propyl benzoate 4-Ethylguaiacol Isobutyl benzoate Eugenol Dihydroeugenol α-Copaene β-Elemene Cinnamic acid Isoamyl benzoate trans-α-Bergamotene 3-Methylbut-3-enyl benzoate β-Caryophyllene Ethyl cinnamate Unknown Valencene Ledene Δ-Guaiene Allyl cinnamate (E)-Nerolidol Isobutyl cinnamate Benzyl benzoate Cinnamyl benzoate Benzyl cinnamate (E)-Cinnamyl cinnamate

RI 876 932 962 1011 1025 1037 1071 1138 1147 1232 1234 1247 1254 1306 1331 1344 1385 1394 1396 1415 1417 1422 1430 1436 1470 1483 1493 1502 1524 1550 1601 1742 2033 2048 2344

Siam benzoin – 0.4 – – 0.1 – 1.5 12.5 1.1 1.5 – 0.2 0.1 tr 1.1 tr tr tr – 0.1 – 0.3 tr – 0.3 tr tr 0.1 – – – 80.1 – – –

Sumatra benzoin 2.3 0.9 tr tr 0.4 1.8 0.5 1.7 0.2 0.9 0.7 0.1 0.6 – 0.8 tr tr – 3.5 – 0.2 – – 0.1 2.2 tr tr tr 0.5 0.4 0.1 76.1 1.4 3.3 0.9

abdominal muscles, allowing excess wind to flow normally and relieving gas pain. Benzoin essential oil also aids in the improvement of appetite and general digestion. This benzoin essential oil can help to prevent stomach acidity, which can lead to a variety of diseases. The region where Styrax benzoin is cultivated, people use it to treat stomachaches [47].

22

Chemistry, Biological Activities, and Uses of Benzoin Resin

571

Table 4 Solid-phase microextraction (SPME) studies of Siam and Sumatra benzoin volatile extracts S. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42

Compounds Ethanol Toluene Styrene Benzaldehyde α-Pinene 6-Methyl-5-hepten-2-one β-Pinene Trimethylbenzene Phenyl acetaldehyde α-Phellandrene Isoterpinolene p-Cymene 1,8-Cineole Benzylformate Acetophenone γ-Terpinene Linalool oxide Methyl benzoate Linalool Benzoic acid Ethyl benzoate Terpinen-4-ol Allyl benzoate (E)-Cinnamaldehyde Propyl benzoate 4-Ethylguaiacol Isobutyl benzoate Eugenol Δ-Elemene α-Ylangene α-Copaene β-Elemene trans-α-Bergamotene β-Caryophyllene Unknown Germacrene D Valencene α-Muurolene Ledene Δ-Guaiene Δ-Cadinene Benzyl benzoate

Siam benzoin Fiber A 4.5 13.5 2.5 13.6 19.1 – 1.4 0.3 – 0.2 – 2.2 15.0 – 0.2 0.1 1.8 16.0 – 1.3 1.4 tr 0.7 – – – – tr 0.9 1.0 1.6 0.7 – 0.6 1.1 – 0.1 tr 0.2 – tr –

Fiber B 4.2 1.2 0.5 28.2 – 0.3 0.4 0.3 – – 0.1 1.0 5.8 0.1 tr 0.2 1.0 33.7 0.3 0.9 5.3 0.1 5.7 – 1.0 0.2 0.1 0.6 0.5 0.1 0.9 0.5 – 0.4 0.7 0.3 tr 0.3 0.3 0.1 0.1 1.6

Sumatra benzoin Fiber A Fiber B 2.7 3.1 tr – 61.3 51.0 13.2 16.5 – – 0.7 0.9 – – – – 0.1 0.3 – – – – 0.2 0.2 6.1 4.3 – – 6.2 11.2 – – 0.1 tr 3.5 3.6 – – 0.2 tr 0.6 0.7 0.1 0.1 0.4 1.1 – 0.3 0.1 0.2 0.1 0.4 – tr tr 0.2 0.3 0.2 tr tr 0.4 0.3 0.2 0.1 0.3 0.3 0.1 0.2 2.5 2.7 – – tr tr – – tr 0.1 – – tr 0.1 – 0.3

572

M. Sohail Akhtar and T. Alam

Table 5 Solid-phase microextraction (SPME) studies of crushed Siam and Sumatra benzoin resins S. No. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35

3.4

Compounds Ethanol Acetic acid 3-Buten-2-ol Propanoic acid Toluene Ethylbenzene Styrene Benzaldehyde α-Pinene Phenol 6-Methyl-5-hepten-2-one Phenyl acetaldehyde Isoterpinolene Benzyl alcohol p-Cymene 1,8-Cineole Acetophenone Benzylformate Linalool oxide Methyl benzoate Benzoic acid Ethyl benzoate Allyl benzoate (E)-Cinnamaldehyde Propyl benzoate 4-Ethylguaiacol Isobutyl benzoate Eugenol Δ-Elemene Vanillin α-Copaene β-Caryophyllene Unknown Germacrene D Benzyl benzoate

Siam benzoin Fiber A 0.2 4.1 0.6 0.4 66.4 0.2 5.0 4.4 4.5 – – – – 2.4 0.4 0.6 0.4 0.2 tr 2.0 4.8 1.4 – – – – – – 0.5 0.1 0.1 0.3 1.7 – –

Fiber B 1.5 1.1 – 0.1 1.2 – – 5.9 – – – – 0.1 11.2 0.3 – – 0.8 0.3 8.7 43.4 12.1 tr – 0.5 0.5 0.7 1.6 – 3.2 – – 0.7 0.1 4.1

Sumatra benzoin Fiber A Fiber B 0.4 0.7 0.8 0.9 – – – – 0.3 – – – 90.4 70.1 1.3 3.2 0.2 – 0.7 2.3 – tr – 0.1 – – – 0.4 0.3 0.3 0.3 0.4 1.5 7.6 – – – tr 0.3 tr 0.6 3.9 – 1.3 – tr – 1.0 – 0.2 – 0.1 – tr – 0.2 – – – 0.4 – – – – 22.3 7.5 – – – 0.3

Diuretic Activity

Natural diuretic characterizations are found in benzoin essential oil, which helps to increase urine production as well as urination frequency. Toxins are effectively cleansed and removed from the blood stream using diuretics. Styrax benzoin has diuretic effects

22

Chemistry, Biological Activities, and Uses of Benzoin Resin

573

as it stimulates and encourages the amount and frequency of urination, as well as helping to remove harmful contaminants from the blood stream through urination [48].

3.5

Antioxidant Activity

Several studies show that the essential oils of benzoin resin of three types of Styrax (red, white, and gray) have antioxidants, which can be extracted using steam distillation, cold pressing, or organic solvents. However, the red resin have stronger antioxidant properties due to the high content of phenolic and flavonoids [49]. In one of the biological studies conducted in Indonesia, the black benzoin used in this study was purchased from a local market in North Sumatra and the free radical scavenging test results exhibited that black Sumatran incense has very good free radical scavenging properties against DPPH (2,2-diphenyl-1-picrylhydrazyl) [50]. Styrax sumatrana, an Indonesian native benzoin resin, contained phenolic and flavonoid compounds. The free radical scavenging activities of the plant extracts were found in the range of 15.28–31.74 mg/L [51].

3.6

Hepatoprotective Activity

Jaundiced rats with temporal induced hyperbilirubinemia using phenylhydrazine were treated with the benzoin extract and it was found that in an appropriate dose, the rat’s bilirubin levels were back to normal, and a smaller dose significantly lowered bilirubin levels [52].

3.7

Antimicrobial Activity

The ethyl acetate extract of the benzoin resin obtained from North Sumatra has the potential to inhibit the growth of gram-positive bacteria S. aureus. The results of antibacterial activity on S. aureus showed that it could be bacteriostatic and bactericidal [53]. The gum resins from Styrax benzoin harvested in Singapore. In the majority of the cases examined, S. benzoin resins in the pure state as well as titanium and anatase oxides (TiO2-P25), molybdenum trioxide (MoO3), and copper oxide (Cu2O) incorporated in the resins exhibited bacteriostatic activity against E. coli, inhibiting its growth and biofilm formation [54]. Silver nanoparticles (AgNPs) prepared by incorporating benzoin resin water extract showed very good antimicrobial activity against various Gram-negative, Gram-positive bacteria, and fungus [55].

3.8

Memory Enhancer

Styrax benzoin called incense resin extract improved learning and memory ability. Its extract improved the number of dendrite branching in the dentate gyrus [56].

574

3.9

M. Sohail Akhtar and T. Alam

Topical Adhesive and Antiseptic Activities

One of the experiments was done on a 42-year-old lady suffering from colorectal cancer with many surgical complications mainly associated with unsuitable adhesion of a colostomy bag. The use of benzoin tincture as an agent to strengthen the adhesiveness of hydrocolloid extra thin and strip paste in deep abdominal folds of fecal fistula had found to be very effective. The character of benzoin tincture solution as a topical adhesive as well as antiseptic makes it more effective in this domain [57].

3.10

Sedative and Anticonvulsive Activities

Styrax orientalis has found anticonvulsant and sedative activity after intranasal and oral administration in the mice. Additionally, Styrax exhibited potent efficacy after intranasal administration at a lower dosage than by intragastric route and fast onset of action [58].

3.11

Anti-Inflammatory Activity

Styrax benzoin treat infections of the skin, topically stop light skin bleeding, and relieve swelling [59].

3.12

Anti-Allergic Activity

Styrax benzoin showed anti-allergic activity in one of the studies and described that it lowers the production of IL4 [60].

4

Toxicity Profile for Benzoin Resin

The solution made up of 10% resin benzoin did not produce skin irritation in guinea pigs. However, it is reported that the material can cause skin sensitization in humans. It has low acute toxicity in rats, when treated orally, and in rabbits, when treated dermally [61].

5

Traditional Uses of Benzoin Resin

Since resin processing methods are largely traditional, there seems to be an increased need to introduce effective measures to enhance resin extraction [62]. Benzoin oil is being used to flavor food, drinks, even alcoholic drinks, as well as to varnish furniture.

22

Chemistry, Biological Activities, and Uses of Benzoin Resin

575

In stomach-related problems like flatulence and squeezing, benzoin essential oil may give alleviation. This essential oil has carminative properties just as having the option to alleviate gas and aggravation in the digestive organs. It assists with loosening up the stomach muscles empowering the excess wind to pass normally and diminishes torment identified with gas. Benzoin essential oil additionally improves general absorption and makes a difference refine your hunger. A particular medical advantage of the essential oil of benzoin is forestalling the acidity that occurs in the stomach and keeps away numerous illness that are brought about by gastric acidity. In the area where Styrax benzoin is cultivated, individuals use it to reduce the stomach pain [7]. The Styrax benzoin resin is commonly used in incense and also used as a preservative and fragrance compound in perfumes, cosmetics, and soaps. Benzoin is also used as a flavoring agent in food, soft drinks, and alcoholic beverages [63]. Because of the presence of cinnamates in Sumatra benzoin, it is used in the production of chocolate flavors. In Indonesia and China, benzoin is widely used in tobacco industry to make flavorings tobacco [64]. Benzoin has been used in cosmetics to enhance skin since early times. Benzoin and glycerin have been used to cure cracked hands and lips. Lac Virginis is a cosmetic formulation prepared by adding numerous quantities of rose water around 20–100 parts with 1 part of tincture of benzoin and has been used as a skin cleanser and face rinse [65]. Benzoin resin fumes can sterilize the environmental air and prevent bacterial growth, minimizing airborne transmission, and promote a healthy atmosphere. The benzoin resins produce a pleasant smell that stimulates the nervous system and improves mood. In addition, benzoin oil comprises various bioactive ingredients and is used as a sedative, relaxant, decrease stress, anxiety, and nervousness [66]. Tincture benzoin is used for enhancing the adhesive property of tape and as a solvent in tincture podophyllin. It is safe to use, though, it can rarely cause allergic contact dermatitis, and it is used in the treatment of venereal warts [67]. Benzoin is also used as an expectorant and diuretic. It has antiseptic and protective properties when used externally. It is used as an inhalation in the treatment of upper respiratory tract infection. It is also used in industries to fix the odor of perfumes, cosmetics, incense, and also mask the taste of some disagreeable pharmaceutical drugs [68]. Styrax benzoin Dryand is called Sumatra benzoin and it is used in perfumes, cosmetic lotions, and to prepare compound benzoin. It is also used in the treatment of catarrh of the upper respiratory tract in the form of compound benzoin tincture and is one of the main ingredients of Friar’s Balsam. Siam benzoin is used in culinary; it is used to formulate benzoinated lard, fixatives, cosmetics, and perfumery. It is superior to the Styrax benzoin Dryand concerning the antioxidative effect [69]. Styrax benzoin or benzoin resin is an antiseptic and effective natural treatment for sore throats and respiratory problems. Cold sores are treated with Styrax benzoin tincture which is used as a mouthwash. Dentists use benzoin resins tincture as an anti-inflammatory medication during dental surgeries. Benzoin resins are generally used in products for the treatment of skin diseases or dermatology. Benzoin resins

576

M. Sohail Akhtar and T. Alam

are often used in cosmetics to treat skin conditions such as irritated or dry skin, cuts, and inflamed skin. Muscle pain, impaired breathing, gout, and inflammation are also treated with benzoin resins [4].

6

Conclusions

The current review is an up-to-date phytochemical and pharmacological studies performed on benzoin. A thorough systematic literature review revealed that benzoin is an important medicinal plant with a broad pharmacological spectrum. The plant has been extensively studied in terms of pharmacological activities, and the results indicate potent antioxidant, antimicrobial, antiasthmatic, anti-inflammatory, and anti-allergic activities. The research has value specifically the resin Styrax benzoin is used as the solubility enhancer for several pharmaceutical compounds. Styrax has proven to be a very valuable genus to the discovery and utilization of medicinal natural products and drug discovery particularly lignans, norlignans, saponins, and pentacyclic triterpenes. Through research and experiment, we can see benzoin resin absolute is a precious resin, and it can be used as a good fixative in aromatherapy. In this context, more research on benzoin is needed to uncover hidden areas and practical clinical applications that can benefit humanity.

References 1. Fernandez X, Lizzani-Cuvelier L, Loiseau AM, Perichet C, Delbecque C (2003) Volatile constituents of benzoin gums: Siam and Sumatra. Flavour Fragr J 18(4):328–333 2. Garcia-Fernandez C (2004) Benzoin, a resin produced by Styrax trees in North Sumatra Province, Indonesia. In: Kuster K, Belcher B (eds) Forest products, livelihoods and conservation: case studies of non-timber forest product systems, vol 1 – Asia. CIFOR, Bogor, pp 151–168 3. Li QL, Li BG, Qi HY, Gao XP, Zhang GL (2005) Four new benzofurans from seeds of Styrax perkinsiae. Planta Med 71:847–851 4. Coppen J (1999) Benzoin: production, uses, and international trade. Perfum Flavor 24(3):11–22 5. Filippi JJ, Castel C, Fernandez X, Rouillard M, Gaysinski M, Lavoine-Hanneguelle S (2009) An unusual acenaphthylene-type sesquiterpene hydrocarbon from Siam and Sumatra benzoin gum. Phytochem Lett 2(4):216–219 6. Castel C, Fernandez X, Lizzani-Cuvelier L, Loiseau AM, Perichet C, Delbecque C (2006a) Volatile constituents of benzoin gums: Siam and Sumatra. Flavour Fragr J 21(1):59–67 7. Sharif A, Nawaz H, Rehman R, Mushtaq A, Rashid U (2016) Review on the bioactive potential of benzoin resin. Int J Chem Biochem Sci 10(1):106–110 8. Gianno R, Erhardt D, Endt PW, Hopwood W, Baker MT (1990) Archaeological resins from shipwrecks off the coasts of Sarpan and Thailand. Masca Res Papers Sci Archaeol 7:59–67 9. Chong HHK, Benjoins (1998) Styrax et storax, thèse de doctoratenpharmacie, université de Montpellier 10. Hovaneissian M, Archier P, Mathe C, Vieillescazes C (2006) Contribution de la chimieanalytique à l’étude des exsudatsvégétaux styrax, storax et benjoin. C R Chim 9(9): 1192–1202 11. Lobdell M (2013) Styrax in cultivation: evaluation of an underrepresented ornamental genus. The University of Delaware

22

Chemistry, Biological Activities, and Uses of Benzoin Resin

577

12. Burger P, Casale A, Kerdudo A, Michel T, Laville R, Chagnaud F, Fernandez X (2016) New insights in the chemical composition of benzoin balsams. Food Chem 210:613–622 13. Kiew R (1982) Germination and seedling survival in kemenyan, Styrax benzoin. Malaysian For 45(1):69–80 14. https://www.itis.gov/servlet/SingleRpt/SingleRpt?search_topic¼TSN&search_ value¼18147#null 15. https://mangalorespice.com/products/loban-dhoop-gum-benzoin 16. Moon HI, Seo DW, Kim KH, Cho KH, Eun HC, Chung JH (2005a) Erythrodiol-3-acetate, a pentacyclic triterpenoid from Styrax japonica, expressions of matrix metalloproteinase-1,2 in cultured human skin fibroblasts. J Ethnopharmacol 97:567–571 17. Moon HI, Kim MR, Woo ER, Chung JH (2005b) Triterpenoid from Styrax japonica Sieb. Et Zucc, and its effects on the expression of matrix metalloproteinases-1 and type 1 procollagen caused by ultraviolet irradiated cultured primary human skin fibroblasts. Biol Pharm Bull 28: 2003–2006 18. Kim MR, Lee HH, Hahm KS, Moon YH, Woo ER (2004) Pentacyclic triterpenoids and their cytotoxicity from the stem bark of Styrax japonica S et Z arch. Pharm Res 27:283–286 19. Min BS, Na MK, Oh SR, Ahn KS, Jeong GS, Li G, Lee SK, Joung H, Lee HK (2004) New furofuran and butyrolactone lignans with antioxidant activity from the stem bark of Styrax japonica. J Nat Prod 67:1980–1984 20. Min BS, Oh SR, Ahn KS, Kim JH, Lee J, Kim DY, Kim EH, Lee HK (2004b) Planta Med 70: 1210–1215 21. Kim MR, Moon HI, Chung JH, Moon YH, Hahm KS, Woo ER (2004b) Chem Pharm Bull 52: 1466–1469 22. Wang F, Hua HM, Bian X, Pei YH, Jing YK (2006) Triterpenoids from the resin of Styrax tonkinensis and their antiproliferative and differentiation effects in human leukemia HL-60 cells. J Nat Prod 69:807–810 23. Wang F, Hua HM, Bian X, Pei YH, Jing YK (2006b) Two new aromatic compounds from the resin of Styrax tonkinensis (pier.) Craib. J Asian Nat Prod Res 8:137–141 24. Bruneton J (2009) Pharmacognosy, phytochemistry, medicinal plants. TCE & Doc, Paris 25. Kashio M, Johnson DV (2001) Balsamic resin from Styrax species. www.fao.org/docrep/005/ ac776e/ac776e00.htm, 20/2/2014 26. Tchapla A, Bleton J, Goursaud S, Méjanelle P (1999) Contribution à la connaissance des substances organiquesutiliséesen Egypteancienne. L’apport de techniques physico-chimiquesd’analyse. In: Encyclopédie religieuse de l’Universvégétal. Croyancesphytoreligieuses de l’Egypteancienne, vol I, pp 445–487 27. Kawai S, Sugiyama N (1939) Synthesis of the two egonol degradation products, dihydroconiferyl alcohol, and styraxinoaldehyde. Ber, 72 B: 367-380, apud chemical abstracts 33:37882 28. http://www.fao.org/fileadmin/user_upload/jecfa_additives/docs/monograph11/ 29. Reinitzer F (1914) Untersuchungen uber Siambenzoe. I VerfahrenzurdarstellungeinesneuenKrystallisier ten Bestanteils der Siambenzoe. Arch Pharm 252:341–349 30. Schroeder HA (1968) P-Hydroxycinnamyl compounds of Siam benzoin gum. Phytochemistry 7:57–61 31. Saleh MIR, Abdel-Azim HM, El-Shaer N (1980) Spectrophotometric estimation of Cinnamic and benzoic acids in balsam Tolu and benzoin. JAOAC 63(6):1195–1199 32. Nitta A, Shohei T, Sakamaki E, Yoshinobu S (1984) On the source and evaluation of gum benzoin. J Pharm Soc Jpn 104:592–600, apud Chemical Abstracts 101:107386 33. Castel C, Fernandez X, Lizzani-cuvelier L, Perichet C, Lavoine S (2006b) Characterization of the chemical composition of a by product from Siam Benzoin. Gum J Agric Food Chem 54: 8848–8854 34. Fernandez X, Castel C, Lizzani-Cuvelier L, Delbecque C, Venzal SP (2006) Volatile constituents of benzoin gums: Siam and Sumatra, part 3. Fast characterization with an electronic nose. Flavour Fragr J 21:439–446

578

M. Sohail Akhtar and T. Alam

35. Huneck S (1963) Triterpene IV Die triterpensäuren des balsams von Liquidambar orientalis M. Tetrahedron 19:479–482 36. Hovaneissian M, Archier P, Mathe C, Culioli G, Vieillescazes V (2008) Analytical investigation of styrax and benzoin balsams by HPLC-PAD-fluorimetry and GC-MS. Phytochem Anal 19: 301–310 37. Pastorova I, Koster CG, Boon JJ (1997) Analytical study of free and ester bound benzoic and cinnamic acids of gum benzoin resins by GC-MS and HPLC-frit FAB-MS. Phytochem Anal 8: 63–73 38. Djerassi C, Thomas GH, Jeger O (1955) The stereochemistry of sumaresinolic acid and its conversion to oleanolic acid. Helv Chim Acta 38:1304–1307 39. Reinitzer F (1921) Siam benzoin II Siaresinolic acid. Arch Pharm 259:1–6. Chemical Abstracts 15:15260 40. Reynolds JEF (1982) Martindale: the extra pharmacopoeia. The Farmaceutical Press, London 41. Huang KC (1999) The pharmacology of Chinese herbs. CRC Press, New York 42. Popravko SA, Sokolov IV, Torgov IV (1984) Derivatives of unsaturated aromatic alcohols in propolis and styrax resin. Khimiya prirodnykh soedinenii 19:152–160 43. El-Razek MA (2018) Triterpenes from Styrax benzoin. Der Pharma Chem 10(1):30–34. http:// www.derpharmachemica.com/archive.html 44. Seddon P, Khan Y (2003) Respiratory problems in children with neurological impairment. Arc Dis Child 88(1):75–78 45. Shen T, Li GH, Wang XN, Lou HX (2012) The genus Commiphora: a review of its traditional uses, phytochemistry, and pharmacology. J Ethnopharmacol 142(2):319–330 46. Dattner AM (2003) From medical herbalism to phytotherapy in dermatology: back to the future. Dermatol Ther 16(2):106–113 47. Lev E, Amar Z (2000) Ethnopharmacological survey of traditional drugs sold in Israel at the end of the 20th century. J Ethnopharmacol 72(1–2):191–205 48. Lawless J (1995) The illustrated encyclopedia of essential oils: the complete guide to the use of oils in aromatherapy and herbalism. Element Books Ltd, Shaftesbury. ISBN 1852306610 49. Hacini Z, Khedja F, Habib I, Kendour Z, Debba Z (2018) Evaluation of antibacterial and antioxidant activities of three types of benzoin resin. Eur J Chem 9(4):408–411 50. Hidayat N, Yati, Elsa K, Krisanti A, Gozan M (2020) Extraction and antioxidant activity test of black Sumatran incense. AIP Conference Proceedings. https://doi.org/10.1063/1.5139354. Published Online: 10 December 2019 51. Hidayat A, Iswanto AH, Susilowati A, Rachmat HH (2018) Radical scavenging activity of Kemenyan resin produced by an Indonesian native plant, Styrax sumatrana. J Korean Wood Sci Technol 46(4):346–354 52. Raju S, Rao UMV, Reddy SA, Ramya K, Kumar GV (2011) Effect of benzoin resin on the serum bilirubin levels in temporary jaundice induced by phenylhydrazine: A preliminary study. Pharm Pharmacol 3(3):68–71 53. Gayatri A, Rohaeti E, Batubara I (2019) Gum benzoin (Styrax benzoin) as antibacterial against Staphylococcus aureus. Al-Kimia 7(2):208–217 54. Horst DJ, Tebcherani SM, Kubaski E, Vieira R (2016) Bactericidal activity of oleo-gum resins doped with metal oxides. Int J Eng Res Appl 6(12):65–72 55. Du J, Singh H, Yi TH (2016) Antibacterial, anti-biofilm and anticancer potentials of green synthesized silver nanoparticles using benzoin gum (Styrax benzoin) extract. Bioprocess Biosyst Eng 39(12):1923–1931 56. Alawiyah K, Juliandi B, Boediono A, Sasai N (2020) Oral administration of incense resin (Styrax benzoin) extract enhances spatial learning, memory, and dendrite complexity of mice. Braz Arch Biol Technol 63:e20180379 57. Vijay K, Nitesh, Yashwant R, Swapna VM, Ashok K, Ranjit KS, Vikas C, Ni K (2019) Effectiveness of benzoin tincture in management of complex fecal fistula with deep abdominal folds. Open J Clin Med Case Rep 5(17):1601

22

Chemistry, Biological Activities, and Uses of Benzoin Resin

579

58. Guo J, Duan J, Tang Y, Li Y (2011) Sedative and anticonvulsant activities of styrax after oral and intranasal administration in mice. Pharm Biol 49(10):1034–1038. https://doi.org/10.3109/ 13880209.2011.561438 59. Aswandi A, Kholibrina CR (2021) Ethnopharmacological properties of essential oils from natural forests in Northern Sumatra. Earth Environ Sci 715:012077 60. Kumari HVM, Sofia HN, Manickavasakam K, Mohan S, Karthikeyan K (2015) Siddha medicine indicated for iyaeraippunoi (bronchial asthma) – a review. World J Pharm Res 4(3): 802–848 61. https://www.bibra-information.co.uk/downloads/toxicity-profile-for-gum-benzoin-1989/ 62. Moyler DA, Clery RA (1997) The aromatic resins: their chemistry and uses. R Soc Chem 214: 96–115 63. Abdulmumeen HA, Risikat AN, Sururah AR (2012) Food: its preservatives, additives, and applications. Int J Chem Biol Sci 1:36–47 64. Bedigian D (2003) Monograph on benzoin (balsamic resin from Styrax species). Econ Bot 57 (3):427–428 65. Manvi S, Sharma R (2017) Tincture benzoin in dermatology. J Med Sci Clin Res 5(08):26154– 26158 66. Alruways MW, Elrayah IE, Mansi MA (2020) Effect of benzoin resin fumes on indoor environmental microbes. Int J Med Res Health Sci 9(12):52–58 67. Bhatt KD, Fernandes R, Dhurat R (2006) Contact dermatitis to compound tincture of benzoin applied under occlusion. Indian J Dermatol Venereol Leprol 72(1):3 68. Kokate CK, Purohit AP, Gokhale SB (2019) Pharmacognosy. Nirali Prakashan, Pune 69. Shah BN, Seth AK (2017) Textbook of pharmacognosy and phytochemistry. CBS Publishers & Distributors Pvt Ltd, New Delhi

Ethnobotany, Chemistry, and Biological Activities of Some Commiphora Species Resins

23

Aman Dekebo, Seifu Juniedi, Xuebo Hu, and Chuleui Jung

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Botanical Description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Resins Derived from Two Commercially Important Commiphora Species . . . . . . . . . . . . . . . 3.1 Myrrh from Commiphora myrrha . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Opopanax from Commiphora guidottii . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Ethnobotanical Information on Some Commiphora Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Phytochemical Constituents and Pharmacological Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

582 584 584 584 586 586 587 602 603

Abstract

The genus Commiphora (Burseraceae) comprises about 150–200 species, most of which grow in the dry bushlands of tropical Africa and Madagascar, Arabia, India, and South America. To date, more than 300 compounds belonging to different classes of compounds have been reported from the genus, though terpenoids are the A. Dekebo (*) Department of Applied Chemistry, Adama Science and Technology University, Adama, Ethiopia S. Juniedi Department of Applied Biology, Adama Science and Technology University, Adama, Ethiopia e-mail: [email protected] X. Hu Lab of Drug Discovery and Molecular Engineering, College of Plant Science and Technology, Huazhong (Central China) Agricultural University, Wuhan, China e-mail: [email protected] C. Jung Agricultural Science and Technology Research Institute Andong National University, Andong, Republic of Korea Department of Plant Medicals, Andong National University, Andong, Republic of Korea e-mail: [email protected] © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_27

581

582

A. Dekebo et al.

most abundant constituents. Diterpenes, sesquiterpenes, and monoterpenes were reported from different Commiphora species. These include dammarane triterpenes from C. dalzielii and C. confusa. Mansumbinones or dammarane triterpenes from C. kua, lignans, and its epimer picropolygamain were reported from the resins of C. kua and C. erlangeriana. C. myrrha, C. sphaerocarpa, C. holtziana, and C. kataf constitute monoterpenes and sesquiterpenes. Some of these compounds showed different biological activities. Ethnobotanical information gathered from local people revealed that the resins of these species enjoy a wide array of traditional uses such as human medicine, treatment for maladies of cattle, and insect repellents. In this chapter, we collected relevant information by searching three scientific databases (Web of Science, Google Scholar, Scopus), covering the time period from 1950 to 2021. The literature review revealed that the resins of Commiphora are of considerable medicinal, cultural, and economic significance; and thus, detailed research such as sustainable conservation, value addition, and preclinical and clinical studies are required for further utilization and commercialization of underutilized resins of Commiphora species. Here we review the ethnobotanical, phytochemical composition, and pharmacological activities of the resins obtained from several Commiphora species. Keywords

Commiphora guidottii · Commiphora myrrha · Ethnobotany · Lignans · Myrrh · Opopanax · Steroids · Triterpenes Abbreviations

A549 A2780 EpH4 and MG1361 HeLa and EAhy926 IC50 L929 and RAW 264.7 LPS MCF-10A, MCF-7, MDAMB-231, SKBR3, and BT474 MIA-Paca-2 NO SNU-638

1

Adenocarcinomic human alveolar non-small lung cancer cell lines Ovarian cancer cell line Murine mammary cancer cell lines Human cell lines Inhibitory concentration at 50% Murine cell lines Lipopolysaccharide Human breast cancer cell lines Pancreatic cancer cell line Nitric oxide Stomach cancer cell line

Introduction

Ethiopia is well known since ancient times as the source of a variety of natural products such as civet, coffee, myrrh, frankincense, etc. Thus, myrrh and frankincense originating from this part of the world are mentioned in the

23

Ethnobotany, Chemistry, and Biological Activities of Some. . .

583

Bible on several occasions. The gifts presented by the Maji to the infant Christ symbolized: “Gold for royalty, frankincense for divinity, and myrrh for suffering”[1]. Still today myrrh, the related opopanax is also known as sweet or scented myrrh, and frankincense is a valued product both in local and international markets. They are used as incense in different cultural and religious rituals, as components of local medicines, and as insect and snake repellants. In the international market, these resins enjoy high demand because they are extracted or distilled for use as components of perfumes, aromatherapy, and skincare products. According to information obtained from the Ethiopian Natural Gums Processing and Marketing Enterprise (NGPME), in the period 1996–2000 on average 70 tons of myrrh per year were exported from Ethiopia by the Enterprise which resulted in average annual earnings of US$ 237,000 from myrrh (personal communication). The total export volume shows consistent increase over time, growing from 1648 tons in 1999/2000 to 4612 tons in 2007/2008 [2]. The price of myrrh in the local market was 150 Ksh/kg ($1.9) for grade one and 100 Ksh/kg ($1.3) for grade two in Kenya [3]. In general, the supply of these products far exceeds the demand, indicating the high potential of these products for the economic development of Ethiopia and other neighboring countries such as Somalia and Kenya. Mostly these natural products are consumed for domestic purposes in Ethiopia with about 60% of which is used in religious ceremonies [4]. The exported amount of gums and resins remains much lower than the domestic market, but it has been increasing since the mid-1990s. The major importing countries in that period were China, United Arab Emirates, Germany, Egypt, and Guatemala [4]. Gums and gum resins are used as traditional medicines, insecticides, and hygienic and sanitation detergents. The limitation in the botanical knowledge of the family Burseraceae had hindered the chemical work on resins from properly identified species. Many previous reports on the chemistry of resins of Commiphora species were based on materials obtained from markets in Europe or the Middle East. This meant that the origins of the studied materials and the botanical identities of the source plants were very much uncertain. The publication of Volume 3 of the Flora of Ethiopia [5], which gave detailed taxonomic accounts of several taxa belonging to the genera Commiphora, opened new avenues for chemical studies of resins derived from properly identified species. There were some review articles based on phytochemical constituents and biological activities of resins from different Commiphora species. As resins of some Commiphora species are traditionally and economically important, detailed and updated information on these species is required from time to time. Here we include information gathered from different sources on ethnobotanical, botanical, pharmacological, and phytochemicals for some common and important Commiphora species resins from 1950 to 2021 and their prospects.

584

2

A. Dekebo et al.

Botanical Description

The family Burseraceae, with 17 genera and over 500 species, is widespread in tropical and subtropical countries. This family is the dominant component of the tree flora in the semiarid bushlands of East and Southwest Africa [6]. The AcaciaCommiphora woodlands of Northern Kenya, Southern and Eastern Ethiopia, and Somalia are particularly, dominated by species of the genera Acacia (Leguminosae), Commiphora Jacq., and Boswellia Roxb. ex Colebr. (both Burseraceae). Many of these species yield resins when the bark is damaged intentionally or naturally. Most of these species were little known because of poor botanical descriptions which were based on insufficient materials [7]. In Ethiopia there are only two genera, namely, Boswellia and Commiphora that belong to the family Burseraceae [5]. These genera produce resins that have considerable commercial, medicinal, and cultural uses. Although the history of resins from the Burseraceae family dates as far back as the times of the pharaohs of ancient Egypt, it is quite surprising to note that the chemistry of these resins is not yet fully known. The genus Commiphora Jacq., comprising 150–200 species, occurs in the dry bushlands of tropical Africa and Madagascar, Arabia, India, and South America. These trees or shrubs are characterized by an outer bark often papery and peeling, an inner bark usually greenish, containing ducts that form large interconnecting cavities from which the gum-resin, usually aromatic, flows freely on wounding or from natural fissures. Many species are leafless most of the year and usually set flowers and fruit when leafless, making the collection of fertile botanical specimens difficult [5].

3

Resins Derived from Two Commercially Important Commiphora Species

3.1

Myrrh from Commiphora myrrha

C. myrrha (Nees) Engl. (Fig. 1) is the most popular member of the genus Commiphora, yielding one of the most important resins of all times, commonly known as myrrh (Fig. 2). Myrrh is a natural oleo-gum resin, which produces the characteristic odor, ranging in color from yellowish-brown to reddish-brown. It comprises 3–8% essential oil, 30–60% water-soluble, and 25–40% alcohol-soluble components [8]. Myrrh was most likely employed by ancient Egyptians for embalming the dead. It gives a biting-burning, somewhat acrid-aromatic taste used as mouthwashes and toothpaste, and is an important component in salve used in treating hemorrhoids and wounds. Internally, myrrh is used as a cure for indigestion, ulcers, and bronchial congestion [1]. The alcoholic solution when concentrated after filtration yields the so-called absolute, while the hexane extract yields a “resinoid.” Steam and hydro-distillation yield essential oil, which is in high demand. The essential oil and the absolute and resinoid are used as fixatives in the manufacture of perfumes [9].

23

Ethnobotany, Chemistry, and Biological Activities of Some. . .

585

Fig. 1 Picture of C. myrrha tree

Fig. 2 Picture of A: myrrh (resin of C. myrrha); B: opopanax (resin of C. guidottii)

Other oleo-gum resins resembling myrrh are produced by various species of Commiphora such as C. africana (A. Rich.) Engl., C. habessinica (Berg) Engl., C. kua (J.F Royal) Vollesen, C. schimperi (Berg) Engl., etc. These resins are

586

A. Dekebo et al.

Fig. 3 Picture of C. guidottii tree

sometimes found in true myrrh (resin of C. myrrha) as adulterants. The presence of adulterants in myrrh has contributed to a lack of clarity in the chemistry of true myrrh. This is because most previous reports were based on analyses of commercial samples, which include resins from other species [10].

3.2

Opopanax from Commiphora guidottii

Opopanax (Fig. 2) is another commercial product of Commiphora species. Gum opopanax was believed to be the sun-dried exudate obtained from the bark of C. erythraea (Ehrenb.) Engl. [1], a species known to be widely distributed in Ethiopia, Sudan, Kenya, Somalia, north Tanzania, and Arabia. Contrary to this belief, the botanical origin of opopanax, also known as scented myrrh, bissabol (Hindi), habakhadi (Somali), and abeked (Amharic), was confirmed to be C. guidottii Chiov., a species (Fig. 3) occurring widely in southern Ethiopia and Somalia [11]. Opopanax is exported to China as well as to perfume-producing companies in Europe because its essential oil and resinoid are regarded as useful fixatives in perfumery [11].

4

Ethnobotanical Information on Some Commiphora Species

The monumental botanical report on the Burseraceae of Ethiopia by Vollesen [5] has revealed the occurrence of over 52 Commiphora species in Ethiopia. The first author of this chapter undertook field studies in different regions in Ethiopia, such as Gode

23

Ethnobotany, Chemistry, and Biological Activities of Some. . .

587

(Ogaden), Borena (Sidamo), Sof Omar (Bale), Awash National Park (Shewa), and North Kenya (Samburu and Isiolo Districts), to collect plant specimens for identification, gather resins for chemical constituent identification, and evaluate their biological activities. At the same time, useful ethnobotanical information was recorded by interviewing elders in the communities where the plants occur. In the course of this study, resins and botanical specimens of Commiphora species were collected. The plants were identified by Dr. Kaj Vollesen, Kew Botanic Gardens, UK, and Ms. Pat Curry. Voucher specimens of all the studied species have been deposited in Kew Botanic Gardens, UK, and the National Herbarium of Addis Ababa University, Ethiopia [12]. Resins of the genus Commiphora are widely used as incense, be it at home or in public places. Interviews of members of communities in the study areas where the plants grow revealed that the resins of these species enjoy a wide array of traditional uses not only as human medicine but also in treating maladies of cattle and camels and as insect repellents. Table 1 summarizes the ethnobotanical information gathered in this study and those reported by other workers. In some instances, the fruits, resins, and other parts of the plants are used as food additives and as chewing gums; whereas resins of only a few species are commercially important for local people; however, they utilize a variety of resins for different purposes. Myrrh is used as a remedy against stomachache and to decrease the libido of young men during Koran studies. Its smoke is used to chase away snakes. The resin of C. guidottii, commonly known in commerce as opopanax, is locally used to treat stomach complaints and to facilitate the withdrawal of the placenta. Opopanax is also mixed with feed and given to cows and buffaloes to improve the quantity and quality of milk they produce. The resin of C. sphaerocarpa is used against cough, diarrhea, and headache and ticks of cattle. The resin of C. holtziana mixed with milk or urine of camel is used to kill ticks. The resin of C. holtziana is also used to treat snakebite [12]. Ethnobotanical notes on herbarium specimens of Commiphora species deposited at the National Herbarium in Addis Ababa University also reveal some interesting uses of resins by different communities in Ethiopia. Thus, resins of C. kua and C. habessinica were used as a soap substitute in Borena; C. tubuk as glue; C. coronillifolia for making ink; C. gowlello against swelling of people and livestock; C. incisa to treat skin disease; and C. ogadensis against joint ringworm. Without a doubt, the most popular of all the resins is that of C. myrrha, which is used as incense, snake and fly repellent, and as a remedy for joint problems [12].

5

Phytochemical Constituents and Pharmacological Studies

Out of the 150–200 species of Commiphora, very few species have so far been chemically investigated. The main classes of secondary metabolites present in the resins of Commiphora species are terpenoids (monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids), steroids, and rarely lignans (Table 2). C. mukul Engl. is a plant well known in the Indian traditional medical system. It is the most widely studied species of the genus. The oleo-gum-resin exudate of this plant is locally known as guggulu gum or Indian bdellium. Guggulu is believed to be effective to treat rheumatoid arthritis, obesity, and other allied disorders.

588

A. Dekebo et al.

Table 1 Ethnomedicinal uses and pharmacological activities of some Commiphora species Species Commiphora myrrha

Traditional use The resin used against stomachache, decrease libido, mixed with powdered charcoal to make ink. Incense: repel snakes, used on Good Friday in Ethiopian orthodox church. Skin ulcer, empyrosis, wound, fracture, oral ulcer Toothache, pain, tumor, arthritis, inflammatory diseases, and diseases caused by blood stagnation, dysmenorrhea, rheumatism, Hemiplegia, and acroanesthesia Wounds, worms, sepsis, cough, snakebite, infections in mouth, teeth, and eyes

Pharmacological activity

Antitumor

[13]

Antiinflammatory

[14]

Analgesic

Antioxidant Antimicrobial

C. opobalsamum

C. mukul

C. caudata C. berryi

Pharyngitis, tonsillitis, gingivitis, ulcers, cough, proctitis, sinusitis, and skin inflammation Nasal congestion caused by the common cold, wounds, and infection of the buccal cavity Oral diseases Sore throats, oral mucosal and gingival irritations Skin ulcer, empyrosis, wound, fracture, oral ulcer Dyspepsia, colic, joint pain, promoting urine output, expelling renal calculi, liver, and stomach diseases

Bone fracture, wound, skin disorders, inflammatory Arthritis, mouth ulcer, cardiovascular disease, lipid disorder, obesity, and hypothyroidism

Inflammation, pain, and relieving stomach aches Cold, fever, and wound

Ref. [12]

[15] [16] [17]

[18]

[19] [20] Antiulcer

[21]

Antiproliferative

[22]

Hypotensive Hepatoprotective Antiinflammatory Antiinflammatory Hypolipidemic

[23] [24] [25]

Antihypothyroidism Antibacterial Antidiabetic Antiproliferative Analgesic, antiinflammatory Gastric antiulcer

[31]

[26–28] [29, 30]

[32, 33] [34, 35] [36, 37] [38] [39] (continued)

23

Ethnobotany, Chemistry, and Biological Activities of Some. . .

589

Table 1 (continued) Species

Traditional use

Molluscicide C. holtziana C. confusa C. kua

C. erlangeriana

Kill and repel ticks on camel and cattle Resin: chewing gums and incense Microbial infection Snakebite, gonorrhea, and stomach disorders Trunk: sucked to quench thirst; resin: as incense, for healing wounds, to reduce the swelling of udder Stem: to make home utensils Resin: toxic to animals, used to kill hyenas Fruit: edible (human)

C. harveyi C. merkeri

Wounds, anthelmintic agent, and snakebite Infection

C. guidottii

Resin: against stomach complaints in particular diarrhea, and to facilitate withdrawal of placenta Against wounds and diarrhea

C. schimperii C. habessinica C. africana C. erythaea

C. tenuis C. cyclophylla C. hodai C. holtziana

C. incisa

C. kataf

Malaria Resin for smoothening of skin Resin: as a soap substitute Eye pain Expelling tapeworms Wound healing Resin: incense, repels insects To treat skin diseases resulted due to attack by ticks To treat wound Resin: varnish Resin mixed with charcoal to write on Koran boards Resin: Prophylactic against snakebite, mixed with milk or camels’ urine to kill ticks Resin: chewing gum, incense, adhesive, to treat swelling of the udder of livestock, sticking thorn can be extracted by applying resin The bark is used as tea

Pharmacological activity Hepatoprotective Antioxidant Antimicrobial Antioxidant Antiectoparasitic

Ref. [39] [39] [41] [41] [42] [12] [43] [12]

[24] Antitumor Antimicrobial Antiinflammatory

[44] [45] [46] [12]

Smooth muscle relaxing effect Wound healing Anti-malarial

Anti-tick Antibacterial

[47, 48] [49] [49] [12] [12] [50] [40] [50] [12] [51] [52] [12] [12] [12]

[12]

[12] (continued)

590

A. Dekebo et al.

Table 1 (continued) Species C. monoica C. rostrata

Pharmacological activity

Traditional use Resin: to treat itching Bark: tea, chewed against cough; fluid resin: to treat eye diseases, perfume; branches: tooth stick; resin: poisonous, incense to repel mosquitoes and flies Fruit edible; resin: against cough, diarrhea, and headache, against ticks of cattle

C. sphaerocarpa

Ref. [12] [12, 43]

[12]

Extensive pharmacological studies on the crude extract, some of its fractions, and pure constituents from guggulu gum have revealed significant anti-inflammatory [27], hypolipidemic, and hypocholesterolemic [55] activities, thus providing support to the use of this medicinal plant since ancient times. The bioactive constituents are mainly steroids with the most prominent being 4,17(20)-(trans)-pregnadiene-3,16-dione (1), 4,17(20)-(cis)-pregnadiene-3,16-dione (2), guggulsterol-I (3), guggulsterol-II (4), guggulsterol-III (5) [53], 20α-hydroxy-4-pregnen-3-one (6), 20β-hydroxy-4-pregnen-3-one (7), 16β-hydroxy-4,17(20)Z-pregnadien-3-one (8), 16α-hydroxy-4-pregnen-3-one (9) [54], and Z-guggulsterone (10) [55]. The diterpenoids cembrene-A (11) and mukulol (12) were also reported to occur in guggulu [56]. OH

H O

O

OH OH

H

O

1

OH

O

O

2

OH

3

OH

HO

H

4

OH

OH

H

H

OH

O

OH

O

5

O

6

O

OH

O

9

OH

H

R1

H

1

R

H 1

H R

H R2

13

O

H

H

H O

OH OH

H OH

H

12

11

10

OH H

8

H

H

O

O

7

2

14 : R + R = O 1

2

1

2

15: R = H; R = OH 16: R = H; R = OAc

H

2

H 17 = R 1 = OH, R 2 = H 18 = R 1 = OAc, R 2 = H

Species C. mukul C. mukul C. mukul C. mukul C. mukul C. mukul C. mukul C. mukul C. mukul C. mukul C. mukul C. mukul C. dalzielii

C. dalzielii

C. dalzielii

C. dalzielii

C. confusa C. confusa C. kua C. kua

Structure no. 1 2 3 4 5 6 7 8 9 10 11 12 13

14

15

16

17 18 19 20

Plant part Resin Resin Resin Resin Resin Resin Resin Resin Resin Resin Resin Resin Stem bark Stem bark Stem bark Stem bark Resin Resin Resin Resin Triterpene Triterpene Lignan

Triterpene

Triterpene

Triterpene

Compound class Steroid Steroid Steroid Steroid Steroid Steroid Steroid Steroid Steroid Steroid Diterpenoid Diterpenoid Triterpene

Table 2 Phytochemicals reported from some Commiphora species

(3R,20S)-3,20-Dihydroxydammar-24-ene (3R,20S)-3-Acetoxy-20-hydroxydammar-24-ene Polygamain Picropolygamain

Cabraleadiol 3-acetate

Cabraleadiol

Cabraleone

Compound name 4,17(20)-(trans)-Pregnadiene-3,16-dione 4,17(20)-(cis)-Pregnadiene-3,16-dione Guggulsterol-I Guggulsterol-II Guggulsterol-III 20α-Hydroxy-4-pregnen-3-one 20β-Hydroxy-4-pregnen-3-one 16β-Hydroxy-4,17(20)Z-pregnadien-3-one 16α-Hydroxy-4-pregnen-3-one Z-Guggulsterone Cembrene-A Mukulol Isofouquierone

Ethnobotany, Chemistry, and Biological Activities of Some. . . (continued)

[58] [58] [59–61] [59–61]

[57]

[57]

[57]

Ref. [53] [53] [53] [53] [53] [54] [54] [54] [54] [55] [56] [56] [57]

23 591

Species C. kua C. kua C. kua C. kua C. kua

C. kua

C. kua

C. kua

C. kua

C. kua

C. kua C. kua C. kua C. kua C. kua C. kua C. kua

C. incisa C. incisa

Structure no. 21 22 23 24 25

26

27

28

29

30

31 32 33 34 35 36 37

38 39

Table 2 (continued)

Resin Resin

Plant part Resin Resin Resin Resin Stem bark Stem bark Stem bark Stem bark Stem bark Stem bark Resin Resin Resin Resin Resin Resin Resin Triterpene derivatives Triterpene derivatives Monoterpene Monoterpene Monoterpene Monoterpene Sesquiterpene derivative Triterpene Triterpene

Triterpene derivatives

Triterpene derivatives

Triterpene derivatives

Triterpene derivatives

Triterpene derivatives

Compound class Triterpene derivatives Triterpene derivatives Triterpene Triterpene derivatives Triterpene derivatives

15α-Hydroxymansumbinone 28-Acetoxy-15α-hydroxymansumbinone α-Pinene p-Cymene α-Thujene β-Pinene Bisabolene, 2-methyl-5-(50 -hydroxy-10 ,50 -dimethyl-30 -hexenyl) phenol 1α-Acetoxy-9,19-cyclolanost-24-en-3β-ol 29-Norlanost-8,24-dien-1α,2α,3β-triol

16-Oxo-mansumbin-3(28),13(17)-dien-3-oic acid

3β-Hydroxymansumbin-13(17)-en-16-one

Mansumbin-13(17)-en-3,16-dione

16-Hydroperoxy-3,4-seco-mansumbin-3(28),13(17)-dien-3-oic acid

16-Hydroperoxymansumbin-13(17)-en-3β-ol

Compound name Mansumbinone Mansumbinol 16(S),20(R)-Dihydroxydammar-24-en-3-one 3,4-Seco-mansumbinoic acid 16-Hydroperoxymansumbin-13(17)-en-3-one

[61] [61]

[63] [63] [64] [64] [64] [64] [64]

[62].

[62].

[62].

[62]

[62]

Ref. [59–61] [59–61] [59–61] [59–61] [62].

592 A. Dekebo et al.

C. erlangeriana C. erlangeriana C. erlangeriana C. erlangeriana C. myrrha

C. myrrha

C. myrrha

C. myrrha C. myrrha C. myrrha C. myrrha C. myrrha C. myrrha C. myrrha C. myrrha C. myrrha C. myrrha

C. myrrha

C. myrrha C. myrrha C. myrrha C. myrrha

40 41 42 43 44

45

46

47 48 49 50 51 52 53 54 55 56

57

58 59 60 61

Resin Resin Resin Resin

Resin

Resin Resin Resin Resin Resin Resin Resin Resin Resin Resin

Resin

Resin

Resin Resin Resin Resin Resin

Lignan Lignan Lignan Lignan Sesquiterpene derivative Sesquiterpene derivative Sesquiterpene derivative Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene derivative Sesquiterpene derivative Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene 4,5-Dihydrofuranodiene-6-one

2-Acetoxyfuranodiene

Elemol Furanodiene Furanodienone Isofuranogermacrene Curzerenone Lindestrene Furanoeudesma-1,3-diene Furanoeudesma-1,4-diene-6-one 1(10)Z,4Z-Furanodiene-6-one 2-Methoxy-furanodiene

3-Methoxy-8,12-epoxygermacra-1,7,10(15),11-tetraen-6-one

5-Acetoxy-2-methoxy-8,12-epoxygermacra-1(10),7,11-trien-6-one

Erlangerin A Erlangerin B Erlangerin C Erlangerin D 1(10),2-Methoxy-8,12-epoxygermacra-1(10),7,11-trien-6-one

Ethnobotany, Chemistry, and Biological Activities of Some. . . (continued)

[66–68]

[66–68]

[66–68] [66–68] [66–68] [66–68] [66–68] [66–68] [66–68] [66–68] [66–68] [66–68]

[66–68]

[66–68]

[65] [65] [65] [65] [66–68]

23 593

Species C. myrrha

C. myrrha

C. myrrha C. myrrha C. myrrha C. myrrha

C. myrrha C. guidottii C. guidottii C. guidottii C. guidottii C. guidottii C. guidottii C. guidottii

Structure no. 62

63

64 65 66 67

68 69 70 71 72 73 74 75

Table 2 (continued)

Resin Resin Resin Resin Resin Resin Resin Resin

Resin Resin Resin Resin

Resin

Plant part Resin

Compound class Sesquiterpene derivative Sesquiterpene derivative Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene derivative Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Sesquiterpene Commiterpenes A T-Cadinol

Commiphoins A Commiphoins B Commiphoins C Commipholinone

1,2-Epoxyfurano-10(15)-germacren-6-one

Compound name rel-2R-Methyl-5S-acetoxy-4R-furanogermacr-1(10)Z-en-6-one

[70]] [48] [47] [47] [47] [47] [47] [47]

[70] [70] [70] [70]

[69]

Ref. [69]

594 A. Dekebo et al.

76 77 78 79 80 81 82 83 84 85 86 87 88

C. guidottii C. guidottii C. guidottii C. guidottii C. africana C. africana C. africana C. africana C. africana C. africana C. africana C. habessinica C. habessinica

Resin Resin Resin Resin Resin Resin Resin Resin Resin Resin Resin Resin Resin

Monoterpene Sesquiterpene Sesquiterpene Sesquiterpene Monoterpene Monoterpene Monoterpene Monoterpene Monoterpene Monoterpene Triterpene Sterol Sterol

β-Ocimene β-Bisabolene α-Bisabolol Farnesol Myrcene Car-3-ene Limonene Camphene Terpinen-4-ol Verbenone Commafric A Cholesterol Lathosterol [71] [71] [71] [71] [72] [72] [72] [72] [72] [72] [73] [74] [74]

23 Ethnobotany, Chemistry, and Biological Activities of Some. . . 595

596

A. Dekebo et al.

C. dalzielii Hutch. is a shrub or small tree indigenous to the coastal area of Ghana. The petrol extract of the stem bark of this species has led to the isolation of four dammarane triterpenes: isofouquierone (13), cabraleone (14), cabraleadiol (15), and cabraleadiol 3-acetate (16) [57]. Dammarane triterpenes, (3R,20S)-3,20dihydroxydammar-24-ene (17) and (3R,20S)-3-acetoxy-20-hydroxydammar-24ene (18) along with cabraleadiol 3-acetate (16), were reported from the resin of C. confusa [58]. O

O

O

O

H

O

O

O

OH

H

O

O

R

O

O

R

1 2

H

O

1

O 2

1

H H 1

21: R + R = O

20

19

OH

H

2

23: R = OH, R = H

2

22: R = OH; R = H

The resin of C. kua yielded epimeric aryltetralin lignans, namely, polygamain (19) and its epimer picropolygamain (20) [59]. It also afforded interesting triterpenes, which have lost the side chain attached to C-17, including mansumbinone (21), mansumbinol (22), 16(S),20(R)-dihydroxydammar-24-en-3-one (23), and 3,4seco-mansumbinoic acid (24). The source of mansumbinones was first reported as C. incisa Chiov., and later this was changed to C. kua by the same workers [70–72]. It was found that mansumbinoic acid (24) was 2.4 times more active in its antiinflammatory activity than mansumbinone (21) [75]. H

OOH

O

OOH HO 2 C

R H

1

R

H

H

HO 2 C

2

R

H 1

R

1

H

2

2

25: R + R = O

24

1

2

27

26: R = OH; R = H

1

O

2

28: R + R = O 1

2

29: R = OH; R = H

H

HO 2 C H

H O

H

R

30

OH

H

31 R = H

33

OH

OAc

OH

35

34

32 R = OAc

36

OH HO

37

HO

HO 38

39

From the stem bark of C. kua, Provan et al. [62] reported three more C22 mansumbinanes, namely, 16-hydroperoxymansumbin-13(17)-en-3-one (25),

23

Ethnobotany, Chemistry, and Biological Activities of Some. . .

597

16-hydroperoxymansumbin-13(17)-en-3β-ol (26), and 16-hydroperoxy-3,4-secomansumbin-3(28),13(17)-dien-3-oic acid (27). These compounds proved to be unstable and rapidly degraded to give mansumbin-13(17)-en-3,16-dione (28), 3β-hydroxymansumbin-13(17)-en-16-one (29), and 16-oxo-mansumbin-3(28),13(17)dien-3-oic acid (30), respectively. Moreover, two new octanordammarane triterpenes, 15α-hydroxymansumbinone (31) and 28-acetoxy-15α-hydroxymansumbinone (32), were reported from the resin of C. kua [63]. The essential oil obtained by steam distillation of the oleo-resin of C. kua (syn. C. flaviflora) yielded α-pinene (44.3%, 33), p-cymene (28.8%, 34), α-thujene (22.4%, 35), and β-pinene (10%, 36) as major components, while the residue remaining after steam distillation on repeated column chromatography afforded the new bisabolene, 2-methyl-5-(50 -hydroxy-10 ,50 -dimethyl-30 -hexenyl)phenol (37) [64]. The resin of C. incisa yielded two novel triterpenes, 1α-acetoxy-9,19cyclolanost-24-en-3β-ol (38) and 29-norlanost-8,24-dien-1α,2α,3β-triol (39) [61]. Four lignans namely erlangerin A–D (40–43) were reported from the resin of C. erlangeriana [65]. The resin of C. erlangeriana is considered by local people as poisonous to humans and animals. Erlangerin C (42) and D (43) effected cytotoxicity in the murine macrophage cells (RAW 264.7) and a cytostatic effect in HeLa, EAhy926, and L929 cells in a dose-dependent manner. On contrary, erlangerins A (40) and B (41) suppressed cell viability at relatively higher concentrations compared with erlangerins C (42) and D (43) [44]. Me O M eO

Me O OH

H

MeO O

M eO

OH O

OM e

O M eO OMe

OAc O

O O

40

O O

H

O

O O OM e

OAc O

MeO

OM e OMe

41

42

OH

O

O O

OAc O

OM e MeO

OM e OMe

43

Myrrh the resin of C. myrrha is mentioned in old literature such as the Chinese Materia Medica, the Bible, and other ancient writings because of its use as medicine, perfume, incense, to embalm the dead, etc. Resins originating from species other than C. myrrha contaminate myrrh of commerce. Tucker [1] has reported that the resins of many other species of Commiphora are known to pass for myrrh. A complicating factor in the study of the chemistry of myrrh is the fact that most previous chemical studies including those reports of [66–68] were based on materials obtained from the market. Consequently, such reports on myrrh were vague with regard to the geographical and botanical source of the investigated resins. Over a dozen compounds were, thus, reported to occur in myrrh such as 1(10),2-methoxy-8,12-epoxygermacra-1(10),7,11trien-6-one (44), 5-acetoxy-2-methoxy-8,12-epoxygermacra-1(10),7,11-trien-6-one (45), 3-methoxy-8,12-epoxygermacra-1,7,10(15),11-tetraen-6-one (46), elemol (47),

598

A. Dekebo et al.

furanodiene (48), furanodienone (49), isofuranogermacrene (syn. curzerene) (50), curzerenone (51), lindestrene (52), furanoeudesma-1,3-diene (53), furanoeudesma-1,4diene-6-one (54), 1(10)Z,4Z-furanodiene-6-one (55), 2-methoxy-furanodiene (56), 2-acetoxyfuranodiene (57), 4,5-dihydrofuranodiene-6-one (58), etc. Myrrh has been used since ancient times as a painkiller. These analgesic effects have been shown to be mainly due to two furanosesquiterpenes, furanoeudesma-1,3-diene (53) and isofuranogermacrene (syn. curzerene) (50), which are present in myrrh [76]. The resin of C. myrrha possesses antihyperglycemic properties due to two furanosesquiterpenes, namely, furanoeudesma-1,3-diene (53) and 2-acetoxyfuranodiene (57) [77]. Dolara et al. [78] reported a mixture of furanodiene-6-one (49) and methoxyfuranoguaia-9-ene-8-one (59) isolated from myrrh showed antimicrobial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, and Candida albicans, MIC (0.18 to 2.8 μg/ml). Compounds 49 and 59 were also reported to have anesthetic activity. Bao et al. [79] reported two new cadinene sesquiterpenes named myrrhterpenes A (60) and B (61), along with 18 known compounds previously reported from the resin of C. myrrha. They examined the anti-inflammatory activity of isolated compounds by measuring the inhibitory effects on the NO production in LPS-induced RAW 264.7 macrophage cells and reported two new compounds 60 and 61 displayed strong anti-inflammatory activities with IC50 values of 1.35 μM and 0.80 μM, respectively. Moreover, ten other compounds showed potent inhibition with an IC50 value of 0.72–18.36 μM [79]. Zhu et al. [69] isolated a novel compound rel-2R-methyl-5S-acetoxy-4Rfuranogermacr-1(10)Z-en-6-one (62) along with the known compounds, 44, 46, 51, 55, and 63 from myrrh purchased from Meixing Co, Shanghai, China. Comparison of the results with previous reports on myrrh indicates that the material analyzed by Zhu et al. [69] is most likely loaded with adulterants. A new furanosesquiterpene, (1E)-8,12-epoxygermacra-1,7,10,11-tetraen-6-one, was isolated from the resin of C. sphaerocarpa together with the known compounds curzerenone (51), furanodienone (49), (1E)-3-methoxy-8,12-epoxygermacra-1,7,10,11-tetraen-6-one (46), (1(10) E,2R*,4R*)-2-methoxy-8,12-epoxygermacra-1 (10),7,11-trien-6-one (44), and dihydropyrocurzerenone [10]. Though compounds 44, 46, 49, and 51 were reported [66–69] as constituents of the resin of C. myrrha (myrrh), they were not found in the true myrrh but were identified as constituents of other related adulterant resins such as those from C. sphaerocarpa, C. holtziana, and C. kataf [10, 80]. Isofuranogermacrene (50) and furanoeudesma-1,3-diene (53) were reported to have significant analgesic effects [76]. Commiphoins A–C (64–66), three new cadinane-type sesquiterpenes, along with the two known compounds 67 and 68 were isolated from the resinous exudates of C. myrrha [70]. Compounds 64, 65, 67, and 68 were reported to have antiAlzheimer’s disease bioactivities [70]. Additionally, some of the constituents of true myrrh have activities against the tick larvae, Rhipicephalus appendiculatus [81]. The antimicrobial activity of essential oils extracted from frankincense (Boswellia rivae, B. neglecta, and B. papyrifera) and essential oils obtained from the resins of C.

Ethnobotany, Chemistry, and Biological Activities of Some. . .

23

599

guidotti and C. myrrha of Ethiopian origin were investigated independently and in combination to determine their anti-infective properties [82]. Bio-assay of the frankincense and myrrh oils showed synergistic, additive, and noninteractive activities. Interestingly, there was no antagonism observed in the mixed frankincense and myrrh oils samples tested. When evaluated at different ratios of combinations against Bacillus cereus, the major interactions were synergistic and additive effects, with strong synergism exhibited between essential oils of resins from B. papyrifera and C. myrrha [82]. The reason for synergistic activity of the mixed frankincense–myrrh oils is still not well known [83]. Chen et al. [84] reported composition of triterpenes increases and sesquiterpenes decreases after dissolution of frankincense and myrrh. They showed sesquiterpenes inhibited the release of NO generated by LPS-induced macrophage cells in rats. Other researchers reported there are chemical and physical changes such as solubilization, oxidation, reduction, hydrolysis, etc. occurring when frankincense and myrrh were mixed [85]. C. hotziana Engl. is a large tree characterized by a blue-green bark. Provan et al. [72] studied the essential oils of the resin of C. holtziana and identified compounds 44, 45, 46, and 51. Cavanagh et al. [86] reported furanogermacranes, 44, 45, 46, 51, and 63, from the resin of this plant.

M eO

MeO

O

O

O

OO

O 44

O

O

O

O

O

H

O 51

50

49 R

47

46

O 45 O

O

OH

M eO

48 O

O

H 52

O 54

53 MeO

O

O

O

OH OH O

O

O

O O 58

56: R = OMe

O 55

O 59

57: R = OAc O

O

OH 61

O

O

M eO

O

OAc 62

O

60

O 63

Examination of the resin of C. guidottii (opoponax) yielded sesquiterpene hydrocarbons and furanodiene (48) [87]. Bioassay-guided fractionation of an ethyl acetate extract of this resin, using the guinea pig ileum test to monitor its pharmacological activity, resulted in the isolation of the sesquiterpene (+)-T-cadinol (69), as the major bioactive component of the plant [48]. T-cadinol exhibited a concentration-

600

A. Dekebo et al.

dependent smooth muscle relaxing effect, which explains the traditional use of the resin to cure stomach complaints including diarrhea. Andersson et al. [47] isolated minor compounds 70–75 from the polar fraction of scented myrrh and found out that these compounds were less potent than T-cadinol. Coatings of opoponax essential oil or individual terpenoids were tested for larvicidal or anti-settlement activity against cypris larvae of barnacle Balanus amphitrite [71]. These workers identified main ingredients such as β-ocimene (76), β-bisabolene (77), α-bisabolol (78), and farnesol (79) in the essential oil opoponax. Among these constituents of opoponax, farnesol (79) and α-bisabolol (78) showed antifouling activity by inhibiting cypris larvae of the barnacle Balanus amphitrite with the LC50 values of 18 and 88 respectively after 48 h [71]. β-Bisabolene (77) and α-bisabolol (78), were also tested for their ability to selectively kill breast cancer cells. Only β-bisabolene showed selective cytotoxic activity against mouse cells (IC50 in normal Eph4: >200 μg/ml, MG1361: 65.49 μg/ml, 4 T1: 48.99 μg/ml) and human breast cancer cells (IC50 in normal MCF-10A: 114.3 μg/ml, MCF-7: 66.91 μg/ml, MDA-MB-231: 98.39 μg/ml, SKBR3: 70.62 μg/ml and BT474: 74.3 μg/ml) [88]. Ointment formulations of both the oil and resin of C. guidotti were found to be non-irritant at the concentrations used and showed a significant increase in wound contraction rate, shorter epithelization time, and higher skin breaking strength. The antibacterial and antifungal activities of the oil and resin in this plant were comparable with the standard antibiotics ciprofloxacin and griseofulvin, respectively [49]. OH O

O

O

HO

O

OH

65

64 OH

HO

O

67

69

68 OH

OH

OH

O

OH

O

O

66 OH

OH

OH O

OH

HO HO

OH 70

71

72

73

OH

O 74

75

Some Commiphora species such as C. rostrata trees, which ooze out oily resins, are not prone to damage by herbivores or pathogens [89]. When the branches of such trees are bent or as a response to attacking predators or pathogens, aromatic oil exudes out. After a short time, this is converted to a white sticky substance at the wound site which presumably acts to protect and prevent water loss from the wound. The fluid resin oil from C. rostrata is distinguished by the presence of homologous ketones such as 2-octanone, 2-nonanone, 2-decanone, etc. The occurrence of large quantities of aliphatic ketones in such exudates implies that these substances are responsible for chemical defense [89].

23

Ethnobotany, Chemistry, and Biological Activities of Some. . .

601

Three Commiphora species growing in arid parts of northern and eastern Kenya were characterized by the production of aromatic resins. Volatile oils obtained by steam distillation of resins from C. africana, C. campestris Engl., and C. ogadensis Chiov. were examined by GC and GC-MS and reported to be entirely composed of monoterpenoids [72]. All three resins were characterized by having large amounts of α-pinene (33) in their oils. Other constituents that were important markers of individual species include β-pinene (36), myrcene (80), car-3-ene (81), and limonene (82) (C. ogadensis); p-cymene (32), α-thujene (35), camphene (83), terpinen-4-ol (84), and verbenone (85) (C. africana) [72]. Dinku et al. [73] reported a new tricyclic triterpene acid (3S,4S,14S,7E,17E,21Z)3,30-dihydroxypodioda-7,17,21-trien-4-carboxylic acid (commafric A) (86) from a crude methanolic extract of C. africana and its exhibited significant antiproliferative effects against non-small cell lung cancer (A549). The chloroform fraction of C. habessinica significantly inhibited cell proliferation of A549, A2780, MIA-PaCa2, and SNU-638, with dose-dependent relation in vitro. A mixture of cholesterol (87) and lathosterol (88) isolated from the resin of the plant exhibited moderate cytotoxicity which is greater than the individual compound towards A549 and A2780 [74]. Examination of the fluid exudate obtained upon wounding the bark of C. tenuis indicated α-pinee (33) as the major component [52]. The exudate showed antibacterial activities against Staphylococcus aureus, Proteus mirabilis, and Escherichia coli bacterial strains.

OH OH 76

77

79

78

HO 81

82

83

O

84

85

HO HOOC

80

86 OH

HO HO 87

88

602

6

A. Dekebo et al.

Conclusion

The ethnobotanical, botanical, phytochemical, and pharmacological activities reviewed indicted resins of Commiphora have a lot of prospects to be used as traditional medicines and in pharmaceutical industries. However, further studies are still required to confirm their safety and efficacy. Phytochemicals reported from solvent extracts and essential oils of the plants were reviewed. The plants have mainly terpenoids with a different number of carbons such as triterpenes, diterpenes, sesquiterpenes, and monoterpenes. Dammarane triterpenes were reported from C. dalzielii and C. confusa. Mansumbinones or dammarane triterpenes were reported from C. kua. Some of these compounds isolated from these plants showed anti-inflammatory activities. Lignans and its epimer picropolygamain were reported from the resins of C. kua and C. erlangeriana. Resins of C. myrrha, C. sphaerocarpa, C. holtziana, and C. kataf were reported constituting mainly furanosesquiterpenes. Monoterpenes and sesquiterpenes were reported from the essential oils of resins of different Commiphora species. Ethiopia, Somalia, Kenya, and some Asian countries such as India have a large, as yet, the properly unexploited potential to produce Commiphora resins resources. However, the vegetation resources are diminishing rapidly due to the continuous pressure from deforestation for agricultural activities, construction, and firewood with an increase in population. Even though the genus Commiphora has several species, the information reported on their phytochemicals, botanicals, pharmacological aspects is still limited. Some of the problems include botanical authentication of their botanical specimens and problems connected with accessibility for studies due to lack of transportation as most of these plants are found in semiarid regions. Absence of strategies and action plans for the development, sustainable utilization, and conservation of these resources has significant socio-economic, cultural, and ecological importance. The other main obstacle for conducting research on Commiphora species is that research facilities are not conducive in those remote arid regions. We believe research and development efforts are important for the conservation, production, and commercialization of these renewable natural resources for the benefit of the livelihood of local people, international companies involved in the business, pharmaceutical, and other industries. Mechanisms to promote the countries’ potential for value addition and industrialization of gum resin products should be one of the priority international collaboration areas in the future to achieve sustainable development. Therefore, international collaboration and sharing of resources for the research is important to explore further these Commiphora resins which might enable to isolate more bioactive compounds which have a potential to cure various diseases such as cancer and viral diseases which are challenging the world. Acknowledgments Financial support for this work was partly obtained from the Basic Science Research Programme through the National Research Foundation of Korea (NRF), funded by the Ministry of Education (NRF-2018R1A6A1A03024862). AD is grateful to the World Academy of Sciences (TWAS) and the United Nations Educational, Scientific and Cultural Organization (UNESCO) for supporting this research with funds under the TWAS Research Grant Award_20274 RG/CHE/AF/AC_G – FR3240314163). We thank Prof. Ermias Degne for his assistance.

23

Ethnobotany, Chemistry, and Biological Activities of Some. . .

603

References 1. Tucker AO (1986) Frankincense and myrrh. Econ Bot 40:425–433 2. Kassa H (2011) Preliminary value chain analysis of gum and resin marketing in Ethiopia: issues for policy and research. Center for International Forestry Research. https://www.cifor.org/ knowledge/publication/3422/. Accessed 15 Feb 2021 3. Hassan B, Glover EK, Luukkanen O, Chikamai B, Jamnadass R, Iiyama M, Kanninen M (2011) The role of Boswellia and Commiphora species in rural livelihood security and climate change adaptation in the horn of Africa: a case study of northeastern Kenya. Int J Soc Forestry 4:86–112 4. Lemenih M, Kassa H (2011) Gums and resins of Ethiopia. CIFOR brief, (3). https://www.jstor. org/stable/resrep01894?seq¼1#metadata_info_tab_contents. Accessed 5 Apr 2021 5. Vollesen K (1989) Burseraceae. In: Hedberg I, Edwards S (eds) Flora of Ethiopia, volume 3. Pittosporaceae to Araliaceae. National Herbarium, Addis Ababa University, Uppsala University, Addis Ababa, Uppsala 6. Hostettmann K, Chinyanganya F, Maillard M, Wolfender J. (1996) Chemistry, biological, and pharmacological properties of African medicinal plants. Proceedings of the first international IOCD-symposium Victoria Falls. University of Zimbabwe Publications, Harare 7. Waterman PG, Grundon MF (1983) Chemistry and chemical taxonomy of the Rutales. In: Structural diversity and distribution of alkaloids in the Rutales. Academic, London 8. Guenther E (1950) The essential oils. Vol. 4. Oil of citronella. D. Van Nostrand 65:131 9. Coppen JJ (1995) Flavours and fragrances of plant origin. FAO, Rome 10. Dekebo A, Dagne E, Sterner O (2002) Furanosesquiterpenes from Commiphora sphaerocarpa and related adulterants of true myrrh. Fitoterapia 73:48–55 11. Thulin M, Claeson P (1991) The botanical origin of scented myrrh (blssabol or habak hadi). Econ Bot 45:487–494 12. Dekebo A (2002) Chemical studies of the resins of some Boswellia and Commiphora species. Dissertation, Addis Ababa University 13. Shoemaker M, Hamilton B, Dairkee SH, Cohen I, Campbell MJ (2005) In vitro anticancer activity of twelve Chinese medicinal herbs. Phytother Res 19:649–651 14. Su S, Wang T, Chen T, Duan J-a YL, Tang Y (2011) Cytotoxicity activity of extracts and compounds from Commiphora myrrha resin against human gynecologic cancer cells. J Med Plant Res 5:1382–1389 15. Racine P, Auffray B (2005) Quenching of singlet molecular oxygen by Commiphora myrrha extracts and menthofuran. Fitoterapia 76:316–323 16. Omer S, Adam S, Mohammed O (2011) Antimicrobial activity of Commiphora myrrha against some bacteria and Candida albicans isolated from gazelles at King Khalid Wildlife Research Centre. Res J Med Plant 5:65–71 17. Bruneton J (1995) Pharmacognosy, phytochemistry, medicinal plants. Lavoisier publishing, Paris 18. Bradley P (1992) British herbal compendium. Volume 1. A handbook of scientific information on widely used plant drugs. Companion to volume 1 of the British Herbal Pharmacopoeia. https:// www.agris.fao.org/agris-search/search.do?recordID¼GB9406989. Accessed 14 July 2021 19. Schilcher H (1997) Phytotherapy in pediatrics: a handbook for physicians and pharmacists. Medpharm Scientific Publishers, Berlin 20. Tyler VE, Foster S (1993) The honest herbal: a sensible guide to the use of herbs and related remedies. Pharmaceutical Products Press, New York 21. Al-Howiriny T, Al-Sohaibani M, Al-Said M, Al-Yahya M, El-Tahir K, Rafatullah S (2005) Effect of Commiphora opobalsamum (L.) Engl.(Balessan) on experimental gastric ulcers and secretion in rats. J Ethnopharmacol 98:287–294 22. Shen T, Wan W, Yuan H, Kong F, Guo H, Fan P, Lou H (2007) Secondary metabolites from Commiphora opobalsamum and their antiproliferative effect on human prostate cancer cells. Phytochemistry 68:1331–1337 23. Abdul-Ghani A-S, Amin R (1997) Effect of aqueous extract of Commiphora opobalsamum on blood pressure and heart rate in rats. J Ethnopharmacol 57:219–222

604

A. Dekebo et al.

24. Al-Howiriny T, Al-Sohaibani M, Al-Said M, Al-Yahya M, El-Tahir K, Rafatullah S (2004) Hepatoprotective properties of Commiphora opobalsamum (“Balessan”), a traditional medicinal plant of Saudi Arabia. Drugs Exp Clin Res 30:213–220 25. Al-Howiriny TA, Al-Yahya MA, Al-Said MS, El-Tahir KE, Rafatullah S (2004) Studies on the pharmacological activities of an ethanol extract of balessan (Commiphora opobalsamum). Pak J Biol Sci 7:1933–1936 26. Sharma J (1977) Comparison of the anti-inflammatory activity of Commiphora mukul (an indigenous drug) with those of phenylbutazone and ibuprofen in experimental arthritis induced by mycobacterial adjuvant. Arzneim Forsch 27:1455–1457 27. Arora R, Kapoor V, Gupta S, Sharma R (1971) Isolation of a crystalline steroidal compound from Commiphora mukul and its anti-inflammatory activity. Indian J Exp Biol 9:403 28. Francis JA, Raja SN, Nair MG (2004) Bioactive terpenoids and guggulusteroids from Commiphora mukul gum resin of potential anti-inflammatory interest. Chem Biodivers 1: 1842–1853 29. Singh RB, Niaz MA, Ghosh S (1994) Hypolipidemic and antioxidant effects of Commiphora mukul as an adjunct to dietary therapy in patients with hypercholesterolemia. Cardiovasc Drugs Ther 8:659–664 30. Wang X, Greilberger J, Ledinski G, Kager G, Paigen B, Jürgens G (2004) The hypolipidemic natural product Commiphora mukul and its component guggulsterone inhibit oxidative modification of LDL. Atherosclerosis 172:239–246 31. Singha MB, Sarma T, Lahkar M (2019) Anti-hypothyroid potential of bauhinia variegate and Commiphora mukul extracts in albino wistar rats: a histopathological investigation. J Pharmacogn Phytochem 8:1736–1740 32. Saeed MA, Sabir A (2004) Antibacterial activities of some constituents from oleo-gum-resin of Commiphora mukul. Fitoterapia 75:204–208 33. Sultana N, Jahan S (2005) Studies on the constituents of Commiphora mukul. Z Naturforsch B 60:1202–1206 34. Sotoudeh R, Mousa-Al-Reza Hadjzadeh ZG, Aghaei A (2019) The anti-diabetic and antioxidant effects of a combination of Commiphora mukul, Commiphora myrrha and Terminalia chebula in diabetic rats. Avicenna J Phytomed 9:454–464 35. Sharma B, Salunke R, Srivastava S, Majumder C, Roy P (2009) Effects of guggulsterone isolated from Commiphora mukul in high-fat diet-induced diabetic rats. Food Chem Toxicol 47: 2631–2639 36. Madasu C, Karri S, Sangaraju R, Sistla R, Uppuluri MV (2020) Synthesis and biological evaluation of some novel 1, 2, 3-triazole hybrids of myrrhanone B isolated from Commiphora mukul gum resin: identification of potent antiproliferative leads active against prostate cancer cells (PC-3). Eur J Med Chem 188:111974 37. Shen T, Zhang L, Wang Y-Y, Fan P-H, Wang X-N, Lin ZM, Lou HX (2012) Steroids from Commiphora mukul display antiproliferative effect against human prostate cancer PC3 cells via induction of apoptosis. Bioorg Med Chem Lett 22:4801–4806 38. Annu W, Latha P, Shaji J, Anuja G, Suja S, Sini S, Shyamal S, Shine VJ, Shikha P, Rajasekharan S (2010) Anti-inflammatory, analgesic and anti-lipid peroxidation studies on leaves of Commiphora caudata (Wight & Arn.) Engl. Indian J Nat Prod Resour 1:44–48 39. Shankar NG, Manavalan R, Venkappayya D, Raj CD (2008) Hepatoprotective and antioxidant effects of Commiphora berryi (Arn) Engl bark extract against CCl4-induced oxidative damage in rats. Food Chem Toxicol 46:3182–3185 40. Shen T, Li G-H, Wang X-N, Lou H-X (2012) The genus Commiphora: a review of its traditional uses, phytochemistry, and pharmacology. J Ethnopharmacol 142:319–330 41. Kumari R, Meyyappan A, Nandi D, Agrawalla BK, Chowdhury AA, Selvamani P, Latha S, Giri VS, Mukherjee J, Bandyopadhyay S, Jaisankar P (2011) Antioxidant and antibacterial activities of bark extracts from Commiphora berryi and Commiphora caudata. Nat Prod Res 25:1454– 1462

23

Ethnobotany, Chemistry, and Biological Activities of Some. . .

605

42. Birkett MA, Al Abassi S, Kröber T, Chamberlain K, Hooper AM, Guerin PM, Pettersson J, Pickett JA, Slade R, Wadhams LJ (2008) Antiectoparasitic activity of the gum resin, gum haggar, from the East African plant, Commiphora holtziana. Phytochemistry 69:1710–1715 43. Curry P (2000) Gum and resin research project II. Saltlick, Isiolo 44. Habtemariam S (2003) Cytotoxic and cytostatic activity of erlangerins from Commiphora erlangeriana. Toxicon 41:723–727 45. Suleiman MM, McGaw L, Naidoo V, Eloff J (2010) Detection of antimicrobial compounds by bioautography of different extracts of leaves of selected south African tree species. Afr J Tradit Complement Altern Med 7:64–78 46. Fourie TG, Snyckers FO (1989) A pentacyclic triterpene with anti-inflammatory and analgesic activity from the roots of Commiphora merkeri. J Nat Prod 52:1129–1131 47. Andersson M, Bergendorff O, Shan R, Zygmunt P, Sterner O (1997) Minor components with smooth muscle relaxing properties from scented myrrh (Commiphora guidotti). Planta Med 63: 251–254 48. Claeson P, Andersson R, Samuelsson G (1990) T-Cadinal: a sesquiterpene with smooth muscle relaxing and antidiarrhoeal properties isolated from scented myrrh. Planta Med 56:685–685 49. Gebrehiwot M, Asres K, Bisrat D, Mazumder A, Lindemann P, Bucar F (2015) Evaluation of the wound healing property of Commiphora guidottii Chiov. ex. Guid. BMC Complement Altern Med 15:1–11 50. Gradé JT, Tabuti JR, Van Damme P (2009) Ethnoveterinary knowledge in pastoral Karamoja, Uganda. J Ethnopharmacol 122:273–293 51. Carroll J, Maradufu A, Warthen J Jr (1989) An extract of Commiphora erythraea: a repellent and toxicant against ticks. Entomol Exp Appl 53:111–116 52. Asres K, Tei A, Moges G, Sporer F, Wink M (1998) Terpenoid composition of the woundinduced bark exudate of Commiphora tenuis from Ethiopia. Planta Med 64:473–475 53. Patil V, Nayak U, Dev S (1972) Chemistry of ayurvedic crude drugs—I: Guggulu (resin from Commiphora mukul)—1: steroidal constituents. Tetrahedron 28:2341–2352 54. Bajaj AG, Dev S (1982) Chemistry of ayurvedic crude drugs—V: Guggulu (resin from Commiphora mukul)—5 some new steroidal components and, the stereochemistry of guggulsterol-I at C-20 and C-22. Tetrahedron 38:2949–2954 55. Tripathi YB, Malhotra O, Tripathi S (1984) Thyroid-stimulating action of Z-guggulsterone obtained from Commiphora mukul. Planta Med 50:78–80 56. Patil V, Nayak U, Dev S (1973) Chemistry of ayurvedic crude drugs—II: Guggulu (resin from Commiphora mukul)-2: Diterpenoid constituents. Tetrahedron 29:341–348 57. Waterman PG, Ampofo S (1985) Dammarane triterpenes from the stem bark of Commiphora dalzielii. Phytochemistry 24:2925–2928 58. Dekebo A, Dagne E, Curry P, Gautun OR, Aasen AJ (2002) Dammarane triterpenes from the resins of Commiphora confusa. Bull Chem Soc Ethiop 16:81–86 59. Provan GJ, Waterman PG (1985) Picropolygamain: a new lignan from Commiphora incisa resin1, 2. Planta Med 51:271–272 60. Provan GJ, Waterman PG (1986) The mansumbinanes: octanordammaranes from the resin of Commiphora incisa. Phytochemistry 25:917–922 61. Waterman PG (1988) Major triterpenes from the resins of Commiphora incisa and C. kua and their potential chemotaxonomic significance. Phytochemistry 27:3841–3843 62. Provan GJ, Gray AI, Waterman PG (1992) Mansumbinane derivatives from the stem bark of Commiphora kua. Phytochemistry 31:2065–2068 63. Dekebo A, Dagne E, Hansen LK, Gautun OR, Aasen AJ (2002) Two octanordammarane triterpenes from Commiphora kua. Phytochemistry 59:399–403 64. Manguro LO, Mukonyi KM, Githiomi JK (1996) Bisabolenes and furanosesquiterpenoids of Kenyan Commiphora kua resin. Planta Med 62:84–85 65. Dekebo A, Lang M, Polborn K, Dagne E, Steglich W (2002) Four lignans from Commiphora erlangeriana. J Nat Prod 65:1252–1257

606

A. Dekebo et al.

66. Brieskorn CH, Noble P (1983) Two furanoeudesmanes from the essential oil of myrrh. Phytochemistry 22:187–189 67. Brieskorn CH, Noble P (1982) Inhaltsstoffe des etherischen Öls der Myrrhe. Planta Med 44: 87–90 68. Brieskorn CH, Noble P (1980) Drei neue furanogermacrene aus myrrhe. Tetrahedron Lett 21: 1511–1514 69. Zhu N, Kikuzaki H, Sheng S, Sang S, Rafi MM, Wang M, Nakatani N, DiPaola RS, Rosen RT, Ho CT (2001) Furanosesquiterpenoids of Commiphora myrrha. J Nat Prod 64:1460–1462 70. Yu Y-F, Liu Y-H, Chen X-H, Zhi D-J, Qi F-M, Zhang ZP, Li YQ, Zhang ZX, Fei DQ (2020) Cadinane-type sesquiterpenes from the resinous exudates of Commiphora myrrha and their anti-Alzheimer’s disease bioactivities. Fitoterapia 142:104536 71. Pope EC, Ali A, Conlan SL, Bowen ID, Clare AS, Rowley AF (2008) Myrrh-derived terpenoids as inhibitors of marine biofouling. Aquat Biol 4:175–185 72. Provan GJ, Gray AI, Waterman PG (1987) Monoterpene-rich resins from some Kenyan Burseraceae. Flavour Fragr J 2:115–118 73. Dinku W, Isaksson J, Rylandsholm FG, Bouř P, Brichtová E, Choi SU, Lee SH, Jung YS, No ZS, Svendsen JS, Aasen AJ, Dekebo A (2020) Anti-proliferative activity of a novel tricyclic triterpenoid acid from Commiphora africana resin against four human cancer cell lines. Appl Biol Chem 63:1–11 74. Dinku WCS, Lee S-H, Jung Y-S, No ZS, Dekebo A (2019) Antiproliferative effect of sterols from resin of Commiphora habessinica. J Pharm Nutr Sci 9:71–80 75. Duwiejua M, Zeitlin I, Waterman P, Chapman J, Mhango G, Provan G (1993) Antiinflammatory activity of resins from some species of the plant family Burseraceae. Planta Med 59:12–16 76. Dolara P, Luceri C, Ghelardini C, Monserrat C, Aiolli S, Luceri F, Lodovici M, Menichetti S, Romanelli MN (1996) Analgesic effects of myrrh. Nature 379:29–29 77. Ubillas RP, Mendez CD, Jolad SD, Luo J, King SR, Carlson TJ, Fort DM (1999) Antihyperglycemic furanosesquiterpenes from Commiphora myrrha. Planta Med 65:778–779 78. Dolara P, Corte B, Ghelardini C, Pugliese AM, Cerbai E, Menichetti S, Nostro AL (2000) Local anesthetic, antibacterial and antifungal properties of sesquiterpenes from myrrh. Planta Med 66: 356–358 79. Bao S, Li C, Li H, Wang J, Luan J, Zhang Y, Chen L, Hu Y, Wang X (2021) Myrrhterpenes A and B, anti-inflammatory cadinane sesquiterpenes from the resin of Commiphora myrrha. Phytochem Lett 44:190–194 80. Dekebo A, Dagne E, Hansen LK, Gautun OR, Aasen AJ (2000) Crystal structures of two furanosesquiterpenes from Commiphora sphaerocarpa. Tetrahedron Lett 41:9875–9878 81. Maradufu A (1982) Furanosesquiterpenoids of Commiphora erythraea and C. myrrha. Phytochemistry 21:677–680 82. De Rapper S, Van Vuuren S, Kamatou G, Viljoen A, Dagne E (2012) The additive and synergistic antimicrobial effects of select frankincense and myrrh oils–a combination from the pharaonic pharmacopoeia. Lett Appl Microbiol 54:352–358 83. Cao B, Wei X-C, Xu X-R, Zhang H-Z, Luo C-H, Feng B, Xu RC, Zhao SY, Du XJ, Han L, Zhang DK (2019) Seeing the unseen of the combination of two natural resins, frankincense, and myrrh: changes in chemical constituents and pharmacological activities. Molecules 24:3076 84. Chen T, Su S-L, Duan J-A, Shang E-X, Qian D-W, Tang Y-P (2013) Change in the dissolution of chemical components of frankincense-myrrh before and after their compatibility and effect on no release of LPS-induced macrophage cells. Zhongguo Zhong yao za zhi¼ Zhongguo zhongyao zazhi: Chin J Chin Mat Med 38:179–185 85. Marongiu B, Piras A, Porcedda S, Scorciapino A (2005) Chemical composition of the essential oil and supercritical CO2 extract of Commiphora myrrha (Nees) Engl. and of Acorus calamus L. J Agric Food Chem 53:7939–7943

23

Ethnobotany, Chemistry, and Biological Activities of Some. . .

607

86. Cavanagh IS, Cole MD, Cavanagh IS, Gibbons S, Gray AI, Provan GJ, Waterman PG (1993) A novel sesquiterpene, 1, 2-epoxyfurano-10 (15)-germacren-6-one, from the resin of Commiphora holtziana Engl. Flavour Fragr J 8:39–41 87. Craveiro A, Corsano S, Proietti G, Strappaghetti G (1983) Constituents of essential oil of Commiphora guidotti. Planta Med 48:97–98 88. Yeo SK, Ali AY, Hayward OA, Turnham D, Jackson T, Bowen ID, Clarkson R (2016) β-Bisabolene, a sesquiterpene from the essential oil extract of opoponax (Commiphora guidottii), exhibits cytotoxicity in breast cancer cell lines. Phytother Res 30:418–425 89. McDowell PG, Lwande W, Deans SG, Waterman PG (1988) Volatile resin exudate from the stem bark of Commiphora rostrata: potential role in plant defense. Phytochemistry 27:2519– 2521

Chemistry, Biological Activities, and Uses of Araucaria Resin

24

Ajay Kumar, Swati Singh, Munmun Kumar Singh, Atul Gupta, Sudeep Tandon, and Ram Swaroop Verma

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Botanical Aspects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Chemistry and Biological Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Araucaria angustifolia (Bertol.) Kuntze . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Araucaria araucana (Molina) K.Koch . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Araucaria bernieri J.Buchholz . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Araucaria bidwillii Hook. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5 Araucaria columnaris (G.Forst.) Hook. (syn. Araucaria excelsa (Lamb.) R.Br.) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6 Araucaria cunninghamii Mudie . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7 Araucaria heterophylla (Salisb.) Franco . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8 Araucaria hunsteinii K.Schum. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9 Araucaria laubenfelsii Corbasson . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10 Araucaria luxurians (Brongn. & Gris) de Laub. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11 Araucaria montana Brongn. & Gris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.12 Araucaria muelleri (Carriere) Brongn. & Gris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.13 Araucaria nemorosa de Laub. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.14 Araucaria scopulorum de Laub. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

610 611 612 612 613 614 614 615 616 618 619 620 620 620 620 620 621 621 624

A. Kumar Bioprospection and Product Development Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, India Government Pharmacy College, BRD Medical College Campus, Gorakhpur, India S. Singh · M. K. Singh · A. Gupta · S. Tandon · R. S. Verma (*) Phytochemistry Division, CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, India Academy of Scientific and Innovative Research (AcSIR), Ghaziabad, India e-mail: [email protected]; [email protected]; [email protected]; [email protected] © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_28

609

610

A. Kumar et al.

Abstract

The members of the genus Araucaria (Araucariaceae) are evergreen coniferous trees, widely used for medicinal, ornamental, and timber purposes. This overview includes the phytochemical, medicinal properties, and biological activities of various species of Araucaria. In this study, the most recent scientific research has been compiled from various publications to focus on the untapped potential of Araucaria species. There are twenty species in the genus Araucaria. The species of Araucaria have been found to produce resins, a complex combination of terpenoids and phenolics, with terpenoid resins being the majority. Besides, the prevalence of diterpenoids in the species of Araucaria, bioflavonoids, isoflavones, sesquiterpenes, polysaccharides, phenylpropanoids, lignans, and other phenolics have also been isolated. Phyllocladene, hibaene, 16-kaurene, luxuriadiene, and sclarene were the most abundant diterpenoids, whereas β-caryophyllene, germacrene D, bicyclogermacrene, and spathulenol were the most widely distributed sesquiterpenoids. Monoterpenoids are often identified as α-pinene, sabinene, myrcene, limonene, and γ-terpinene. A thorough review of the literature revealed that different species of Araucaria possess a diverse range of biological activities, including antibacterial, cytotoxic, antiinflammatory, gastro-protective, wound healing, antidiabetic, anti-rheumatoid, anticancer, antidepressant, and sedative properties. Studies showed a lot of potential in exploring the phytochemical and pharmacological properties of Araucaria species, specifically resins and essential oils. Keywords

Araucaria · Biological activity · Essential oil · Labdane diterpene · Resin · Terpenoids List of Abbreviations

GC-MS MTT

1

gas chromatography-mass spectrometry 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide

Introduction

Medicinal plants are the gift of nature to us to live a healthy and illness-free life. Since ancient times, people have sought nature for solutions to various illnesses [1, 2]. Araucaria is an important genus of the Araucariaceae family that has long been used in traditional medicine as an essential oil, resin, and human nutrition [3–6]. Araucaria species are abundant in bioactive compounds and have been used for centuries by many cultures worldwide [7, 8]. The Araucariaceae family has 41 species divided into 3 genera of cone-bearing trees (Araucaria, Agathis, and Wollemia). The genus Araucaria alone includes 20 species [9–11]. Numerous species of the genus Araucaria are cultivated for aesthetic and wood uses. In contrast, others, including Araucaria araucana (Molina) K.Koch, Araucaria angustifolia (Bertol.) Kuntze, Araucaria

24

Chemistry, Biological Activities, and Uses of Araucaria Resin

611

heterophylla (Salisb.) Franco, Araucaria bidwillii Hook., and Araucaria cunninghamii Mudie, are used medicinally [12]. Brazil, South America, Australia, Chile, New Guinea, New Caledonia, Norfolk Island, and many more tropical and subtropical zones of the Southern Hemisphere are its native habitat [13]. Fossil evidence suggests that it once existed in the northern hemisphere as well [14]. Oceania, an area of the South Pacific Ocean, is home to 17 species, 13 of which are indigenous to the small archipelago of New Caledonia. The last two species (A. araucana and A. angustifolia) are abundant in southern South America [15, 16]. Their distinctive and recognizable crown silhouette effortlessly identifies the araucarias. Most species are marine and range from sea level to 2500 m. These trees are frequently appearing in the coastal forest that comes into touch with the beach. Their leaves are coated with a thick waxy covering which protects them from harm caused by salt-laden air [17]. Twisted branches and stiff, flat, pointed leaves characterize the evergreen trees of this species. Certain species have tightly packed leaves that give the stems a scaly appearance. Male and female cones are often formed on separate individuals of the plant having edible seeds. Female cones are usually spherical [18]. Resins are reported in many species of Araucaria. Resins are a complex mixture of terpenoid and/or phenolic compounds, with the majority being terpenoid resins [19]. Terpenes are chemo-systematic markers for the conifers. The tetracyclic diterpenes, beyeranes, occur merely in a few members of Cupressaceae and Araucariaceae. However, kauranes show a wide distribution in the conifers, particularly in Araucariaceae [20]. The characteristic compounds in the genus Araucaria are labdane diterpenes and bioflavonoids [21–23]. Many labdanetype diterpenes have been reported to have antibacterial and antifungal activities [24, 25]. Araucarian are rich in essential oils and the majority of which are composed of monoterpenoids such as pinene, thujene, limonene, etc. Additionally, sesquiterpenoids and diterpenoids are also found in essential oils [5, 26]. This genus is also rich in various phytoconstituents, such as phenolics. The most often seen pharmacological action of Araucaria species in contemporary, traditional medicine is anti-inflammatory [27, 28]. Additionally, it possesses antiulcer, wounds healing, anti-rheumatoid, antiviral [4], anti-infectives, antifungal [29], antioxidant, neuroprotective [30], gastro-protective [6, 31], antidepressant [32], and antidiabetic and anticoagulant effects [12, 33]. The present chapter focuses on phytochemistry, pharmacological activities, clinical research, and the application of Araucaria gums, resins, and latex. This chapter will help natural product researchers worldwide become aware of the unexplored potential of Araucaria species.

2

Botanical Aspects

The family members of Araucariaceae comprise 10 to 90 m in height, although the most common mature size is around 50 m. The Araucariaceae has 41 species divided into 3 genera of cone-bearing trees (Araucaria, Agathis, and Wollemia). Agathis and Wollemia have been recovered as a monophyletic group in the most recent morphological, molecular, and combined phylogenetic analyses [34]. Agathis and Wollemia are also easily distinguished from Araucaria by leaf morphology and anatomy

612

A. Kumar et al.

[35]. The genus Araucaria includes 20 species further classified into four sections [10]. The species of genus Araucaria are predominantly dioecious trees, though monoecious species can also occur. However, some trees are also able to modify their sex gradually [36]. The genus has two distinct leaf morphologies. The first one is characterized by sessile, imbricate, usually erect, and relatively small leaves persistent on falling branches that are typical of the Araucaria section Eutacta; and the second one is characterized as sessile leaves with broad, flat lamina and acute apices that are characteristic of Araucaria sections Araucaria, Intermedia, and Bunya [35, 37, 38].

3

Chemistry and Biological Activities

3.1

Araucaria angustifolia (Bertol.) Kuntze

A. angustifolia is also referred to as Brazilian pine and Parana pine. Its seeds, known locally as pinhao are typically consumed after boiling or make flour [39]. In Brazil, the leaves of A. angustifolia are used as emollient, antiseptic, and to treat respiratory infections and rheumatisms. Their dyes are also used to treat wounds and herpes eruptions [40]. The infusions prepared from the plant’s bark are used topically to treat muscular tensions and varicose veins. The syrup produced by the resin is used to treat respiratory infections [41]. A study from Brazil reported pinoresinol, pinoresinol monomethyl ether, eudesmin, hinokiresinol, isolariciresinol, and (
) seco-isolariciresinol in the resin of A. angustifolia [42]. The volatile oil extracted from the leaves of A. angustifolia is found to be rich in diterpenes, including hibaene (¼ beyerene; 29.7%) and phyllocladene (20.1%), and sesquiterpenes, such as germacrene D (8.6%), bicyclogermacrene (3.4%), spathulenol (2.2%), α-cadinol (1.4%), and δ-cadinene (1.0%) [26]. GC-MS analysis of the twigs and leaves shows sesquiterpenoids such as ionene, n-methyl naphthalene, dihydro-arcurcumene, 1,3,4-trimethyl-2-(4-methylpentyl)benzene, calamenene, norcadalene, calamene, cadalene, pentamethyl-dihydroindene-1, pentamethyl-dihydroindene-2, and chamazulene. The diterpenoids present in the twigs and leaves are mainly monoaromatic labdane, abietane-type, such as 19-norabietatriene, 18-norabietatriene, dehydroabietane, 1-methyl-10,18-bisnorabieta-8,11,13-triene, 1,2,3,4tetrahydroretene, retene, 9-methyl-retene, 2-methyl-retene, and some related abietane-type diterpenoids, like pentamethyl phenanthrene, and isohexylalkylaromatic hydrocarbons such as 2,6-dimethyl-1-(4-methylpentyl)naphthalene, and 6-ethyl-2-dimethyl-1-(4-methylpentyl)naphthalene. In addition, pimarane-type, Ent-beyerane, 16β(H)-phyllocladanes, and Ent-16β(H)-kauranes are also identified in A. angustifolia [5]. The plant’s ethanol, water, hydroalcoholic, and ethyl acetate extracts showed good antioxidant properties [43–45]. Human salivary and porcine pancreatic α-amylase are effectively inhibited by the A. angustifolia coat extract due to its high condensed tannin content [46]. The resin extract of A. angustifolia exhibited antibacterial effects against Rhizopus stolonifer, Aspergillus niger, Fusarium moniliforme, Aspergillus terreus, Penicillium citrinum, Cladosporium

24

Chemistry, Biological Activities, and Uses of Araucaria Resin

613

cladosporioides, Aureobasidium pullulans, Chaetomium globosum, Aspergillus restrictus, Penicillium frequentans, and Penicillium funiculosum [47]. The ethyl acetate and n-butanol fractions of A. angustifolia showed strong antiviral effects against HSV-1 with IC50 values equal to 8.19 and 11.04 μg/mL, respectively [4]. However, the water extract exerts an antiproliferative activity against human laryngeal cancer (HEp-2) cell lines [48]. This extract also exhibited antimutagenic effects against H2O2 in three different loci [44].

3.2

Araucaria araucana (Molina) K.Koch

A. araucana, a native of Chile, is known as “monkey puzzle” or Chile pine. The plant’s resin has been used by Amerindian Mapuche tribes located in Southern Chile and Argentina to treat contusions and ulcers and help the cicatrization of skin wounds [6, 31]. High-quality goods are manufactured from the wood of this species due to their durability against biological deterioration. Lignans, namely secoisolariciresinol, pinoresinol, eudesmin, lariciresinol, and lariciresinol-4-methyl ether, were isolated from the wood of this plant and also demonstrated antifungal and antibacterial activity [49, 50]. Chemical investigations on the resin essential oil of A. araucana have been conducted. Five labdane derivatives have been isolated from chloroform fractions of the oleoresin, including 15-acetyloxy-imbricatolal, 15-acetyloxy-imbricatolic acid, 15-hydroxy-imbricatolal, 15-formyloxy-imbricatolal, and 15-hydroxy-imbricatolic acid [31, 51]. Other labdane derivative isolated is 19-oxo-labd-8(17)-en-ol-15 [52]. It has been reported that the essential oil of the twig of the plant contains geraniolene, limonene, δ-cadinene, α-cadinol, hibaene, trachylobane, kaurene (¼ 16-kaurene), atisirene, and isokaurene [49]. GC-MS analyses of the twigs and leaves show the presence of several sesquiterpenoids, including ionene, n-methyl naphthalene, tetramethyl-octahydro-naphthalene, dihydro-arcurcumene, 1,3,4-trimethyl-2-(4-methylpentyl)benzene, calamenene, norcadalene, calamene,cadalene, pentamethyl-dihydroindene-1, pentamethyl-dihydroindene-2, and chamazulene. The diterpenoids present in the twigs and leaves mainly include monoaromatic labdane, abietane-type such as 1-methyl-10,18-bisnorabieta-8,11,13triene, 1,2,3,4-tetrahydroretene, and isohexyl-alkylaromatic hydrocarbons such as 2,6-dimethyl-1-(4-methylpentyl)naphthalene, and 6-ethyl-2-dimethyl-1-(4-methylpentyl)naphthalene. In addition, Ent-beyerane and Ent-16β(H)-kauranes are also identified in A. angustifolia [5]. Diverse animal studies revealed that many terpenes or derivatives possess gastroprotective effects [53, 54]. The gastroprotective effects of resin constituents, imbricatolic acid, 15-hydroxyimbricatolal, and 15acetoxyimbricatolic acid have been studied in ethanol-HCl induced lesions at different dosages. It showed that 15-hydroxyimbricatolal and 15-acetoxyimbricatolic acid (100 mg/kg) is equally effective as lansoprazole (20 mg/kg). The cytotoxicity of resin diterpenes is found to be greater for 15-acetoxyimbricatolic acid (IC50 125 μM) and lower for 15-hydroxyimbricatolal (IC50 290 μM) [31]. The methanol extract of the wood possessed moderate antibacterial (against Citrobacter pilifera, Bacillus subtilis,

614

A. Kumar et al.

Micrococcus luteus, and Staphylococcus aureus) and antifungal (against Mucor miehei, Paecilomycesvariotii, Ceratocystis pilifera, and Trametes versicolor) activities [55].

3.3

Araucaria bernieri J.Buchholz

It is about a 50 m tall tree with small triangular scale-like leaves and bluish-white cones and is found at elevations of up to 700 m. A. bernieri is distributed in New Caledonia at low densities. Their numbers have also decreased due to the felling of trees, fire, and mining activities [56, 57]. GC-MS analyses of the twigs and leaves show the presence of sesquiterpenoids such as ionene, n-methyl naphthalene, tetramethyl-octahydro-naphthalene, dihydro-ar-curcumene, ar-curcumene, calamenene, norcadalene, calamene, cadalene, pentamethyl-dihydroindene-1, and chamazulene, and diterpenoids such as abietane-type: 19-norabietatriene, 18-norabietatriene, dehydroabietane, 1,2,3,4-tetrahydroretene, simonellite, retene, 9-methyl-retene, 2-methyl-retene, pentamethyl phenanthrene, 2,6-dimethyl-1-(4-methylpentyl)naphthalene, and 6-ethyl-2-dimethyl-1-(4-methylpentyl)naphthalene, and pimarane-type, Ent-beyerane, 16β(H)-phyllocladanes, Ent-16β(H)-kauranes, along with several unidentified compounds [5].

3.4

Araucaria bidwillii Hook.

A. bidwillii, native to eastern Australia, having diverse economic and agricultural uses, is a traditional remedy for the treatment of amenorrhea [12, 58]. The Lahu tribes of Northern Thailand is also employed it to treat insomnia [59]. Fractionation of the polysaccharide gum exudate of A. bidwillii revealed the predominance of the acidic polysaccharide arabinogalactan [60]. The water-soluble fraction of A. bidwillii gum had been partially hydrolyzed with a dilute mineral acid, yielded two neutral oligosaccharides and two acidic disaccharides [61]. The steam-volatile oil of A. bidwillii is rich in diterpenes, mainly represented by hibaene (76%), 16-kaurene (1.7%), and several other unidentified diterpene hydrocarbons. Sesquiterpenes are primarily described, with the principal component being spathulenol (3.2%). Monoterpenes are present in minimal amounts, totaling not more than 1%, with the most prominent member being α-pinene (0.5%) [26]. The essential oil from the leaves of A. bidwillii collected from Germany is mainly composed of monoterpene and sesquiterpene hydrocarbons with only a minor portion of diterpenes [62]. GC-MS analyses of the twigs and leaves show the presence of several sesquiterpenoids, including trimethyl naphthalene, tetramethyl-octahydro-naphthalene, dihydro-arcurcumene, 1,3,4-trimethyl-2-(4-methylpentyl)benzene, calamenene, norcadalene, calamine cadalene, pentamethyl-dihydroindene-1, pentamethyl-dihydroindene-2, and chamazulene. The diterpenoids present in the twigs and leaves are mainly included monoaromatic labdane, abietane-type such as 19-norabietatriene,

24

Chemistry, Biological Activities, and Uses of Araucaria Resin

615

18-norabietatriene, dehydroabietane, 1-methyl-10,18-bisnorabieta-8,11,13-triene, 1,2,3,4-tetrahydroretene, simonellite, retene, 9-methyl-retene, 2-methyl-retene, related abietane-type diterpenoids, including pentamethyl phenanthrene, and isohexyl-alkylaromatic hydrocarbons such as 2,6-dimethyl-1-(4-methylpentyl)naphthalene, and 6-ethyl-2-dimethyl-1-(4-methylpentyl)naphthalene [5]. The essential oil of A. bidwillii is found to be rich in diterpene hydrocarbons (39.27%), oxygenated sesquiterpenes (21.34%), and sesquiterpene hydrocarbons (17.44%). The primary volatile compounds reported are beyerene (35.65%), trans-nerolidol (13.66%), γ-elemene (6.09%), and germacrene D (5.53%), with small quantities of τ-muurolol, τ-cadinol, α-pinene, and kaur-15-ene [63]. Chemical analysis of a methanolic extract of A. bidwillii leaves revealed the presence of five labdane diterpenoids, namely 7-hydroxy-labda-8(17),13(16),14-trien-19-yl-(E)-coumarate; 7-hydroxy-labda-8 (17),13(16),14-trien-19-yl-(Z)-coumarate; 7-hydroxy-labda-8(17),13(16),14-trien19-yl-70 -O-methyl-(E)-coumarate; 7-hydroxy-labda-8(17),13(16),14-trien-19-yl70 -O-methyl-(Z )-coumarate; and 7-oxocallitrisic acid; and two triterpenoids, namely 2-O-acetyl-11-keto-boswellic acid and β-sitosterol-3-O-glucopyranoside. In addition, phloretic acid and two methylated-bisflavonoids, namely agathisflavone40 ,7,700 - trimethyl ether and cupressuflavone-40 ,7,700 -trimethyl ether, were also isolated [64]. The MTT test has been performed to assess the anticancer activity of A. bidwillii essential oil using three human cancer cell lines, namely Caco-2, Hep-G2, and MCF-7. The IC50 values are determined to be 1.32, 1.67, and 1.10 μg/mL, respectively, for the cell lines mentioned above [63]. Another study on antiproliferative activity of diterpenoids, namely 7-hydroxy-labda-8(17),13 (16),14-trien-19-yl-(E)-coumarate and 7-hydroxy-labda-8(17),13(16),14-trien-19yl-(Z )-coumarate, against the mouse lymphoma (L5178Y) cell line revealed IC50 values of 2.22 and 1.42 μM, respectively. The performance of both compounds is better than that of the kahalalide F, a reference drug (IC50 4.30 mM) [64]. The ethanol extract of the leaves exerts strong anti-inflammatory and antinociceptive effects [65]. In addition, the extracts prepared from the leaves using methanol and ethyl acetate exhibit good antitumor activity against chronic myelogenic leukemia cancer cell lines (HL-60 and K-562) with IC50 values equal to 33.11 and 39.81 μg/mL, respectively, for the former and 28.18 and 34.64 μg/mL, respectively, for the latter [66]. The methanolic extract of oleoresin is found to significantly augment the sleeping time of the pentobarbitone. It also depicts significant anti-inflammatory and analgesic activity [67]. Moreover, the oleoresin of the plant possesses good antipyretic activity on female albino rats at the dose of 100 mg/kg [68].

3.5

Araucaria columnaris (G.Forst.) Hook. (syn. Araucaria excelsa (Lamb.) R.Br.)

Briggs’ investigation on A. excelsa essential oil revealed the presence of α-pinene (70%) and phyllocladene (10%) as significant components [69]. Further, isolation of

616

A. Kumar et al.

compound from mother essential oil yielded crystalline isophyllocladene [70]. The essential oil from the leaves of A. columnaris was analyzed earlier. It was found to be free from monoterpenes. Sesquiterpenes, namely δ-cadinene, τ-cadinol, and spathulenol, are reported with individual component concentrations of less than 1%. However, the oil contains a large proportion of diterpenoids, including luxuriadiene (13-epi-dolabradiene) (23.3%), hibaene (9.4%), sclarene (5.7%), and 16-kaurene (2.2%), along with unidentified diterpene hydrocarbons B (C20H32: 32.5%) and E (10.3%) [26]. The ethanolic extract prepared from the branches of A. columnaris showed good antioxidant and antiradical activities [71, 72]. The extracts from the leaves possess medium antioxidant properties and good α-amylase inhibitory and antibacterial activity [73–75]. The methanolic extract of the bark possesses potent antimicrobial activity against Staphylococcus aureus, Escherichia coli, and Bacillus subtilis and showed cytotoxic activity against HEK (human kidney) cancer cell line with an IC50 value of 95.0 μg/mL [76].

3.6

Araucaria cunninghamii Mudie

A. cunninghamii, also known as Bunya tree, Hoop pine, Richmond River pine, and White pine, is widespread but native to South Wales and Australia [77]. Its medicinal properties are described in many traditional medicines [78]. The Yali tribes of New Guinea use it for rituals, and its bark is used for insulating roofs [79]. The volatile oil steam-distilled from resin contains n-nonane, n-undecane, α-pinene, (
)-β-pinene, myrcene, ()-limonene, terpinolene in addition to caryophyllene, and humulene [80]. An analysis of A. cunninghamii oleoresin revealed the presence of 11 labdane diterpenes. These are methyl communate; methyl isocupressate; 15-hydroxy-8,E-13labdadien-19-oic acid; methyl acetyl-isocupressate; methyl 15-acetoxy8E,13-labdadien-19-oate; methyl 7-oxo-19-acetoxy-8,E-13-labdadien-15-oate; 8E-13-labdadiene-15,19-diol; 15-hydroxy-8E-13-labdadien-19-al; 15-acetoxy-8, E-13-labdadien-19-ol; 15-acetoxy-8E-13-labdadien-19-al; and 8E-13-labdadien15,19-diacetate [21]. The oil produced from the short-time distillation of the Australian tree’s sapwood contains mostly α-copaene (31.1%), with hexanal (11.5%) and β-farnesene (11.3%). In comparison, heartwood oil is high in decadienal (37.0%), hexanal (9.5%), and propionic, butyric, valeric, and octanoic acids (10.3%) [81]. The volatile oil extracted from the leaves of A. cunninghamii is found to contain diterpenes, including 16-kaurene (53.0%) and hibaene (29.3%), sesquiterpenes, including β-caryophyllene (5.5%), and monoterpenes, including α-pinene (1.8%) and β-pinene (1.4%) [26]. The leaf oil composition of A. cunninghamii studied in Nigeria is characterized by higher amounts of α-pinene (14.8%), terpinen-4-ol (14.7%), shyobunol (8.9%), and spathulenol (8.8%) [82]. Further, six more diterpenoids and shikimic acid derivatives have been identified from A. cunninghamii aerial parts. These are ent-19-(Z )-coumaroyloxylabda-8(17),13 (16),14-triene; ent-19-(E)-coumaroyloxylabda-8(17),13(16),14-triene; shikimic

24

Chemistry, Biological Activities, and Uses of Araucaria Resin

617

acid N-butyl ester; 5-(Z )-coumaroyloxyquinic acid N-butyl ester; 5-(E)coumaroyloxyquinic acid N-butyl ester; and labda-8(14),15(16)-dien-3β-ol [58]. GC-MS analyses of the twigs and leaves show the presence of several sesquiterpenoids, including trimethyl naphthalene, tetramethyl-octahydro-naphthalene, dihydro-ar-curcumene, ar-curcumene, 1,3,4-trimethyl-2-(4-methylpentyl)benzene, calamenene, norcadalene, calamene,cadalene, pentamethyl-dihydroindene-1, pentamethyl-dihydroindene-2, and chamazulene. The diterpenoids present in the twigs and leaves mainly include monoaromatic labdane, abietane-type diterpenoids such as 19-norabietatriene, 18-norabietatriene, dehydroabietane, 1-methyl-10,18bisnorabieta-8,11,13-triene, 1,2,3,4-tetrahydroretene, retene, 9-methyl-retene, 2-methyl-retene, related abietane-type diterpenoids, including pentamethyl phenanthrene, and isohexylalkylaromatic hydrocarbons, including 2,6-dimethyl-1(4-methylpentyl)naphthalene, and 6-ethyl-2-dimethyl-1-(4-methylpentyl)naphthalene [5]. The essential oil from the fresh leaves is found to be rich in diterpenes (49.2%), monoterpenes (20.9%), and sesquiterpenes (17.6%). The major compounds of the oil are beyerene (34.6%) and α-pinene (16.2%), along with germacrene D (9.8%), kaurene (5.1%), 13-epi-dolabradiene (4.8%), β-selinene (3.6%), n-nonane (3.1%), (E)-β-farnesene (2.0%), kaur-15-ene (1.9%), β-caryophyllene (1.5%), and dolabradiene (1.2%). However, the oil extracted from senescent leaves contains beyerene (44.4%), caryophyllene oxide (17.9%), 13-epi-dolabradiene (4.2%), α-pinene (3.3%), kaurene (1.7%), n-nonane (1.2%), and n-undecane (1.1%). The volatile resin oil contains sesquiterpene (70.4%) and oxygenated sesquiterpenes (15.2%). The resin oil is mostly composed of β-caryophyllene (60.8%), caryophyllene oxide (13.4%), and (E)-β-farnesene (4.9%), with minor amounts of allo-aromadendrene, bicyclogermacrene, n-undecane, and (3Z )-hexenyl hexanoate [83]. The leaves’ essential oil of A. cunninghamii is found to be effective against Staphylococcus aureus, Bacillus subtilis, Staphylococcus epidermidis, and Streptococcus mutans with a minimum inhibitory concentration of 250 μg/mL. In contrast, the resin essential oil is shown to be active against Staphylococcus aureus strains alone [83]. Compounds, ent-19-(Z )-coumaroyloxylabda-8(17),13(16),14-triene and labda-8(14),15(16)-dien-3β-ol are found to be active against E. coli with minimum inhibitory concentration values of 31.9 and 36.3 μM, respectively, but had no impact on Staphylococcus aureus, Candida albicans, Enterococcus faecalis, Bacillus cereus, and Pseudomonas aeruginosa. Additionally, ent-19-(Z )coumaroyloxylabda-8(17),13(16),14-triene also exhibits anticancer activity against human leukaemia (HL-60) and human hepatocellular carcinoma (SMMC-7721) cells, with IC50 values of 8.90 and 11.53 μM, respectively [58]. Moreover, the leaf extracts of the plant exhibited good antifungal activity against Alternaria alternata, Colletotrichum falcatum, Fusarium oxysporum, Pyriculariaoryzae, Sclerotinia rolfsii, Sclerotinia sclerotiorum, and Tillatia indica, and also showed antioxidant activity [29, 84]. The methanolic extract of the resin showed strong α-glucosidase inhibition activity with an inhibition value of 48.48%. However, the dichloromethane extract of the resin shows potent cytotoxic activity against Chang liver cells with an IC50 value of 92.9 μg/mL [53].

618

3.7

A. Kumar et al.

Araucaria heterophylla (Salisb.) Franco

A. heterophylla has been traditionally used to cure toothache and its antioxidant property [85]. The acid fraction of A. heterophylla oleoresin yields communic acid, sandaracopimaric acid, abietic acid, and cupressic acid; however, its neutral fraction yields abietinol, manool, abietinal, torulosal, and torulosol [20]. Labdane diterpenes, specifically labda 8(17),14-diene, 13-epi-cupressic acid, and 13-O-acetyl-13-epicupressic acid, has been claimed to be present in the resin [86]. The composition of the essential oils yielded from A. heterophylla leaves vary due to geographical regions. The yield of essential oil from A. heterophylla leaves from Egypt, Hawaii, and India is reported to be 0.25%, 0.20%, and 0.10% (v/w), respectively [63, 83, 87]. The volatile leaf oil of A. heterophylla has a different composition from other Australian araucarias. The principal component of the oil is monoterpenes with a predominance of α-pinene (52.4%), followed by limonene (1.5%), sabinene (0.7%), and γ-terpinene (0.7%). The principal sesquiterpenes identified are β-caryophyllene (3.1%) and germacrene-D (1.9%). However, major diterpenes detected in this oil are phyllocladene (32.2%), with lesser amounts of 16-kaurene (0.6%), and an unidentified diterpene hydrocarbon (2.3%) [26]. On the other hand, the leaf oil of A. heterophylla from Hawaii is characterized by β-caryophyllene (24.4%), β-pinene (0.2%), limonene (0.1%), etc. [87]. GC-MS analyses of the twigs and leaves show several sesquiterpenoids, including ionene, n-methyl naphthalene, tetramethyl-octahydro-naphthalene, dihydro-ar-curcumene, ar-curcumene, 1,3,4-trimethyl-2(4-methylpentyl)benzene, calamenene, norcadalene, calamene, cadalene, pentamethyl-dihydroindene-1, pentamethyl-dihydroindene-2, and chamazulene. The diterpenoids present in the twigs and leaves are mainly included monoaromatic labdane, abietane-type diterpenoids such as 19-norabietatriene, 18-norabietatriene, dehydroabietane, 1-methyl-10,18-bisnorabieta-8,11,13-triene, 1,2,3,4-tetrahydroretene, retene, 9-methyl-retene, related abietane-type diterpenoids, including pentamethyl phenanthrene, and isohexyl-alkylaromatic hydrocarbons, including 2,6-dimethyl-1-(4-methylpentyl)naphthalene, and 6-ethyl-2-dimethyl-1-(4-methylpentyl)naphthalene [5]. The leaf and resin oil composition of A. heterophylla grown in India have been analyzed. The leaf oil is primarily characterized by the presence of diterpene hydrocarbons (92.5%), while the resin oil is mainly composed of sesquiterpene hydrocarbons (84.5%). Major constituents of leaf oil are 13-epidolabradiene (42.7%), beyerene (22.2%), rimuene (¼ 5, 15-rosadiene; 13.7%), dolabradiene (3.9%), pimaradiene (2.8%), germacrene D (1.7%), isopimara-9(11), 15-diene (1.5%), abietadiene (1.4%), sclarene (1.2%), and 13-epi-manool (1.1%). The main components of the resin oil are α-copaene (29.9%), germacrene D (21.4%), γ-gurjunene (9.7%), δ-cadinene (7.1%), sandaracopimara-8(14),15-diene (6.5%), trans-nerolidol (3.8%), α-muurolene (2.8%), β-caryophyllene (2.4%), δ-amorphene (2.3%), β-oplopenone (2.0%), β-copaene (1.5%), and trans-muurola4(14),5-diene (1.1%) [83]. The GC-MS study of essential oil extracted from A. heterophylla leaves revealed the presence of monoterpenoids (83.01%),

24

Chemistry, Biological Activities, and Uses of Araucaria Resin

619

sesquiterpenes (6.69%), and diterpenes (4.34%). α-Pinene (70.85%) is the major volatile constituent identified in the essential oil, followed by D-limonene, phyllocladane, γ-terpinene, germacrene D, β-caryophyllene, sabinene, and camphene with concentrations below 5% [63]. The resin essential oil of Egyptian A. heterophylla is characterized by higher amounts of monoterpenes (66.53%) and sesquiterpenes (30.85%). The primary components of the resin oil are α-pinene (44.88%), germacrene D (10.25%) accompanied with α-copaene, and sabinene [64]. Antibacterial activity against the strain of Staphylococcus aureus (MTCC 96 and MTCC 2940) revealed that the essential oil from resin is active with a zone of inhibition of 7 mm at a minimum inhibitory concentration of 250 μg/mL. In contrast, the essential oil from leaves is found not active. The minimum bactericidal concentration of resin essential oil is 1000 μg/mL; however, foliage essential oil is >1000 μg/mL [83]. A. heterophylla resin extracts are found cytotoxic to breast cancer cell lines (MCF7 and HCT116), with IC50 values of 0.54 and 0.94 g/ml, equivalent to doxorubicin. The resin isolates labda-8(17)14-diene and 3-O-acetyl-13-epi-cupressic acid are moderately cytotoxic to both cell lines, with IC50 values lower than the resin extract (IC50 2.33–8.04 g/ml) [86]. Moreover, the dose-dependent antiulcerogenic investigation in rats shown that resin extract had a curative ratio of 55.87 (100 mg/kg BW) and 63.26 (200 mg/kg BW). In contrast, the standard ranitidine had a curative ratio of 61.64 at 100 mg/kg BW [86]. The resin essential oil from A. heterophylla (at the doses of 100 mg/kg and 200 mg/kg) significantly reduced rat paw induced edema compared to the reference medication (indomethacin at 10 mg/kg), and the reduction in inflammation reached 32.0%, 30.3%, and 39.0%, respectively. In an antipyretic study, resin essential oil decreased rectal temperature after 60 min (37.04  0.43  C), and maximum reduction was achieved after 120 min (36.62  0.33  C), which was comparable to paracetamol [64]. Moreover, the resin extract showed strong cytotoxic activity against colon (HCT116) and breast (MCF7) human cancer cell lines with IC50 values equal to 0.54 and 0.94 μg/mL, respectively, which are quite similar to those observed for doxorubicin (0.70 and 0.96 μg/mL, respectively) [86]. In a study, the leaf extracts prepared using n-butanol, ethyl acetate, water, petroleum ether, and dichloromethane exhibit moderate to strong anticancer activity against HEPG-2 (hepatocellular carcinoma), MCF-7, PC-3 (human prostate cancer), and Hela (epithelioid carcinoma) cell lines [88].

3.8

Araucaria hunsteinii K.Schum.

A. hunsteinii is an evergreen tree that grows to a height of approximately 50–80 m in the mountains of Papua New Guinea. However, habitat degradation, timber harvesting, and wildfires threaten its extinction [89]. The plant’s wood is used to make treated poles and piles, plywood, furniture, crates, and pulp and paper [90]. A. hunsteinii essential oil investigation revealed the presence of α-pinene (18.2%), germacrene-D (5.1%), and sclarene (10.7%) as significant constituents [26].

620

3.9

A. Kumar et al.

Araucaria laubenfelsii Corbasson

GC-MS analyses of the twigs and leaves of A. laubenfelsii show several sesquiterpenoids, including ionene, n-methyl naphthalene, tetramethyl-octahydronaphthalene, dihydro-ar-curcumene, ar-curcumene, 1,3,4-trimethyl-2-(4-methylpentyl)benzene, calamenene, norcadalene, calamene,cadalene, pentamethyldihydroindene-1, pentamethyl-dihydroindene-2, and chamazulene. The diterpenoids in the twigs and leaves mainly include abietane-types such as bis-simonellite, 19-norabietatriene, 18-norabietatriene, dehydroabietane, 1,2,3,4-tetrahydroretene, simonellite, retene, 9-methyl-retene, related abietane-type diterpenoids, including pentamethyl phenanthrene [5].

3.10

Araucaria luxurians (Brongn. & Gris) de Laub.

The essential oil from A. luxurians is found to be rich in diterpenes. The main diterpenes were luxuriadiene (65.6%), 5,15-rosadiene (19.6%), and 16-kaurene (1.9%). Sesquiterpenes contributed only a minor fraction, mainly represented by βcaryophyllene, and δ-cadinene, which were present in less than 1% [26].

3.11

Araucaria montana Brongn. & Gris

The volatile oil extracted from the leaves of A. montana is rich in diterpenes, including phyllocladene (61.0%) and 16-kaurene (22.8%). α-Pinene (3.2%), βcaryophyllene (3.1%), and bicyclogermacrene (2.0%) were the other terpenoids present in the oil [26].

3.12

Araucaria muelleri (Carriere) Brongn. & Gris

Sclarene (20.1%), luxuriadiene (18.8%), along with some unidentified hydrocarbons, named B (C20H32: 25.1%), E (C20H32: 9.7%), and F (C20H32: 4.0%), have been identified as the main diterpenes in the volatile oil of A. muelleri. Sesquiterpenes, including β-caryophyllene germacrene-D and spathulenol, are detected in minor amounts. Among the many monoterpenes, myrcene is present up to a level of 0.7% in this oil [26].

3.13

Araucaria nemorosa de Laub.

GC-MS analyses of the twigs and leaves of A. nemorosa show several sesquiterpenoids, including n-methyl naphthalene, tetramethyl-octahydro-naphthalene, dihydro-ar-curcumene, ar-curcumene, 1,3,4-trimethyl-2-(4-methylpentyl)

24

Chemistry, Biological Activities, and Uses of Araucaria Resin

621

benzene, calamenene, norcadalene, calamene,cadalene, pentamethyl-dihydroindene1, pentamethyl-dihydroindene-2, and chamazulene. The diterpenoids present in the twigs and leaves are mainly included monoaromatic labdane, abietane-type diterpenoids such as bis-simonellite, dehydroabietane, 1-methyl-10,18-bisnorabieta-8,11,13-triene, 1,2,3,4-tetrahydroretene, simonellite, retene, 2-methyl-retene, related abietane-type diterpenoids, and isohexyl-alkylaromatic hydrocarbons, including 2,6-dimethyl-1-(4-methylpentyl)naphthalene, and 6-ethyl-2-dimethyl-1(4-methylpentyl)naphthalene [5].

3.14

Araucaria scopulorum de Laub.

A. scopulorum contains diterpenoids, mainly phyllocladan-16α-ol (41.0%) and luxuriadiene (10%). τ-Cadinol (4.0%), calamenene (3.1%), δ-cadinene (6.0%), germacrene-D (2.0%), β-caryophyllene (2.5%), and α-copaene (6.0%) are the main sesquiterpenes present in the oil. β-Pinene (1.9%) is the dominant monoterpenes detected in this oil [26]. Among the 14 investigated Araucaria species, the information regarding chemistry, biological activity, and uses of the essential oil or resin of about seven species are very scanty. However, phytoconstituents frequently identified in various species of Araucaria are monoterpenoids, sesquiterpenoids, diterpenoids, and lignans. The structures of the representative monoterpenoids, sesquiterpenoids, diterpenoids, and lignans are depicted in Figs. 1, 2, and 3.

4

Conclusions

Plants and their exudates have been used as traditional remedies for centuries, but their efficacy is rarely proven. The importance of Araucaria species in conventional medicine is mainly linked to resinous extracts and essential oils. These plants’ resin and essential oils have been used to treat rheumatic diseases, ulcerative colitis, infection, wound, asthma, cough, gastric ulcer, and used as immunomodulators and perfume. The present chapter focuses on the phytochemical and pharmacological profiles of essential oils and resins from several Araucaria species. A thorough review of the literature found that information on about 14 species is available irregularly. These species have been subjected to chemical investigation and evaluation of the therapeutic qualities of their essential oils and resins. Terpenoids discovered are mainly isolated from the essential oil and resin. Besides the prevalence of diterpenoids in most species, lignans have also been documented from the few. Phyllocladene, hibaene, 16-kaurene, luxuriadiene, and sclarene are the most abundant diterpenoids, whereas β-caryophyllene, germacrene D, bicyclogermacrene, α-cadinol, and spathulenol are the most widely available sesquiterpenes. Monoterpenoids are often identified as α-pinene, β-pinene, limonene, γ-terpinene, myrcene, limonene, and sabinene. However, none can be designated

622

A. Kumar et al.

Fig. 1 Structure of some mono- and sesquiterpenoids present in species of Araucaria

as chemotaxonomic markers at the genus level since they are widespread constituents of various essential oils. Additionally, diterpenes and other polar compounds have been used as chemotaxonomic markers at the genus level, even if their occurrence seems, now, to be extended at the whole family level [8]. Fractionation of gum exudate of A. bidwillii indicated that the main component is the acidic polysaccharide arabinogalactan with 1,6 linkage. Although monoterpenes are found in all the species, the essential oil obtained from A. columnaris is monoterpene-free. The highest amount of monoterpenes (83%) is reported in the essential oil of A. heterophylla. However, the highest concentration of diterpene (luxuriadiene, 65%) is found in the essential oil of A. luxurians. The antibacterial properties have been observed in the resin and essential oil of A. cunninghamii, A. heterophylla, and A. angustifolia. The antibacterial action may be attributed to diterpenoids present in the oil [24]. The essential oils from A. cunninghamii, A. heterophylla, and A. bidwillii are antiproliferative against various cancerous cell lines. Resin constituents, 15-hydroxyimbricatolal, and 15-acetoxyimbricatolic showed gastroprotective effects comparable to the lansoprazole [6]. Labdane diterpenes are responsible for antialgal, antimicrobial, and antiproliferative activities [24, 25, 58, 91]. Although certain Araucaria species have many uses, including lumber, food, and traditional medicine, relatively little medicinal and phytochemical research has been conducted. Significantly, very few reports are there in the literature

24

Chemistry, Biological Activities, and Uses of Araucaria Resin

Fig. 2 Structure of some diterpenoids present in species of Araucaria

623

624

A. Kumar et al.

Fig. 3 Structure of some lignans present in species of Araucaria

related to analyses of the essential oil and resin constituents. Phytochemical investigations of the resin and essential oil of several other Araucaria speciessuch as Araucaria biramulata, Araucaria humboldtensis, Araucaria rulei, Araucaria schmidii, Araucaria subulata, and Araucaria lefipanensis is still unexplored. Studies on the phytochemical and pharmacological features, particularly resins and essential oils, have revealed much of the future of Araucaria species. Acknowledgments The authors are thankful to the director of CSIR-Central Institute of Medicinal and Aromatic Plants (CSIR-CIMAP) for providing the necessary facilities.

References 1. Pan SY, Litscher G, Gao SH, Zhou SF, Yu ZL, Chen HQ, Zhang SF, Tang MK, Sun JN, Ko KM (2014) Historical perspective of traditional indigenous medical practices: the current renaissance and conservation of herbal resources. Evid Based Complement Alternat Med 525340 2. Petrovska BB (2012) Historical review of medicinal plants usage. Pharmacogn Rev 6:1–5 3. Ahamed KN, Kumar V, Raja S, Mukherjee K, Kumar Mukherjee P (2005) Anti-nociceptive and antiinflammatory activity of Araucaria bidwillii Hook. Iran J Pharmacol Ther 4:105–100 4. Freitas AM, Almeida MT, Andrighetti-Frohner CR, Cardozo FT, Barardi CR, Farias MR, Simoes CM (2009) Antiviral activity-guided fractionation from Araucaria angustifolia leaves extract. J Ethnopharmacol 126:512–517 5. Lu Y, Hautevelle Y, Michels R (2013) Determination of the molecular signature of fossil conifers by experimental palaeochemotaxonomy – Part 1: the Araucariaceae family. Biogeosciences 10:1943–1962

24

Chemistry, Biological Activities, and Uses of Araucaria Resin

625

6. Schmeda-Hirschmann G, Astudillo L, Rodríguez J, Theoduloz C, Yanez T (2005) Gastroprotective effect of the Mapuche crude drug Araucaria araucana resin and its main constituents. J Ethnopharmacol 101:271–276 7. Branco C, Rodrigues T, Dreher de Lima E, Calloni C, Scola G, Salvador M (2016) Chemical constituents and biological activities of Araucaria angustifolia (Bertol.) O. Kuntze: a review. J Organic Inorganic Chem 2:10 8. Frezza C, Venditti A, De Vita D, Toniolo C, Franceschin M, Ventrone A, Tomassini L, Foddai S, Guiso M, Nicoletti M, Bianco A (2020) Phytochemistry, chemotaxonomy, and biological activities of the Araucariaceae family-a review. Plants (Basel) 9(7):888. https://doi.org/10. 3390/plants9070888 9. Rundel PW (2019) A Neogene heritage: conifer distributions and endemism in mediterraneanclimate ecosystems. Front Ecol Evol 7:364 10. Wilde MH, Eames AJ (1952) The ovule and ‘Seed’ of Araucaria bidwilli with discussion of the taxonomy of the Genus II. Taxonomy Ann Bot 16:28–49 11. Zonneveld BJM (2012) Genome sizes of all 19 Araucaria species are correlated with their geographical distribution. Plant Syst Evol 298:1249–1255 12. Aslam M, Choudhary B, Uzair M, Ijaz A (2013) Phytochemical and ethno-pharmacological review of the genus Araucaria – review. Trop J Pharm Res 12:651–659 13. Nimsch H (2011) The genus Araucaria – An illustrated overview of its species. Kessel Publishing House, Remagen-Oberwinter, p 37 14. Hill RS (1995) Conifer origin, evolution and diversification in the southern hemisphere. In: Enright NJ and Hill RS (eds) Ecology of the Southern conifers, Melbourne University Press, Australia 15. Brandao JHSG, Rodrigues NF, Eguiluz M, Guzman F, Margis R (2019) Araucaria angustifolia chloroplast genome sequence and its relation to other Araucariaceae. Genet Mol Biol 42:671–676 16. Lu Y, Ran JH, Guo DM, Yang ZY, Wang XQ (2014) Phylogeny and divergence times of gymnosperms inferred from single-copy nuclear genes. PLoS One 9:e107679 17. Banks JCG (2004) Tropical ecosystems. Southern Hemisphere conifers. In: Burley J (ed) Encyclopedia of forest sciences. Elsevier, Oxford 18. Anonymous (2018) Araucaria description & species. In: Britannica, TEoE (ed) The Encyclopedia Britannica. Encyclopedia Britannica, Chicago 19. Seyfullah LJ, Beimforde C, Dal Corso J, Perrichot V, Rikkinen J, Schmidt AR (2018) Production and preservation of resins – past and present. Biol Rev 93:1684–1714 20. Otto A, Wilde V (2001) Sesqui-, di-, and triterpenoids as chemosystematic markers in extant conifers – a review. Bot Rev 67:141–238 21. Caputo R, Dovinola V, Mangoni L (1974) New diterpenes from Araucaria cunighami. Phytochemistry 13:475–478 22. Khan NU, Ansari WH, Rahman W, Okigawa M, Kawano N (1971) Two new Biflavonyls fromAraucaria cunninghamii. Chem Pharm Bull 19:1500–1501 23. Rahman W, Bhatnagar SP (1968) A new biflavonyl AC3 from Araucaria cunninghamii. Tetrahedron Lett 9:675–678 24. Jung M, Ko I, Lee S, Choi SJ, Youn BH, Kim SK (1998) A concise synthesis and in vitro cytotoxicity of new labdane diterpenes. Bioorg Med Chem Lett 8:3295–3298 25. Tanaka R, Ohtsu H, Iwamoto M, Minami T, Tokuda H, Nishino H, Matsunaga S, Yoshitake A (2000) Cancer chemopreventive agents, labdane diterpenoids from the stem bark of Thuja standishii (Gord.). Carr Cancer Lett 161:165–170 26. Brophy JJ, Goldsack RJ, Wu MZ, Fookes CJ, Forster PI (2000) The steam volatile oil of Wollemia nobilis and its comparison with other members of the Araucariaceae (Agathis and Araucaria). Biochem Syst Ecol 28:563–578 27. Mota MRL, Criddle DN, Alencar NMN, Gomes RC, Meireles AVP, Santi-Gadelha T, Gadelha CAA, Oliveira CC, Benevides RG, Cavada BS, Assreuy AMS (2006) Modulation of acute inflammation by achitin-binding lectin from Araucaria angustifolia seeds via mast cells. Naunyn Schmiedeberg’s Arch Pharmacol 374:1–10

626

A. Kumar et al.

28. Talaat AN, Ebada SS, Labib RM, Esmat A, Youssef FS, Singab ANB (2018) Verification of the anti-inflammatory activity of the polyphenolic-rich fraction of Araucaria bidwillii hook. Using phytohaemagglutinin-stimulated human peripheral blood mononuclear cells and virtual screening. J Ethnopharmacol 226:44–47 29. Sati SC, Joshi S (2013) Antifungal potential of Araucaria cunninghamii sweet (Araucariaceae) plant extracts. Int J Pharmacol Toxicol 3:15–21 30. Mukherjee PK, Ahamed KFHN, Kumar V, Mukherjee K, Houghton PJ (2007) Protective effect of biflavones from Araucaria bidwillii hook in rat cerebral ischemia/reperfusion induced oxidative stress. Behav Brain Res 178:221–228 31. Schmeda-Hirschmanna G, Astudillo L, Sepulveda B, Rodríguez JA, Theoduloz C, Yanez T, Palenzuela JA (2005) Gastroprotective effect and cytotoxicity of natural and semisynthetic labdane diterpenes from Araucaria araucana resin. Z Naturforsch C 60:511–522 32. Vasconcelos SMM, Lima SR, Soares PM, Assreuy AMS, de Sousa FCF, Lobato RFG, Vasconcelos GS, Santi-Gadelha T, Bezerra EHS, Cavada BS, Patrocinio MCA (2009) Central action of Araucaria angustifolia seed lectin in mice. Epilepsy Behav 15:291–293 33. Koul S, Ahmad A, Chaudhary A, Pandurangan D, Koul M (2015) A mini review on chemistry and biology of Araucaria angustifolia (Araucariaceae). Int J Pharm Sci Lett 5:535–538 34. Andruchow-Colombo A, Escapa IH, Cuneo NR, Gandolfo MA (2018) Araucaria lefipanensis (Araucariaceae), a new species with dimorphic leaves from the late cretaceous of Patagonia, Argentina. Am J Bot 105:1067–1087 35. Chambers TC, Drinnan AN, McLoughlin S (1998) Some morphological features of Wollemi pine (Wollemia nobilis: Araucariaceae) and their comparison to cretaceous plant fossils. Int J Plant Sci 159:160–171 36. Simpson MG (2010) Plant systematics. Academic Press, Cambridge, MA 37. Stockey RA (1982) The Araucariaceae: an evolutionary perspective. Rev Palaeobot Palynol 37: 133–154 38. Farjon A (2010) A handbook of the World’s conifers. Brill, Leiden 39. Cordenunsi BR, De Menezes WE, Genovese MI, Colli C, De Souza GA, Lajolo FM (2004) Chemical composition and glycemic index of Brazilian pine (Araucaria angustifolia) seeds. J Agric Food Chem 52:3412–3416 40. Andrighetti-Frohner CR, Sincero TCM, Da Silva AC, Savi LA, Gaido CM, Bettega JMR, Mancini M, De Almeida MTR, Barbosa RA, Farias MR (2005) Antiviral evaluation of plants from Brazilian Atlantic tropical forest. Fitoterapia 76:374–378 41. Peralta RM, Koehnlein EA, Oliveira RF, Correa VG, Correa RC, Bertonha L, Bracht A, Ferreira ICFR (2016) Biological activities and chemical constituents of Araucaria angustifolia. An effort to recover a species threatened by extinction. Trends Food Sci Technol 54:85–93 42. Anderegg RJ, Rowe JW (1973) Lignans, the major component of resin from Araucaria angustifolia knots. Holzforschung 28:171–175 43. Seccon A, Rosa DW, Freitas RA, Biavatti MW, Creczynski-Pasa TB (2010) Antioxidant activity and low cytotoxicity of extracts and isolated compounds from Araucaria angustifolia dead bark. Redox Rep 15:234–242 44. Michelon F, CS Branco, Calloni C, Giazzon I, Agostini F, Spada PKW, Salvador M (2012) Araucaria angustifolia: a potential nutraceutical with antioxidant and antimutagenic activities. Curr Nutr Food Sci 8:155–159 45. De Freitas TB, Santos CHK, da Silva MV, Shirai MA, Dias MI, Barros L, Barreiro MF, Ferreira ICFR, Goncalves OH, Leimann FV (2018) Antioxidants extraction from Pinhao (Araucaria angustifolia (Bertol.) Kuntze) coats and application to zein films. Food Packag Shelf Life 15:28–34 46. da Silva SM, Koehnlein EA, Bracht A, Castoldi R, de Morais GR, Baesso ML, Peralta RA, de Souza CGM, de Sa-Nakanishi AB, Peralta RM (2014) Inhibition of salivary and pancreatic α-amylases by a pinhão coat (Araucaria angustifolia) extract rich in condensed tannin. Int Food Res J 56:1–8 47. Otsuka K, Sakurada K, Nakamura H (1995) Extractantimicrobial agent from resion ofAraucaria angustifolia. Kishimoto Sangyo Co., Okayama

24

Chemistry, Biological Activities, and Uses of Araucaria Resin

627

48. Dos Santos Branco C, De Lima ED, Rodrigues TS, Scheffel TB, Scola G, Laurino CCFC, Moura S, Salvador M (2015) Mitochondria and redox homoeostasis as chemotherapeutic targets of Araucaria angustifolia (Bert.) O. Kuntze in human larynx HEp-2 cancer cells. Chem Biol Interact 231:108–118 49. Briggs LH, White GW (1975) Constituents of the essential oil of Araucaria araucana. Tetrahedron 31:1311–1314 50. Haupt M, Leithoff H, Meier D, Puls J, Richter HG, Faix O (2003) Heartwood extractives and natural durability of plantation-grown teakwood (Tectona grandis L.) – a case study. Holz Roh Werkst 61:473–474 51. Garbarino JA, Oyarzún ML, Gambaro V (1987) Labdane Diterpenes from Araucaria araucana. J Nat Prod 50:935–936 52. Bruns K (1968) Diterpene-V: Uber die C13-konfiguration der diterpene aus Araucaria imbricata, pavon (araucariaceae). Tetrahedron 24:3417–3423 53. Matsuda H, Li Y, Murakami T, Yamahara J, Yoshikawa M (1998) Protective effects of oleanolic acid oligoglycosides on ethanol- or indomethacin-induced gastric mucosal lesions in rats. Life Sci 63:245–250 54. Wada H, Kodato S, Kawamori M, Morikawa T, Nakai H, Takeda M, Saito S, Onoda Y, Tamaki H (1985) Antiulcer activity of dehydroabietic acid derivatives. Chem Pharm Bull 33:1472–1487 55. Cespedes CL, Avila JG, Garcıa AM, Becerra J, Flores C, Aqueveque P, Bittner M, Hoeneisen M, Martinez M, Silva M (2006) Antifungal and antibacterial activities of Araucaria araucana (Mol.) K. Koch heartwood lignans. Z Naturforsch C 61:35–43 56. Jaffre T (1995) Distribution and ecology of the conifers of New Caledonia. In: Enright NJ, Hill RS (eds) Ecology of the Southern conifers. Melbourne University Press, Carlton 57. Sarrailh JM, Chauvin JP, Pieters R (2008) Araucaria bernieri Buchholz In: Bois et forets des tropiques. CIRAD Tropical Woods and Forests Campus International de Baillarguet, France 58. Chen J, Chen J-J, Yang L-Q, Hua L, Gao K (2011) Labdane diterpenoids and shikimic acid derivatives from Araucaria cunninghamii. Planta Med 77:485–488 59. Anderson EF (1986) Ethnobotany of hill tribes of northern Thailand II Lahu medicinal plants. Econ Bot 40:442–450 60. Aspinall GO, McKenna JP(1968) Araucaria bidwillii gum: Part II1. Further studies on the polysaccharide components. Carbohydr Res 7:244–254 61. Aspinall GO, Molloy JA, Whitehead CC (1970) Araucaria bidwillii gum: Part III. Partial acid hydrolysis of the gum. Carbohydr Res 12:143–146 62. Pietsch M, Konig WA (2000) Enantiomers of sesquiterpene and diterpene hydrocarbons in Araucaria species. Phytochem Anal 11:99–105 63. Elkady WM, Ayoub IM (2018) Chemical profiling and antiproliferative effect of essential oils of two Araucaria species cultivated in Egypt. Ind Crop Prod 118:188–195 64. Ebada SS, Talaat AN, Labib RM, Mandi A, Kurtan T, Muller WEG, Singab A, Proksch P (2017) Cytotoxic labdane diterpenes and bisflavonoid atropisomers from leaves of Araucaria bidwillii. Tetrahedron 73:3048–3055 65. Nazeer Ahamed KFH, Kumar V, Raja S, Mukherjee K, Mukherjee PK (2005) Anti-nociceptive and anti-inflammatory activity of Araucaria bidwillii hook. Iran J Pharmacol 4:105–109 66. Nazeer Ahamed KFH, Kumar V, Manikandan L, Wahile AM, Mukherjee K, Saha BP, Mukherjee PK (2005) Brine shrimp lethality and cytotoxicity assay of Araucaria bidwillii hook in human carcinoma cell lines. Orient Pharm Exp Med 5:21–28 67. Dhanasekaran S, Ravishankar S, Devi KS, Suresh B, Sethuraman M, Rajan S (1993) Pharmacological studies of Araucaria bidwilli hook. Anc Sci Life 13((1–2)):137–142 68. Suresh B, Dhanasekaran S, Elango K, Sethuraman M, Rajan S (1995) Anti-pyretic activity of some plants in female albino rats: a preliminary report. Anc Sci Life 14:253–257 69. Briggs LH (1941) The essential oil of Araucaria excelsa (Norfolk Island pine). J Soc Chem Ind 60:222–226 70. Briggs LH, Taylor WI (1947) The occurrence of isophyllocladene in the essential oil of Araucaria excelsa. J Soc Chem Ind 66:168–168

628

A. Kumar et al.

71. Michael HN, Awad HM, El-Sayed NH, Pare PW (2010) Chemical and antioxidant investigations: Norfolk pine needles (Araucaria excelsa). Pharm Biol 48:534–538 72. Patial PK, Cannoo DS (2019) Phytochemical profile, antioxidant potential and DFT study of Araucaria columnaris (G. Forst.) hook. Branch extracts. Nat Prod Res 1–5, https://doi.org/10. 1080/14786419.2019.1696330 73. Verma S, Mohanta T, Revathy T, Suthindhiran K, Jayasri MA (2013) Phytochemical and pharmacological evaluation of selected plants. Am J Biochem Biotechnol 9:291–299 74. Zaffar M, Munis MFH, Rasul F, Masood S, Hassan SW, Imran M, Nasim W, Zakir A, Quraishi UM, Chaudhary HJ (2014) Biological assays of plant extracts from Araucaria columnaris and Cycas revoluta. J Food Agric Environ 12:128–131 75. Joshi S, Sati S, Kumar P (2016) Antibacterial potential and ethnomedical relevance of Kumaun Himalayan gymnosperms. J Phytopharmacol 5:190–200 76. Saranya Devi K, Sruthy P, Anjana JC, Rathinamala J (2015) Identification of bioactive compounds and toxicity study of Araucaria columnaris bark extract on human embryonic kidney cell line. Asian J Biotechnol 7:129–136 77. Warman CK (1999) Trees of India (medicinal, commercial, religious and ornamental): a ColourAtlas. CBS Publishers & Distributors, New Delhi 78. Kirtikar KR, Basu BD (1935) Indian medicinal plants. Periodical Experts, Delhi 79. Milliken W (2000) Ethnobotany of the Yali. Online 80. Gallagher M, Sutherland M (1960) Terpenoid chemistry. IV. The turpentine of Araucaria cunninghamii Ait. Aust J Chem 13:367–371 81. Franich RA, McDonald AG, Steward D (1999) Essential oil of the wood of Araucaria cunninghamii Aiton ex D. Don. J Essent Oil Res 11:38–40 82. Olawore NO, Ogunwande IA (2005) Analysis of the leaf oil of Araucaria cunninghamii sweet. Grown in Nigeria. J Essent Oil Res 17:459–461 83. Verma RS, Padalia RC, Goswami P, Verma SK, Chauhan A, Darokar MP (2014) Chemical composition and antibacterial activity of foliage and resin essential oils of Araucaria cunninghamii Aiton ex D.Don and Araucaria heterophylla (Salisb.) Franco from India. Ind Crop Prod 61:410–416 84. Gautam V, Arora S, Kapoor D, Bhardwaj R (2014) Free radical scavenging activity and HPLC analysis of Araucaria cunninghamiiAiton ex D. Don leaf extract. J Stress Physiol Biochem 10: 176–185 85. Bussmann RW (2008) Antibacterial activity of northern-Peruvian medicinal plants. Arnaldoa 15:127–148 86. Abdel-Sattar E, Monem ARA, Ezzat SM, El-Halawany AM, Mouneir SM (2009) Chemical and biological investigation of Araucaria heterophylla Salisb. Resin Zeitschrift für Naturforschung C64:819–823 87. Chen J, Lichwa J, Ray C (2007) Essential oils of selected Hawaiian plants and associated litters. J Essent Oil Res 19:276–278 88. Hamed MM, Ghareeb MA, Shafei AA, Abdel-Aziz MS, Tolba SS (2019) The in vitro evaluation of antioxidant, anticancer and antimicrobial properties of Araucaria heterophylla grown in Egypt. Pharmacology 1:221–235 89. Thomas P (2013) IUCN red list of threatened species: Araucaria hunsteinii. https://doi.org/10. 2305/IUCN.UK.2013-1.RLTS.T32836A2825399.en 90. Wyatt-Smith J (1980) The wood utilization potential of the araucarias in forestry problems of the genus Araucaria. Proceedings of IURFO Meeting, 21–28 October 1979, FUPEF, Curitiba 91. Dimas K, Demetzos C, Marsellos M, Sotiriadou R, Malamas M, Kokkinopoulos D (1998) Cytotoxic activity of labdane type diterpenes against human leukemic cell lines in vitro. Planta Med 64:208–211

Chemistry, Biological Activities, and Uses of Asafetida

25

Sonia Singh, Neetu Agrawal, and Prabhat Kumar Upadhyay

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Traditional Uses of Asafetida . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Bioactive Components in Asafetida . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Coumarin and Its Derivatives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Sulfur-containing components . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Biological Activity of Asafetida . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Blood Sugar Level Property . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Hepatoprotective Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Antimutagenicity Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Hypochloesteremic Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6 Hypersensitivity Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.7 Anxiolytic and Anthelmintic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.8 Cytotoxicity and Anticonvulsant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.9 Relaxant Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.10 Neuroprotective Effect . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.11 Antispasmodic and Hypotensive Effects . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

630 631 632 632 632 635 635 636 637 637 637 637 637 638 638 639 639 640 652

Abstract

The herbal crude drug asafoetida is considered a traditionally significant phytoremedy for various diseases in different countries. It is an oleo-gum-resin mainly obtained from Ferula species mainly the roots of Ferula asafoetida being utilized for several purposes in medicines. It is not only employed as spices and condiments for flavor purposes in curry but also used in the management of GIT disorders, asthma, whooping cough, hypertension, etc. Various phytochemical components such as sesquiterpene coumarins, coumarins, diterpene coumarins, S. Singh (*) · N. Agrawal · P. K. Upadhyay Institute of Pharmaceutical Research, GLA University, Mathura, UP, India e-mail: [email protected]; [email protected]; [email protected] © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_31

629

630

S. Singh et al.

sulfur-containing compounds have been extracted from the herb. The current book chapter summarizes the detailed information concerning the ethnobotanical uses, bioactive components, and pharmacological activities of Ferula asafoetida. Keywords

Apiaceae · Asafetida · Coumarins · Ferula · Sesquiterpene Abbreviations

CAP CCl4 GIT MTT NPT MFOS

1

Compound action potential Carbon tetrachloride Gastrointestinal tract (3-(4, 5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide) Novelty preference test Mixed function oxidase

Introduction

For thousands of years, species and condiments are used as one of the special accessories in food to enhance the flavor sensory and flavor quality of foodstuff [1] although spices are known to contain various therapeutical properties. Therefore, with respect to this, several dietary spices and condiments have been well documented in many works of literature along with their experimented physiological impacts on human health [2–4]. Asafetida is considered as a flavoring ingredient of food supplements and has been well documented in literature as a traditional drug to cure several diseases and infections worldwide. The biological source of asafetida as an oleo-gum-resin obtained from the root and stem exudates of several species of Ferula belonging to the family Umbelliferae. These species may include F. foetida, F. narthex, F. rigidula, F. alliacea, F. rubricaulis, and so on [5–7]. Around 60 species of Ferula are distributed in the central region of Asia especially Iraq, Afghanistan, Iran, Turkey, Africa, and Europe. Out of these species, Ferula foetida is considered to be the most important herbal drug and is indigenous to Iran and Afghanistan [8–10]. In India, the drug is known as hingu/hing. Different vernacular names of asafoetida are discussed in Table 1. The herbal plant asafetida is a perennial containing a strong sulfurous unpleasant odor and taste. It grows not more than 2 m in height. Generally, the plant is obtained via an incision in the roots and stems. The oleo-gum-resin occurs in tear as well as mass forms in the market. In India, it is a very popular spice involved in Indian cuisine [11]. Traditionally, it has been employed in various diseases including epilepsy, ulcer, asthma, cough, bronchitis, digestion problems, and stomachache. The drug has sedative, diuretic, and aphrodisiac properties. Recent experimental work revealed the various pharmacological profile of asafetida such as antifungal, antioxidant, antidiabetic, antiviral, antibacterial, and hypotensive. However, the oleo-gum-resin is used to reduce the acidity and is used as carminative [12–26].

25

Chemistry, Biological Activities, and Uses of Asafetida

631

Table 1 Synonyms of asafetida are used in different countries [27–29] Countries India United States Bangladesh China Finland Greece Norway Italy England Russia Pakistan Afghanistan England Denmark France Iran Myanmar Netherlands Germany Spain Sweden Sri Lanka Tanzania Turkey Russia

2

Synonyms Ingu, Hing, Hengu, Inguva, Perungayam, Hingu, Kayam, Raamathan, Perunkaya Stinking gum, Devil’s dung, Asafoetida Hing Amei Pirunpaska, Hajupihka, Asafetida, Pirunpihka Aza Dyvelsdrekk Assafetida Asafetida Asafetida Kama, Anjadana, Anguza Anguza, Kama Asafoetida Dyvelsdrak Asafetide, Ferule persique, Asafoetida Zaz Sheingho Godenvoedsel, Asafetida, Sagapeen Asant, Asafoetida, Asafetida, Stinkasant Asafoetida Dyvelstrack Perunkayan Mvuje Setan-bokosu Asafetida

Traditional Uses of Asafetida

The drug asafetida is used as a remedy in flatulence. The drug has been roasted in a clarified butter/ghee/water and then used in the treatment of gastric-related disorders. Usually, the local people from the Shimoga region (India) are generally used asafetida to reduce stomachache. Traditionally, it is also used as an antispasmodic, anthelmintic, laxative, and diuretic. The aqueous extract is administered orally in the treatment of expulsion of worms from the stomach. The Iranian people used this drug as an antihelminthic, carminative agent, antispasmodic, and even as a laxative for the elderly patient. The asafetida is used as an effective medicine in nervous disorders and hysteria. In Nepal, it is used as a diuretic and laxative. Additionally, it is used as an anticonvulsant activity. The Americans use the crude drug orally as a brain and nerve stimulant. In Ayurveda, the drug asafoetida is used in the management of angina pectoris, asthma,

632

S. Singh et al.

whooping cough, bronchitis, and additionally as a pulmonary stimulant. In Iran, it is used in the treatment of respiratory disorders. In Afghanistan, the gum of dried drug is used in the treatment of whooping cough. Traditionally, it is used as an aphrodisiac. Despite all these, it is used to reduce the elevated acid levels in GIT [27–29].

3

Bioactive Components in Asafetida

The oleo-gum-resin (crude drug), of Ferula asafoetida, usually contains 10–17% of volatile oil, 25% of gum, and 40–64% of the resin. The gum contains galactose, arabinose, glucuronic acid, rhamnose, glucose, polysaccharides, glucuronic acid, and glycoproteins; the fraction of resin includes ferulic acids along with its derivatives such as esters, sesquiterpenes, coumarins, terpenoids. The volatile oil mainly consists of sulfur-containing components some monoterpenes and terpenoids. The presence of sulfur components in asafetida is mainly responsible for pharmacological activities and thereby can be employed in the pharmaceutical industries for formulation. Some important sulfur-containing components are such as 2-butyl-3(methylthio)-propyl-1-propenyldisulfide and 2-butyl-1-propenyldisulfide [30, 31].

3.1

Coumarin and Its Derivatives

In 1935, Tsukervanik et al. was the first researcher’s group who have identified the active components present in the Ferula genus. Varieties of sesquiterpene coumarin have been isolated from Ferula asafoetida. However, the difference in the chemical structure of sesquiterpene coumarins was maybe because of the different sources from where they have been collected for experiment work [32, 33]. Umbelliprenin, 8-hydroxyumbelliprenin, as a coumarin A-B, tadshiferin, 5-hydroxy umbelliprenin, 8-acetoxy-5,5-hydroxy umbelliprenin, assafoetidin, galbanic acid, franesiferol A-C, gummosin, conferol, asafoetidinol A-B are present as sesquiterpene coumarins in asafetida [33]. Other components reported to be present in asafetida are epi-samarcandin, ferocaulicin, epi-samarcandin acetate, kamolonol, saradaferin, foetidine, 10-R-karatavincinol, 10-R-acetoxy-11-hydroxyumbelliprenin, methyl galbanate, feselol, lehmferin, epi-conferdione, ligupersin A, polyanthinin, microlobin, umbelliferone (Fig. 1) [33, 34].

3.2

Sulfur-containing components

The sulfur-containing components are responsible for the odor and taste of the crude drug asafetida. Sulfur components include 2,3-dimethylthiirane, 2-methyl-2-propanethiol, 1-methyl thio-(E)-1-propene, 1-methylthio-(Z)-1-propene-5-methyl propane thioate, dimethyl disulfide, 2-(methylthio)-butane, methyl-(Z)-1-propenyl disulfide,

25

Chemistry, Biological Activities, and Uses of Asafetida

633

Fig. 1 Chemical structures of Phyto-constituents in Asafoetida

3,4-dimethylthiophene, methyl-(E)-1-propenyl disulfide, 2-butyl methyldisulfide, dimethyltrisulfide, dipropydisulfide, 2-butyl vinyldisulfide, 2,3,4-trimethylthiophene, 2-butyl propyldisulfide, 2-butyl ethyldisulfide, methyl-1-(methylthio)propyldisulfide, 2-butyl-1-propenyl disulfide, methyl-1-(methylthio) ethyl disulfide, di-2-butylsulfide, 1-(methylthio)propyl-1-propenyldisulfide, 1-(methylthio)propyl propyl sulfide,

634

S. Singh et al.

Fig. 2 Chemical structures of Phyto-constituents in Asafoetida

asadisulfide, 2-butyl methyltrisulfide, di-2-butyl tetrasulfide, and di-2-butyl trisulfide (Fig. 2) [9, 13, 35, 36]. Some other polysulfide compounds reported from the roots of Ferula foetida are foetisulfide A-C. It also contains some other active secondary metabolites such as diterpenes such as picealactone C; 7-oxo-callitrisic acid; 15-hydroxy-6-en-dehydroabietic acid; phenolic compounds such as 3,4-dimethoxycinnamyl-3-(3,4-diacetoxy phenyl) acrylate, vanillin; acetylene such as falcarinolone and other miscellaneous compounds like fletidone, taraxacin, oleic acid, luteolin-7-β-D-glucopyranoside [8, 12, 13, 37] (Fig. 3) (Table 2).

25

Chemistry, Biological Activities, and Uses of Asafetida

635

Fig. 3 Chemical structures of Phyto-constituents in Asafoetida

4

Biological Activity of Asafetida

4.1

Antioxidant Activity

Mallikarjuna et al. evaluated a study to evaluate the antioxidant activity and modulatory activity on the rat’s tissue differentiation and MNU-induced mammary carcinogenesis in animal models. Two different doses (1.25% and 2.5% w/w) of drug asafetida potentially restored the antioxidant level in MNU treated rat groups.

636

S. Singh et al.

Table 2 Secondary metabolites present in asafetida Chemical class of metabolites Coumarins, sesquiterpene coumarins

Sulfur components

Diterpenes components Phenolic components Sesquiterpene components Miscellaneous

Secondary metabolites Umbelliprenin; 8-hydroxyumbelliprenin; 5-hydroxyumbelliprenin; galbanic acid; gummosin; coniferol; tadshiferin; 8-acetoxy-5-hydroxyumbelliprenin; epi-samarcandin; farnesiferol A-C; asafoetidin; asacoumarin A; ferocaulicin; assafoetidinol A-B; kamolonol; polyanthinin; foetidin; saradaferin; lehmferin; feselol; methyl galbanate; 10(R)-karatavicinol; 10(R)acetoxy-11-hydroxyumbelliprenin; ligupersin A; microlobin; epiconferdione; umbelliferone 1-(Methylthio)prenyl disulfide; 2-butyl-1propenyldisulfide; 2-methyl-2-propanethiol; 2-butyl-3(methylthio)-2-propenyldisulfide; 2,3-dimethylthiirane; 1-methylthio-1-propene (E) and (Z); 2-(methylthio) butane; S-methylpropanethioate; dimethyldisulfide; dipropyl disulfide; methyl-1-propenyl disulfide (E) and (Z); 2-butylmethyl disulfide; 2,3,4-trimethylthiophene; dipropyl disulfide; 2-butyl-1-vinyl disulfide;methyl-1(methyl thio)-propyldisulfide; 2-butyl-1-propenyl disulfide; methyl-1-(methylthio)-ethyldisulfide; di-2butyldisulfide; asadisulfide; 1-(methylthio)propylpropyl disulfide; foetisulfide A-C; 2-butyl methyltrisulfide; di-2butyl tetrasulfide; di-2-butyltrisulfide 15-Hydroxy-6-en-dehydroabietic acid; 7-oxocallitristic acid; picealactone C 3,4-Dimethoxycinnamyl-3-(3,4-diacetoxyphenyl) acrylate; vanillin Fetidone A; taraxacin

Reference [33, 34], [38–43]

Arabinose; galactose; beta-sitosterol; glucuronic acid; ferulic acid; rhamnose; luteolin-7-β-D-glucopyranoside, oleic acid, falcarinolone

[8, 37– 45]

[37–39]

[30] [36] [38]

Moreover, the treatment with asafetida significantly reduced the diameter of mammary tumors and even delayed the occurrence of tumors. The antioxidant profile was evaluated by using TBARS in the rat’s liver which revealed a marked inhibition of lipid peroxidation [46].

4.2

Blood Sugar Level Property

A combination of Commiphora myrrh, Nigella sativa, Aloe vera, Boswellia serrata, and Ferula foetida collectively used in the management of diabetes were investigated for the hypolipidemic profile using streptozotocin-induced diabetes in rats. The plant extracts significantly lowered the level of ketone bodies in both fasted control and diabeticinduced rats although the plant extract remarkably reduced the triglyceride level and

25

Chemistry, Biological Activities, and Uses of Asafetida

637

even prevented the reduction of body weight in diabetic rats [47]. Another study was conducted on the plant mixture extracts of Myrrh odorata, Aloe species, and Nigella sativa in streptozotocin-induced diabetic rat model. The extract mixture decreased the concentration of blood glucose level ( p < 0.005) in the tested animals [48].

4.3

Hepatoprotective Activity

Soni et al. demonstrated the inhibitory effects of some food additives including turmeric, curcumin, ellagic acid, garlic, and asafetida against liver toxicity induced by aflatoxin B1 in ducklings. Results revealed the protective effects of these foods against liver damage by inhibiting liver necrosis and tissue degeneration, fatty changes, and biliary hyperplasia [49]. Sambaiah et al. investigated the effect of spice mixture containing piperine, curcumin, capsaicin, ginger, cumin, cinnamon, fenugreek, tamarind, mustard, and asafetida on hepatic MFOS in rat models, where all these species stimulated the cytochrome P450 levels as well as N-demethylase property [50].

4.4

Antimutagenicity Activity

The investigation was carried out in some species such as pepper, turmeric, curcumin, eugenol, ginger, mustard, and garlic for antimutagenicity activity using strains of Salmonella typhimurium (TA100 and TA1535). Results showed that some of the extracts of the spices can ameliorate the mutagen effects particularly found present in the food [51].

4.5

Hypochloesteremic Effects

Researchers observed that asafetida at 1.5% doses was failed to decrease the cholesterol levels in an atherogenic diet-fed rats [52].

4.6

Hypersensitivity Activity

A randomized double-blind trial of asafetida was conducted in 50 patients affected with an irritable colon, where it was found to be effective in reducing the irritation at a 1% significant level [53].

4.7

Anxiolytic and Anthelmintic Activity

The binary combinations including allicin from Allium sativum, ferulic acid, umbelliferone from Ferula foetida, and eugenol from Syzgium aromaticum were studied for in vitro anthelmintic effect against Fasciola gigantica [54]. Rohit

638

S. Singh et al.

Gundamaraju et al. studied the antihelminthic activity of Ferula foetida against Pheretima posthuma. Results revealed that aqueous extracts of Ferula foetida exhibited significant effective antihelminthic activity at 100 mg/ml concentration against piperazine citrate, standard drug [55].

4.8

Cytotoxicity and Anticonvulsant Activity

Oleo-gum-resin of Ferula asafoetida was evaluated for cytotoxicity and anticonvulsant activity where brine shrimp (Artemia salina) was used as a model assay in the prescreening method for determining cytotoxicity [56]. Extracts of asafetida were investigated for a protective effect against fat lowering obesity and liver steatosis in obese diabetic rat models. The study revealed that the administration of extract markedly reduced the abdominal fat, body weight, and the size of epididymal adipocyte and serum leptin ( p < 0.05) in diabetic rats [57].

4.9

Relaxant Effect

Zahra et al. investigated the smooth muscle relaxant effect of aqueous extract of Ferula foetida on guinea pig animal models. Different concentrations of tested drug (2,5 and 10 mg/ml), standard drug theophylline (0.25, 0.5, and 0.75 mM), and saline were investigated on guinea pig’s nonincubated tracheal smooth muscle which has been precontracted with a dose of 10 μM, methacholine, called as a group I; preincubated smooth muscle tissues with propranolol and chlorpheniramine which have been contracted by using methacholine, considered as group II and in group III, the preincubated smooth muscle tissues by propranolol, have been contracted by methacholine. Results revealed that all different concentrations of the drug theophylline tested in group I and then different concentrations of drug extract tested in three groups demonstrated potential relaxant effects when compared against saline ( p < 0.001). From the experiment, it was assumed that the significant smooth muscle effect of the drug Ferula foetida was due to blockage of the muscarinic receptor [58]. Another researcher Bayrami et al. demonstrated the relaxant effects of asafetida and its active component umbelliprenin on guinea pig’s tracheal tissues. Three cumulative concentrations (2, 5, and 10 mg/ml) of aqueous extract of asafetida, 0.04, 0.2, and 0.4 mg/ml of umbelliprenin and 0.05, 0.1, and 0.15 mg/ml of theophylline and saline were tested on precontracted guinea pig’s tracheal tissues by using 60 mmol/L potassium chloride as a group I and methacholine (10 μmol/L) considered as group II. All concentrations of theophylline ( p < 0.01) and 10 mg/ml of aqueous extract of asafetida ( p < 0.05) revealed significant smooth muscle relaxant effects on tracheal tissues as compared to that of saline. Moreover, higher concentrations of 0.2 and 0.4 mg/ml of umbelliprenin showed potential effect ( p < 0.001) when compared to the saline group. The above results concluded that

25

Chemistry, Biological Activities, and Uses of Asafetida

639

the significant potent relaxant effect of asafetida aqueous extract on smooth muscle is due to the presence of umbelliprenin [59]. Bagherii et al. investigated the three different doses (0.1%, 0.2%, and 0.3%) of asafetida and essential oils (isolated from the seeds of Ferula foetida) for relaxant effectiveness against acetylcholine-induced concentration in rat’s ileum. Results statistically supported the antispasmodic effect of asafetida and its essential oil [60].

4.10

Neuroprotective Effect

Tayeboon et al. investigated the synergistic effects of Ferula foetida and Cymbopogon citratus extracts on glutamate-induced neurotoxicity in rat’s cerebellar neurons. The cerebellar granule neurons of rats were treated with the essential oil of C. citratus and extracts of F. asafoetida at a concentration of 100 μg/mL before, after, and during exposure to glutamate (30 μM). The MTT assay was used to evaluate the cellular viability including cell cycle and apoptosis. Results showed glutamateinduced enhancement in the cellular viability when treated with the F. asafoetida extracts and essential oils of C. citratus. However, through flow cytometric analysis, the drug extracts treatment markedly decreased the necrotic rate ( p < 0.001). The combination of both herbal drugs exerted neuroprotective effects in glutamateinduced nephrotoxicity. Additionally, these beneficial effects of showing antiapoptotic activity are due to arrest in the G0G1 phase cell cycle phase. Another investigation was carried out with in vitro and in vivo studies where the important role of Ferula species in the management of peripheral neuropathy. In vitro studies were examined to observe the response of sciatic nerves treated with asafetida. And even in vivo studies were evaluated to analyze the effect of oleo-gum-resin on amelioration of peripheral neuropathy in Balb/c mice [61]. Treatment with asafetida showed elevated amplitude and nerve-reduced latent period of CAP in in vitro studies. The behavioral and histological studies revealed the facilitated healing effect of asafetida in peripheral nerves, thereby the crude drug exerted neuroprotectant effects via stimulation of axonal regeneration and remyelination [62].

4.11

Antispasmodic and Hypotensive Effects

Fatehi investigated the effects of asafetida extract on the contractile responses of guinea pig’s ileum that have been investigated using histamine, potassium chloride, and acetylcholine. The therapeutic effect of crude extract was also studied on the mean arterial blood pressure of rats. Treatment with gum extract showed relaxation in the precontracted ileum induced by 10 μM, acetylcholine, 10 μM histamine, and 28 μM potassium chloride. However, the preincubated preparations with 100 μM indomethacin, 1 μM propranolol, 100 μM atropine, and 25 μM chlorpheniramine were then

640

S. Singh et al.

Fig. 4 Pharmacological activities of Asafoetida

contracted with potassium chloride and further exposed to gum extract at a dose of 3 mg/ml did not show relaxation effect. It also showed that the gum extract potentially decreased the mean arterial blood pressure. From the above observations, it has been concluded that the relaxant components present in the gum would interfere with muscarinic, histaminic, and adrenergic receptor activities or even with the calcium ions mobilization responsible for contraction effect (Fig. 4) (Table 3) [63].

5

Conclusions

The oleo-gum-resin asafetida has been obtained from different regions of countries, where Ferula asafoetida is known to be the main biological source of obtaining various secondary metabolites of the drug. The plant is indigenous to Asia including mainly Afghanistan and Iran. Though this plant is not native to India, it contains mainly excellent applications in cookery, sausages, and several herbal as well as pharmaceutical formulations. Traditionally, the drug has been employed for ethnobotanical medicines in other countries including Nepal, America, and Malaysia. Recent research claimed the traditional utilization of Ferula asafoetida as antispasmodic, antibacterial, antidiuretic, antifungal, and anthelmintic. Various applications in aspects of pharmaceutical fields have been carried out with asafetida as elaborated in Table 3. It is believed that the detailed collective information on the bioactive components and pharmacological activities of Ferula asafoetida may provide detailed applications as needed in various formulations.

Gum aqueous extract used for the formulation of silver nanoparticles

Tested against MCF-7 cell lines; antimicrobial activity against C. albicans, K. pneumoniae, E. coli

Effective in the inhibition of multiplication of cancer cells

Potent effect

Oleoresins

Leaf extract showed a higher percentage of phenolic and flavonoid compounds 15.40% carvacrol and 9.75% α-bisabolol; and the gum extract showed 20.91% of (Z )-b-ocimene 4, 17.62% (E)-1propenyl-sec-butyldisulfide, umbelliprenin, ferulic acid –

Antimicrobial, cytotoxic

DPPH scavenging, ferric reducing power, MIC property (Staphylococcus aureus, Escherichia coli, Saccharomyces cerevisiae, Aspergillus niger)

Leaf, gum

Antimicrobial, antioxidant

Asafetida and cucumin encapsulation onto TNF Turmeric nanofiber Hydroethanolic

(continued)

[67]

[66]

[65]

–

References [64]

Anticolitis

Observations Potent and significant activity Protective effect

Part used –

Pharmacological activity Ovicidal, larvicidal

Chemical constituents Allyl disulfide, diallyl trisulfide –

Table 3 Biological activities of Ferula foetida Experimental model Culex pipiens, C. restuans larvae Dextran sulfate sodium (5%) induced colitis

Chemistry, Biological Activities, and Uses of Asafetida

Extract/formulation used Essential oils

25 641

Roots

Roots

Resins

Antinociceptive

Antimicrobial

Part used Gum Resins

Antihyperglycemic

Pharmacological activity Inhibition of farnesyltransferase activity

Table 3 (continued)

Alcohol and aqueous extracts

Oleo-gum-resin

Oleo-gum-resin

Extract/formulation used –

Agar disc diffusion

Hot plate/acetic acidinduced writhing test

Streptozotocin-induced diabetic rats

Experimental model –

–

–

Chemical constituents Galbanic acid karatavicinol, umbelliprenin, farnesiferol B, farnesiferol C as these constituents inhibited the activity of farnesyltransferase Phenolic acids such as ferulic acid, tannin Potentially decreased the serum glucose concentration as compared to diabetic rats Significant effect on acute and chronic pain in mice; effects may be due to the involvement of central opioid pathways and peripheral antiinflammatory action Showed inhibitory zone of about 4–16 mm diameter for antimicrobial activity

Observations Inhibited the proliferation of oncogenic rastransformed NIH3T3/Hras-F

[22]

[70]

[69]

References [68]

642 S. Singh et al.

Essential oil

Aqueous extract

Aqueous extract

Essential oil

Oleo-gum resins

Oleo-gum resins

–

–

–

Vasodilatory

Antioxidant, the effect of ischemicreperfusion injury in isolated rat hearts. Smooth muscle relaxant effects

Memory enhancing effects

Anticancer

Essential oil

Oleo gum resins

Learning and memory

Petroleum ether hot water, ethanol, hexane –

Red and white varieties of gum

Antibacterial

Elevated plus maze, passive avoidance paradigm In vitro cytotoxicity in two human liver cancer cell lines

–

–

Shuttle box apparatus induced via D-galactose and sodium nitrite for 60 days Phenylephrine and potassium channel blockers

Agar disc diffusion

Dithiolane

–

–

–

–

–

–

Antiproliferative activity in human liver carcinoma cell lines

Relaxant effect on tracheal smooth muscle Improvement in memory

Showed vasodilatory effect on denudedendothelium aortic ring mediated via potassium channels activation and reduced intracellular calcium release. Moderate effect in the treatment of acute myocardial infarction.

Against grampositive and gramnegative bacteria Significant activity

Chemistry, Biological Activities, and Uses of Asafetida (continued)

[76]

[75]

[60]

[74]

[73]

[72]

[71]

25 643

Seeds

Smooth relaxant effect

Essential oil

Asdamarin, a combination of Ferula foetida oleo resin with Silybum marianum extract

–

Gastric emptying effect Phenol red method in rat models

1,2-Dimethylhydrazine induced rat colon carcinogenesis

–

Oleo-gum-resins

Chemopreventive

Experimental model Lipoxygenase inhibitory, antioxidant

Trichoderma harzianum and Pleurotus species

Extract/formulation used –

Methanol extract

Oleo-gum-resins

Part used –

Antifungal, allelopathic

Pharmacological activity Antitumor, antimetastasis

Table 3 (continued)

–

–

–

–

Chemical constituents – Observations Reduced lung, liver, kidney metastasis. Even reduced the increased necrosis Fungistatic and fungicidal properties at higher concentrations Showed maximum protective effect at 10 mg–100 g for the treatment of colon cancer Improved the delay in gastric emptying with significant enhancement in gastrointestinal transit time Essential oil at the concentrations of 0.2% and 0.3% significantly reduced Ach (10.4 M) induced contractions.

[80]

[79]

[78]

[15]

References [77]

644 S. Singh et al.

Essential oils

Combination of essential oil of asafetida and Shirazi thyme

–

Essential oils

–

Seeds

–

–

–

–

Antitumor

Antibacterial

Antidiabetic

Antiproliferative

Nootropic

–

–

Cytotoxic effects

NPT on y-maze and Open field test on Open field box in mice model

MTT assay

Alloxan-induced diabetes in rat models

3-(4,5-Dimethylthiazol2-yl)-2,5diphenyltetrazolium bromide assay –

DPPH free radical scavenging assay; inhibitory effect against lipid peroxidation catalyzed using soybean lipoxygenase

–

Essential oils

Trans propenyl sec-butyl disulfide, eudesmol (10-epu-γ), cis propenyl sec-butyl disulfide –

Ferulic acid

–

Protective effect for maintaining the integrity of pancreatic beta-cells Decreased the viability of MCF7 cells; strong cytotoxic effect of essential oil on breast cancer cells. A significant effect for nootropic activity

Potentially reduced the rate of infiltration in C57BL/6 mice (P < 0.01) and showed reduced demyelination Potential effect in decreasing viability of breast cancer cells at 500 μg/ml. Antibacterial compounds and this property increased by increasing their concentration

Chemistry, Biological Activities, and Uses of Asafetida (continued)

[84]

[83]

[17]

[82]

[81]

[81]

25 645

Acetone, petroleum ether

–

Murraya koenigii, Coriandrum sativum, Ferula foetida, Trigonella foenum-graceum

–

Roots

Essential oils

Larvicidal

Anticonvulsant

Diuretic

Antispasmodic

–

Oleo-gum-resins

–

Oleo-gum-resins

Cytotoxic effects

–

Extract/formulation used Methanol extract

Gum-resins water

Part used –

Anxiolytic, analgesic, sedative

Pharmacological activity Thrombolysis

Table 3 (continued)

Measuring urine volume and sodium, potassium, urea, creatinine content in urine and serum Contractile response of rat’s aorta rings

Chemical and amygdalakindled rats

Elevated plus-maze, hole-board test, hot plate, the motor activity meter Cytotoxic effects against MCF-7 and PC-3 cell lines and NIH cells Against A. aegypti larvae

Experimental model –

–

–

Terpenoid compounds

–

Gummosin

–

Chemical constituents Ferulic acid, coumarins, sulfur compounds

Vasodilatory effect

Moderate activity against PC-3, MCF-7 cell lines The synergistic activity showed comparatively poor larvicidal activity when tested individually. Protective effect against chemical and electrical kindling induced seizure model –

Observations Thrombolytic activity at a dose of 800 μL comparable with Streptokinase –

[90]

[89]

[88]

[87]

[86]

[62]

References [85]

646 S. Singh et al.

–

Essential oils

–

Hydroalcoholic extract extracts of Ferula foetida and Allium sativum Aqueous

Aqueous

Aqueous extract

–

Oleo-gum-resins

–

–

–

–

Hepatoprotective and antidyslipidemic effect

Vasodilatory effect

Antiurolithiasic, hepatoprotective

Antiparasitic

In vitro antiparasitic

Relaxant effects

Relaxant effects

Precontraction of tracheal chains of guinea pig using potassium chloride and methacholine Smooth muscle tracheal model in guinea pig

Larvicidal effect on the Strongylus spp. larval

AgainstTrichomonas vaginalis

CCl4 induced hepatotoxicity associated dyslipidemia and oxidative stress in rats Using phenylephrine, potassium channel blockers, and glibenclamide Ethylene glycol-induced lithiasis in Wistar rats

–

–

–

–

–

–

–

Significantly lowered the effect when compared to atropine induced in an animal model

The extract showed a potent effect as compared to Umbelliprenin

Reduction in serum level; antioxidant and antihyperlipidemic activity Relaxed the precontracted rings in a concentrationdependent manner. Significantly reduced the elevated levels of ions and reduced the elevated levels of serum biomarkers Effective in the treatment of parasitic infections Potentially killed over 90% of the larvae

Chemistry, Biological Activities, and Uses of Asafetida (continued)

[95]

[59]

[94]

[93]

[92]

[90]

[91]

25 647

Extract/formulation used Aqueous

80% methanol

Aqueous

Including 14 spices (50 mg asafetida) –

Aqueous

Part used Oleo-gum-resins

–

–

–

–

–

Antiapoptotic effects

Memory enhancing

Digestive enzyme activity

Digestive enzyme activity

Antispasmodic

Pharmacological activity Neuroprotective

Table 3 (continued)

Contraction induced by histamine, potassium chloride, and

D-Galactose and sodium nitrite induced dementia in mice models An experiment performed in Wistar albino rat models –

Glutamate induced neurotoxicity

Experimental model Induction of sciatic nerve pain in mice

–

–

Sulfur compounds, sesquiterpene coumarin –

–

Chemical constituents –

Affected the trypsin and chymotrypsin activities Stimulated the digestive action and titers of digestive enzymes in pancreatic tissues Reduced the blood pressure in experimented rats

Observations Increased amplitude and decreased the latent period of nerve compound action potential, facilitate the healing process in peripheral nerves Beneficial effects in neurological disorders; attained antiapoptotic effects in cerebellar granule neurons Protective effect against amnesia

[63]

[97]

[96]

[72]

[61]

References [62]

648 S. Singh et al.

–

Oleo-gum -resins

–

–

Hepatoprotective

Antimicrobial and antioxidant

Antimicrobial

Antimicrobial

Acetone, petroleum ether, ethanol, methanol, aqueous, carbon tetrachloride extracts Volatile oils

Benzene, chloroform, ethanol, petroleum ether, aqueous extract of Ferula asafoetida, Momardica charantia, Nardostachys jatamansi Essential oils

Tested against E. coli, Pseudomonas aeruginosa, Staphylococcus aureus, Bacillus subtilis, Aspergillus niger Various bacterial strains

Experimented against Gram-negative and Gram-positive bacteria, fungi

acetylcholine in guinea pig ileum Carbon tetrachlorideinduced liver toxicity in rats

Volatile oils of two varieties (Irani and Pathani)

–

Essential oils

–

Pathani oil showed good antibacterial and Irani oil revealed fungicidal

Improved the oxidative stability of fatty foods while in storage conditions; safe and effective antimicrobial Alcoholic and aqueous extracts showed potential effects

and even decreased the contraction Reduced the elevated levels of serum enzymes

(continued)

[23]

[22]

[21]

[98]

25 Chemistry, Biological Activities, and Uses of Asafetida 649

Essential oil

Included 90 formulations (neem oil, nicotinic acid, asafetida, α,β-unsaturated carbonyl compounds) Essential oils of black cumin, asafetida, neem

Seeds

–

Seeds

Antifungal

Antifungal

Antifungal

Essential oils (around 20 species)

–

Antifungal

Extract/formulation used Chloroform, methanol, ethanol, ethyl acetate, aqueous extract

Part used –

Pharmacological activity Antibacterial and antifungal

Table 3 (continued)

Against fungal strains such as Fusarium oxysporum, F. niuale, F. monoliforme, Aspergillus niger, A. flavus, Alternaria alternata

Against fungal strains

Against fungal strains

Gram-positive/ fungal strains

Experimental model Klebsiella pneumonia, E. coli, Bacillus subtilis, Staphylococcus aureus

–

–

Essential oils

Essential oils

Chemical constituents –

Inhibited the fungal growth of all strains except A. flavus, at a concentration of 0.1% and 0.15%

Observations Methanolic extract showed the highest activity for antimicrobial and antifungal Inhibitory activity against fungal strains Increased antifungal activity with increased essential oil concentration Revealed significant antifungal activity

[102]

[101]

[100]

[99]

References [25]

650 S. Singh et al.

Benzene, petroleum ether, ethyl acetate, methanol, acetone, aqueous – –

Essential oil Aqueous

Aqueous

–

–

–

–

Oleo-gum -resins

–

Anticarcinogenic activity

Anticarcinogenic activity

Anticarcinogenic activity

Antiquorum sensing activity Antihyperglycemic effect

“–”: not known

Antagonistic effect

70% ethanol

–

Anticarcinogenic activity

Tested on muscarinic receptors antagonist/ saline on methacholine concentration-response curve in tracheal smooth muscles treated with beta-adrenergic receptors antagonists

1,2-dimethylhydrazine induced in SpragueDawley rats Against Pseudomonas aeruginosa Streptozotocin induced diabetes

Tested in SpragueDawley rats

7,12dimethylbenzathracence/ croton oil-induced carcinogenicity in Swiss albino mice –

–

–

–

–

–

–

–

Acted as a virulence inhibitors Decreased the blood glucose level in male Wistar rats Potent effect; blockade of histamine receptor affects muscarinic receptors inhibitory property of asafetida

Decreased the multiplication of tumor cell growth Potent activity

Reversed the ornithine decarboxylase activity

Decreased the papilloma formation

[105]

[69]

[104]

[78]

[46]

[20]

[103]

25 Chemistry, Biological Activities, and Uses of Asafetida 651

652

S. Singh et al.

References 1. Pruthi JS (1980) Spices and condiments: chemistry, microbiology, technology. Academic, New York, pp 1–449 2. Srinivasan K (2005) Role of spices beyond food flavoring: nutraceuticals with multiple health effects. Food Rev Int 21(2):167–188 3. Srinivasan K (2011) Spices for taste and flavor: nutraceuticals for human health. In: Spices: the elixir of life. London, pp 43–63 4. Srinivasan K (2013) Dietary spices as beneficial modulators of lipid profile in conditions of metabolic disorders and diseases. Food Funct 4(4):503–521 5. Sahebkar A, Iranshahi M (2010) Biological activities of essential oils from the genus ferula (Apiaceae). Asian Biomed 4(6):835–847 6. Anonymous (2003) The Ayurvedic Formulary of India, part-I. Ministry of Health and Family Welfare, Department of Indian Systems of Medicine & Homeopathy, Government of India, New Delhi, pp 64–66 7. Duan H, Takaishi Y, Tori M et al (2002) Polysulfide derivatives from Ferula foetida. J Nat Prod 65(11):1667–1669 8. Rajanikanth B, Ravindranath B, Shankaranarayana ML (1984) Volatile polysulphides of asafoetida. Phytochemistry 23(4):899–900 9. Takeoka G (2001) Volatile constituents of asafoetida. In: Takeoka GR (ed) Aroma active compounds in foods. American Chemical Society, Washington, pp 33–44 10. Evans WC (2002) Volatile oils and resins, Trease and Evans Pharmacognosy. W.B. Saunders, London, pp 255–290 11. Tyler VE, Brady LR, Robbers JE (1976) Pharmacognosy. Lea & Febiger, Philadelphia, pp 456–465 12. Zargari A (1996) Medicinal plants. Tehran University Publications, Tehran, pp 592–602 13. Lee CL, Chiang LC, Cheng LH et al (2009) Influenza A (H1N1) antiviral and cytotoxic agents from Ferula assa-foetida. J Nat Prod 72(9):1568–1572 14. Dehpour AA, Ebrahimzadeh MA, Fazel NS et al (2009) Antioxidant activity of the methanol extract of Ferula asafoetida and its essential oil composition. Grasas Aceites 60(4):405–412 15. Angelini P, Pagiotti R, Venanzoni R et al (2009) Antifungal and allelopathic effects of asafoetida against Trichoderma harzianum and Pleurotus spp. Allelopathy J 23(2):357–368 16. Aruna K, Sivaramakrishnan VM (1992) Anticarcinogenic effects of some Indian plant products. Food Chem Toxicol 30(11):953–956 17. Abu-Zaiton AS (2010) Anti-diabetic activity of Ferula asafoetida extract in normal and alloxan-induced diabetic rats. Pak J Biol Sci 13(2):97–100 18. Kumar P, Singh DK (2006) Molluscicidal activity of Ferula foetida, Syzygium aromaticum and Carum carvi and their active components against the snail Lymnaea acuminata. Chemosphere 63(9):1568–1574 19. Khajeh M, Yamini Y, Bahramifar N et al (2005) Comparison of essential oils compositions of Ferula assa-foetida obtained by supercritical carbon dioxide extraction and hydrodistillation methods. Food Chem 91:639–644 20. Saleem M, Alam A, Sultana S (2001) Asafoetida inhibits early events of carcinogenesis: a chemopreventive study. Life Sci 68(16):1913–1921 21. Kavoosi G, Rowshan V (2013) Chemical composition, antioxidant and antimicrobial activities of essential oil obtained from Ferula assa-foetida oleo-gum-resin: effect of collection time. Food Chem 138(4):2180–2187 22. Shrivastava V, Bhardwaj U, Sharma V et al (2012) Antimicrobial activities of asafoetida resin extracts (a potential Indian spice). J Pharm Res 5(10):5022–5024 23. Divya K, Ramalakshmi K, Murthy PS et al (2014) Volatile oils from Ferula foetida varieties and their antimicrobial activity. LWT – Food Sci Technol 59(2):774–779 24. Padhye S, Rai S, Lamba NN et al (2014) Spices as potent antibacterial agents against Staphylococcus aureus. ARPN J Sci Technol 4(1):46–51

25

Chemistry, Biological Activities, and Uses of Asafetida

653

25. Patil SD, Shinde S, Kandpile P et al (2015) Evaluation of antimicrobial activity of asafoetida. Int J Pharm Sci Res 6(2):722–727 26. Bhatnager R, Rani R, Dang AS (2015) Antibacterial activity of Ferula foetida: a comparison of red and white type. J Appl Biol Biotechnol 3:18–21 27. Kapoor LD (2001) Handbook of ayurvedic medicinal plants. CRC Press, New York, pp 185–190 28. Gogte VVM(2000) Ayurvedic pharmacology and therapeutic uses of medicinal plants (Dravyagunavignyan). Bharatiya Vidya Bhavan, Mumbai, 285 29. Rajakumar N, Shivanna MB (2009) Ethno-medicinal application of plants in the eastern region of Shimoga district, Karnataka, India. J Ethnopharmacol 126:64–73 30. Mahendra P, Bisht S (2012) Ferula foetida: traditional uses and pharmacological activity. Pharmacogn Rev 6(12):141–146 31. Iranshahy M, Iranshahi M (2011) Traditional uses, phytochemistry and pharmacology of asafoetida (Ferula assa-foetida oleo-gum-resin) – a review. J Ethnopharmacol 134(1):1–10 32. Iranshahi M, Kalategi F, Rezaee R et al (2008) Cancer chemopreventive activity of terpenoid coumarins from Ferula species. Planta Med 74(02):147–150 33. Abd El-Razek MH, Ohta S, Ahmed AA et al (2001) Sesquiterpene coumarins from the roots of Ferula assa-foetida. Phytochemistry 58(8):1289–1295 34. Appendino G, Maxia L, Bascope M et al (2006) A meroterpenoid NF-κB inhibitor and drimane sesquiterpenoids from asafetida. J Nat Prod 69(7):1101–1104 35. Bandyopadhyay D, Basak B, Chatterjee A et al (2006) A new sesquiterpenoid coumarin from Ferula asafoetida. Nat Prod Res 20(10):961–965 36. Kajimoto T, Yahiro K, Nohara T (1989) Sesquiterpenoid and disulphide derivatives from Ferula assa-foetida. Phytochemistry 28(6):1761–1763 37. Abd El-Razek MH et al (2007) A new ester isolated from Ferula assa-foetida L. Biosci Biotechnol Biochem 71(9):2300–2303 38. Christensen LP, Brandt K et al (2006) Bioactive polyacetylenes in food plants of the Apiaceae family: occurrence, bioactivity and analysis. J Pharm Biomed Anal 41(3):683–693 39. Amalraj A, Gopi S (2017) Biological activities and medicinal properties of asafoetida: a review. J Tradit Complement Med 7(3):347–359 40. Appendino G, Tagliapietra S, Mario NG et al (1993) Sesquiterpene coumarin ethers from asafoetida. Phytochemistry 35(1):183–186 41. Mohammadhosseini M, Venditti A, Sarker SD et al (2019) The genus Ferula: ethnobotany, phytochemistry and bioactivities–a review. Ind Crop Prod 129:350–394 42. Caglioti L, Naef H, Arigoni D et al (1958) Zur Kenntnis der Sesquiterpene und Azulene. 126. Mitteilung. Über die Inhaltsstoffe der Asa foetida I. Farnesiferol A. Helv Chim Acta 41(7): 2278–2292 43. Caglioti L, Naef H, Arigoni D et al (1959) Zur Kenntnis der Sesquiterpene und Azulene. 127. Mitteilung. Über die Inhaltsstoffe der Asa foetida II. Farnesiferol B und C. Helv Chim Acta 42(7):2557–2570 44. Banerji A, Mallick B, Chatterjee A et al (1988) Assafoetidin and ferocolicin, two sesquiterpenoid coumarins from Ferula asafoetida Regel. Tetrahedron Lett 29(13):1557–1560 45. Hofer O, Widhalm M, Greger H (1984) Circular dichroism of sesquiterpene-umbelliferone ethers and structure elucidation of a new derivative isolated from the gum resin “Asa Foetida”. Monatsh Chem 115(10):1207–1218 46. Mallikarjuna GU, Dhanalakshmi S, Raisuddin S et al (2003) Chemomodulatory influence of Ferula foetida on mammary epithelial differentiation, hepatic drug metabolizing enzymes, antioxidant profiles and N-methyl-N-nitrosourea-induced mammary carcinogenesis in rats. Breast Cancer Res Treat 81(1):1–10 47. Al-Awadi F, Shoukry M (1988) The lipid lowering effect of an anti-diabetic plant extract. Acta Diabetol 25(1):1–5 48. Al-Awadi FM, Khattar MA, Gumaa KA (1985) On the mechanism of the hypoglycaemic effect of a plant extract. Diabetologia 28(7):432–434

654

S. Singh et al.

49. Soni KB, Rajan A, Kuttan R (1993) Inhibition of aflatoxin-induced liver damage in ducklings by food additives. Mycotoxin Res 9(1):22–26 50. Sambaiah K, Srinivasan K (1989) Influence of spices and spice principles on hepatic mixed function oxygenase system in rats. Indian J Biochem Biophys 26(4):254–258 51. Soudamini KK, Unnikrishnan MC, Sukumaran K et al (1995) Mutagenicity and antimutagenicity of selected spices. Indian J Physiol Pharmacol 39:347–353 52. Kamanna VS, Chandrasekhara N (1982) Effect of garlic (Allium sativum Linn.) on serum lipoproteins and lipoprotein cholesterol levels in albino rats rendered hypercholesteremic by feeding cholesterol. Lipids 17(7):483–488 53. Rahlfs VW, Mössinger P (1979) Asa foetida in the treatment of the irritable colon: a doubleblind trial (author’s transl). Dtsch Med Wochenschr 104(4):140–143 54. Alqasoumi S (2012) Anxiolytic effect of Ferula asafoetida L. in rodents. J Pharmacogn Phytotherapy 4(6):86–90 55. Gundamaraju R (2013) Evaluation of anthelmintic activity of Ferula foetida “Hing-A natural Indian spice” aqueous extract. Asian Pac J Trop Dis 3(3):189–191 56. Bagheri SM, Sahebkar A, Gohari AR et al (2010) Evaluation of cytotoxicity and anticonvulsant activity of some Iranian medicinal Ferula species. Pharm Biol 48(3):242–246 57. Azizian H, Rezvani ME, EsmaeilI DM et al (2015) Antii-obesity, fat lowering and liver steatosis protective effects of Ferula foetida gum in type 2 diabetic rats: possible involvement of leptin. Iran J Diabetes Obes 4(3):120–126 58. Gholamnejad Z, Byrami G, Boskabady M et al (2012) Possible mechanism (s) of the relaxant effect of asafoetida (Ferula assa-foetida) oleo-gum-resin extract on guinea-pig tracheal smooth muscle. Avicenna J Phytomed 2(1):10–16 59. Bayrami G, Boskabady MH, Iranshahi M et al (2013) Relaxant effects of asafoetida extract and its constituent umbelliprenin on guinea-pig tracheal smooth muscle. Chin J Integr Med 1–6. https://doi.org/10.1007/s11655-013-1550-3. 60. Bagheri SM, Hejazian SH, Dashti-R MH (2014) The relaxant effect of seed fs essential oil and oleogum-resin of Ferula assa-foetida on isolated rat’s ileum. Ann Med Health Sci Res 4(2):238–241 61. Tayeboon GS, Tavakoli F, Hassani S et al (2013) Effects of Cymbopogon citratus and Ferula assafoetida extracts on glutamate-induced neurotoxicity. In Vitro Cell Dev Biol Anim 49(9):706–715 62. Moghadam FH, Dehghan M, Zarepur E et al (2014) Oleo gum resin of Ferula assa-foetida L. ameliorates peripheral neuropathy in mice. J Ethnopharmacol 154(1):183–189 63. Fatehi M, Farifteh F, Fatehi-Hassanabad Z (2004) Antispasmodic and hypotensive effects of Ferula foetida gum extract. J Ethnopharmacol 91(2–3):321–324 64. Muturi EJ, Ramirez JL, Zilkowski B et al (2018) Ovicidal and larvicidal effects of garlic and asafoetida essential oils against West Nile virus vectors. J Insect Sci 18(2):43 65. Gopi S, Amalraj A, Jude S et al (2017) Preparation, characterization and anti-colitis activity of curcumin-asafoetida complex encapsulated in turmeric nanofiber. Mater Sci Eng C 81:20–31 66. Niazmand R, Razavizadeh BM (2021) Ferula foetida: chemical composition, thermal behavior, antioxidant and antimicrobial activities of leaf and gum hydroalcoholic extracts. J Food Sci Technol 58(6):2148–2159 67. Devanesan S, Ponmurugan K, AlSalhi MS et al (2020) Cytotoxic and antimicrobial efficacy of silver nanoparticles synthesized using a traditional phytoproduct, asafoetida gum. Int J Nanomedicine 15:4351–4362 68. Cha MR, Choi YH, Choi CW et al (2011) Galbanic acid, a cytotoxic sesquiterpene from the gum resin of Ferula foetida, blocks protein farnesyltransferase. Planta Med 77(01):52–54 69. Iranshahi M, Alizadeh M et al (2012) Antihyperglycemic effect of asafoetida (Ferula asafoetida Oleo-Gum-Resin) in streptozotocin-induced diabetic rats. World Appl Sci J 17(2):157–162 70. Bagheri SM, Dashti-R MH, Morshedi A et al (2014) Antinociceptive effect of Ferula assafoetida oleo-gum-resin in mice. Res Pharm Sci 9(3):207–212 71. Bhatnager R, Rani R, Dang AS (2015) Antibacterial activity of Ferula foetida: a comparison of red and white type. J Appl Biol Biotechnol 18–21 72. Bagheri SM, Dashti-R MH (2015) Influence of asafoetida on prevention and treatment of memory impairment induced by d-galactose and NaNO2 in mice. Am J Alzheimers Dis 30(6):607–612

25

Chemistry, Biological Activities, and Uses of Asafetida

655

73. Esmaeili H, Esmailidehaj M, Zarch SE et al (2020) Role of the potassium channels in vasorelaxant effect of asafoetida essential oil. Avicenna J Phytomed 10(4):407–416 74. Esmaeili H, Hafezimoghadam Z, Esmailidehaj M et al (2018) The effect of asafoetida essential oil on myocardial ischemic-reperfusion injury in isolated rat hearts. Avicenna J Phytomed 8(4): 338–349 75. Vijayalakshmi SA, Bhat P, Chaturvedi A et al (2012) Evaluation of the effect of Ferula foetida Linn. Gum extract on learning and memory in Wistar rats. Indian J Pharmacol 44(1):82–87 76. Verma S, Khambhala P, Joshi S et al (2019) Evaluating the role of dithiolane rich fraction of Ferula foetida (apiaceae) for its antiproliferative and apoptotic properties: in vitro studies. Exp Oncol 41(2):90–94 77. Bagheri SM, Abdian-Asl A, Moghadam MT et al (2017) Antitumor effect of Ferula assa foetida oleo gum resin against breast cancer induced by 4T1 cells in BALB/c mice. J Ayurveda Integr Med 8(3):152–158 78. Panwar R, Rana S, Dhawan DK et al (2015) Chemopreventive efficacy of different doses of Ferula foetida oleo-gum-resin against 1, 2-dimethylhydrazine (DMH) induced rat colon carcinogenesis. J Phytopharm 4(6):282–286 79. Illuri R, Venkataramana SH, Daguet D et al (2019) Sub-acute and acute toxicity of Ferula foetida and Silybum marianum formulation and effect of the formulation on delaying gastric emptying. BMC Complement Altern Med 19(1):159 80. Bagheri SM, Maghsoudi MJ, Yadegari M (2020) Preventive effect of Ferula foetida oleo gum resin on histopathology in cuprizone-induced demyelination mice. Int J Prev Med 11:179 81. Bagheri SM, Asl AA, Shams A et al (2017) Evaluation of cytotoxicity effects of oleo-gumresin and its essential oil of Ferula assa-foetida and ferulic acid on 4T1 breast cancer cells. Indian J Med Paediatr Oncol 38(2):116–120 82. Mallahi T, Ramezanian A, Saharkhiz MJ et al (2018) Antimicrobial activities of asafoetida and shirazi thyme essential oils improve the vase life of gerbera cut flowers. Acta Ecol Sin 38(3): 228–233 83. Bagheri SM, Javidmehr D, Ghaffari M et al (2020) Chemical compositions and antiproliferative effect of essential oil of asafoetida on MCF7 human breast cancer cell line and female wistar rats. Cancer Transl Med 6(2):34–39 84. Narayanan R, Gilbert B, Ravichandran S et al (2017) Psychopharmacological characterization of effects of Ferula foetida Linn formulation in mouse on a Y-maze, EPM, and open field apparatus. Int J Basic Clin Pharm 6:2254–2258 85. Patil S, Gaikwad S, Deshmukh N et al (2015) Phytochemical investigation and in -vitro thrombolytic activity of methanolic extract of Ferula foetida L. exudates. Pharmanest 6(2): 2828–2830 86. Iranshahy M, Farhadi F, Paknejad B et al (2019) Gummosin, a sesquiterpene coumarin from Ferula assa-foetida is preferentially cytotoxic to human breast and prostate cancer cell lines. Avicenna J Phytomed 9(5):446–453 87. Harve G, Kamath V (2004) Larvicidal activity of plant extracts used alone and in combination with known synthetic larvicidal agents against Aedes aegypti. Indian J Exp Biol 42(12):1216–1219 88. Bagheri SM, Rezvani ME, Vahidi AR et al (2014) Anticonvulsant effect of Ferula assa-foetida oleo gum resin on chemical and amygdala-kindled rats. N Am J Med Sci 6(8):408–412 89. Bagheri SM, Mohammadsadeghi H, Dashti-R MH et al (2016) Effect of Ferula assa-foetida oleo-gum-resin on renal function in normal Wistar rats. Indian J Nephrol 26(6):419–422 90. Esmaeili H, Sharifi M, Esmailidehaj M (2017) Vasodilatory effect of asafoetida essential oil on rat aorta rings: the role of nitric oxide, prostacyclin, and calcium channels. Phytomedicine 36:88–94 91. Sharma V, Bisht S, Singh MF (2018) Hepatoprotective and antidyslipidemic effect of in CCl induced Ferula foetida. Asian J Pharm Sci 4(1):61–65 92. Bagheri SM, Yadegari M, Behpur M et al (2018) Antilithiatic and hepatoprotective effects of Ferula assa-foetida oleo-gum-resin on ethylene glycol-induced lithiasis in rats. Urol Sci 29(4): 180–185 93. Ramadan NI, Al Khadrawy FM (2003) The in vitro effect of Asafoetida on Trichomonas vaginalis. J Egypt Soc Parasitol 33(2):615–630

656

S. Singh et al.

94. Tavassoli M, Jalilzadeh-Amin G, Fard VR et al (2018) The in vitro effect of Ferula foetida and Allium sativum extracts on Strongylus spp. Ann Parasitol 64(1):59–63 95. Khazdair MR, Boskabady MH (2015) The relaxant effect of Ferula asafoetida on smooth muscles and the possible mechanisms. J HerbMed Pharmacol 4(2):40–44 96. Platel K, Srinivasan K (2000) Influence of dietary spices and their active principles on pancreatic digestive enzymes in albino rats. Nahrung 44(1):42–46 97. Ramakrishna Rao R, Platel K, Srinivasan K (2003) In vitro influence of spices and spice-active principles on digestive enzymes of rat pancreas and small intestine. Nahrung 47(6):408–412 98. Dandagi PM, Patil MB, Mastiholimath VS et al (2008) Development and evaluation of hepatoprotective polyherbal formulation containing some indigenous medicinal plants. Indian J Pharm Sci 70(2):265–268 99. Kamble VA, Patil SD (2008) Spice-derived essential oils: effective antifungal and possible therapeutic agents. Int J Geogr Inf Syst 14(3–4):129–143 100. Sitara U, Niaz I, Naseem J, Sultana N (2008) Antifungal effect of essential oils on in vitro growth of pathogenic fungi. Pak J Bot 40(1):409–414 101. Rani A, Jain S, Dureja P (2009) Synergistic fungicidal efficacy of formulations of neem oil, nicotinic acid and Ferula foetida with α, β-unsaturated carbonyl compounds against ITCC 5226 Sclerotium rolfsii & ITCC 0482 Macrophomina phaseolina. J Pestic Sci 34(4):253–258 102. Zangoie M, Parsa S, Jahani M et al (2013) Antifungal effects of asafoetida seed essential oil on in vitro growth of five species of plant pathogenic fungi. Int Res J Appl Basic Sci 4:1159–1162 103. Unnikrishnan MC, Kuttan R (1990) Tumour reducing and anticarcinogenic activity of selected spices. Cancer Lett 51(1):85–89 104. Sepahi E, Tarighi S, Ahmadi FS et al (2015) Inhibition of quorum sensing in Pseudomonas aeruginosa by two herbal essential oils from Apiaceae family. J Microbiol 53(2):176–180 105. Kiyanmehr M, Boskabady MH, Khazdair MR et al (2016) Possible mechanisms for functional antagonistic effect of Ferula asafoetida on muscarinic receptors in tracheal smooth muscle. Malays J Med Sci 23(1):35–43

Chemistry and Applications of Propolis

26

Milena Popova, Boryana Trusheva, and Vassya Bankova

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 How Do Bees Produce Propolis? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Chemistry of Propolis: Ways to Study It . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 High Performance Thin Layer Chromatography (HPTLC) . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 High Performance Liquid Chromatography (HPLC) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Gas Chromatography-Mass Spectrometry (GC-MS) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Nuclear Magnetic Resonance Spectroscopy (NMR) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Propolis Chemistry as Indicator of the Source. Major Chemical Types of Propolis . . . . . . 4.1 Poplar Type Propolis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Aspen Type Propolis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Brazilian Green Propolis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Brazilian Red Propolis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Pacific Propolis Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6 Mediterranean Propolis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.7 Mangifera Propolis Type . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Resins Identified as Sources of Propolis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Biological Activities of Propolis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Applications of Propolis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

658 658 659 660 660 661 661 662 662 663 663 664 664 665 665 666 673 676 678 678

Abstract

Propolis (bee glue) is a sticky resinous product manufactured by honeybees. In this book, dedicated to plant resins, propolis has a very special place: It is the only material which comes not from plants but from animals, from bees. This chapter summarizes the present status of knowledge on propolis: the approaches to its M. Popova · B. Trusheva · V. Bankova (*) Institute of Organic Chemistry with Centre of Phytochemistry, Bulgarian Academy of Sciences, Sofia, Bulgaria e-mail: [email protected]; [email protected]; [email protected] © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_38

657

658

M. Popova et al.

chemical analysis, the different chemical types of propolis, and the numerous plant resins known as propolis botanical sources. It demonstrates the potential of bee glue as a source of new chemical structures and new biologically active compounds due to its chemical diversity, resulting from the diversity of plant sources. The versatile and valuable biological activities of propolis have been reviewed, together with its diverse applications in medicine, dentistry, pharmacy, animal husbandry, beekeeping, food industry. Keywords

Biological activity · Chemical composition · Honeybees · Propolis · Propolis plant sources

1

Introduction

The honeybees Apis mellifera L. apply propolis in their hives as a building material: to block cracks and holes, to repair combs, and to make their nest watertight. But then, propolis has also another important function in the bee colony: It possesses pronounced antimicrobial properties and protects the bees from pests and pathogens, it is regarded as an important element of bees’ “social immunity” [1]. The action against infections is an essential characteristic of propolis and this fact has been recognized and used by humans since ancient times, bee glue has been used in the traditional medicine of many nations. During the last 50 years, the biological action of propolis has been extensively studied and its versatile activities have been proved by well-designed and reliable experiments: antibacterial, antifungal, antiviral, cytotoxic, antioxidant, anti-inflammatory, immunomodulatory activities among others [2–4]. As a result, the commercial interest to propolis is growing steadily, it is applied as a component of numerous products: food additives, cosmetics, and over-the-counter preparations.

2

How Do Bees Produce Propolis?

Bees collect resinous plant material, take it to the hive, and mix it with wax to produce propolis. It is generally accepted that they collect materials, produced by a variety of processes in different parts of plants. These are actively secreted substances and/or substances exuded from plant wounds [5]: lipophilic materials on leaves, leaf buds, and fruits, mucilages, gums, resins, latices, etc. These plant secretions are highly antimicrobial in order to protect vegetative apices, young leaves, and wounded tissues; thus, they provide antimicrobial raw material for bees to make propolis. In some cases, bees may also cut fragments of vegetative tissues to release the resin used in propolis production [6]. In any particular ecosystem, there are numerous resins available to bees, as the secretion of protective antimicrobial material is widespread in the plant kingdom [7]. So how do bees

26

Chemistry and Applications of Propolis

659

choose which resin to collect? The cues used by resin foragers for finding a resin source are virtually unknown, although it is clear that they select specific sources [8]. One hypothesis is that volatile compounds released from the resin play an important role, signaling the availability of a material rich in bioactive compounds [9]. In addition, another recent hypothesis [8] suggests that many materials with good antimicrobial properties, such as latices, resins, and gums, are too sticky and hard to be collected by resin foraging bees, and they cannot be cut with the delicate mandibles of honeybees. Bees normally gather exudates from smooth solid films, which can be scraped by them from the plant surface and attached to their hind legs. Another limitation is the phytogeographic characteristic of the habitat of the bee colony. Honeybees are a very successful species from the evolutionary point of view; they inhabit numerous types of terrestrial ecosystems from the Kalahari Desert and tropical rainforests to the Sub-Arctic regions of Siberia and North America. In every particular ecosystem, bees find appropriate propolis sources but naturally, in locations with different geographic and climatic conditions and different flora, these sources are quite different. Bees have adapted to make the best of the available plants in any habitat, so at diverse geographic locations propolis comes from distinct plant sources with their specific chemical characteristics, which are by far not the same all over the world. Thus, the chemical composition of propolis is highly variable and many different types of propolis can be found [10]. It is important to note that the honeybees A. mellifera are not the only bee species collecting plant resins. In Tropical regions, the major visitors and native pollinators of flowering plants are the stingless bees, belonging to the tribe Meliponini (subfamily Apinae). Stingless bees are eusocial and have a special relationship with plant resins, relying on them for the very existence of their nest. Unlike honeybees which build their nests primarily or even solely out of wax [2, 11], most stingless bees incorporate plant gums, resins, for nest constructions [12]. Resin mixed with wax is used to build protective and supporting nest structures and is called cerumen. These bees benefit also from the repellent properties of resins: Resin, deposited in the vicinity of the nest entrance, entangles termites and ants and prevents invasions [12]. Plant resins are also stored in large deposits within the nests, serving as an antimicrobial agent. In the last years, numerous studies demonstrate the enormous chemical diversity of the resins used for nest construction and defense by stingless bees [13]. In order to enable the wider application of propolis in medicines, cosmetics, and foods, its chemical composition and the possibilities of standardization have to be studied in depth.

3

Chemistry of Propolis: Ways to Study It

Crude propolis consists of plant resins, essential oils, beeswax, and mechanical impurities [14]. Its biological activity is related to the components of the plant resins, which are the major ingredient, and thus, the way to study propolis chemistry includes basic phytochemical approaches in terms of extraction and isolation of individual constituents. Maceration, ultrasound and microwave extractions with

660

M. Popova et al.

hydro-ethanolic mixtures have been used to extract propolis bioactive components [15]. Besides common chromatographic procedures applied for isolation of individual compounds, such as open column chromatography, flash chromatography, and preparative thin layer chromatography, faster methods, capable of chemical profiling and characterization of propolis samples from different geographic origins have been widely applied.

3.1

High Performance Thin Layer Chromatography (HPTLC)

High performance thin layer chromatography (HPTLC) is recognized as a rapid and efficient tool for qualitative and quantitative analysis of natural products. It is based on the classical TLC method but using plates with enhanced characteristics such as smaller particle size and thinner layer of the stationary phase, resulting in better resolution and separation of the components [16]. The main advantage of HPTLC over other chromatographic techniques is the possibility of simultaneous analysis of many samples and standards under the same operating conditions [16, 17]. In propolis analysis, it is mainly used for the needs of fingerprinting, classification, and authentication of samples from different geographical regions. HPTLC conditions optimized regarding the separation of propolis phenolic acids and flavonoids, followed by multivariate analysis, and pattern recognition methods have been developed [17, 18].

3.2

High Performance Liquid Chromatography (HPLC)

Using the separation power of the liquid chromatography in combination with structural information provided by different detectors, high performance liquid chromatography (HPLC) has become one of the preferred techniques for the analysis of propolis [19]. Reversed phase columns, diode array detector (DAD), and mass spectrometric (MS) detectors mostly with electro-spray ionization (ESI) have been set as the most suitable ones [20].

3.2.1 HPLC-DAD HPLC-DAD is the most commonly applied method for substance identification [21]. It is operating by real time acquisition of signals in the range of 200–600 nm and thus is commonly used for compounds which are strong chromophores such as phenolics and flavonoids. The identification of the compounds is mainly based on the comparison of the UV spectrum and retention time with those of standards [22]. In this way, a number of flavonoids, phenolic acids, and their esters have been identified and quantified in propolis collected from different geographical regions [23–26]. An attention should be paid that HPLC-DAD is characterized by low sensitivity for certain compounds like terpenes, due to the lack of specific UV wavelengths that they absorb. In such case, as well as for identification of unknown compounds because of the lack of comparative data, HPLC coupled with MS detector is preferable.

26

Chemistry and Applications of Propolis

661

3.2.2 HPLC-MS Over the years, high-performance liquid chromatography coupled to singlequadrupole mass spectrometry (HPLC–MS) becomes a routine technique for structural identity of various compounds in a complex mixture. It gives information for the molecular mass of the components based on the m/z ratio of the product ions generated by ESI [27]. The compound identification is achieved by subsequent comparison of the data with those of standards and library data. HPLC-DAD-MS is usually applied for target analysis of propolis and/or for its classification [24, 28–30]. 3.2.3 HPLC-MSn HPLC-MSn, in most cases in combination with DAD, provides more exhaustive compound characterization due to the multiple steps of mass spectrometry. Tandem mass spectrometry results in “deconstruction of the molecule piece by piece” [31], which is a key benefit for identification of unknown compounds or tentative structures to be proposed based on the comparison with MS fragmentation pathways of corresponding chemical classes of compounds. The triple quadrupole and orbitrap mass spectrometry, both with negative and positive ESI ionization, have been demonstrated as powerful techniques for identification of propolis polyphenolic and diterpenic components [32–34].

3.3

Gas Chromatography-Mass Spectrometry (GC-MS)

Gas chromatography-mass spectrometry (GC-MS) with electron impact is one of the most frequently applied methods for propolis chemical analysis [32] as it is capable of generating reproducible fragmentation patterns for various molecules [35]. However, as propolis extracts contain metabolites that are not volatile enough for gas chromatography [36], a derivatization procedure is an essential step prior to the analysis. In most cases, N,O-bis(trimethylsilyl)trifluoroacetamide (BSTFA) as a derivatizing agent is used that converts the constituents into trimethylsilylether/ ester (TMS) derivatives. The identification of the constituents is based on the comparison of the data obtained with those of spectral libraries and/or literature data of MS spectra of individual compounds. GC-MS has been successfully applied for the analysis of samples from different geographical regions [13, 37–41] and recently has been demonstrated to be a powerful analytical platform for propolis type dereplication [32].

3.4

Nuclear Magnetic Resonance Spectroscopy (NMR)

Nuclear magnetic resonance (NMR) spectroscopy is a nondestructive technique giving unprecedented information about both chemical structure and content of the compounds in a single experiment [32]. Besides its typical application for structural elucidation of isolated individual constituents, NMR is a powerful tool in chemical profiling and metabolomic studies of biological objects [42]. Proton (1H) and carbon

662

M. Popova et al.

(13C) NMR profiles have been used for comparison of propolis samples of different origin [43, 44], and 1H NMR followed by multivariate analysis of data generated after peak bucketing has been shown as an appropriate tool for propolis classification and quality assessment [45–49].

4

Propolis Chemistry as Indicator of the Source. Major Chemical Types of Propolis

Propolis is a natural product and its chemistry strongly depends on the plants available to the bees for resin collection [50]. Due to the high biodiversity in different geographical and climatic regions, the propolis chemistry is characterized by high complexity and variability, and many compounds with various strictures, generally belonging to the chemical classes of polyphenols and terpenes, have been identified. However, bees do not collect resins chaotically; they have some preferences to certain plant species that gives the opportunity for classification of propolis according to its botanical source [51, 52]. That is why together with chemical profiling, the efforts of the propolis researchers have been focused on determination of its botanical source. It is based on the study of bee behavior and direct comparison between both chemical compositions of propolis samples and suggested plant resins [25, 51, 53]. In the case when no plant material is available, suggestion has been made after the literature search for the resin chemistry [52]. The existence of specific chemical types of propolis gives also the opportunity for the elaboration of propolis standards based on the propolis types determined by the botanical source [32, 52]. Till now, more than 50 plants have been shown as sources of material for propolis production (see Sect. 4), reflecting in distinct propolis chemistry and propolis types formulation. The most well-studied and widespread chemical types with proven botanical origin are known as poplar, green Brazilian, red Brazilian, Pacific, Mediterranean, and Mangifera indica types.

4.1

Poplar Type Propolis

Propolis samples from the regions within the temperate climatic zone such as Europe, North America, nontropical region of Africa, and New Zealand have displayed similar chemical composition [53]. Flavonoids, phenolic acids, and their esters are its characteristic classes of compounds that have been proven to originate from the resins on the surface of poplars’ buds (Populus spp.) [52]. Several species of the genus Populus have been shown as a resin source and the poplar propolis extracts have in common the flavonoids pinocembrin (1), pinobanksin (2), chrysin (3), and galangin (4) as major constituents [53] (Fig. 1). For positive identification of certain species, however, detection of some specific markers is required [32]. In Europe, the most widespread propolis type is the poplar type originating from Populus nigra L. (black poplar) and its taxonomic markers are pinobanksin 3-acetate (5) and esters of substituted cinnamic acids, especially phenylethyl caffeate (CAPE) (6), 3-methyl-3-butenyl caffeate (7), and 3-methyl-2-butenyl caffeate (8) [53] (Fig. 1).

26

Chemistry and Applications of Propolis

O

HO

663

O

HO

R OH

R

O

OH

O 3RH 4 R OH

1RH 2 R OH

O O

HO

HO OR

OCOCH3 OH

HO

O 5

6 R CH2CH2C6H5 7 R CH2CH2C(CH3)CH2 8 R CH2CHC(CH3)2

Fig. 1 Characteristic compounds of poplar type propolis. Major compounds (1–4) and markers for Populus nigra propolis (5–8)

4.2

Aspen Type Propolis

Resin on the surface of Populus tremula L. (Trembling aspen, European aspen) buds is a bioactive ingredient of propolis from northern regions of Europe [53, 54] as well as high-altitude European areas. This propolis type is characterized by high amounts of p-coumaric and ferulic acids in combination with their benzyl and glycerol esters [47, 55]. 2-Acetyl-1,3-di-p-coumaroylglycerol (9) and 1-acetyl-3-feruloyl glycerol (10) are among its marker phenolic glycerides (Fig. 2).

4.3

Brazilian Green Propolis

In Brazil, the most widespread propolis type is the so-called green propolis. The name is associated with its green color originating from Bacharis dracunculifolia DC, a native shrub distributed in the Brazilian cerrado [56]. Till now, it is the only propolis that contains small parts of the vegetative apices of young leaves and buds, cut by the bees [57, 58]. Green propolis is rich in prenylated phenolics [59], the

664

M. Popova et al.

O H2C H3COCO

O

OH HO

CH H2C

H2C

C

O

CH H2C

C

OCOCH3 OCH3 O

C

OH

O

OH

O 10

9

Fig. 2 Representatives of specific compounds for aspen type propolis

COOH

COOH

OCH3 HO

HO

O

12

OH OH

11

O 13

Fig. 3 Some specific compounds of Brazilian green propolis

major one being artepillin C (11), as well as cinnamic acids and flavonoids, such as dihydrocinnamic acid (12) and aromadendrine 40 -methyl ether (13) (Fig. 3).

4.4

Brazilian Red Propolis

The botanical origin of Brazilian red propolis has been proven to be Dalbergia ecastaphyllum (L.) Taub., and in particular the reddish resin exudates from stem wounds caused by insects feeding [60, 61]. It is produced by bees in mangroves regions of Northeastern Brazil [40]. Isoflavones, isoflavans, and pterocarpans have been found among which formononetin (14), biochanin A (15), vestitol (16), and medicarpin (17) are major compounds and markers for its positive assessment [40] (Fig. 4).

4.5

Pacific Propolis Type

Pacific propolis type covers the regions of Taiwan, Okinawa, Hawaii, and Indonesia. It is a representative of so called Macaranga type propolis, having Macaranga tanarius (L.) Müll.Arg. as a botanical source [62]. Surface material of M. tanarius fruits and propolis have identical chemical composition [25], consisting predominantly of prenylated flavanones as propolin C (nymphaeol-A) (18), propolis D (nymphaeol-B) (19), propolin F (isonymphaeol-B) (20), and propolin G (nymphaeol-C) (21) [25, 63] (Fig. 5).

26

Chemistry and Applications of Propolis

HO

O

HO

O

HO

O

665

H H

R

O OCH3

HO

O

OCH3

OCH3

17

16

14 R H 15 R OH

Fig. 4 Major marker compounds of Brazilian red propolis OH

OH OH

HO

O

OH

OH HO

O

O

OH

18

O

19 OH

OH

OH

OH HO

O

O

OH

20

HO

O

O

OH

21

Fig. 5 Chemical markers of Pacific propolis type

4.6

Mediterranean Propolis

Propolis from Mediterranean regions (Greece, Greek islands, and Malta) is quite distinguishable from the other propolis types as its constituents are diterpenes [64]. Diterpene acids, alcohols and aldehydes, in great majority of the labdane type, together with phenolic totarane derivatives have been characterized [65, 66] and found to be typical for the resins of Cypress tree Cupressus sempervirens L. [66, 67]. Among the constituents identified isocupressic acid (22), acetylisocupresic acid (23), isoagatholal (24), and totarol (25) are specific markers for the propolis from regions with Mediterranean subtropical climate (Fig. 6).

4.7

Mangifera Propolis Type

As it is evident from the name, another widely distributed propolis type originates from the mango tree Mangifera indica L. In contrast to the other mentioned tropical

666

M. Popova et al. OR

COOH

OH

OH

CHO

22 R H 23 R COCH3

24

25

Fig. 6 Specific compounds of Mediterranean propolis OH

OH

R2

R2

R1

n

R1

26 R1 H; R2 H; n = 16 28 R1 OH; R2 H; n = 16 30 R1 H; R2 COOH; n = 16

n1

n2

27 R1 H; R2 H; n1 = 11; n2 = 3 29 R1 OH; R2 H; n1 = 11; n2 = 3 31 R1 OH; R2 COOH; n1 = 11; n2 = 3 R COOH

HO

HO 32 R H 33 R COOH

34

Fig. 7 Major specific compounds for Mangifera indica propolis type

propolis types, M. indica has been recognized as a preferred resin source from both Apis mellifera and stingless bee species in tropical regions of Asia, Africa, South and North America, and Oceania (Fiji) [10, 13]. Simultaneous occurrence of phenolic lipids: cardanols (26, 27), cardols (28, 29), anacardic acids (30, 31), and triterpenes, mainly of cycloartane type such as cycloartenol (32), mangiferolic (33) and ambolic acids (34), is an indicator of mango as a resin source [68, 69] (Fig. 7).

5

Resins Identified as Sources of Propolis

In the previous section, the most widespread propolis types and the corresponding botanical sources have been discussed. However, there are much more plant resins which honeybees and/or stingless bees use to produce propolis. A lot of them

26

Chemistry and Applications of Propolis

667

were found in tropical and subtropical areas with rich biodiversity. In some cases, these are rarely found major sources; on the other hand, many of them are playing a secondary role in resin supply for bees and their taxonomic markers have often been identified as minor propolis constituents. In Table 1, all the resins found to be propolis sources till now are listed. Their role as propolis botanical precursors has been proved by chemical comparison of bee glue and the corresponding resin from the same area, by some of the methods described in the previous chapter. Table 1 demonstrates an impressive diversity of plants providing resins to different bee species for propolis production. Over 50 species belonging to 21 plant families have been documented as propolis plant sources by scientifically sound evidence. Among them, Dicotyledons predominate; however, some Gymnosperms and one Monocotyledon (Dracena cochinchinensis) were shown as sources of propolis resins. As mentioned in Sect. 4, in the Temperate zone, the bud exudates of species of the genus Populus and especially of P. nigra are the preferred botanical source of propolis. Isidorov et al. [128] revealed that even if resin sources other than black poplar and trembling aspen (such as horse chestnut, black alder, or Scotch pine) are readily available, bees do not collect resin from them. Even in areas where the black poplars are not native but introduced, such as New Zealand [129], Argentina [130], and South Africa [131], honeybees use their resin for propolis production. Other Populus species have the same function in Asia and North America (see Table 1). Among plant families, Fabaceae is obviously popular with both honeybees A. mellifera and stingless bees in tropical regions of South America, Asia, Africa, and Australia. Another popular propolis source seems to be the resin on the mango (Mangifera indica): Its markers have been found in propolis of A. mellifera and of six species of Meliponini in Tropics all over the world. It is important to note that in this review, no claims of propolis origin based on palynological data have been taken into account. Resins are usually deposited on buds, young leaves, bark, etc., and not in the vicinity of the anther where pollen can be found. Thus, it is not possible to know whether a specific pollen found in propolis is the result of a visit aimed at collecting resin or just a contamination from material obtained by bees for other purposes [6]. Some published reports on propolis botanical sources which lack solid chemical evidence have not been included, too. In some cases, the conclusions contradict the results, for example, PCA and TLC picture do not support the conclusions [132], or there is no comparison of chemical data of propolis and alleged source [133]. In recent years, the amount of propolis plant sources identified by chemical analysis has grown significantly. Nonetheless, there is yet a lot of research to be done in order to reveal the sources of many propolis types with specific chemical composition, different from all the known sources. Obviously, bees are able to choose the appropriate resins from different plant families, according to their availability at the specific location and their suitability to the needs of the colony.

Resin source Plant family Anacardiaceae

Plant species Mangifera indica L.

Tanzania

Brazil

Indonesia, East Java Indonesia, Southeast Sulawesi Indonesia, Banten Indonesia, South Kalimantan Oman Cameroon Fiji Thailand Mexico Cuba Brazil

Geographic origin Myanmar

Table 1 Propolis plant sources, identified by chemical evidence Chemical markers Alkylphenols, alkylresorcinols, anacardic acids, cycloartane triterpenes

[68]

Tetragonula sapiens (Cockerell) Tetragonula laeviceps (Smith) Heterotrigona itama (Cockerell) A.m. A.m. A.m. A.m. A.m. A.m. Scaptotrigona aff. postica (Latreille) Melipona fasciculata (Smith) Meliponula ferruginea (Latreille)

[79]

[78]

[73] [39] [74] [75] [69] [76] [77]

[72]

[72]

[71]

References [70]

A.m.

Bee species A.m.a

668 M. Popova et al.

Clusiaceae

Clusia rosea Jacq. Clusia spp. Clusia minor L. and C. major L. Garcinia mangostana L.

Cistus spp.

Cistus ladanifer L.

Cistaceae

Betulaceae

Asparagaceae

Ferula spp. Araucaria angustifolia (Bertol.) Kuntze Ambrosia ambrosioides (Cav.) W. W.Payne Baccharis dracunculifolia DC

Ferula communis L.

Psiadia arabica Jaub. et Spach. & Psiadia punctulata (DC.) Vatke Dracaena cochinchinensis (Lour.) S.C.Chen Betula spp.

Asteraceae

Araucariaceae

Apiaceae

Rhus javanica L. var. chinensis (Mill.) T.Yamaz Angelica keiskei (Miq.) Koidz.

Cuba Brazil Venezuela Thailand

Portugal (central and south parts) Algeria

Russia, Poland

Vietnam

Saudi Arabia

Mexico, Sonoran Desert Brazil

Iran Brazil

Korea, Jeju Island Malta

Japan (Okayama)

Prenylated benzophenones Prenylated xanthones

Diterpenes of labdane and clerodane type, kaempferol methyl ethers Prenylated benzophenones

Flavonoid aglycones, sesquiterpene coumarates Kaempferol methyl ethers

Homoisoflavanes

A.m.

C-prenylated cinnamic acids, caffeoylquinic acids Flavonoid aglycones and diterpenes

A.m. A.m. A.m. Tetragonula pagdeni (Schwarz)

A.m.

A.m.

Lisotrigona cacciae (Nurse) A.m.

A.m.

A.m.

A.m. A.m.

A.m.

A.m.

A.m.

Methoxyflavonoids

Diterpenic acids

Terpenyl esters of substituted benzoic acids

No compounds identified, fingerprint comparison by HPLC Prenylated chalcones and coumarines

Chemistry and Applications of Propolis (continued)

[91] [92] [93] [94]

[90]

[89]

[88]

[87]

[86]

[57, 58]

[85]

[83] [84]

[82]

[81]

[80]

26 669

Unidentified

Macaranga tanarius (L.) Müll.Arg.

Dipterocarpaceae

Euphorbiaceae

Lepidosperma viscidum R.Br.

Lepidosperma sp.

Cyperaceae

Brazil, Bahia

Symphonia globulifera L.f.

Okinawa Taiwan Indonesia Hawaii

Greek Mediterranean islands Malta Australia, Kangaroo Island Australia, Kangaroo Island Thailand

Colombia Brazil, Bahia

Garcinia spp. and/or Clusia spp. Kielmeyera spp.

Cupressus sempervirens L.

Geographic origin Thailand

Plant species

Cupressaceae

Resin source Plant family

Table 1 (continued)

Prenylated flavanones

Prenylated p-coumarate ester and stilbenes Prenylated p-coumarate ester and stilbenes Triterpenes, triterpenic lactones

Prenylated benzophenones, triterpenoids Diterpenes of labdane, totaran and abietane type

Δ-Tocotrienols Phenylcoumarins

Chemical markers Prenylated xanthones

Tetrigona melanoleuca (Cockerell) A.m. A.m. A.m. A.m.

[71] [101]

[25]

[95]

[100]

[67] [99]

A.m. A.m. A.m.

[38]

[98]

[96] [97]

References [95]

A.m.

Bee species Tetragonula laeviceps (Smith) A.m. Melipona scutellaris (Latreille) A.m.

670 M. Popova et al.

Liquidambar styraciflua L.

Cratoxylum cochinchinense (Lour.) Blume

Hypericaceae

Myroxylon balsamum (L.) Harms Zuccagnia punctata Calv.

Dalbergia sisoo Roxb. Dalbergia spp. Dalbergia spp. Mimosa tenuifolia L.

Prenyl and geranyl xanthones

Cinnamic acid esters

Benzyl cinnamate, benzyl benzoate Chalcones, dihydrochalcones

Neoflavonoids Isoflavonoids Isoflavonoids, pterocarpanes Flavonols and chalcones

Isoflavonoids, pterocarpanes

Brazil

Acacia spp. Dalbergia boehmii Taub. and Dalbergia saxatilis Hook.f. Dalbergia ecastaphyllum (L.) Taubert. Cuba Nepal Nigeria Mexico Btazil, Rio Grande do Norte State El Salvador Argentina, Tucuman p Honduras USA, North Carolina Vietnam

Flavanes, pinitol Methoxylated chalcones and flavonoid aglycones Triterpenes Isoflavonoids

Acacia nilotica (L.) Del. Acacia paradoxa DC

Hamamelidaceae

Fabaceae

Solomon Islands Fiji Oman Australia, Kangaroo Island Yemen Guinea Bissau

Macaranga spp.

Prenylated flavonoids, prenylated stilbenes

Kenya

Macaranga schweinforthii Pax

Lisotrigona cacciae (Nurse)

A.m. A.m.

A.m. A.m.

A.m. A.m. A.m. A.m. Scaptotrigona postica (Latreille)

A.m.

A.m. A.m

A.m. A.m. A.m. A.m.

A.m.

(continued)

[87]

[115] [116]

[112] [113, 114]

[61] [108] [109] [110] [111]

[60, 107]

[105] [106]

[103] [74] [73] [104]

[102]

26 Chemistry and Applications of Propolis 671

a

Turkey, Artvin region Mexico, USA Poland, Russia, Switzerland USA, Minnesota Canada Canada

Populus canadensis Moench

Populus euphratica Oliv.

Myoporum insulare R.Br.

Styrax spp.

Larrea nitida Cav.

Sapindaceae

Scrophulariaceae

Styracaceae

Zygophyllaceae

Apis mellifera L.

Populus trichocarpa Torr. & A. Gray ex Hook Dodonaea humilis Endl.

Populus tremuloides Michx.

Argentina, Andean region

Australia, Kangaroo Island Southern Australia Thailand

China

Populus nigra L.

Salicaceae

Populus fremontii S. Watson Populus tremula L.

Oman Thailand Europe

Azadirachta indica A.Juss

Meliaceae

Geographic origin

Plant species

Resin source Plant family

Table 1 (continued)

Cinnamic acid and benzoic acids esters Lignans

p-Hydroxyacetophenone, benzyl hydroxybenzoate 6,8-Diprenyl-5,7,30 ,40 tetrahydroxyflavanone Serrulatane diterpenes

Phenolic glycerides

Flavonoid aglycones, benzyl, phenethy, cinnamyl caffeates Phenolic glycerides, p-coumaric and ferulic acids Flavonoid aglycones Phenolic glycerides

Flavonoid aglycones, prenylcaffeates

C5-prenyl flavanones

Chemical markers

A.m.

A.m.

A.m.

A.m.

A.m.

A.m.

A.m. A.m.

A.m.

A.m.

A.m.

Bee species Lisotrigona furva (Engel) A.m.

[127]

[126]

[125]

[100]

[124]

[116, 124]

[85] [88, 123]

[122]

[73] [118] [88, 119, 120] [121]

References [117]

672 M. Popova et al.

26

6

Chemistry and Applications of Propolis

673

Biological Activities of Propolis

The resins that bees collect for the “production” of propolis are found on the surface of buds, bark, young leaves, and flowers of plants. They defend them from bacteria, viruses, and fungi, as well as serve for protection against adverse weather conditions. The biological activity of propolis is due to these resins. The use of the beneficial biological properties of bee glue dates back at least to 300 BC [2]. The Egyptians utilized it as an ingredient in embalming corpses, and the ancient Greeks applied it to treat hard-to-heal wounds. Propolis has also been known among Arab healers with its usage as an oral disinfectant, antiseptic, and wound healing agent. It was known to the Incas, too, who employed it as an antipyretic. Later, in the seventeenth century, propolis was listed as an official drug in the London Pharmacopoeia. Between the seventeenth and twentieth century, the bee glue became very popular in Europe on account of its antimicrobial activity [134]. Nowadays it has been proven that propolis is a mixture with a complex and variable chemical composition that possesses a wide range of biological activities, such as antimicrobial [135], antioxidant [136], antiviral [137], antiparasitic [138], anti-inflammatory [136], antitumor [139], immunomodulatory [3], and hepatoprotective [140]. This variety of biological properties results in propolis’ wide implementation in products for use in human and animal health. However, the effects and strength of these biological activities depend on the chemical profile and composition of each propolis type, respectively, on its source resin. The best documented biological properties of propolis are the antimicrobial ones. Regardless of its plant source and chemical composition, propolis always possesses antimicrobial activity. This is not surprising, bearing in mind the role of the bee glue in the hive – it is the “chemical weapon” of bees against pathogens [141]. This bioactivity has been largely investigated due to the need of new treatments against infectious diseases, especially with the increase of pathogens’ resistance to current antibiotics [142]. In a recent review, data concerning the antibacterial potential of propolis against 600 different bacterial strains have been analyzed [143]. It was established that propolis has antibacterial activity against gram-positive (Staphylococci, Streptococci spp., etc.) and gram-negative bacteria (Escherichia coli, Pseudomonas aeruginosa, etc.), and in most cases, the activity against the latter is lower. Propolis is active against both human and bee pathogens. It should also be noted that most of the studies in literature report not only bacteriostatic but also bactericidal action, that is, propolis (mainly Brazilian red and green propolis) is capable of both inhibiting growth and killing bacteria [135]. It has also been found that the presence of bee glue prevents or significantly reduces the development of antibiotic resistance in Staphylococci [144]. It is known that the antibacterial activity of propolis is predominantly due to its phenolic compounds. For poplar type propolis, these are flavonoid aglycones (galangin, pinocembrin, pinobanksin), phenolic acids (p-coumaric acid, caffeic acid), and their esters (isopentenyl caffeates, benzyl caffeate, and benzyl-pcoumarate) [145]. For Mediterranean propolis, the antibacterial activity is attributed to labdane-type diterpenic acids [66].

674

M. Popova et al.

Studies of tropical propolis have led to the discovery of new antibacterial substances such as furofuran lignans in propolis from the Canary Islands, which resin source is unknown, prenylated flavonoids in Pacific type and prenylated benzophenones in Clusia type propolis [145–147]. The main components of Brazilian green propolis, C-prenylated derivatives of p-coumaric acid, and labdane-type diterpenic acids have also proved antibacterial action [148]. For some of its constituents such as p-coumaric acid and artepillin C, it is found that they are active against the gramnegative bacteria Helicobacter pylori, which is known to be the major causative factor in peptic ulcer disease [149]. Later this was confirmed by Banskota et al. for some labdane-type propolis diterpenes such as 15-acetoxyisocupressic acid and agathic acid-15-methyl ester [150]. It was found that extracts of Bulgarian propolis (poplar type) also have significant activity against H. pylori [151]. Synergistic effects of propolis of different types with antibiotic have been demonstrated [152]. Antiquorum sensing (QS) potential of propolis has also been documented [79, 116]. The interest towards this type of studies is growing, as anti-QS compounds are known to have the ability to prohibit bacterial pathogenicity, they give the chance for the development of novel anti-infective agents that do not rely on the use of antibiotics [153]. In most cases, the antifungal activity has also been investigated together with the antibacterial one. There are data in the literature on action of propolis extracts against different strains of pathogenic fungi, and Candida albicans has been found to be most susceptible to propolis [135]. The antifungal activity of bee glue from the temperate zone (poplar type) is associated with the presence of flavonoids (mainly pinocembrin and kaempferol), and for tropical propolis, where these constituents are in small quantities or completely absent, the activity is due to C-prenylated derivatives of p-coumaric acid (Brazilian green propolis) and polyisoprenylated benzophenones (Clusia type). It has been established that the addition of propolis to an antimycotic drug leads to a strong increase in the inhibitory effect against C. albicans [154]. There have been several reports of antiviral activity of propolis extracts, with some flavonoids and aromatic acids being responsible for this [155]. According to Serkedjieva et al. [156] and Amoros et al. [157], the antiviral activity of poplar type propolis is mainly due to the isopentenyl esters of caffeic and ferulic acids. The flavonoid aglycones luteolin and quercetin have also been reported to be highly active, especially against herpesvirus [146]. In 1994, the first report of propolis activity against the HIV virus appeared [158]. It was later confirmed by other authors, as in 2001 Ito and coauthors found anti-HIV activity of methanolic extract of Brazilian propolis, mainly due to the major component, moronic acid [159, 160]. Recently Ripari et al. [161] claimed that propolis could be also extremely promising in the fight against COVID-19 (SARS-CoV-2) due to its immunomodulatory and antiinflammatory action and its effects should be investigated directly on the virus in vitro or on infected individuals alone or in combination with antiviral drugs. With respect to the antimicrobial action of propolis, it should be pointed out that no individual substance isolated from propolis has demonstrated an activity greater than that of the total extract [162–164]. Thus, it seems impossible to attribute the

26

Chemistry and Applications of Propolis

675

activity just to one or two individual components. Obviously, propolis is valuable antimicrobial resource as a natural mixture and not as a source of new powerful antimicrobial, antifungal, and antiviral individual compounds. The bee glue also has antiprotozoan activity. Brazilian green and poplar type propolis are active against Trypanosoma cruzi, the causative agent of the deadly Shaga’s disease. Data exist about antiprotozoan activity of propolis against Leishmania, Plasmodium, and Giardia parasites [138]. One of the most remarkable effects of propolis is its anti-inflammatory activity. This activity is associated with the phenolic components present in propolis. Several studies have associated different types of propolis and its various constituents with anti-inflammatory activity [139]. According to Krol and co-authors, components of poplar-type propolis with anti-inflammatory activity are caffeic acid phenethyl ester (CAPE), chrysin, galangin, kaempferol, and kaempferide [165]. Due to its antiinflammatory properties, bee glue is often used in the treatment of skin diseases and inflammations of the respiratory system [166]. The anti-inflammatory effect of propolis is mainly due to the antiradical activity of its components, which determines its antioxidant properties. Bee glue is a natural source of antioxidants (phenolic and polyphenolic compounds) that protect cells and cellular components from radical damage by blocking and neutralizing them. Thus, the fight against oxidative stress, which is the cause of many serious diseases such as cancer, gastritis, ulcers, atherosclerosis, has become the reason for the increasingly intensive study of the antioxidant properties of propolis. This is also due to the growing demand for natural antioxidants to replace synthetic ones, which cause a number of harmful side effects. There are many reports in the literature on the antioxidant activity of propolis extracts and compounds isolated from them [136, 139]. It is believed that the antioxidant effect of propolis is also the reason of its hepatoprotective activity. Special attention has been paid to the antitumor activity of bee glue, which is also related to its antioxidant properties, and many studies are focused in this direction. Antimetastasis action, inhibition of the processes of formation and development of tumor cells, and induction of apoptosis of tumor cells, both by propolis extracts and by substances isolated from them, have been established [3, 139]. In 1988, the Nakanishi group found that CAPЕ, one of the major components of poplar type bee glue, had strong cytotoxic and antitumor effects [167]. This has been confirmed by other authors through various in vitro and in vivo experiments [168]. Due to the high activity, CAPE has become the subject of more in-depth research related to its mechanism of action. Other components of poplar type propolis such as chrysin, caffeic acid, quercetin, and naringenin have also been found to contribute to antitumor activity of the bee glue [168]. Many studies have shown that the tropical propolis is active as well. Artepillin C, baccharin, and drupanin, components characteristic of Brazilian green propolis, have demonstrated high antitumor (in vitro and in vivo) activity [136, 139]. Diterpenic acids and heterocyclic derivatives of prenylated p-coumaric acids are also cytotoxic [169, 170]. Cuesta-Rubio et al. have found that the benzophenone nemorozone isolated from Cuban propolis (Clusia type) is active against tumor cells, and the

676

M. Popova et al.

Chen’s group have found that prenylflavanones propolin A, propolin B, and propolin C all isolated from Taiwanese propolis (Pacific type) also possess antitumor activity [63, 91]. Studies have demonstrated that bee glue has an antidiabetic effect. It decreases the blood glucose levels in patients with noninsulin-dependent diabetes [3]. Caffeoylquinic acid derivatives and especially 3,4,5-tri-O-caffeoylquinic acid, all isolated from Brazilian propolis, have a strong antihyperglycemic effect [171]. Several studies have shown that propolis reduces the blood pressure and cholesterol levels in the body [172]. Castaldo and Capasso point out that such an action makes it possible to use propolis as a means of preventing and treating atherosclerosis [134]. Many authors describe propolis as a safe and nontoxic natural product, with no adverse effects. Others report toxicity and allergic contact dermatitis generated by its use [173]. They are often provoked by heavy metals in propolis which come into it as a result of occasionally collected by bees asphalt and undried paints [174]. Allergic reactions are sometimes observed, caused by some of the organic components of bee glue. In poplar type propolis, the main organic allergens are caffeates, and in areas where poplars are absent, allergies to other compounds have occurred [175]. As a result of the studies conducted so far, it has been proven that propolis possesses many valuable pharmacological properties, regardless of its different geographical origin and chemical composition. This fact is related to the role of propolis in the hives, namely to ensure the survival of bee colonies. Despite the different flora, bees have adapted to find and collect resinous secretions rich in protective substances. Hence, research on propolis from different regions leads to the discovery of new biologically active compounds with potential for practical application.

7

Applications of Propolis

The remarkable and diverse pharmacological properties of propolis determine the main area of its application: the improvement and protection of human health. Numerous propolis-containing products, such as medical devices, over-the-counter preparations, health foods, and beverages, can be found on the market, especially products related to the medicinal and nutraceutical properties of bee glue and with dermatological applications [176, 177]. A very important application of propolis emerged in the last year: It turned out that the addition of standardized extract of Brazilian green propolis to the standard care procedures resulted in clinical benefits for the hospitalized COVID-19 patients, especially evidenced by a reduction in the length of hospital stay [178]. In addition, many in silco studies revealed the potential of major poplar-type propolis constituents (incl. CAPE) to inhibit SARS-Cov2 viral spike fusion in host cells, viral-host interactions that trigger the cytokine storm, and viral replication [179]. In recent years, the application of propolis in dentistry has dramatically increased. Its usefulness in dentistry and oral health management is based on available in vitro,

26

Chemistry and Applications of Propolis

677

in vivo, and ex vivo studies, as well as human clinical trials. Propolis has been successfully applied for the prevention of dental caries and periodontal diseases, surgical wound healing, as an interim transport medium for avulsed teeth, and in endodontics, orthodontics, and periodontics [180–182]. Research in this field has been particularly active in Brazil and Indonesia. The pharmacological properties of propolis are considered to be of the utmost importance for application in veterinary medicine. Research on the use of propolis in veterinary medicine has proven its beneficial effects in mastitis, wound healing, diarrhea, gastro-intestinal and genital infections, otitis, and dermatitis [135, 183]. Bee glue is useful also in improving the growth performance and productivity of livestock: poultry (chickens [184], laying hens [185], quails [186]), lambs [187], cattle [188] sheep [189], pigs [190], and fish [191]. In general, propolis has a positive effect on the growth and productivity of the test animals and is regarded as a promising alternative to antibiotics in animal feed, as it has the advantage of not inducing resistance in microorganisms [139]. The application of propolis in the food industry is mainly focused on suppressing the effects of microbial and oxidative agents and replacement of artificial preservatives disliked by consumers. Propolis favorably combines antioxidant and antimicrobial properties and low toxicity. This remarkable combination makes it an excellent candidate for preserving different foods [192, 193]. Successful experiments have been performed for utilization of propolis extracts in the preservation of numerous food products: fruit juices [194], fruits [195, 196], vegetables [197], eggs [198], and meat and fish products [199, 200]. However, the large-scale commercial use of propolis as a food preservative is not yet a reality, because it would require reliable standardization. Closely related to food preservation is the application of propolis as an ingredient of the so-called active packaging materials: active packaging films and edible coatings [201]. Such films and coatings based on propolis extract can impact the physical, biochemical, and sensory properties of food (e.g., fruits, vegetables, meat, and fish) during storage. The functionality of these materials is closely related to the type, harvesting method, extraction method of propolis, and the content and composition of bioactive substances in the extract [202]. The application of propolis for producing antimicrobial textile materials for different purposes, such as wound dressing, tissue engineering, medical and hygienic use, has also been studied. Propolis has been used by the incorporation of a small amount of it in electrospun polymer microfibers [203]. In some cases, it was applied as an eco-friendly finish for cotton fabric within the scope of a green strategy [204]. Some other applications of propolis have been reported: as a corrosion inhibitor, as a pesticide in horticulture, for optoelectronic applications, in air filters, etc. It could even contribute to the actions against global warming, because of its ability to reduce the methanogenesis in ruminants [205]. Obviously, propolis has the potential to be used for the development of diverse innovative products, not only medicines and cosmetics but also in the field of the animal husbandry, food industries, packaging, etc.

678

8

M. Popova et al.

Conclusions

In this book, dedicated to plant resins, propolis has a very special place: It is the only material which comes not from plants but from animals, from bees. However, in its essence, it is yet a plant product, the product of plant genomes, as are the resins collected by bees to make propolis. The only animal contribution to it is beeswax and very small amounts of bees’ salivary enzymes. What is very special about bee glue is the fact that there are many different chemical types of propolis according to the diverse sources used by bees for propolis production. It is important to stress that bees do not perform any chemical changes in the resins collected from plants in order to generate propolis. A number of experiments based on parallel analysis of resin of the source plant and resin from bees’ corbiculae and propolis from the beehive (plant resin mixed with wax) have demonstrated that their chemical profiles are identical. No chemical changes could be identified in the secondary plant metabolites, the resin was included in propolis without any chemical interference [10, 58, 104]. Moreover, any enzyme is unlikely to have any activity in resins/exudates (and propolis) due to the low water content and high phenolic content. Propolis has drawn growing attention of the researchers since the 1970s, due to its wide range of valuable pharmacological activities and potential for prevention and treatment of many diseases. At the same time, it has become clear that the chemical composition of propolis is highly variable and that there are many propolis chemical types with distinct chemical profiles determined by their plant sources. The idea that the term “propolis” does not have any chemical connotations, unlike the scientific name of a plant species, resulted in the paradigm shift in the propolis research which occurred during the last decade. It is important to note that any research of propolis’ pharmacological properties without chemical characterization is irreproducible and irrelevant, practically useless and consequently a waste of time and efforts. Because of this, the chemical profiling and characterization of every propolis sample used in studying its possible applications in any possible field is essential. The present knowledge of propolis demonstrates its potential as a source of new chemical structures and new bioactive compounds due to its chemical diversity, resulting from the diversity of plant sources. It also reveals the possibilities propolis to be applied for development of innovative products, mainly in the field of food industries, animal husbandry, beekeeping, etc. For this reason, the development of procedures for chemical profiling and standardization of different propolis types is required. In conclusion, there is no doubt that in unexplored specific ecosystems, propolis plant sources and respectively propolis chemical composition will continue to surprise scientists. The combined efforts of researchers and technologists from different areas are necessary, in order to make better use of this valuable natural material.

References 1. Smone M, Evans JD, Spivak M (2009) Resin collection and social immunity in honey bees. Evolution 63:3016–3022

26

Chemistry and Applications of Propolis

679

2. Ghisalberti EL (1979) Propolis: a review. Bee World 60:59–84 3. Sforcin JM, Bankova V (2011) Propolis: is there a potential for the development of new drugs? J Ethnopharmacol 133:253–260 4. Zulhendri F, Chandrasekaran K, Kowacz M, Ravalia M, Kripal K, Fearnley J, Perera CO (2021) Antiviral, antibacterial, antifungal, and antiparasitic properties of propolis: a review. Foods 10:1360. https://doi.org/10.3390/foods10061360 5. Crane E (1990) Bees and beekeeping: science, practice and world resources. Heinemann Newnes, Oxford 6. Salatino A, Teixeira ÉW, Negri G (2005) Origin and chemical variation of Brazilian propolis. Evid Based Complement Alternat Med 2:33–38 7. Langenheim JH (1990) Plant resins. Am Sci 78:16–24 8. Salatino A, Salatino MLF (2017) Why do honeybees exploit so few plant species as propolis sources? MOJ Food Process Technol 41:58–160. https://doi.org/10.15406/ mojfpt20170400107 9. Simone-Finstrom M, Spivak M (2010) Propolis and bee health: the natural history and significance of resin use by honey bees. Apidologie 41:295–311 10. Bankova V, Popova M, Trusheva B (2018) The phytochemistry of the honeybee. Phytochemistry 155:1–11 11. Michener CD (1969) Comparative social behavior of bees. Annu Rev Entomol 14:299–342 12. Leonhardt SD, Blüthgen N (2009) A sticky affair: resin collection by Bornean stingless bees. Biotropica 41:730–736 13. Popova M, Trusheva B, Bankova V (2021) Propolis of stingless bees: a phytochemist’s guide through the jungle of tropical biodiversity. Phytomedicine 86:153098 14. Burdock GA (1998) Review of the biological properties and toxicity of bee propolis (propolis). Food Chem Toxicol 36:347–363 15. Bankova V, Trusheva B, Popova M (2021) Propolis extraction methods: a review. J Apic Res. https://doi.org/10.1080/0021883920211901426 16. Milojković-Opsenica D, Ristivojević P, Andrić F, Trifković J (2013) Planar chromatographic systems in pattern recognition and fingerprint analysis. Chromatographia 76:1239–1247. https://doi.org/10.1007/s10337-013-2423-9 17. Ristivojević P, Andrić FL, Trifković JD, Vovk I, Stanisavljević LŽ, Tešić ŽL, Milojković-Opsenica DM (2014) Pattern recognition methods and multivariate image analysis in HPTLC fingerprinting of propolis extracts. J Chemom 28:301–310 18. Milojković-Opsenica D, Ristivojević P, Trifković J, Vovk I, Lušić D, Tešić Ž (2016) TLC fingerprinting and pattern recognition methods in the assessment of authenticity of poplar-type propolis. J Chromatogr Sci 54:1077–1083. https://doi.org/10.1093/chromsci/bmw024 19. Markham KR, Mitchell KA, Wilkins AL, Daldy JA, Lu Y (1996) HPLC and GC-MS identification of the major organic constituents in New Zeland propolis. Phytochemistry 42:205–211 20. Sawaya ACHF, Cunha IBS, Marcucci MC (2011) Analytical methods applied to diverse types of Brazilian propolis. Chem Cent J 5:27 21. Herzler M, Herre S, Pragst F (2003) Selectivity of substance Identification by HPLC-DAD in toxicological analysis using a UV spectra library of 2682 compounds. J Anal Toxicol 27:233–242 22. Falcão S, Vilas-Boas M, Estevinho LM, Barros C, Domingues MRM, Cardoso SM (2010) Phenolic characterization of Northeast Portuguese propolis: usual and unusual compounds. Anal Bioanal Chem 396:887–897. https://doi.org/10.1007/s00216-009-3232-8 23. Marcucci MC, Ferreres F, Custódio AR, Ferreira MMC, Bankova VS, García-Viguera C, Bretz WA (2000) Evalution of phenolic compounds in Brazilian propolis from different geographic regions. Z Naturforsch C J Biosci 55:76–81 24. Pellati F, Orlandini G, Pinetti D, Benvenuti S (2011) HPLC-DAD and HPLC-ESI-MS/MS methods for metabolite profiling of propolis extracts. J Pharm Biomed Anal 55:934–948 25. Kumazawa S, Nakamura J, Murase M, Miyagawa M, Ahn M-R, Fukumoto S (2008) Plant origin of Okinawan propolis: honeybee behavior observation and phytochemical analysis. Naturwissenschaften 95:781. https://doi.org/10.1007/s00114-008-0383-y

680

M. Popova et al.

26. Kasiotis KM, Anastasiadou P, Papadopoulos A, Machera K (2017) Revisiting Greek propolis: chromatographic analysis and antioxidant Activity study. PLoS One 12(1):e0170077 27. Ho CS, Lam CWK, Chan MHM, Cheung RCK, Law LK, Lit LCW, N, KF, Suen MWM, Tai HL (2003) Electrospray ionisation mass spectrometry: principles and clinical applications. Clin Biochem Rev 24:3–12 28. Volpi N, Bergonzini G (2006) Analysis of flavonoids from propolis by on-line HPLC– electrospray mass spectrometry. J Pharm Biomed Anal 42:354–361 29. Righi AA, Negri G, Salatino A (2013) Comparative chemistry of propolis from eight Brazilian localities. Evid Based Complement Alternat Med 2013:267878. https://doi.org/10.1155/2013/ 267878 30. Liu Q, Wu H-L, Liu Z, Xiao R, Wang T, Hu Y, Ding Y-J, Yu R-Q (2018) Chemometricsassisted HPLC-DAD as a rapid and interference-free strategy for simultaneous determination of 17 polyphenols in raw propolis. Anal Methods 10:5577–5588 31. Murray KK (2002) Coupling matrix-assisted laser desorption/ionization to liquid separations. Mass Spectrom Rev 16:283–299 32. Bankova V, Bertelli D, Borba R, Conti BJ, da Silva Cunha IB, Danert C, Eberlin MN, Falcão SI, Isla MI, Nieva Moreno MI, Papotti G, Popova M, Santiago KB, Salas A, Sawaya ACHF, Schwab NV, Sforcin JM, Simone-Finstrom M, Spivak M, Trusheva B, Vilas-Boas M, Michael Wilson M, Zampini C (2019) Standard methods for Apis mellifera propolis research. J Apic Res 58:1–49 33. Saftić L, Peršurić Ž, Fornal E, Pavlešić T, Pavelić SK (2019) Targeted and untargeted LC-MS polyphenolic profiling and chemometric analysis of propolis from different regions of Croatia. J Pharm Biomed Anal 165:162–172 34. Pavlovic R, Borgonovo G, Leoni V, Giupponi L, Ceciliani G, Sala S, Bassoli A, Giorgi A (2020) Effectiveness of different analytical methods for the characterization of propolis: a case of study in Northern Italy. Molecules 25:504 35. Garcia A, Barbas C (2011) Gas chromatography-mass spectrometry (GC-MS)-based metabolomics. In: Metz T (ed) Metabolic profiling, methods in molecular biology, vol 708. Humana Press. https://doi.org/10.1007/978-1-61737-985-7_11 36. Greenaway W, Scaysbrook T, Whatley FR (1987) The analysis of bud exudate of Populus x euramericana, and of propolis, by gas chromatography–mass spectrometry. Proc Royal Soc B Biol Sci 232:249–272. https://doi.org/10.1098/rspb19870073 37. Campo Fernández M, Cuesta-Rubio O, Rosado Perez A, Montes De Oca Porto R, Márquez Hernández I, Piccinelli AL, Rastrelli L (2008) GC-MS determination of isoflavonoids in seven red Cuban propolis samples. J Agric Food Chem 56:9927–9932 38. Popova M, Graikou K, Chinou I, Bankova V (2010) GC-MS Profiling of diterpene compounds in Mediterranean propolis from Greece. J Agric Food Chem 58:3167–3176 39. Kardar MN, Zhang T, Coxon GD, Watson DG, Fearnley J, Seidel V (2014) Characterisation of triterpenes and new phenolic lipids in Cameroonian propolis. Phytochemistry 106:156–163 40. Rufatto LC, dos Santos DA, Marinho F, Henriques JAP, Ely MR, Moura S (2017) Red propolis: chemical composition and pharmacological activity. Asian Pac J Trop Biomed 7: 591–598 41. Bankova V, Popova M (2007) Propolis of stingless bees: a promising source of biologically active compounds. Pharmacogn Rev 1:88–92 42. Demarque DP, Dusi RG, de Sousa FDM, Grossi SM, Silvério MRS, Lopes NP, Espindola LS (2020) Mass spectrometry-based metabolomics approach in the isolation of bioactive natural products. Sci Rep 10:1051 43. Bertelli D, Papotti G, Bortolotti L, Marcazzan GL, Plessi M (2012) 1H-NMR simultaneous identification of health-relevant compounds in propolis extracts. Phytochem Anal 23:260–266 44. Cuesta-Rubio O, Piccinelli AL, Campo Fernandez M, Márquez Hernández I, Rosado A, Rastrelli L (2007) Chemical characterization of Cuban propolis by HPLCPDA, HPLC-MS, and NMR: the brown, red, and yellow Cuban varieties of propolis. J Agric Food Chem 55: 7502–7509

26

Chemistry and Applications of Propolis

681

45. Watson DG, Peyfoon E, Zheng L, Lu D, Seidel V, Johnston B, Parkinson JA, Fearnley J (2006) Application of principal components analysis to 1H-NMR data obtained from propolis samples of different geographical origin. Phytochem Anal 17:323–331 46. Papotti G, Bertelli D, Plessi M, Rossi MC (2010) Use of HR-NMR to classify propolis obtained using different harvesting methods. Int J Food Sci Technol 45:1610–1618 47. Anđelković B, Vujisić L, Vučković I, Tešević V, Vajs V, Gođevac D (2017) Metabolomics study of Populus type propolis. J Pharm Biomed Anal 135:217–226 48. Costa AG Jr, Yoshida NC, Garcez WS, Perdomo RT, Matos MFC, Garcez FR (2020) Metabolomics approach rxpands the classification of propolis samples from Midwest Brazil. J Nat Prod 83:333–343 49. Stavropoulou M-I, Stathopoulou K, Cheilari A, Benaki D, Gardikis K, Chinou I, Aligiannis N (2021) NMR metabolic profiling of Greek propolis samples: comparative evaluation of their phytochemical compositions and investigation of their anti-ageing and antioxidant properties. J Pharm Biomed Anal 194:113814 50. Marcucci MC (1995) Propolis: chemical composition, biological properties and therapeutic activity. Apidologie 26:83–99 51. Popravko SA (1978) Chemical composition of propolis, its origin and standardization. In: A remarkable Hive product: PROPOLIS. Apimondia Publ House, Bucharest, pp 15–18 52. Bankova V, Marcucci MC (2000) Standardization of propolis: present status and perspectives. Bee World 81:182–188 53. Bankova VS, De Catro SL, Marcucci MC (2000) Recent advances in chemistry and plant origin. Apidologie 31:3–15 54. Popravko SA, Tikhomirova VI, Vulfson NS (1985) [Comparative study of the chemical composition and biological activity of propolis and its sources] In: Propolis. Apimondia Publishing House, Bucharest, pp 35–37 (in Russian) 55. Bankova V, Popova MP, Bogdanov S, Sabatini A-G (2002) Chemical composition of European propolis: expected and unexpected results. Z Naturforsch C J Biosci 57:30–33 56. Park YK, Paredes-Guzman JF, Aguiar CL, Alencar SM, Fujiwara FY (2004) Chemical constituents in Baccharis dracunculifolia as the main botanical origin of Southeastern Brazilian propolis. J Agric Food Chem 52:1100–1103 57. Kumazawa S, Yoneda M, Shibata I, Kanaeda J, Hamasaka T, Nakayama T (2003) Direct evidence for the plant origin of Brazilian propolis by the observation of honeybee behavior and phytochemical analysis. Chem Pharm Bull 51:740–742 58. Teixeira ÉW, Negri G, Meira RM, Salatino A (2005) Plant origin of green propolis: bee behavior, plant anatomy and chemistry. Evid Based Complement Alternat Med 2:85–92 59. Salatino A, Fernandes-Silva CC, Righi AA, Salatino MLF (2011) Propolis research and the chemistry of plant products. Nat Prod Rep 28:925–936 60. Daugsch A, Moraes CS, Fort P, Park YK (2008) Brazilian red propolis – chemical composition and botanical origin. Evid Based Complement Alternat Med 5:435–441. https://doi.org/10. 1093/ecam/nem057 61. Piccinelli AL, Lotti C, Campone L, Cuesta-Rubio O, Campo Fernandez M, Rastrelli L (2011) Cuban and Brazilian red propolis: botanical origin and comparative analysis by highperformance liquid chromatography–photodiode array detection/electrospray ionization tandem mass spectrometry. J Agric Food Chem 59:6484–6491 62. Shahinozzaman M, Obanda DN, Tawata S (2020) Chemical composition and pharmacological properties of Macaranga-type Pacific propolis: a review. Phytother Res 35:207–222 63. Chen CN, Wu CL, Shy HS, Lin JK (2003) Cytotoxic prenylflavanones from Taiwanese propolis. J Nat Prod 66:503–506 64. Popova MP (2013) Structural basis of antimicrobial activity of Mediterranean propolis. In: Farooqi T, Farooqui AA (eds) Beneficial effects of propolis on human health. NOVA Science Publishers, New York 65. Melliou E, Chinou I (2004) Chemical analysis and antimicrobial activity of Greek propolis. Planta Med 70:515–519

682

M. Popova et al.

66. Popova MP, Chinou IB, Marekov IN, Bankova VS (2009) Terpenes with antimicrobial activity from Cretan propolis. Phytochemistry 70:1262–1271 67. Popova MP, Trusheva B, Cutajar S, Bankova V (2012) Identification of the plant origin of the botanical biomarkers of Mediterranean type propolis. Nat Prod Commun 7:569–570 68. Pujirahayu N, Suzuki T, Katayama T (2019) Cycloartane-type triterpenes and botanical origin of popolis of singless Indonesian bee Tetragonula sapiens. Plan Theory 8:57. https://doi.org/ 10.3390/plants8030057 69. Herrera-López MG, Rubio-Hernández EI, Richomme P, Schinkovitz A, Calvo-Irabién LM, Rodríguez LMP (2020) Resorcinolic lipids from Yucatecan propolis. J Braz Chem Soc 31: 186–192. https://doi.org/10.21577/0103-505320190156 70. Li F, Awale S, Zhang H, Tezuka Y, Esumi H, Kadota S (2009) Chemical constituents of propolis from Myanmar and their preferential cytotoxicity against a human pancreatic cancer cell line. J Nat Prod 72:1283–1287 71. Trusheva B, Popova M, Koendhori EB, Tsvetkova I, Naydenski C, Bankova V (2011) Indonesian propolis: chemical composition, biological activity and botanical origin. Nat Prod Res 25:606–613 72. Fikri AM, Popova M, Sulaeman A, Bankova V (2020) Stingless bees and Mangifera indica: a close relationship? Indian J Nat Prod Resour 11:130–134 73. Popova M, Dimitrova R, Al-Lawati HT, Tsvetkova I, Najdenski H, Bankova V (2013) Omani propolis: chemical profiling, antibacterial activity and new propolis plant sources. Chem Cent J 7:1–8 74. Trusheva B, Stancheva K, Gajbhiye N, Dimitrova R, Popova M, Saraf R, Bankova V (2016) Two new prenylated stilbenes with an irregular sesquiterpenyl side chain from propolis from Fiji Islands. Rec Nat Prod 10:465 75. Sanpa S, Popova M, Tunkasiri T, Eitssayeam S, Bankova V, Chantawannakul P (2017) Chemical profiles and antimicrobial activities of Thai propolis collected from Apis mellifera. Chiang Mai J Sci 44:438–448 76. Gallardo DG, Fajardo M, Alonso YN, Echemendía LSM, Copello JM (2020) Physicalchemical characterization and thin layer chromatographic comparison of a local propolis with the Mangifera indica resin. Pharm Biosci J 8:15–12 77. Negri G, Silva CCF, Coelho GR, Nascimento RMD, Mendonça RZ (2019) Cardanols detected in non-polar propolis extracts from Scaptotrigona aff postica (Hymenoptera, Apidae, Meliponini). Braz J Food Technol 22:e2018265 78. Araujo M, Bufalo M, Conti B, Fernandes ARY Jr, Trusheva B, Bankova V, Sforcin JM (2015) The chemical composition and pharmacological activities of geopropolis produced by Melipona fasciculata Smith in Northeast Brazil. J Mol Pathophysiol 4:12–20 79. Popova M, Gerginova D, Trusheva B, Simova S, Tamfu AN, Ceylan O, Bankova V (2021) A preliminary study of chemical profiles of honey, cerumen, and propolis of the African stingless bee Meliponula ferruginea. Foods 10:997 80. Murase M, Kato M, Sun A, Ono T, Nakamura J, Sato T, Kumazawa S (2008) Rhus javanica var chinensis as a new plant origin of propolis from Okayama, Japan. Biosci Biotechnol Biochem 72:2782–2784 81. Shimomura K, Inu S, Sugiyama Y, Kurosawa M, Nakamura J, Choi SJ, Kumazawa S (2012) Identification of the plant origin of propolis from Jeju Island, Korea, by observation of honeybee behavior and phytochemical analysis. Biosci Biotechnol Biochem 76:2135–2138 82. Popova M, Trusheva B, Antonova D, Cutajar S, Mifsud D, Farrugia C, Bankova V (2011) The specific chemical profile of Mediterranean propolis from Malta. Food Chem 126:1431–1435 83. Trusheva B, Todorov I, Ninova M, Najdenski H, Daneshmand A, Bankova V (2010) Antibacterial mono-and sesquiterpene esters of benzoic acids from Iranian propolis. Chem Cent J 4:1–4. https://doi.org/10.1186/1752-153X-4-8 84. Bankova V, Marcucci MC, Simova S, Nikolova N, Kujumgiev A, Popov S (1996) Antibacterial diterpenic acids from Brazilian propolis. Z Naturforsch C J Biosci 51:277–280 85. Alday E, Valencia D, Garibay-Escobar A, Domínguez-Esquivel Z, Piccinelli AL, Rastrelli L, Velazquez C (2019) Plant origin authentication of Sonoran Desert propolis: an antiproliferative propolis from a semi-arid region. Sci Nat 106:25

26

Chemistry and Applications of Propolis

683

86. Almutairi S, Edrada-Ebel R, Fearnley J, Igoli JO, Alotaibi W, Clements CJ, Watson DG (2014) Isolation of diterpenes and flavonoids from a new type of propolis from Saudi Arabia. Phytochem Lett 10:160–163 87. Georgieva K, Popova M, Dimitrova L, Trusheva B, Thanh LN, Phuong DTL, Bankova V (2019) Phytochemical analysis of Vietnamese propolis produced by the stingless bee Lisotrigona cacciae. PLoS One 14:e0216074 88. Isidorov VA, Szczepaniak L, Bakier S (2014) Rapid GC/MS determination of botanical precursors of Eurasian propolis. Food Chem 142:101–106 89. Falcão SI, Tomás A, Vale N, Gomes P, Freire C, Vilas-Boas M (2013) Phenolic quantification and botanical origin of Portuguese propolis. Ind Crop Prod 49:805–812 90. Piccinelli AL, Mencherini T, Celano R, Mouhoubi Z, Tamendjari A, Aquino RP, Rastrelli L (2013) Chemical composition and antioxidant activity of Algerian propolis. J Agric Food Chem 61:5080–5088 91. Cuesta-Rubio O, Frontana-Uribe BA, Ramírez-Apan T, Cárdenas J (2002) Polyisoprenylated benzophenones in Cuban propolis; biological activity of nemorosone. Z Naturforsch C J Biosci 57:372–378 92. Trusheva B, Popova M, Bankova V, Simova S, Marcucci MC, Miorin PL, Tsvetkova I (2006) Bioactive constituents of Brazilian red propolis. Evid Based Complement Alternat Med 3: 249–254 93. Tomás-Barberán FA, García-Viguera C, Vit-Olivier P, Ferreres F, Tomás-Lorente F (1993) Phytochemical evidence for the botanical origin of tropical propolis from Venezuela. Phytochemistry 34:191–196 94. Ishizu E, Kumazawa S, Honda S, Ohta T, Vongsak B (2019) Component analysis and antiangiogenic activity of Thailand stingless bee propolis. Makara J Technol [Sl] 23:78–83 95. Sanpa S, Popova M, Bankova V, Tunkasiri T, Eitssayeam S, Chantawannakul P (2015) Antibacterial compounds from propolis of Tetragonula laeviceps and Tetrigona melanoleuca (Hymenoptera: Apidae) from Thailand. PLoS One 10:e0126886 96. Popova MP, Trusheva BS, Nedialkov PT, Tsvetkova I, Pardo-Mora DP, Najdenski H, Bankova VS (2020) New Δ-tocotrienol derivatives from Colombian propolis. Nat Prod Res 34:2779–2786 97. da Cunha MG, Rosalen PL, Franchin M, de Alencar SM, Ikegaki M, Ransom T, Beutler JA (2016) Antiproliferative constituents of geopropolis from the bee Melipona scutellaris. Planta Med 82:190–194 98. Ccana-Ccapatinta GV, Mejía JAA, Tanimoto MH, Groppo M, Carvalho JCASD, Bastos JK (2020) Dalbergia ecastaphyllum (L) Taub and Symphonia globulifera Lf: the botanical sources of isoflavonoids and benzophenones in Brazilian red propolis. Molecules 25:2060 99. Duke CC, Tran VH, Duke RK, Abu-Mellal A, Plunkett GT, King DI, Bruhl JJ (2017) A sedge plant as the source of Kangaroo Island propolis rich in prenylated p-coumarate ester and stilbenes. Phytochemistry 134:87–97 100. King DI, Hamid K, Tran VH, Duke RK, Duke C (2021) Kangaroo Island propolis types originating from two Lepidosperma species and Dodonaea humilis. Phytochemistry 188: 112800 101. Inui S, Hosoya T, Kumazawa S (2014) Hawaiian propolis: comparative analysis and botanical origin. Nat Prod Commun 9:165–166 102. Petrova A, Popova M, Kuzmanova C, Tsvetkova I, Naydenski H, Muli E, Bankova V (2010) New biologically active compounds from Kenyan propolis. Fitoterapia 81:509–514 103. Inui S, Hosoya T, Shimamura Y, Masuda S, Ogawa T, Kobayashi H, Kumazawa S (2012) Solophenols B–D and solomonin: new prenylated polyphenols isolated from propolis collected from the Solomon Islands and their antibacterial activity. J Agric Food Chem 60:11765– 11770 104. Tran VH, Duke RK, Abu-Mellal A, Duke CC (2012) Propolis with high flavonoid content collected by honey bees from Acacia paradoxa. Phytochemistry 81:126–132 105. Al-Ghamdi AA, Bayaqoob NI, Rushdi AI, Alattal Y, Simoneit BR, El-Mubarak AH, Al-Mutlaq KF (2017) Chemical compositions and characteristics of organic compounds in propolis from Yemen. Saudi J Biol Sci 24:1094–1103

684

M. Popova et al.

106. Falcão SI, Lopes M, Vilas-Boas M (2019) A first approach to the chemical composition and antioxidant potential of Guinea-Bissau propolis. Nat Prod Commun 14. https://doi.org/10. 1177/1934578X19844138 107. Silva BB, Rosalen PL, Cury JA, Ikegaki M, Souza VC, Esteves A, Alencar SM (2008) Chemical composition and botanical origin of red propolis, a new type of Brazilian propolis. Evid Based Complement Alternat Med 5:313–316 108. Awale S, Shrestha SP, Tezuka Y, Ueda JY, Matsushige K, Kadota S (2005) Neoflavonoids and related constituents from Nepalese propolis and their nitric oxide production inhibitory activity. J Nat Prod 68:858–864 109. Omar RM, Igoli J, Gray AI, Ebiloma GU, Clements C, Fearnley J, Watson DG (2016) Chemical characterisation of Nigerian red propolis and its biological activity against Trypanosoma brucei. Phytochem Anal 27:107–115 110. Lotti C, Campo Fernandez M, Piccinelli AL, Cuesta-Rubio O, Marquez Hernandez I, Rastrelli L (2010) Chemical constituents of red Mexican propolis. J Agric Food Chem 58:2209–2213 111. Ferreira JM, Fernandes-Silva CC, Salatino A, Negri G (2017) Antioxidant activity of a geopropolis from northeast Brazil: chemical characterization and likely botanical origin. Evid Based Complement Alternat Med 2017:024721 112. Popova M, Bankova V, Chimov A, Silva MV (2002) A scientific note on the high toxicity of propolis that comes from Myroxylon balsamum trees. Apidologie 33:87–88 113. Agüero MB, Gonzalez M, Lima B, Svetaz L, Sanchez M, Zacchino S, Tapia A (2010) Argentinean propolis from Zuccagnia punctata Cav (Caesalpinieae) exudates: phytochemical characterization and antifungal activity. J Agric Food Chem 58:194–201 114. Solorzano ER, Bortolini C, Bogialli S, Di Gangi IM, Favaro G, Maldonado L, Pastore P (2017) Use of a LC-DAD-QTOF system for the characterization of the phenolic profile of the argentinean plant Zuccagnia punctata and of the related propolis: new biomarkers. J Funct Foods 33:425–435 115. Lotti C, Piccinelli AL, Arevalo C, Ruiz I, Migliani De Castro GM, Figueira Reis De Sá L, Rastrelli L (2012) Constituents of Hondurian propolis with inhibitory effects on Saccharomyces cerevisiae multidrug resistance protein Pdr5p. J Agric Food Chem 60:10540–10545 116. Savka MA, Dailey L, Popova M, Mihaylova R, Merritt B, Masek M, Bankova V (2015) Chemical composition and disruption of quorum sensing signaling in geographically diverse United States propolis. Evid Based Complement Alternat Med 2015:472593 117. Thanh LN, Oanh VTK, Thoa HT, Phuong DTL, Lien NTP, Giap TH et al (2018) Isolated triterpenes from stingless bee Lisotrigona furva propolis in Vietnam. J Apither Nat 1:73–73 118. Mukaide K, Honda S, Vongsak B, Kumazawa S (2021) Prenylflavonoids from propolis collected in Chiang Mai, Thailand. Phytochem Lett 43:88–93 119. Greenaway W, Scaysbrook T, Whatley FR (1990) The composition and plant origins of propolis: a report of work at Oxford. Bee World 71:107–118 120. Bankova V (2005) Recent trends and important developments in propolis research. Evid Based Complement Alternat Med 2:29–32 121. Wang X, Hu H, Luo Z, Liu Y, Zhang H (2018) A plant origin of Chinese propolis: Populus canadensis Moench. J Apic Res 57:228–245 122. Popova M, Silici S, Kaftanoglu O, Bankova V (2005) Antibacterial activity of Turkish propolis and its qualitative and quantitative chemical composition. Phytomedicine 12:221–228 123. Bankova V, Popova M, Bogdanov S, Sabatini A (2002) Chemical composition of European propolis: expected and unexpected results. Z Naturforsch C J Biosci 57:530–533 124. Christov R, Trusheva B, Popova M, Bankova V, Bertrand M (2006) Chemical composition of propolis from Canada, its antiradical activity and plant origin. Nat Prod Res 20:531–536 125. Aminimoghadamfarouj N, Nematollahi A (2017) Structure elucidation and botanical characterization of diterpenes from a specific type of bee glue. Molecules 22:1185 126. Athikomkulchai S, Awale S, Ruangrungsi N, Ruchirawat S, Kadota S (2013) Chemical constituents of Thai propolis. Fitoterapia 88:96–100 127. Agüero MB, Svetaz L, Sánchez M, Luna L, Lima B, López ML, Tapia A (2011) Argentinean Andean propolis associated with the medicinal plant Larrea nitida Cav (Zygophyllaceae)

26

Chemistry and Applications of Propolis

685

HPLC–MS and GC–MS characterization and antifungal activity. Food Chem Toxicol 49: 1970–1978 128. Isidorov VA, Bakier S, Pirożnikow E, Zambrzycka M, Swiecicka I (2016) Selective behaviour of honeybees in acquiring European propolis plant precursors. J Chem Ecol 42:475–485 129. Catchpole O, Mitchell K, Bloor S, Davis P, Suddes A (2015) Antiproliferative activity of New Zealand propolis and phenolic compounds vs human colorectal adenocarcinoma cells. Fitoterapia 106:167–174 130. Isla MI, Paredes-Guzman JF, Nieva-Moreno MI, Koo H, Park YK (2005) Some chemical composition and biological activity of northern Argentine propolis. J Agric Food Chem 53: 1166–1172 131. Suleman T, Van Vuuren S, Sandasi M, Viljoen AM (2015) Antimicrobial activity and chemometric modelling of South African propolis. J Appl Microbiol 119:981–990 132. Ibrahim RS, Metwally AM (2017) Plant source of Egyptian propolis using multivariateassisted digitally-enhanced TLC data analysis. J Nat Prod Plant Resour 73:20–25 133. Ismail TNNT, Sulaiman SA, Ponnuraj KT, Man CN, Hassan NB (2018) Chemical constituents of Malaysian Apis mellifera propolis. Sains Malays 47:117–122 134. Castaldo S, Capasso F (2002) Propolis, an old remedy used in modern medicine. Fitoterapia 73:S1–S6 135. Santos LM, Fonseca MS, Sokolonski AR, Deegan KR, Araújo RPC, Umsza-Guez MA, Barbosa JDV, Portela RD, Machado BAS (2020) Propolis: types, composition, biological activities, and veterinary product patent prospecting. J Sci Food Agric 100:1369–1382 136. Alvarenga L, Cardozo LFMF, Borges NA, Chermut TR, Ribeiro M, Leite M Jr, Shiels PG, Stenvinkel P, Mafra D (2021) To bee or not to bee? The bee extract propolis as a bioactive compound in the burden of lifestyle diseases. Nutrition 83:111094 137. Amoros M, Sauvager F, Girre L, Cormier M (1992) In vitro antiviral activity of propolis. Apidologie 23:231–240 138. Asfaram S, Fakhar M, Keighobadi M, Akhtari J (2021) Promising anti-protozoan activities of propolis (bee glue) as natural product: a review. Acta Parasitol 66:1–12 139. Silva-Carvalho R, Baltazar F, Almeida-Aguiar C (2015) Propolis: a complex natural product with a plethora of biological activities that can be explored for drug development. Evid Based Complement Alternat Med 2015:206439 140. Babatunde IR, Abdulbasit A, Oladayo MI, Olasile OI, Olamide FR, Gbolahan BW (2015) Hepatoprotective and pancreatoprotective properties of the Ethanolic extract of Nigerian propolis. J Intercult Ethnopharmacol 4:102–108 141. Rusak G (2008) Bioactive constituents of propolis. In: Orsolic N, Basic I (eds) Scientific evidence of the use of propolis in ethnomedicine. Transworld Research Network, Trivandrum 142. Rivera-Yañez N, Rivera-Yañez CR, Pozo-Molina G, Méndez-Catalá CF, Reyes-Reali J, Mendoza-Ramos MI, Méndez-Cruz AR, Nieto-Yañez O (2021) Effects of propolis on infectious diseases of medical relevance. Biology 10:428 143. Przybyłek I, Karpiński TM (2019) Antibacterial properties of propolis. Molecules 24:2047 144. Almuhayawi MS (2020) Propolis as a novel antibacterial agent. Saudi J Biol Sci 27: 3079–3086 145. Farre R, Frasquet I, Sanchez A (2004) Propolis and human health. Ars Pharm 45:21–43 146. Bankova V (2000) Determining quality in propolis samples. J Am Apither Soc 7:11 147. Raghukumar R, Vali L, Watson D, Fearnley J, Seidel V (2010) Antimethicillin-resistant Staphylococcus aureus (MRSA) activity of ‘pacific propolis’ and isolated prenylflavanones. Phytother Res 24:1181–1187 148. Moise AR, Bobiş O (2020) Baccharis dracunculifolia and Dalbergia ecastophyllum, main plant sources for bioactive properties in green and red Brazilian propolis. Plan Theory 9:1619 149. Hashimoto T, Aga H, Tabuchi A, Shibuya T, Chaen H, Fukuda S, Kurimoto M (1998) AntiHelicobacter pylori compounds in Brazilian propolis. Nat Med 5:518–520 150. Banskota AH, Tezuka Y, Adnyana IK, Ishii E, Midorikawa K, Matsushige K, Kadota S (2001) Hepatoprotective and anti-Helicobacter pylori activities of constituents from Brazilian propolis. Phytomedicine 8:16–23

686

M. Popova et al.

151. Boyanova L, Gergova G, Nikolov R, Derejian S, Lazarova E, Katsarov N, Mitov I, Krastev Z (2005) Activity of Bulgarian propolis against 94 Helicobacter pylori strains in vitro by agarwell diffusion, agar dilution and disc diffusion methods. J Med Microbiol 54:481–483 152. Orsi RDO, Fernandes A, Bankova V, Sforcin JM (2012) The effects of Brazilian and Bulgarian propolis in vitro against Salmonella typhi and their synergism with antibiotics acting on the ribosome. Nat Prod Res 26:430–437 153. Asfour HZ (2018) Anti-quorum sensing natural compounds. J Microsc Ultrastruct 6:1 154. Holderna-Kedzia E, Kedzia B (1987) Investigation upon the combined action of propolis and antimycotic drugs on Candida albicans. Herba Pol 33:145–151 155. Pobiega K, Gniewosz M, Kraśniewska K (2017) Antimicrobial and antiviral properties of different types of propolis. Zesz Probl Postepow Nauk Roln 589:69–79 156. Serkedjieva J, Manolova N, Bankova V (1992) Anti-influenza virus effect of some propolis constituents and their analogues (esters of substituted cinnamic acids). J Nat Prod 55:294–297 157. Amoros M, Lurton E, Boustie J, Girre L, Sauvager F, Cormier M (1994) Comparison of the anti-herpes simplex virus activities of propolis and 3-methyl-but-2-enyl caffeate. J Nat Prod 57:644–647 158. Harish Z, Rubinstein A, Golodner M, Elmaliah M, Mizrahchi Y (1997) Suppression of HIV-1 replication by propolis and its immunoregulatory effect. Drug Exp Clin Res 23:89–96 159. Ito J, Chang F-R, Wang H-K, Park YK, Ikegaki M, Kilgore N, Lee K-H (2001) Anti-AIDS agents. 48. Anti-HIV activity of moronic acid derivatives and the new melliferone-related triterpenoid isolated from Brazilian propolis. J Nat Prod 64:1278–1281 160. Gekker G, Hu S, Spivak M, Lokensgard JR, Peterson PK (2005) Anti-HIV-1 activity of propolis in CD4+ lymphocyte and microglial cell cultures. J Ethnopharmacol 102:158–163 161. Ripari N, Sartori AA, Honorio MS, Conte FL, Tasca KI, Santiago KB, Sforcin JM (2021) Propolis antiviral and immunomodulatory activity: a review and perspectives for COVID-19 treatment. J Pharm Pharmacol 73:281–299 162. Kujumgiev A, Bankova V, Igantova A, Popov S (1993) Antibacterial activity of propolis, some of its components and their analogs. Pharmazie 48:785–786 163. Bonvehí JS, Coll FV (1994) The composition, active components and bacteriostatic activity of propolis in dietetics. J Am Oil Chem Soc 71:529–532 164. Bankova V (2005) Chemical diversity of propolis and the problem of standardization. J Ethnopharmacol 100:114–117 165. Krol W, Sheller S, Czuba Z, Matsuno T, Zydowich G, Shani J, Mos M (1996) Inhibition of neutrophils’ chemiluminescence by ethanol extract of propolis (EEP) and its phenolic components. J Ethnopharmcol 55:19–25 166. Cohen HA, Varsano I, Kahan E, Sarrell EM, Uziel Y (2004) Effectiveness of an herbal preparation containing Echinacea, propolis, and vitamin C in preventing respiratory tract infections in children. Arch Pediatr Adolesc Med 158:217–221 167. Gruneberger D, Banerjee R, Eisinger K, Oltz EM, Efros L, Caldwell M, Estevez V, Nakanishi K (1988) Preferential cytotoxicity on tumor cells by caffeic acid phenethyl ester isolated from propolis. Experientia 44:230–232 168. Watanabe MAE, Amarante MK, Conti BJ, Sforcin JM (2011) Cytotoxic constituents of propolis inducing anticancer effects: a review. J Pharm Pharmacol 63:1378–1386 169. Matsuno T, Matsumoto Y, Saito M, Morikawa J (1997) Isolation and characterization of cytotoxic diterpenoidi from propolis. Z Naturforsch C J Biosci 52:702–704 170. Matsuno T, Saito M, Matsumoto Y, Morikawa J (1998) A new benzo-γ-pyran derivative isolated from propolis. Z Naturforsch C J Biosci 53:1037–1039 171. Matsui T, Ebuchi S, Fujise T, Abesundara KJM, Doi S, Yamada H, Matsumoto K (2004) Strong antihyperglycemic effects of water-soluble fraction of Brazilian propolis and its bioactive constituent, 3,4,5-tri-O-caffeoylquinic acid. Biol Pharm Bull 27:1797–1803 172. Kubota Y, Umegaki K, Kobayashi K, Tanaka N, Kagota S, Nakamura K, Kunitomo M, Shinozuka K (2004) Anti-hypertensive effects of Brazilian propolis in spontaneously hypertensive rats. Clin Exp Pharmacol Physiol 31:29–30

26

Chemistry and Applications of Propolis

687

173. Sforcin JM (2016) Biological properties and therapeutic applications of propolis. Phytother Res 30:894–905 174. Banskota AH, Tezuka Y, Kadota S (2001) Recent progress in pharmacological research of propolis. Phytother Res 15:561–571 175. de Groot AC (2013) Propolis: a review of properties, applications, chemical composition, contact allergy, and other adverse effects. Dermatitis 24:263–282 176. Suárez D, Zayas D, Guisado F (2005) Propolis: patents and technology trends for health applications. J Bus Chem 2:1–11 177. Machado BAS, Cruz LS, Nunes SB, Guez MAU, Padilha FF (2012) Prospective study of propolis and related technologies in focus in patent documents deposited in Brazil. Rev GEINTEC 3:221–235 178. Silveira MAD, De Jong D, Berretta AA, dos Santos Galvão EB, Ribeiro JC, Cerqueira-Silva T, da Hora Passos R (2021) Efficacy of Brazilian green propolis (EPP-AF ®) as an adjunct treatment for hospitalized COVID-19 patients: a randomized, controlled clinical trial. Biomed Pharmacother 138:111526 179. Ali AM, Kunugi H (2021) Propolis, bee honey, and their components protect against Coronavirus Disease 2019 (COVID-19): a review of in silico, in vitro, and clinical studies. Molecules 26:1232 180. Zulhendri F, Felitti R, Fearnley J, Ravalia M (2021) The use of propolis in dentistry, oral health, and medicine: a review. J Oral Biosci 63:23–34 181. Abbasi AJ, Mohammadi F, Bayat M, Gema SM, Ghadirian H, Seifi H, Bahrami N (2018) Applications of propolis in dentistry: a review. Ethiop J Health Sci 28:505–512 182. Sardana D, InduShekar KR, Manchanda S, Saraf BG, Sheoran N (2013) Role of propolis in dentistry: review of the literature. Focus Altern Complement Ther 18:118–125 183. Šuran J, Matanović K, Brozić D, Mašek T, Maćešić N, Radin L, Aladrović J, Božić E, Martinec BŠ, Lipar M, Smolec O, Benić M, Radić B, Bačić G (2016) Antimicrobial activity of propolis and its potential uses in veterinary medicine. Vet Stanica 47:381–385 184. Seven PT, Seven I (2008) Effect of dietary Turkish propolis as alternative to antibiotic on performance and digestibility in broilers exposed to heat stress. J Appl Anim Res 34:193–196 185. Seven PT (2008) The effects of dietary Turkish propolis and vitamin C on performance, digestibility, egg production and egg quality in laying hens under different environ-mental temperatures. Asian-Australas J Anim Sci 21:1164–1170 186. Aygun A, Sert D, Copur G (2012) Effects of propolis on eggshell microbial activity, hatchability, and chick performance in Japanese quail (Coturnix coturnix japonica) eggs. Poult Sci 91:1018–1025 187. Ítavo CCBF, Morais MG, Ramos CL, Ítavo LCV, Tomich TR, da Silva JA (2011) Green propolis extract as additive in the diet for lambs in feedlot. Rev Bras Zootecn 40:1991–1996 188. Valero MV, Zeoula LM, de Moura LPP, C Júnior JBG, Sestari BB, do Prado IN (2015) Propolis extract in the diet of crossbred (½ Angus vs ½ Nellore) bulls finished in feedlot: animal performance, feed efficiency and carcass characteristics. Semin Cienc Agrar 36: 1067–1078 189. da Silva FGB, Yamamoto SM, da Silva EMS, Queiroz MAÁ, Gordiano LA, Formiga MA (2015) Propolis extract and sodium monensin on ruminal fermentation and hematological parameters in sheep. Acta Sci Anim Sci 37:273–280 190. Li J, Kim IH (2014) Effects of Saccharomyces cerevisiae cell wall extract and poplar propolis ethanol extract supplementation on growth performance, digestibility, blood profile, fecal microbiota and fecal noxious gas emissions in growing pigs. Anim Sci J 85:698–705 191. Farag MR, Abdelnour SA, Patra AK, Dhama K, Dawood MA, Elnesr SS, Alagawany M (2021) Propolis: properties and composition, health benefits and applications in fish nutrition. Fish Shellfish Immun 115:179–188 192. Irigoiti Y, Navarro A, Yamul D, Libonatti C, Tabera A, Basualdo M (2021) The use of propolis as a functional food ingredient: a review. Trends Food Sci Technol 115:297–306. https://doi. org/10.1016/jtifs202106041

688

M. Popova et al.

193. Bankova V, Popova M, Trusheva B (2016) New emerging fields of application of propolis. Maced J Chem Chem Eng 35:1–11 194. Silici S, Koç NA, Mutlu Sariguzel F, Sagdic O (2005) Mould inhibition in different fruit juices by propolis. Arch Leb 56:87–90 195. Mutton MJR, de Oliveira Filho JH, Costa GHG, Roviero JP, de Freita LA (2014) Green and brown propolis: efficient natural biocides for the control of bacterial contamination of alcoholic fermentation of distilled beverage. Food Sci Technol 34:767–772. https://doi.org/10. 1590/1678-457X6469 196. Candir EE, Ozdemir AE, Soylu EM, Sahinler N, Gül A (2009) Effects of propolis on storage of sweet cherry cultivar Aksehir Napolyon. Asian J Chem 21:2659–2666 197. Alvarez MV, Ponce AG, Mazzucotelli CA, Moreira MR (2015) The impact of biopreservatives and storage temperature in the quality and safety of minimally processed mixed vegetables for soup. J Sci Food Agric 95:962–971 198. Alkan S, Ertürk Ö, Türker İ (2020) Determination of microbial activity and quality traits of eggs coated with propolis. Turk J Agricult Food Sci Technol 8:1380–1384 199. Yazgan H, Burgu A, Durmus M, Kosker AR (2020) The impacts of water and ethanolic extracts of propolis on vacuum packaged sardine fillets inoculated with Morganella psychrotolerans during chilly storage. J Food Saf 40:e12767 200. Ucak I, Khalily R, Carrillo C, Tomasevic I, Barba FJ (2020) Potential of propolis extract as a natural antioxidant and antimicrobial in gelatin films applied to rainbow trout (Oncorhynchus mykiss) fillets. Foods 9:1584 201. Mascheroni E, Guillard V, Nalin F, Mora L, Piergiovanni L (2010) Diffusivity of propolis compounds in polylactic acid polymer for the development of anti-microbial packaging films. J Food Eng 98:294–301. https://doi.org/10.1016/jjfoodeng200912028 202. Yong H, Liu J (2021) Active packaging films and edible coatings based on polyphenol-rich propolis extract: a review. Compr Rev Food Sci Food Saf 20:2106–2145 203. Sharaf S, El-Naggar ME (2018) Eco-friendly technology for preparation, characterization and promotion of honey bee propolis extract loaded cellulose acetate nanofibers in medical domains. Cellulose 25:5195–5204 204. Abramiuc D, Ciobanu L, Muresan R, Chiosac M, Muresan A (2013) Antibacterial finishing of cotton fabrics using biologically active natural compounds. Fibers Polym 14:1826–1833 205. Morsy AS, Soltan YA, Sallam SMA, Kreuzer M, Alencar SM, Abdalla AL (2015) Comparison of the in vitro efficiency of supplementary bee propolis extracts of different origin in enhancing the ruminal degradability of organic matter and mitigating the formation of methane. Animal Feed Sci Technol 199:51–60

Propolis: A Multifaceted Approach for Wound Healing

27

Gregorio Bonsignore, Simona Martinotti, and Elia Ranzato

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Composition and Different Types of Propolis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Biological Properties . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Propolis Standardization . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

690 690 691 693 694 694

Abstract

An increasing number of anecdotal observations demonstrate the biological properties of propolis. Some scientific evidence nowadays supports the basis of these activities, in particular for wound healing practice. Moreover, the variability in propolis “sourcing” determines a great propolis extract diversity that could be solved by the use of new extraction methods to produce comparable activities data. Keywords

Aquaporin-3 · Propolis · ROS · Standardization · Wound healing Abbreviations

AQP-3 H2O2 M.E.D. ROS TGF-β

Aquaporin-3 Hydrogen peroxide Multi-dynamic extraction Reactive oxygen species Transforming growth factor β

G. Bonsignore · S. Martinotti (*) · E. Ranzato DiSIT- Dipartimento di Scienze e Innovazione Tecnologica, University of Piemonte Orientale, Alessandria, Italy e-mail: [email protected]; [email protected]; [email protected] © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_39

689

690

1

G. Bonsignore et al.

Introduction

Apis mellifera produces a huge variety of products of great interest for humankind (e.g., honey, royal jelly). Moreover, bees produce also propolis, a resinous mixture used as a building insulating material or to keep in good health the beehive [1]. Propolis is a balsamic and resinous product with a complex and variable composition, and it is considered to be a matrix with a high biotechnological potential [2]. Propolis possesses a complex chemical composition, including aldehydes, aromatic acids, phenols, polysaccharides, tannins, and terpenes [3–5]. Propolis is utilized for numerous applications due to its composition. In particular, propolis displays several activities [2, 6] such as antioxidant properties, antimicrobial, and antiviral abilities, antiparasitic efficacy, antitumor action, anti-inflammatory as well as immunomodulatory, hepatoprotective, and hypotensive behavior [5]. These properties suggested some applications for propolis, especially for human and animal health [2]. For its interesting potential, propolis was used in the past in different cultures, such as old Egyptians and Greeks [7]. In ancient times, Abu Ali bin Sina, known as Avicenna, distinguished two kinds of wax, the clean and the black wax. Clean wax composed the comb wells where the bees rear the brood and stored the honey, and the black was the hive filth. After Avicenna, it was clarified that the black wax was propolis. Propolis was also extensively used in folk medicine to cure some diseases and as an “embalming” substance [5]. The propolis regular intake has been proposed in traditional medicine as a way to promote health-enhancing resistance to infections. During the Middle Ages, propolis was not so popular and its use disappeared. Propolis’s interest came back during the Renaissance for growing attention to ancient and forgotten approaches and treatments [8]. Moreover, propolis was accepted in Europe as an antibacterial compound from the seventeenth century [9]. The first scientific description of propolis, with particular attention to chemical composition and properties, refers to 1908 [10].

2

Composition and Different Types of Propolis

Propolis production starts when bees, using their mandibles, pick up parts of plants to obtain resin, then manipulated and picked by their legs [11]. Resin is mixed by bees with their saliva which partially hydrolyses it [6, 12]. Then propolis is cemented and mixed with wax in the hives [11]. In the decades, the composition and chemical properties of propolis were extensively studied and characterized [13]. Propolis contains more than 250 diverse compounds, like β-amylase [14], many polyphenols (pinocembrin, acacetin, chrysin, rutin, catechin, naringenin, galangin, luteolin, kaempferol, apigenin, myricetin, and quercetin), vitamins, two phenolic acids (cinnamic acid and caffeic acid), one stilbene derivative (resveratrol), and inorganic compounds [15–17]. The exact chemical composition depends on the propolis extract. Propolis extract can be obtained using different solvents such as ethanol, methanol, and acetate but, today, it is possible to obtain them using

27

Propolis: A Multifaceted Approach for Wound Healing

691

eco-friendly technologies (e.g., supercritical fluid extraction) [2]. Great percentages of caffeic acid, chrysin, galangin, and quercetin are described in aqueous-ethanolic propolis extract; however, the ethanolic preparation shows a different composition, containing more chrysin, caffeic acids, and resveratrol [5]. The aqueous-glycolic propolis preparation contains more flavonoids, caffeic acid, and a large portion of non-identified compounds [18]. Propolis composition is also strictly dependent on the geographic area where bees collected resins due to the specific flora of each region. There are many types of propolis. For example, only in Brazil, scientists described 14 different types of this bee product. Propolis differs in botanic origin, chemical composition, and properties (chemical and physical) [19, 20]. The bigger propolis production is obtained from Baccharis dracunculifolia (wild rosemary). Bees obtain a green resinous substance by the fragmentation and the manipulation of wild rosemary [21]. Propolis could be distinguished into three main types: Brown Propolis: Brown propolis may be derived from different botanic families such as Asteraceae, Bignoniaceae, Fabaceae, Malvaceae, and Urticaceae [22]. Some Brazilian and Cuban regions are the most important producers [23, 24]. Its botanical source is linked to Araucaria spp., even if some molecules are from B. dracunculifolia. Red Propolis: Its main botanic source is Dalbergia ecastophyllum (L.) Taub. (Fabaceae) [25]. This propolis is produced in several countries around the world, for example, China, but in particular it is produced in Central America (Cuba, Mexico, and Venezuela) [26–30]. It is also typical production from a specific region of Brazil (Alagoas, Bahia, Paraìba, Penambuco). Red propolis is rich in triterpenoids, phenolics, and isoflavonoids [20]. Yellow Propolis: It is produced both in Brazil and Cuba (according to its secondary metabolites) [19, 23, 31].

3

Biological Properties

As already mentioned, propolis displays several biological activities, but very little scientific information is available [5]. The most known biological activity of propolis is its antibacterial action. Propolis shows bacteriostatic and bactericidal effects against some bacterial species (among them also antibiotic-resistant organisms) [2]. The antibacterial activity of propolis is obtained from the direct action on the microorganisms and the stimulation of the immune system [32]. In fact, the permeability of microorganisms can be changed by propolis which can also disrupt membrane potential and ATP production. In addition, propolis decreases bacterial mobility [33]. Antimicrobial properties of propolis are due to the flavonoid, in particular pinocembrin (which is also an antimycotic), galangin, and pinobanksin. It is necessary a lower propolis minimum inhibitory concentration on gram-positive bacteria than on gram-negative bacteria [2]. This condition is explained by the composition

692

G. Bonsignore et al.

of a gram-negative membrane, which produces hydrolytic enzymes that limit the effective components of propolis (e.g., Artepillin C) [34, 35]. Propolis is also effective as an antiviral. Some authors have described that propolis does not allow viral entry into the cells and causes viral RNA degradation [36–39]. Propolis is an alternative promising therapy against fungi. Today, there are a few antifungal drugs, and, in addition, fungi are becoming resistant to treatments. This situation affects both the cost and the duration of therapies (which causes an increase of side effects) [40, 41]. Propolis can inhibit aflatoxigenic fungi through the reduction of conidia germination in vitro [42]. Furthermore, some in vivo studies with Brazilian propolis have shown how it can be used as a mouth rinse to prevent or treat oral candidiasis (C. albicans, C. tropicalis, C. krusei, and C. guillermondi). In fact, patients with full dentures treated with propolis showed a little percentage of infections [43, 44]. Boisard et al. (2015) studied a French propolis mixture and its antifungal activity against C. albicans, C. glabrata (yeasts), and A. fumigatus (a filamentous fungus). The study showed a correlation between antifungal activity and high flavonoid contents [45]. Propolis contains also pinocembrin, an important antifungal compound, showing the ability to inhibit Penicillium italicum mycelial growth, interfering with respiration and energy homeostasis of the pathogen, causing in addition a disorder of metabolism and the disruption of the cell membrane [46]. Besides its well-known properties, propolis is well tolerated by human skin; in fact, it can be employed to treat burns. Propolis is very helpful in wound healing thanks to its antimicrobial and anti-inflammatory properties. Moreover, propolis can enhance skin cell proliferation, activation, and growth [47]. Quantitative and qualitative studies, about collagen types I and III expressions and degradation in case of injury, showed how it promotes a favorable biochemical environment for wound repair [48]. Propolis is also able to quench free radicals in the skin [49]. This is very important for wound repair; in fact, oxygen is involved both in disinfection and in repair cascade signaling. Moreover, it can help to remodel the extracellular matrix through its flavonoid compounds which reduce lipid peroxidation and prevent necrosis [48]. Propolis is also an anti-inflammatory compound against acute and chronic inflammation, it can inhibit, in a concentration-dependent manner, cyclooxygenase activity [50]. Moreover, in vitro studies demonstrated how propolis can exert immune-modulatory and immune-stimulatory effects on macrophages. On the contrary, in vivo propolis increases mice CD4/CD8 ratio in T cell [51], as a result, it increases wound healing and reepithelialization in diabetic mice [51]. Propolis stimulates also the expression of TGF-β (transforming growth factor β) which is very important to control hemostasis and inflammation during the early phases of wound repair [52]. In order to explain the possible mechanisms of effects of propolis in keratinocytes, and more in general the keratinocyte involvement in wound repair boosted by propolis, Martinotti and colleagues [53] investigated its effect on the human keratinocyte cell line. Scratch assays demonstrated that propolis promotes a significant increase in wound repair capacity of keratinocytes, as well as propolis, boosts the keratinocyte migration phenotype.

27

Propolis: A Multifaceted Approach for Wound Healing

693

More interestingly, they showed that hydrogen peroxide (released in a low amount by propolis [54]) should be the main mediation of propolis regenerative potential. Some authors have already reported the production of hydrogen peroxide (H2O2) induced by propolis exposure [53, 54]. The formation of H2O2 can take place without the participation of cells but requires the presence of transition metal ions such as iron. Flavonoids of propolis can serve as temporary carriers of electrons received from transition metal ions that are relayed to oxygen molecules to subsequently generate superoxide and H2O2. It is to note that the H2O2 production is very low (around 0.5 ng/mL). At these concentrations, H2O2 can show a positive role as a major redox metabolite operative in redox sensing, signaling, and redox regulation. Meanwhile, propolis possesses also a well-known antioxidant activity, which has great implications for propolis exerting a wide range of pharmacological actions [53]. The hydrogen peroxide released in the extracellular milieu by propolis could enter the keratinocytes through a specific protein present in the plasma membrane (i.e., the aquaporin-3, AQP-3). This entry can induce modulation of intracellular responses leading to wound repair. Taken together, these in vitro data and other in vivo observations, as well as a lot of anecdotal reports on propolis efficacy for wound repair, suggest that propolis could be utilized as wound treatment in clinical settings. Moreover, the role of AQP-3 in wound healing supported by propolis makes this beehive product very interesting for skin disorder management by the aquaporin expression modulation.

4

Propolis Standardization

Propolis is a natural substance, produced by bees, the composition of which is different according to its botanical and geographical origins [55]. However, different types of propolis have the same chemical nature (essential oil, esters, flavonoids, mineral salts, phenolic acids, pollen, resin, and wax) [56]. For the use of a natural product in the field drug, food, and cosmetic industries, some aspects are required to be standardized: chemical and biological analysis, quality of extraction processes and procedures, and impurities removal (preserving plant secondary metabolites and in particular polyphenols) [57, 58]. The large use of propolis as an antibacterial agent is limited by the chemical composition and consequent variation in antimicrobial efficacy. Currently, extraction for propolis use is carried out with a solvent, like 70% ethanol. However, this method shows some limitations for the amounts of the bioactive compound [59, 60] and the effectiveness of the extracted molecules. An interesting propolis extraction method is multi-dynamic extraction (MED). It is a polar type propolis polyphenolic [61] mixture which allows a non-ethanolic extraction. MED allows to reach a standardized polyphenol content, with 5–20% phenolic acid, 50–80% flavonoids, and 40% w/w of six active compounds like galangin, chrysin, pinocembrin, apigenin, pinobanksin, and quercetin [62]. MED propolis is prepared by combining a mixture of propolis samples and following some steps. The first is the aqueous extraction from dewaxed propolis,

694

G. Bonsignore et al.

then a series of extractions on the residue through an ethanol/water mixture. Moreover, the procedure follows another high-ethanolic extraction from the residue. The next step is the combination of extract and concentration by distillation. The last aspects are the concentrated analysis of HPLC and an antimicrobial assay to assess the efficacy of propolis an antibacterial agent [63]. This approach allowed to obtain a more reproducible chemical composition as well as antibacterial property, independently from the starting raw propolis chemical composition [64].

5

Conclusions

A huge number of studies are demonstrating the biological properties of propolis such as antibacterial, anti-inflammatory, metabolic, and nutraceutical activities demonstrating its great potential for several applications. Bees produce propolis by collecting and reprocessing the bud’s resin from many different plants, depending on climate, season, and geographical flora. This variability in propolis “sourcing” determines a great quantitative and qualitative unpredictability in the active molecules (such as polyphenols), affecting the extract activities and the applicability of the final product. The problem of standardizing propolis, that is, maintaining the components completeness, could be solved by the use of new extraction methods (such as MED) to produce comparable activity data.

References 1. Greenaway W, Scasbroock T, Whatley F (1990) The composition and plant origins of propolis: a report of work at Oxford. Bee World 71 2. Santos LM, Fonseca MS, Sokolonski AR, Deegan KR, Araújo RP, Umsza-Guez MA et al (2020) Propolis: types, composition, biological activities, and veterinary product patent prospecting. J Sci Food Agric 100(4):1369–1382. https://doi.org/10.1002/jsfa.10024 3. As_s M (1989) “El oro p_rpura de las abejas” (CIDA: Centro deInformaci_n y documentaci_n agropecuaria, ed.) 1:66 4. Koo M, Park Y (1997) Investigation of flavonoid aglycones in popolis collected by two different varieties of bee in the same region. Biosci Biotech Biochem 61:367–369 5. Martinotti S, Ranzato E (2015) Propolis: a new frontier for wound healing? Burns Trauma 3:9. https://doi.org/10.1186/s41038-015-0010-z 6. Ghisalberti E (1970) Propolis: a review. Bee World 60:59–84 7. Makashvili Z (1978) From the history of propolis. In remarkable hive product: propolis. Scientific data and suggestions concerning its composition, properties and possible use in therapeutics. APIMONDIA standing commission on beekeeping technology and equipment. Bucharest 8. Hegazi A (2000) Propolis: an overview. Congreso Internacional de propoleos. Buenos Aires – Argentina 9. Toreti VC, Sato HH, Pastore GM, Park YK (2013) Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evid Based Complement Alternat Med 2013:697390. https://doi.org/10.1155/2013/697390 10. Fokt H, Pereira A, Ferreira A, Cunha A, Aguiar C (2010) How do bees prevent hive infections? The antimicrobial properties of propolis. Curr Res Technol Educ Top Appl Microbiol Microbial Biotechnol 1:481–493

27

Propolis: A Multifaceted Approach for Wound Healing

695

11. Meyer W (1956) Propolis bees and their activities. Bee World 37:25–36 12. Zhang C, Zheng H, Hu F (2011) Extraction, partial characterization, and storage stability of. J Food Sci 76:75–79 13. Ivanov T (1980) Composition and physico-chemical properties of propolis. Zhivotnovudni Nauki 17:96–103 14. Kaczmarek F, Debowski W (1983) β- Amylase in propolis. Acta Poloniae Pharmacentica 40:121 15. Bankova V, Popov S, Manolova N (1988) The chemical composition of some propolis fractions with antiviral action. Acta Microbiol Bulg 23:52 16. Bankova V, Povov S, Marekov N (1982) High performance liquid chromatographic analysis of flavonoids from propolis. J Chromatogr 242:135–143 17. Bankova V, Popov S, Marekov N (1983) A study on flavonoids of propolis. J Natural Products 46:471–474 18. Volpi N (2004) Separation of flavonoids and phenolic acids from propolis by capillary zone electrophoresis. Electrophoresis 25:1872–1878 19. Park YK, Alencar SM, Aguiar CL (2002) Botanical origin and chemical composition of Brazilian propolis. J Agric Food Chem 50(9):2502–2506. https://doi.org/10.1021/jf011432b 20. Ferreira J, Fernandes-Silva C, Salantino A, Negri G, Message D (2017) New propolis type from north-East Brazil: chemical composition, antioxidant activity and botanical origin. J Sci Food Agric 97:3552–3558 21. Teixeira EW, Negri G, Meira RM, Message D, Salatino A (2005) Plant origin of green propolis: bee behavior, plant anatomy and chemistry. Evid Based Complement Alternat Med 2(1):85–92. https://doi.org/10.1093/ecam/neh055 22. Gomes M, Ítavo C, Leal C, Ítavo L, Lunas R (2016) Atividade antibacteriana in vitro da propolis marrom. Pesqui Vet Bras 36:279–282 23. Machado B, Dantas-Silva R, Barreto G, Costa S, Silva D, Brandão H (2016) Chemical composition and biological activity of extracts obtained by supercritical extraction and ethanolic extraction of brown, green and red propolis derived from different geographic regions in Brazil. PLoS One 2016:11 24. Sawaya A, Cunha I, Marcucci M, Aidar D, Silva E, Carvalho C (2007) Electrospray ionization mass spectrometry fingerprinting of propolis of native Brazilian stingless bees. Apidologie 38: 93–103 25. Daugsch A, Moraes CS, Fort P, Park YK (2008) Brazilian red propolis – chemical composition and botanical origin. Evid Based Complement Alternat Med 5(4):435–441. https://doi.org/10. 1093/ecam/nem057 26. Campo-Fernández M, Cuesta-Rubio O, Rosado-Perez A, Porto R, Márquez-Hernánde I, Piccinelli A (2008) GC-MS determination of isoflavonoids in seven red Cuban propolis samples. J Agric Food 56:9927–9932 27. Piccinelli A, Lotti C, Campone L, Cuesta-Rubio O, Campo-Fernandez M, Rastrelli L (2011) Cuban and Brazilian red propolis: botanical origin and comparative analysis by highperformance liquid chromatography à photodiode array detection/electrospray ionization tandem mass spectrometry. J Agric Food Chem 59:6484–6491 28. Lotti C, Campo-Fernandez M, Piccinelli A, Cuesta-Rubio O, Márquez-Hernández I, Rastrelli L (2010) Chemical constituents of red Mexican propolis. J Agric Food Chem 58:2209–2213 29. Izuta H, Shimazawa M, Tsuruma K, Araki Y, Mishima S, Hara H (2009) Bee products prevent VEGF-induced angiogenesis in human umbilical vein endothelial cells. BMC Complement Altern Med 9:1–10 30. Trusheva B, Popova M, Naydenski H, Tsvetkova I, Rodriguez J, Bankova V (2004) New polyisoprenylated benzophenones from Venezuelan propolis. Fitoterapia 75:683–689 31. Cuesta-Rubio O, Piccinelli A, Fernandez M, Hernández I, Rosado A, Rastrelli L (2007) Chemical characterization of Cuban propolis by HPLC-PDA, HPLC-MS, and NMR: the brown, red, and yellow Cuban varieties of propolis. J Agric Food Chem 55:7502–7509 32. Sforcin JM, Bankova V (2011) Propolis: is there a potential for the development of new drugs? J Ethnopharmacol 133(2):253–260. https://doi.org/10.1016/j.jep.2010.10.032

696

G. Bonsignore et al.

33. Przybyłek I, Karpiński TM (2019) Antibacterial properties of propolis. Molecules 24(11). https://doi.org/10.3390/molecules24112047 34. Sforcin JM (2016) Biological properties and therapeutic applications of propolis. Phytother Res 30(6):894–905. https://doi.org/10.1002/ptr.5605 35. Kedzia B, Hołderna-Kedzia E (2013) The antibiotic activity of native and European propolis. Post Fitoter 2:97–107 36. Búfalo MC, Figueiredo AS, de Sousa JP, Candeias JM, Bastos JK, Sforcin JM (2009) Antipoliovirus activity of Baccharis dracunculifolia and propolis by cell viability determination and real-time PCR. J Appl Microbiol 107(5):1669–1680. https://doi.org/10.1111/j.1365-2672.2009. 04354.x 37. Gekker G, Hu S, Spivak M, Lokensgard JR, Peterson PK (2005) Anti-HIV-1 activity of propolis in CD4(+) lymphocyte and microglial cell cultures. J Ethnopharmacol 102(2):158–163. https:// doi.org/10.1016/j.jep.2005.05.045 38. Huleihel M, Isanu V (2002) Anti-herpes simplex virus effect of an aqueous extract of propolis. Isr Med Assoc J 4(11 Suppl):923–927 39. Vynograd N, Vynograd I, Sosnowski Z (2000) A comparative multi-centre study of the efficacy of propolis, acyclovir and placebo in the treatment of genital herpes (HSV). Phytomedicine 7:1–6 40. Dota KF, Consolaro ME, Svidzinski TI, Bruschi ML (2011) Antifungal activity of Brazilian propolis microparticles against yeasts isolated from vulvovaginal candidiasis. Evid Based Complement Alternat Med:201953. https://doi.org/10.1093/ecam/neq029 41. Netíková L, Bogusch P, Heneberg P (2013) Czech ethanol-free propolis extract displays inhibitory activity against a broad spectrum of bacterial and fungal pathogens. J Food Sci 78(9):M1421–M1429. https://doi.org/10.1111/1750-3841.12230 42. Ghaly MF, Ezzat SM, Sarhan MM (1998) Use of propolis and ultragriseofulvin to inhibit aflatoxigenic fungi. Folia Microbiol (Praha) 43(2):156–160. https://doi.org/10.1007/ BF02816502 43. Bankova V, Boudourova-Krasteva G, Sforcin JM, Frete X, Kujumgiev A, Maimoni-Rodella R et al (1999) Phytochemical evidence for the plant origin of Brazilian propolis from São Paulo state. Z Naturforsch C J Biosci 54(5–6):401–405. https://doi.org/10.1515/znc-1999-5-616 44. Kujumgiev A, Tsvetkova I, Serkedjieva Y, Bankova V, Christov R, Popov S (1999) Antibacterial, antifungal and antiviral activity of propolis of different geographic origin. J Ethnopharmacol 64(3):235–240. https://doi.org/10.1016/s0378-8741(98)00131-7 45. Boisard S, Le Ray AM, Landreau A, Kempf M, Cassisa V, Flurin C et al (2015) Antifungal and antibacterial metabolites from a French poplar type propolis. Evid Based Complement Alternat Med:319240. https://doi.org/10.1155/2015/319240 46. Peng L, Yang S, Cheng Y, Chen F, Pan S, Fan G (2012) Antifungal activity and action mode of pinocembrin from propolis against Penicillium italicum. Food Sci Biotechnol 21:1533–1539 47. Sehn E, Hernandes L, Franco SL, Gonçalves CC, Baesso ML Dynamics of reepithelialisation and penetration rate of a bee propolis formulation during cutaneous wounds healing. Anal Chim Acta 635(1):115–120. https://doi.org/10.1016/j.aca.2009.01.019 48. Olczyk P, Komosinska-Vassev K, Winsz-Szczotka K, Stojko J, Klimek K, Kozma EM (2013) Propolis induces chondroitin/dermatan sulphate and hyaluronic acid accumulation in the skin of burned wound. Evid Based Complement Alternat Med:290675. https://doi.org/10.1155/2013/ 290675 49. Olczyk P, Wisowski G, Komosinska-Vassev K, Stojko J, Klimek K, Olczyk M et al (2013) Propolis modifies collagen types I and III accumulation in the matrix of burnt tissue. Evid Based Complement Alternat Med:423809. https://doi.org/10.1155/2013/423809 50. Rossi A, Longo R, Russo A, Borrelli F, Sautebin L (2002) The role of the phenethyl ester of caffeic acid (CAPE) in the inhibition of rat lung cyclooxygenase activity by propolis. Fitoterapia 73(Suppl 1):S30–S37. https://doi.org/10.1016/s0367-326x(02)00188-0 51. Toreti VC, Sato HH, Pastore GM, Park YK (2013) Recent progress of propolis for its biological and chemical compositions and its botanical origin. Evid Based Complement Alternat Med:697390. https://doi.org/10.1155/2013/697390

27

Propolis: A Multifaceted Approach for Wound Healing

697

52. de Moura SA, Negri G, Salatino A, Lima LD, Dourado LP, Mendes JB et al (2011) Aqueous extract of Brazilian green propolis: primary components, evaluation of inflammation and wound healing by using subcutaneous implanted sponges. Evid Based Complement Alternat Med:748283. https://doi.org/10.1093/ecam/nep112 53. Martinotti S, Pellavio G, Laforenza U, Ranzato E (2019) Propolis induces AQP3 expression: a possible way of action in wound healing. Molecule 24(8):1544. https://doi.org/10.3390/ molecules24081544 54. Stojko A, Scheller S, Szwarnowiecka I, Tustanowski J, Ostach H, Obuszko Z (1978) Biological properties and clinical application of propolis. VIII. Experimental observation on the influence of ethanol extract of propolis (EEP) on the regeneration of bone tissue. Arzneimittelforschung 28(1):35–37 55. Bankova V, Bertelli D, Borba R, Conti BJ, da Silva Cunha IB, Danert C et al (2016) Standard methods for Apis mellifera propolis research. J Apic Res 58:1–49 56. Zabaiou N, Fouache A, Trousson A, Baron S, Zellagui A, Lahouel M et al (2017) Biological properties of propolis extracts: something new from an ancient product. Chem Phys Lipids 207 (Pt B):214–222. https://doi.org/10.1016/j.chemphyslip.2017.04.005 57. Gómez-Caravaca AM, Gómez-Romero M, Arráez-Román D, Segura-Carretero A, FernándezGutiérrez A (2006) Advances in the analysis of phenolic compounds in products derived from bees. J Pharm Biomed Anal 41:1220–1234 58. Bankova V, Popova M, Trusheva B (2014) Propolis volatile compounds: chemical diversity and biological activity: a review. Chem Cent J 8:28 59. Woisky RG, Salatino A (1998) Analysis of propolis: some parameters and procedures for chemical quality control. J Apic Res 37:99–105 60. Pietta PG, Gardana C, Pietta AM (2002) Analytical methods for quality control of propolis. Fitoterapia 73:7–20 61. Galeotti F, Maccari F, Fachini A, Volpi N (2018) Chemical composition and antioxidant activity of propolis prepared in different forms and in different solvents useful for finished products. Foods 7:41 62. Volpi N, Fachini A (2017) Procedimento per l’ottenimento di estratti integrali di propoli ricchi in polifenoli e dot, dati di attività antibatterica e sua applicazione nella prevenzione e trattamento di processi infettivi di origine batterica. UfficioItaliano Brevetti e Marchi, No. 0001425516 (02/02/2017) 63. Zaccaria V, Garzarella EU, Di Giovanni C, Galeotti F, Gisone L, Campoccia D et al (2019) Multi dynamic extraction: an innovative method to obtain a standardized chemically and biologically reproducible polyphenol extract from poplar-type propolis to be used for its antiinfective properties. Materials (Basel) 12(22):3746. https://doi.org/10.3390/ma12223746 64. Curti V, Zaccaria V, Tsetegho Sokeng AJ, Dacrema M, Masiello I, Mascaro A et al (2019) Bioavailability and in vivo antioxidant activity of a standardized polyphenol mixture extracted from brown propolis. Int J Mol Sci 20(5):1250. https://doi.org/10.3390/ijms20051250

Part IV Plant Latexes

Chemistry, Biological Activity, and Uses of Clusia Latex

28

Claudio Augusto Gomes da Camara, Anita Jocelyne Marsaioli, Volker Bittrich, and Marcilio Martins de Moraes

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Characterization of Clusia Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Ethnobotany and Traditional Uses of Clusia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Other Uses of the Species of Clusia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Use of Clusia Latex in Folk Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Pharmacological Properties of Clusia Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Antitumoral Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Anti-Inflammatory and Antinociceptive Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Antiviral Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Anti-obesity and Antidiabetic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6 Antimicrobial and Antiparasitic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.7 Antivenom and Antihemorrhagic Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.8 Antihypertensive Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Chemical Constituents and Biological Properties of Clusia Latex . . . . . . . . . . . . . . . . . . . . . . . . 6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

702 704 707 719 721 724 725 729 732 734 735 739 744 745 748 755 755

Abstract

Plants of the genus Clusia L. have had considerable importance to numerous traditional communities, providing food, remedies, and raw materials for crafts. These plants occur in southern Mexico, the Caribbean, the Amazon Forest, the Andes, and even reach southern Brazil. The genus is characterized by the C. A. G. da Camara (*) · M. M. de Moraes Departamento de Química, Universidade Federal Rural de Pernambuco, Recife, PE, Brazil e-mail: [email protected] A. J. Marsaioli Instituto de Química, Universidade Estadual de Campinas, Campinas, SP, Brazil V. Bittrich Campinas, Brazil © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_32

701

702

C. A. G. da Camara et al.

production of latex in nearly all tissues of the plant. Interrelations between traditional neotropical people of the Americas and these plants have been quite diversified in terms of the number of species and the use of the products obtained from different parts of the plant for the treatment of diseases and even with magic connotations. Medicinal knowledge of these species based on their uses and forms of preparation has demonstrated the relevance of these plants and their importance to traditional communities. This chapter presents evidence of the importance of species of Clusia related to the different types of use, particularly medicinal purposes for primary health care among different traditional people. Ethnobotanical and ethnopharmacological aspects of these species are also addressed, with an emphasis on bioactive compounds, chemical composition, and biological activity. Keywords

Biological activity · Chemical composition · Clusia spp. · Clusiaceae · Ethnobotany · Ethnopharmacology · Latex · Traditional use Abbreviations

DCM EtOAc EtOH MeOH PPBs PS

1

Dichloromethane Ethyl acetate Ethanol Methanol Polyprenylated benzophenones Polysaccharide

Introduction

Besides competing with each other for nutrients from the soil, vegetal species have developed innumerous defense mechanisms against microbes, herbivores, and other animals throughout their evolutionary processes, which have resulted in enormous biodiversity of plants and insects. As a response to environmental pressure, morphological and biochemical adaptations have emerged in plants in the form of organelles, channels, or ducts for the storage and release of a large variety of toxic substances produced through different biosynthetic pathways [1]. Indeed, many plants can store a wide range of liquids and fluids, such as latex, resins, mucilage, and gums, in specialized cells, channels, and/or intercellular cavities. The terminology for the milky exudate rich in resins typically found in most Guttiferae, including species of Clusia, as well as some other families remains inconsistent. To a lesser extent, this also applies to the structures of the plant that contain the exudate. As this inconsistent use has caused some confusion in the literature, a short discussion is merited. The term latex has transformed its meaning/use in the botanical, chemical, and pharmaceutical literature. The Latin word means “fluid, liquid, sap, or juice” [2], but it

28

Chemistry, Biological Activity, and Uses of Clusia Latex

703

was mainly used with regards to an often milky fluid – an emulsion in which various small particles (mostly organic compounds) are suspended or dispersed [3–5]. Latexproducing plants of the clusioid clade [6] normally have schizogenous channels lined with an epithelium, the cells of which produce the latex compounds. Part of the Podostemaceae, however, is reported to have isolated (sometimes multinuclear) cells or tubes with latex content [7]. The position of this family, which was largely neglected in review articles on laticifers and latex [3, 8–10], in the clusioid clade is currently uncertain (see https://treeoflife.kew.org/tree-of-life). Like all members of the family Clusiaceae, species of Clusia have latex in nearly all tissues. The quantity and color vary among different species as well as among different organs within the same plant. The latex, which is mainly extracted from the fruit, adventitious roots, leaves, trunk, and stem bark of species of Clusia, has been prepared in various forms for different types of treatments in traditional communities distributed throughout the Neotropical region, where these plants are abundant. The role of laticifers or secretory canals and latex in plants is not yet fully clear, but it is generally assumed that these structures store nutrients or that the latex has the function of distributing nutrients to different parts of the plant [11, 12]. Other functions described for latex production units include the regulation of water storage and oxygen transport as well as the protection of the plant against natural enemies, more precisely, microorganisms and herbivores [13, 14]. Kniep [15] was one of the first researchers to discuss possible ecological adaptations for explaining the evolution of latex in plants, such as wound closure and defense against herbivores. Kniep offered experimental support for the latter theory by draining the latex from the plants of various families. Caterpillars and other insects use a similar strategy to diminish the latex content in parts of the leaves by cutting the veins [16, 11]. Latex serves as a defense against herbivorous insects by its chemical content and by flooding the insect or its mouth parts with the sticky fluid. Konno [17] discussed in detail the rich chemical defense of the latex of various angiosperm families but omitted latex from schizogenous channels. Besides being more numerous, plant species that occur in the tropics are greater latex producers than those found in temperate regions. Indeed, approximately 14% of tropical plant species are latex producers in comparison to 6% of temperate-climate species [9]. Comparisons between closely related plant groups led to the hypothesis that latex is directly related to plant survival and the richness of clades [18–20]. Species of Clusia are very rarely attacked by herbivores, which indicate that latex is an effective defense mechanism. If caterpillars attack these plants, as only observed once (on C. schomburgkiana leaves, Fig. 1), they are likely to be specialists. The leaves of cultivated artificial hybrids, however, have been observed being attacked by caterpillars on more than one occasion, and even once by leaf-cutter ants (pers. obs.). The latex of these hybrids may be less effective as a defense against herbivores than that of natural species. The same had also been observed regarding protection from attacks by microorganisms. Researchers have investigated the role of latex in susceptibility between artificial hybrid and parental species of Clusia [21]. To the best of our knowledge, there has never been any occurrence of insects cutting into

704

C. A. G. da Camara et al.

Fig. 1 (a) Gregarious caterpillars of the moth family Limacocidae feeding on Clusia schomburgkiana leaf. (b) Leaf-cutting ant (Atta sexdens) foraging on Clusia lanceolata x Clusia flava. (c) Underside of leaves of C. renggeriodes attacked by Trigona bees

leaves to interrupt latex flow to the distal parts in species of Clusia. Perhaps the carnose coriaceous leaves offer a hindrance to this strategy. This chapter presents evidence of the importance of species of Clusia related to the different types of use, particularly medicinal purposes for primary health care among different traditional people. Ethnobotanical and ethnopharmacological aspects of these species are also addressed, with an emphasis on bioactive compounds, chemical composition, and biological activity.

2

Characterization of Clusia Latex

In the nineteenth century, it was discovered that some latex-producing or -containing structures in plants are either surrounded by their cell wall [8, 22] or are schizogenous or lysigenous lacunas, or ducts surrounded by the walls of the sheath

28

Chemistry, Biological Activity, and Uses of Clusia Latex

705

of other (epithelial) cells that secrete latex compounds into the intercellular space [23–25]. For unclear reasons [8], latex-containing cells were later generally called laticifers [26–28]. The same term, however, was also used, albeit rarely, for the intercellular schizogenous ducts [29]. A general problem with terminologies regards whether they can or even should change, which can cause some confusion; all the more so if authors treat their preferred definition simply as a fact. Thus, the term latex can be defined based on consistency, chemical composition, anatomy, and ecological function, or some combination of these aspects. More recently, the term has often been used as exclusively a product of cellular laticifers. However, as Hagel et al. [10] states, “. . . some latex-bearing plants defy the traditional classification of laticifers,” for example, some cacti (Mammillaria) “have epithelia-lined, schizolysigenous latex ducts.” Konno [17], however, simply asserts that “by definition,” latex is an exudate in elongated laticifers cells, which is historically hardly correct. Similarly, Prado and Demarco [30] and Alencar et al. [31] – using a definition based on anatomy and some histochemical data – conclude that the milky fluid in the ducts of Clusiaceae and Calophyllaceae is a “resin.” This would considerably expand the usual definition of “resin” to include milky emulsions, which promises further confusion. There is no doubt that the exudate from Clusiaceae contains considerable quantities of resins, as has been well known since the nineteenth century [32, 33]. The term latex also continues to be used in the more general sense, however, as an aqueous emulsion containing various compounds, regardless of its anatomical origin. Another characteristic of latex is that it coagulates outside the plant. A purely technical chemical definition for latex in a very strict sense is mentioned by Stevens [34] (2001 onwards): “polymers made up of isoprene units in the cis-configuration,” that is, a definition that excludes exudates with guttapercha rather than natural rubber as a component. Schizogenous channels or ducts and cellular laticifers evolved several times independently in angiosperms [18]. The guayule, Parthenium argentatum A. Gray, even has both schizogenous resin channels and rubber-containing laticifer cells [35]. The confusion caused by different definitions and different uses of the terms “laticifer” and “latex” led to dubious interpretations when the distribution of latex in higher plants or its ecological importance or use by humans was discussed. Thus, Metcalfe [3] and Hagel et al. [10] included Alismataceae, but excluded Clusiaceae (under Theales) from their review articles, although the latex of both families occurs in schizogenous ducts [29, 36–37]. Upadhyai [38] used the definition of latex as produced by cellular laticifers but included members of Clusiaceae in his overview. Very recently [39], the Alismataceae were cited as having articulated laticifers based on a study by Govindarajalu [40] on Sagittaria guayanensis Kunth, who indeed used this term following Stant [29], but clearly described its “laticifers” as schizogenous canals surrounded by typical epithelial cells. If the ecological role of latex as a defense mechanism against herbivores or microorganisms and its impact on plant diversification is considered [18], it makes much more sense to include latex occurring in schizogenous channels [19, 20], with Clusiaceae considered producers of latex rather than excluding this family, as done by Agrawal and Konno [11]. It should perhaps be remembered that, although there are different types of nectaries

706

C. A. G. da Camara et al.

[41], the sugary exudate (also containing various other substances) is sensibly always called nectar. In any case, it seems important for authors to state explicitly in which sense they use a term like “latex” to avoid further confusion. Here, we use the term in the classical sense as an aqueous emulsion or suspension of various small particles irrespective of their origin or position in the plant. This aqueous suspension is generally composed of numerous compounds belonging to a variety of classes, including inorganic constituents and primary compounds. Among the secondary compounds in these suspensions, terpenoids, fatty acids, aromatic compounds, and alkaloids are commonly found [13, 17]. Anonymous/Reichenbach [24] was the first anatomist to emphasize that latexcontaining structures in Clusia and Alismataceae are single or branched intercellular channels without their cell wall, correcting earlier publications [42]. The author also observed that these channels are surrounded by a simple series of thin-walled cells (later mainly called the epithel). Unger [36] supported this interpretation in a detailed study of Alisma plantago. Hanstein [43], although agreeing that Clusia and Alisma have canals, considered them incorrectly as developed by the dissolution of cells (lysigenous) rather than intercellular canals created through a schizogenous process. Trécul [33] worked with fresh material from several Clusiaceae, including species of Clusia, observing the following: “Comme tous les latex troubles, cesuc propre estcomposé de deux parties: d’un liquidelimpide et de globules en suspension.” [Like all cloudy latexes, this clean juice is made up of two parts: a clear liquid and globules in suspension.] The diameter of these globules varied within the same plant, but also between different species. The globules could fuse and even form “columns.” Trécul [33] also identified globules in the latex as composed of what he called an oleoresin and observed the occurrence of complete solidification. The distribution of the channels in different parts of Clusiaceae plants was studied in detail by van Tieghem [44, 45] (as “canauxsécréteurs” and “organesoléorésineux”) and Müller [46]. Alencar et al. [31] studied the anatomy of latex channels (termed “resin ducts” by the authors) in a number of Clusia species without floral resin (with the only exception of C. diamantina Bittrich). The authors found considerable variation in the presence and distribution of channels in the stamens. This variation, in part, seems to reflect phylogenetic groups within Clusia, the ecological significance of which is enigmatic for the time being. This study also showed the considerable similarity between the structure of latex channels and resin channels in the stamens and staminodes of C. diamantina, the flowers of which offer floral resin to pollinating bees. Stingless bees of the tribe Trigonini are important pollinators of various species of Clusia [47] when collecting floral resin (Fig. 2), which is used for the construction and protection of nests [48–50]. These bees also collect coagulated latex from the wounds of plants (Fig. 3), likely attracted by volatile compounds. At times, bees intentionally inflict wounds on leaves (Fig. 1c) and likely use the latex for the same purpose as the floral resin. While the removal of resin from flowers reflects mutualism, bees behave more like parasites when it comes to latex.

28

Chemistry, Biological Activity, and Uses of Clusia Latex

707

Fig. 2 (a) Euglossa bee with resin visiting C. grandiflora male flower; (b) Ptilotrigona bee collecting resin from staminodes of C. lepranthafemale flower; (c) Trigona bee collecting latex from the broken leaf of C. gardneri; (d) Trigona collecting latex from a branch-slashed of C. mexiae

3

Ethnobotany and Traditional Uses of Clusia

Since the beginning of humanity, humans have drawn upon nature to meet their needs. With the discovery of impressive amounts of pollen in a Neanderthal tomb in Iraq (Shanidar IV) dating back more than 50,000 years ago, Leroi-Gourhan [51] suggested that the selection of plants to be used at the funeral and placed in the tomb was not only due to the beauty of the flowers but also for their antiseptic, antipyretic, and anti-inflammatory properties [52], which were likely used in the hope of increasing the chances of survival among Neanderthals. Beyond any doubt, plants have been of considerable importance to humans for providing food, remedies, and raw materials for the fabrication of utensils ranging from crafts to items for the construction of buildings. Among the immense vegetal biodiversity, species of the genus Clusia L. are recognized for their social, ecological, and pharmacological importance. These plants play fundamental roles in the lives of many traditional people (indigenous communities, Afro-Brazilian settlements, rural and riverine communities) in many countries of Latin America. Even with Western medicine available and (apparently) within everyone’s reach, the use of folk medicine is often the cheapest and most accessible means for cures among these people. Moreover, plants of this genus provide raw materials for building and repairing the roofs of homes, firewood for cooking food, and the making of utensils, such as baskets.

708

C. A. G. da Camara et al.

Fig. 3 Ornamental Clusia species (a) Female flower of C. lanceolata; (b) Female flower of C. fluminensis; (c) Male flower of C. spiritu-sanctensis; (d) Male flower of C. hoffmannseggiana; (e) Female flower of C. criuva; (f) Male flower of C. hilariana; (g) Female flower of C. mexiae; (h) Male flower of C. insignis

The genus Clusia is one of the largest in the family and is composed of 300 to 400 semi-epiphytic, climbing/creeping, shrub, and arboreal species [53]. Sixty-eight species are found in Brazil, 23 of which are endemic to the country [54]. With

28

Chemistry, Biological Activity, and Uses of Clusia Latex

709

predominant occurrence in the neotropical region, these plants span from southern Mexico and the Caribbean to the Guiana Shield, Amazon Forest, and the Andes, even reaching southern Brazil. The Amazon has the largest record of species of Clusia, but there are also occurrences in dry forests and rocky savannas in Peru and Brazil [55]. Interrelations between traditional neotropical people, especially those of the Americas, and species of the genus have been quite diversified in terms of the number of species and the use of the products obtained from different parts of the plants for the treatment of diseases and even with magic connotations. Species of Clusia have also been used in religious rituals of the Maroons (African slaves who escaped European dominance and formed independent settlements known as quilombos). The aerial roots of Clusia grandiflora are used in Winti (Afro-Surinamese religion) rituals [56]. C. insignis and C. grandiflora are used in religious ceremonies as complementary herbs for Hoasca tea. According to followers of the religious sect União do Vegetal, the addition of these plants to the traditional tea is due to their medicinal properties [57]. Early in the nineteenth century, Tussac [32] and Descourtilz [58] reported various uses of the latex from Clusia rosea Jacq. in the Antilles: It is used like tar to caulk canoes and fishermen coat their nets with it. Furthermore, the gummi juice was used for book-binders and also as an excellent rubber. Different from some Asian species of the rather closely related genus Garcinia, the dried latex of Clusia spp. was very rarely used as gummigutta or gamboge (e.g., for Clusia rosea) [59, 60]. Gamboge from Garcinia spp. is a source of yellow pigment-containing xanthones [61], formerly used for dying the robes of monks as well as in paintings, illumination, and gold varnish. Table 1 lists species of Clusia used in folk medicine by traditional neotropical communities for the treatment of different types of diseases and symptoms. There are records of the use of every part of the plant (leaves, stem, stem bark, aerial roots, underground roots, flowers, and fruit.), including latex, in the preparation of remedies. However, the part of the plant selected for the obtainment of the latex is not always informed in the literature, and the species cited, especially in older studies, are often incorrect due to the lack of reliable taxonomic treatments at the time. Today, the identification of the correct names for these plants is rarely possible, as only a few explorers, such as the great Harvard ethnobotanist R. E. Schultes, collected voucher specimens. Many of the plants presented in Table 1 have been used in phytotherapy since ancient times by natives of various ethnicities as well as neo-urban societies for the treatment of diseases caused by different etiological agents of an endogenous (hormonal, metabolic, immunological, neurogenic factors, etc.) or exogenous (trauma, pathogenic microorganisms, etc.) origin. Many remedies described by traditional people are prepared from different parts of the plant. As latex is found in practically all tissues of the plant, it is plausible that the phytotherapeutic properties of these medications are also attributable to this substance. The forms of preparing plant matrices as medication are maceration, decoction, and infusion. There are also records of the preparation of blends with different parts of the same plant, mixed with another plant species or with the addition of processed

710

C. A. G. da Camara et al.

Table 1 Species of Clusia, traditional people, parts of plant/latex, and type of use in traditional medicine Species C. alata Planch. &Triana

Vernacular name Chagualo

C. alba Jacq. (C. nemorosa)

Cebola-brava

C. amazonica Planch. & Triana

Copei

Ree-ka-ne-to-ma; Pap-ka; Ka-hee-wa’-ka Renaquilla; Eñsesrec”h (Peru)

C. burle-marxii Bittrich

Leite-de-mocó, Pau-de-mocó

C. chiribiquetensis Maguire

Ta-te-pe-ka-me

C. coclensis Standl.

Azahar de monte, Copey o Copeicillo

C. columnaris Engl.

Dee-ka’-da; Be-bam, Ree-ka-re-to-mee-seema-ma; (Col) Chagualo (Bra)

Traditional people/Use/Part of plant/application Colombia/Migraine (intense headache)/Latex/Decoction, drink Indigenous and rural communities of Amazonas (Brazil)/Healing agent, laxative/Latex (entire plant)/ Poultice with cocoa butter Venezuela (Piaroa people)/ Hansen’s disease/Roots and stem bark/Decoction, baths Colombia (Makuna, Puinave, and Yukuna people of upper Rio Negro)/Diuretic/Fruit/ Decoction, drink Peru (Chayahuita people)/ Antidiarrhea/Leaves/ Decoction, drink Peru, Indigenous and neo-urban communities/ Health tonic, postpartum; Healing/Stem bark and roots/ Alcoholic maceration, drink, topical application Peru (Yanesha people)/Health tonic/Leaves/Decoction, drink, and ingestion of leaves. Chapada Diamantina, Bahia (Brazil)/latex/Healing agent, antiseptic, wounds/Latex and leaves/Maceration, topical application Indigenous Karijonas people of upper Rio Negro (Colombia)/Healing agent, wounds caused by fungi/ Latex from leaves/poultice Indigenous, peasants of Altos de Campana region (Panama)/Arterial hypertension/Leaves/ Infusion, drink Colombia, Upper Rio Negro (Barasana, Kubeos, and Makús people), and indigenous groups of Brazil/ toothache (gums and tooth)/ Latex/Topical application

References [62]

[63]

[64]

[65]

[66]

[67]

[68]

[69]

[65]

[70]

[65, 71]

(continued)

28

Chemistry, Biological Activity, and Uses of Clusia Latex

711

Table 1 (continued) Species C. criuva Cambess.

Vernacular name –

C. cuneata Benth.

Mang-yik

C. ellipticifolia Cuatrec. C. aff. flavida (Benth.) Pipoly

–

C. flava Jacq.

–

C. flavida (Benth.) Pipoly

Copeicillo

C. fluminensis Planch. & Triana

Abaneiro, Mangue bravo

C. fockeana Miq.

Mang-yik (Guy)

C. grandiflora Splitg.

Renaco, Shashkina

Cebola-brava (Bra)

Patakwik (FGui, Palikur); Nuu-yik (Guy Patamona)

Traditional people/Use/Part of plant/application Brazil (Rio de Janeiro)/ laxative/Latex, drink Guyane (Patamona people)/ Anti-dysentery, antidiarrhea/ Roots/Decoction, drink Indigenous Patamona of Guyane/Healing agent, Wounds/Latex/Topical application Colombia/Hansen’s disease, headaches, and healing agent Peru (Quechuan)/ Rheumatism/Stems/ Decoction. Mexico, Yucatan region/ Carminative, Headache, healing agent (wounds, cuts) and syphilis/Leaves/Infusion, drink; topical application Venezuela/Leaves/Healing agent, wounds (cracked feet)/ Leaves/Poultice Brazil, the southeastern region, coastal region/ Healing agent, antiseptic/ Latex/Poultice (mixed with cassava flour) Guyane (Patamona people)/ Antidiarrhea/Stem bark/ Decoction, drink. Antivenom, healing agent (wounds, external ulcers)/powder from young twigs/Poultice Indigenous Patamona of Guyane/Antivenom, healing agent (wounds, external ulcers)/Latex from stems/ topical application Brazil (Marudá people of Pará)/Cough medication/ flowers or fruit/syrup, drink Guyane/Health tonic/Entire plant, blends with other species (Smilax, Strychnos, Doliocarpus, Philodendron, and Bauhinia scala-simiae)/ Decoction/Drink. Back pain/ Roots/Decoction, baths French Guiana (Palikur

References [72] [73]

[73]

[62] [74]

[75]

[71]

[72, 63]

[73]

[73]

[76]

[73]

(continued)

712

C. A. G. da Camara et al.

Table 1 (continued) Species

Vernacular name

Kupa-rope (Guy)

Patakwik; (FGui, Palikur); Nuu-yik (Guy Patamona)

Kypy (WaimiriAtroari, Bra);

C. hilariana Schltdl. C. hammeliana Pipoly

Huesca (Peru); Chuagulo (Ecu)

C. aff. hoffmannseggiana Schltdl.

Came.

C. hoffmannseggiana Schltdl. (C. palmicida Rich. ex Planch. & Triana)

Mata-pau; Cebolagrande-da-mata

Traditional people/Use/Part of plant/application people)/Back pain/Aerial roots/Infusion in water or wine, drink Guyane (Patamona people)/ Healing agent, wounds, cuts/ Wood/Decoction, drink; topical application, Communities on the coast of Guyane/Aphrodisiac/Blend with Lygodiumsp/Decoction, drink Guyane (Kurupukari and Patamona people)/Healing agent, myiasis, wounds, in general,/Latex from stem bark/Maceration, topical application French Guiana (Palikur people)/Aches in body/Latex of aerial roots/Poultice. Suriname (Tiriyo people)/ Aching bones/Latex from vine/baths Brazil (Waimiri-Atroari, in states of Roraima and Amazonas)/Healing agent, wounds/Latex/Poultice Brazil (Rio de Janeiro)/strong laxative/Latex/Drink Peru (Yanesha people)/Health tonic/Leaves/Maceration, drink. Ecuador (Shuar people)/ Healing agent, antirheumatic, antidysentery, antidiarrhea/ Leaves/Infusion/Topical application, drink Peru (Quechuan people)/ Rheumatism/Stems and Tovomitabrasiliensis/ Maceration Guyane/Aphrodisiac/Cortex of root, sugar, and other plants/Drink. Antimalarial/ Roots and leaves of Stiinaphyllonsinatum/ Decoction, drink

References

[77]

[73]

[78]

[72] [79] [80]

[74]

[56]

(continued)

28

Chemistry, Biological Activity, and Uses of Clusia Latex

713

Table 1 (continued) Species

Vernacular name Cebola-brava

Ka-ro-yik

Ka-ro-yik

C. huberi Pipoly

Tari-yek

C. insignis Mart.

Cebola-grande-damata (Bra); Parcouri, Kufa (Col);

C. cf. lechleri Rusby

Incienso

C. aff. lineata (Benth.) Planch. & Triana

Came, Renaco

C. lopezii Maguire

Copis

Traditional people/Use/Part of plant/application Indigenous and rural communities of Amazonas (Brazil)/Healing agent/ Poultice, cocoa butter. laxative/Latex from every part of plant/Decoction, drink Guyane (Patamona people)/ Aphrodisiac, back pain/Aerial roota/Decoction/Drink. Antidysentery/Stem bark/ decoction, drink Indigenous of Guyane (Patamona)/Healing agent, myiasis (wounds caused by larvae of botfly, Dermatobia hominis)/Latex/Topical application Venezuela (Pemon people of Amazon)/Vermifuge/Dried leaves and stem bark/ Decoction/Drink Neo-urban, Amazonas, Manaus-Brazil/Emetic and Diuretic/Fruits/Drinks Indigenous people, Brazil (northern region)/healing agent, nipple fissures/latex and resina floral/ointment mixed with milk and fat from tapir Traditional use in Bolivia/ Susto of babies or to bring good luck/Dried Latex/ Inhalation of aromatic smoke (sahumar) Peru (Quechuan)/Health tonic; rheumatism and bone fracture/Bark and stem/ Decoction. Vaginal pain/ Stems/Maceration/Drink, topical application Indigenous people of Comisaria del Vaupés in upper Rio Negro (Colombia)/ toothache (dental caries)/ Latex/Topical application

References [63]

[73]

[73]

[71]

[78]

[72]

[81]

[74]

[65]

(continued)

714

C. A. G. da Camara et al.

Table 1 (continued) Species C. aff. loretensis Engl.

Vernacular name Came, Renaco

C. martini Sagotex Engl.

–

C. microstemon Planch. & Triana (C. gaudichaudii Choisy ex Planch. & Triana)

Apuí

–

–

Apuí

C. minor L. (C. parviflora Willd.)

–

Copei, Matapalo (Ven); Quiripiti (Ven)

Mulajaldi (Col)

Mangue-do-mato

C. nemorosa G. Mey.

Mang-yik (Guy Patamona); Patakwik (FGui Palikur)

Traditional people/Use/Part of plant/application Peru (Quechuan)/Health tonic, bone fracture/ Decoction/Bark and stem/ Drink/Topical application Indigenous of Guyane/ Healing agent, wounds, myiasis/Latex of stem bark/ Topical application Brazil, Amazon/(indigenous region of Yutaje, municipality of Manapiare)/analgesic Colombia (Makunas people) and Brazil, Amazon region/ Sprains/Crushed leaves/ Poultice Indigenous Witoto people of upper Rio Negro (Colombia)/ toothache (gums and tooth)/ Latex/Topical application Brazil (Indigenous of upper Rio Negro, Amazonas)/ toothache (gums and tooth)/ Crushed leaves/Topical application Peru, coastal cities of Trujillo and Chiclayo/Arterial hypertension/Decoction/ Fruit/Drink The traditional rural community of Valle de la Cruz (Venezuela)/Verruga/ Latex/Topical application Indigenous Kaggabba people (Colombia)/treatment of vitiligo Indigenous of Guyane/ Healing agent, wounds, myiasis/Latex of stem bark/ Topical application Guyane (Patamona people)/ Healing agent, wounds, cuts/ Stem bark/Maceration with water/Topical application Indigenous of French Guiana (Palikur)/Body aches/Latex of aerial roots/Poultice. Guyana (Patamona people)/

References [74]

[63]

[82]

[65, 71]

[65]

[65]

[83]

[84]

[85]

[63]

[73]

[73]

(continued)

28

Chemistry, Biological Activity, and Uses of Clusia Latex

715

Table 1 (continued) Species

Vernacular name

C. aff. nemorosa G. Mey.

Poripori

C. nigrolineata P. F. Stevens

Apuí-de-SantoAntonio

C. obdeltifolia Bittrich

Leite-de-mocó, Pau-de-mocó, Pé-de-mocó

C. obovata (Planch. & Triana) Pipoly

Modé (Guy); Apui (Bra)

C. octandra (Poepp.) Pipoly

Menitame (Ecu)

C. octopetala Cuatrec.

Capé

C. opaca Maguire

Baniha, Copei, Cupi, Upihi (Ven); Pai-nañ-ge (Bra)

C. palmana Standl. C. pallida Engl.

Azahar de monte, Copey, Copeicillo Mata palo

C. panapanari (Aublet) Choisy

Mang-yik (Guy Patamona)

Traditional people/Use/Part of plant/application Healing agent (cracked heels, persistent sores, and ‘bush yaws’), dermal leishmaniasis/ Latex from stems/poultice Indigenous Yanomami people, Amazonas (Brazil) - Healing agent, wounds/Latex from fruit or aerial roots/Poultice Brazil(river communities of Manacapuru, Amazonas)/ Chest pa/in/Leaves/Topical application The northern portion of the state of Minas Gerais to the central region of the state of Bahia (Brazil)/latex/Healing agent, antiseptic, wounds/ Latex and leaves/Maceration/ Topical application Venezuela (ethnic groups of Amazon)/Vermifuge/Dried leaves and bark Venezuela (ethnic groups of Amazon)/Contraceptive/ Flowers/Decoction, drink Colombia (La Vega region, Cundinamarca)/Skin condition, arterial hypertension/Latex from fruit/poultice, infusion, drink Colombia (Taiwano people of upper Rio Negro) and indigenous groups do Brazil/ Rheumatism/Sprains/Blend, Latex of stem bark and palm oil, Oenocarpus bataua Mart/ Poultice Costa Rica/arterial hypertension Ecuador (Shuar people)/ Antitetanic, bone fractures, antihemorrhagic. Health tonic/Leaves/Decoction Guyane (Patamona people)/ Anti-bloody dysentery/ Shavings of stem bark/ Decoction, drink

References

[86]

[87]

[69]

[71]

[71]

[88]

[65, 71]

[89] [80]

[73]

(continued)

716

C. A. G. da Camara et al.

Table 1 (continued) Species

Vernacular name

–

C. penduliflora Engl.

Wapui (Col); Apuí, Uapuí, Wapui (Bra)

C. planchoniana Engl.

–

C. purpurea (Splitg.) Engl.

Cebola brava

C. quadrangula Bartlett

Copé, Copey (Hon)

C. radicans Pav. ex Planch. & Triana C. renggerioides Planch. & Triana

Ila (quichua, Ecu)

C. retusa Poir.

Cebola-brava

C. rosea Jacq.

Mata-pau (Bra)

Yukuna; Cebola brava (Bra)

Traditional people/Use/Part of plant/application Guyane (Patamona people)/ Body aches/Latex from aerial roots/poultice, laxative/Latex from stem bark/macerated with water, drink Indigenous of Guyana/Health tonic, carminative, febrifuge/ Latex from fruit/decoction, drink Colombia (Karijona people) and Brazil, Rio Vaupés, Brazilian Amazon/ Antifungal, Healing agent, open wounds, feet/Leaves/ Poultice Colombia (Kuripako people of upper Rio Negro) and indigenous groups of Brazil/ toothache (gums and tooth)/ Latex/Topical application Brazil (Tiriyó people, Amapá)/Healing agent, wounds/Twigs and leaves/ Decoction, topical application Indigenous Paya people (Honduras) and traditional people of Guatemala, Panama/Bacterial skin infection (Bactericide, boils, and pimples)/Latex/Poultice Peru/Bone fracture/Latex/ Topical application Colombia (Witoto people) and Brazil, Amazon region/ Anti-dysentery/Flowers/ Infusion, drink Indigenous and rural communities of Amazonas (Brazil)/Healing agent (poultice, cocoa butter)/ laxative/Latex from all parts of plant/Decoction, drink Brazil, indigenous people of Amazon/Wounds, Healing agent, rheumatism/Stem bark/ Decoction, topical application

References [73]

[63]

[65, 71]

[65, 71]

[90]

[71, 91]

[71] [65, 71]

[63]

[92]

(continued)

28

Chemistry, Biological Activity, and Uses of Clusia Latex

717

Table 1 (continued) Species

Vernacular name Cupay (Guy)

Camé (Peru)

Tampaco (Ven)

C. rotundata Standl. C. salvinii Donn. Sm.

Azahar de monte, Copey, Copeicillo Oreja de coyote

Kopo

C. schultesii Maguire

Palo culebra (Peru)

C. scrobiculata Benoist

Mang-yik (Guy Patamona).

C. spathulifolia Engl.

Cupí; Cupi, Apuí (Bra)

C. trochiformis Vesque

Renaquillo

C. uvitana Pittier

Galdi

Traditional people/Use/Part of plant/application Guuane/Cough medication/ Flowers/Decoction, drink/ laxative/Latex from fruit and stem bark/Maceration, drink Peru/Peruvian Amazon/ Vaginal cleansing and uterine prolapse/Stem bark/ Decoction, drink. Healing agent, wounds/Leaves or fruit/Decoction, topical application Other indigenous people of South America/Pain, fractures/Latex/Poultice Costa Rica/arterial hypertension Mexico, Veracruz region/ Gonorrhea, kidney pain/ Leaves/Maceration, drink Mayan, Lacandon people, state of Chiapas (Mexico)/ Rheumatism/Branches/ Decoction, drink Colombia/Healing agent, wounds/Leaves/Poultice Guyane (Patamona people)/ Anti-dysentery/Roots/ Decoction, drink Indigenous of Guyana (Patamona)/Body aches/ Latex from aerial roots/ Poultice Colombia, Amazon (Taiwano people) and Brazil, Rio Vaupés, Amazon/Vermifuge/ Homemade powder from stem bark mixed with “fariña”/Ingestion Ecuador (Shuar people)/ Hypoglycemic, laxative, prevention of respiratory diseases/Leaves/Infusion, drink, Inhalation Indigenous Kaggabba people (Colombia)/Vitiligo

References [73]

[93]

[71]

[89] [94]

[95]

[65] [73]

[73]

[65, 71]

[80]

[85]

Col Colombia, Bra Brazil, Guy Guyane, FGui French Guiana, Ecu Ecuador, Ven Venezuela, Hon Honduras

718

C. A. G. da Camara et al.

plant derivatives, such as fariña. Products obtained through the decoction or infusion of water, wine, or alcohol of different parts of the plant have been used as beverages, baths, or for washing wounds. For non-processed plant matrices, the mode of use is through poultice, the in natura application of the plant product directly on the affected part of the body, or the ingestion of cold (maceration) or hot (decoction, infusion) beverages. The categories and subcategories of the main uses of Clusia in folk medicine by traditional people can be summarized as follows: (i) Diseases of the respiratory system – reports of the use of plants for the treatment of cough, influenza, the common cold; (ii) Infectious and parasitic diseases– leprosy, syphilis, gonorrhea, fungal infection, parasitic worms, boils, pimples, warts, myiasis, leishmaniasis; (iii) Diseases of the digestive system – anti-diarrhea, anti-dysenteric, anti-flatulent, laxative; (iv) Diseases of the genitourinary system – uterine prolapse, vaginal pain, kidney pain, weak urinary flow (diuretic), contraceptive; (v) Conditions with external causes – skin wounds and ulcers (healing agent, antiseptic), bone fractures, joint dislocation, and sprains; (vi) Joint diseases – rheumatism; (vii) Undefined pain and afflictions – toothache (anesthetic), headache, body aches, chest pain, back pain, bone pain; (viii) Cardiovascular diseases – arterial hypertension, diabetes, hypoglycemia, low libido (aphrodisiac); (ix) General and systemic diseases – strengthening of organs for restoration of normal functioning (health tonic), lowering fever (antipyretic); (x) Stings and bites – snakebite (antivenom), antihemorrhagic. Desvaux [96] reported that Clusia galactodendron Desv. produces large quantities of latex, supposedly belonging to the so-called “cow-trees,” which offer drinkable “milk.” The latex of this species was also reported to treat intestinal problems, especially severe diarrhea. However, C. galactodendron is a synonym of C. minor and the plant was most likely confused with an Apocynaceae of the genus Lacmellea H. Karst (B. Hammel, pers. comm.), most probably L. edulis (Arn.) Markgr. To the best of our knowledge, the species of Clusia never produce large quantities of latex and none is palatable, possibly due to the rather high resin content. Reports of drinkable Clusia latex soon disappeared from the literature, but the case of C. galactodendron was never discussed. Some species are used for the maintenance of beauty, with an emphasis on benefits to the skin. The climate of the largest tropical forest in the world (Amazon) is warm and humid, which facilitates the development of numerous skin conditions. One form of prevention is to maintain the skin adequately hydrated. For such, the indigenous Yanesha people in Peru prepare a decoction with leaves of Clusia trochiformis Vesque to make a lotion for the maintenance of soft skin [68, 79]. The indigenous Waimiri-Atroari people, who inhabit the southeastern portion of the Brazilian state of Roraima and the northeastern portion of the state of Amazonas, inhale smoke from the woody base of the male flowers of marabia (indigenous denomination for Clusia sp.) to relieve pain and fever. The woody bases also sometimes serve to adorn garments worn by the women [78]. Various plants in the Amazon are used to assist different indigenous groups in fishing activities due to their toxic properties, such as the crushed roots of

28

Chemistry, Biological Activity, and Uses of Clusia Latex

719

C. hammeliana used by indigenous people of the Venezuelan Amazon [71]. In the Homoxi region of Brazil, the Yanomami people used the fruit of a vine (Clusia sp.; (kree or kreemanatosh) to poison fish [97]. In the proximities of Manaus (state of Amazonas, Brazil), the fruit of Clusia insignis is used as a diuretic and emetic, a possibility for the treatment of poisoning by certain toxic substances [78]. Some studies on the medicinal properties of Clusia fail to mention the part of the plant and/or the form of preparation and use of the medication. However, uses in folk medicine are listed here. For instance, C. minor, C. palmana, and C. rotundata are used as folk remedies in Costa Rica for arterial hypertension [89]. C. minor and C. uvitana are used as folk remedies among indigenous people of the Kaggabba group in Colombia for the treatment of vitiligo [85]. The leaves of C. alata are used in Colombian folk medicine for their detergent property. C. ellipticifolia is used in the treatment of Hansen’s disease, headache, and topical applications for the healing of the navel of newborns [62]. C. fluminensis has been used by traditional people on the southeastern coast of Brazil for the treatment of wounds as an antiseptic and healing agent. The milky sap of this plant is used by fishers for the rapid healing of wounds. The latex is sometimes mixed with cassava flour to serve as a poultice to accelerate the healing of abscesses [72, 63]. According to Martius [98] and Peckolt [72], indigenous people in the Amazon of the Guianas prepared an ointment with either cocoa butter or animal fat as well as the latex and floral resin of C. insignis, which they sold to the colonizers for the healing of nipple fissures and scratches. As evidenced by the descriptions of the medicinal uses of species of Clusia listed in Table 1, traditional people have a vast knowledge of medicinal plants and are aware of their biological properties as well as their effects for the curing of various diseases. The proof of their mastery of the empirical knowledge regarding the biological properties of these plants lies in the expansion of therapeutic or prophylactic uses in ethnoveterinary medicine. Myiasis by a larval stage of the botfly, Dermatobia hominis, which can infect several animals (mainly bovines and humans), leads to secondary bacterial infections (abscesses) and bleeding. For the control of these ulcers and expulsion of the larvae, traditional rural communities in southeastern Brazil have used different parts of C. fluminensis to treat wounds on cattle [63]. The indigenous Patamona people of Guyana have used latex from C. grandiflora and C. cf. hoffmannseggiana for this same purpose [73].

3.1

Other Uses of the Species of Clusia

Other forms of the use of Clusia by traditional communities not related to human or veterinary medicine, merit attention due to the economic value. Examples are plants selected for ornamental purposes or technological use, such as a source of heat (fire wood), raw material for the construction of houses, or wood for various purposes. There are references to the use of stem bark and roots for the fabrication of household utensils and craftwork as well as the use of latex for the maintenance of watercraft.

720

C. A. G. da Camara et al.

Since ancient times, humanity has cultivated plants as ornaments for decorative purposes in the home, and many are currently selected to compose the scenario of parks and gardens. The interest in species of Clusia for ornamental purposes is due to the diversity of the flowers, which are often large and attractive. The coriaceous leaves exhibit an intense, bright green color, and shrub species are excellent for hedges. C. rosea is the best known among the ornamental species. As white marks appear when scratched, its leaves are used for playing cards among the local population of Costa Rica [99]. Throughout Central America, the leaves were also used to leave messages due to the shortage of paper in some countries. Among the endemic species in Brazil that are grown for ornamental purposes, those of the Atlantic Forest stand out for being relatively small and flowering easily, such as C. lanceolata Cambess, C. fluminensis, and C. hilariana [100–102]. Other species native to Brazil that stand out for their large, eye-catching flowers are C. grandiflora, C. insignis, and C. mexiae P. F. Stevens [101]. In different states of Brazil, C. aff. burchellii Engl. (state of Maranhão), C. criuva (Minas Gerais, Rio de Janeiro, and the Rio Grande do Sul), and C. fluminensis (Rio de Janeiro and São Paulo) have been used in civil construction, fence making, and as charcoal. The stem bark of the latter two species were used in the tannery industry due to the high tanning content (75). In a more recent ethnobotanical study on the use of plant species by traditional rural communities of northeastern and southeastern Brazil – more specifically, the Ipiranga quilombo communities located in the municipality of Conde in the state of Paraíba, Rio Formosoin the state of Pernambuco, and Restinga de Carapebus in the state of Rio de Janeiro – the wood from C. nemorosa [103, 104]., C. criuva, and C. hilariana has been widely used in the construction and repair of houses (fabrication of roof beams) as well as the production of firewood and charcoal for cooking food [102]. Pio Corrêa [63] mentions the species C. alba (C. nemorosa), C. martinii, C. criuva ssp. parviflora, and C. hoffmannseggiana (as C. palmicida), the wood of which is used in the building of fences on ranches. The aerial roots of various hemiepiphytes of the genus Clusia have high commercial value in traditional craftwork, used as weaving material for baskets and furniture. The underground roots of C. multiflora Kunth and adventitious roots of C. alata, C. crenata, and C. lineata are raw materials for basket making (panniers) [55]. The aerial roots of C. grandiflora and C. Hoffmannseggiana are used in the furniture industry and for basket making among the indigenous people of the Carib group (NW Guyana) [105, 106]. Indigenous women of the Waimiri-Atroari group of the states of Amazonas and Roraima in northern Brazil use the woody bases of the male flowers (dried after falling to the ground) of some species of Clusia sp. (known locally as marabia) to adorn their garments [78]. Latex has also been employed by traditional people as a sealant for the repair of watercraft [32]. Due to its adhesive capacity and excellent sealing quality, the thick yellowish latex from the stems of C. nemorosa and C. retusa has been used by different indigenous people in the border region between Guyana and Brazil to caulk canoes and boats [63].

28

3.2

Chemistry, Biological Activity, and Uses of Clusia Latex

721

Use of Clusia Latex in Folk Medicine

Clusia latex is a sticky aqueous emulsion found in all parts of the plant that exudes when damage is caused to the intercellular canals (Fig. 4.) The latex of different species may be colorless, white, green, yellow, yellowishgreen, or beige. Da Camara et al. [21] found that the color of the latex from both the branches and fruit was beige in C. nemorosa and yellowish-green in C. paralicola. However, the coloration can also vary among different parts of the same plant. For instance, the latex of C. spathulifolia is predominantly white, but that of the fruit is slightly yellow [65].

Fig. 4 Latex of different parts of Clusia plants. (a) Branch latex of C. nemorosa, (b) Fruit latex of C. lanceolata, (c) Branch latex of C. lanceolata; (d) Latex channels in a leaf of C. renggerioides

722

C. A. G. da Camara et al.

According to Pio Corrêa [63], DeFilipps et al. [73], Quattrocchi [71], and Schultes [65], species of the family Clusiaceae have considerable medicinal value to indigenous communities of the Amazon in Guyana, Brazil, and Colombia. The latex from plants of the genus Clusia has particular importance to these people for the cure of various illnesses. There are reports of the use of latex obtained from different parts of the plant, that is, flowers, stem bark, fruit, leaves, and roots. The different processes and applications of latex make the species of Clusia particularly special and relevant to traditional people of the Americas, especially South America. According to the ethnobotanical studies compiled in Table 1, the main medicinal properties attributed to species of Clusia regard subcategories of uses, such as anesthetic, febrifuge, emetic, antiviral, and anti-leishmaniasis. Although the literature consulted does not represent a complete ethnobotanical study of indigenous areas of South America (because many areas have not yet been studied), the available data demonstrate that the use of latex from different parts of the plant (leaves, stems, trunk, and roots) by indigenous people of Guyana, French Guiana, and the northwestern Amazon in Colombia has been mainly to treat wounds (healing agent/antiseptic) and diseases of the digestive system. Moreover, latex is the main product used by traditional people for the treatment of infections caused by microorganisms (Table 1). For instance, indigenous communities of the Patamona group (Guyana) use the latex from C. nemorosa to treat chronic bacterial infection in a disease known as bush yaws, which affects the skin, bone, and cartilage [72]. Indigenous people of the Karijonas group (Colombia) and natives of the Brazilian Amazon use latex from the leaves of C. chiribiquetensis and C. penduliflora, respectively, in the form of poultice to treat fungal skin infections on the legs or feet [65, 71]. Traditional people of Guatemala and Panama and indigenous communities of the Paya group (Honduras) prepare a poultice from the latex of C. quadrangular and use it to treat infections caused by bacteria (boils and pimples) [71, 91]. Indigenous people of the upper Rio Negro in the Colombian Amazon use latex as an analgesic to relieve toothaches. The latex is applied directly to the cavity (C. lopezii) or a finger dipped in latex is rubbed over the gums and teeth (C. microstemon, C. planchoniana) [65]. The investigation of medicinal knowledge related to plants of the genus Clusia based on uses and forms of preparation by traditional people demonstrates the importance of latex to these communities and also shows that the different forms of treatment for diseases using medicinal plants are not limited to human medicine. The traditional uses of this product by the numerous communities that live in harmony with plants, reflect the relevance of these plants and respective latexes of different colors, viscosity, and applications to traditional people. Indeed, indigenous communities, caboclos, riparian communities, rubber tappers, quilombolos, fishers, small rural farmers, etc. have a wealth of knowledge regarding the environment in which they live, and the medicinal uses of latex. Reports of blends used in the preparation of remedies using different parts of the plant mention latex as one of the constituents. For instance, indigenous communities of the Taiwano group of the upper Rio Negro in Colombia prepare a poultice from

28

Chemistry, Biological Activity, and Uses of Clusia Latex

723

the latex (colorless) and ground stem bark of C. opaca mixed with palm oil (Oenocarpus bataua Mart.) for use in sprains and to treat rheumatism. The Carijona (another Colombian indigenous group) prepares a poultice from the fleshy leaves and yellow latex of C. chiribiquetensis, which is applied to wounds on the legs and feet likely caused by fungi [65]. Besides topical use involving the direct application of latex or in the form of blends for the preparation of poultices, latex has also been administered orally through maceration or decoction in water or the preparation of medicinal baths. Theodor Peckolt was a German pharmacist and naturalist who came to Brazil at 26 years of age and dedicated his life to the discovery of novel remedies. Considered the father of Brazilian phytochemistry, Peckolt investigated approximately six thousand plants, most of which pertained to the Atlantic Forest biome [107]. In the search for novel phytotherapeutic agents, Peckolt himself tested the effectiveness of the new medications. With the aim of finding a laxative to replace gamboge – a yellow powder prepared with the latex from the stems of some species of the genus Garcinia (Clusiaceae), and commonly found in several countries of Asia [61], Peckolt took a beverage prepared with the 20 grams of dried latex from Clusia mexiae P. F. Stevens (sub. C. arrudea Planch. & Triana ex Engl.) in powder form dissolved in alcohol. The symptoms were nausea, an increase in diuresis, abdominal pain, and two intense aqueous bowel movements. Peckolt also tested the latex of C. criuva and C. hilariana, which is recommended for combatting constipation [72]. Another example of the importance of latex in traditional medicine regards the treatment of bone fractures. The bark and stems of the species C. aff. lineata and C. aff. loretensis are used in traditional Peruvian medicine by the Quechua in the occurrence of lower limb fractures. However, the source consulted, failed to detail the form of preparation and use on the fractured limb [74]. Indigenous people of the Piaroa group of the middle Orinoco River basin in the Venezuelan Amazon use the stem bark from C. renggerioides as a splint to immobilize fractured limbs [64]. Besides providing better bone calcification due to immobilization, the vegetal matrix is impregnated with latex due to its removal from the plant. The use of the impregnated stem bark and reports of the anesthetic, antiseptic, and healing properties of the latex suggest that the odds of successful treatment are great. Reports of the medicinal use of Clusia are common, with the latex used as a healing agent for wounds (Table 1). According to Lans [108], a strap is made from the stem bark of C. rosea, which is used by men (“man’s waist pain”) for reproductive purposes in traditional medicine in Trinidad and Tobago. However, the term “man’s waist pain” related to reproductive problems is not explained. Clusia has also been used in traditional medicine as a treatment for cultural illnesses with magic-religious connotations. In this case, a novel form of the administration of latex is described. The dried latex from Clusia cf. lechleri is easily found in marketplaces in the cities of La Paz and El Alto in Bolivia and is used to treat a disease known as susto, which can affect children and adults. The latex is also used to protect against curses or to bring luck. The treatment is a ritual known in Spanish as sahumar, which consists of inhaling the smoke from

724

C. A. G. da Camara et al.

the burned latex [81]. In Guatemala, Clusia is burned to disinfect a home where someone is ill with an infectious disease [109]. Many plants play an important role in the rituals and beliefs of traditional people. According to indigenous communities of the Waimiri-Atroari group, who inhabit the state of Roraima and Amazonas in Brazil, the latex from the stem of Clusia insignis (“kypy”) placed on the eyes “increases the likelihood of finding turtles.” The meaning behind this superstition may be linked to myth or spiritual concepts, but may also have a metaphoric origin; saying that latex on the eyes helps find turtles is a metaphoric way of saying that it improves or unblocks the vision, likely when the water of the river is turbid [78].

4

Pharmacological Properties of Clusia Species

Traditional knowledge related to the use of medicinal plants for phytotherapeutic purposes such as an invigorating tonic, antioxidant or for the treatment of common diseases, such as infection caused by microorganisms or parasites, different forms of cancer, diabetes, arterial hypertension, illnesses caused by arboviruses, human immunodeficiency virus, etc., have drawn the attention of the scientific community to the real therapeutic potential of plants. Thus, bioprospecting studies have been conducted with medicinal plants in the search for active constituents with these pharmacological properties. Among medicinal plants, those of the genus Clusia stand out for the production of biologically active substances belonging to the chemical groups of terpenoids, flavonoids, biflavonoids, tannins, dihydrophenanthrene derivatives, tocotrienolic acid derivatives, benzophenones, and xanthones, which may be prenylated or geranylated. In a search of electronic databases, such as Web of Science and Chemical Abstracts, using the term “Clusia,” sixty-two species were found in studies addressing phytochemical results and/or the assessment of the biological properties of extracts and/or isolated chemical constituents. Nineteen of these 62 species are described in Table 1 (C. fluminensis, C. nemorosa, C. grandiflora, C. burle-marxii, C. minor, C. panapanari, C. parviflora Engl. (Clusia criuva ssp. parviflora Vesque) C. rosea, C. alata, C. columnaris, C. flava, C. obdeltifolia, C. uvitana, C. coclensis, C. quadrangula, C. salvinii, C. insignis, C. renggerioides, and C. ellipticifolia). Pharmacological studies have demonstrated that Clusia extracts or their constituents have anticancer, anti-inflammatory, antinociceptive, antiviral, anti-obesity, antidiabetic, antioxidant, antimicrobial, antiparasitic, antivenom, and antihypertensive properties. These studies report the properties of isolated chemical constituents as well as aqueous or organic extracts from different parts of the plant or latex used by traditional people in the form of an infusion, decoction, and/or maceration. Chemical/pharmacological studies conducted with species of Clusia have confirmed many of the phytotherapeutic treatments performed with crude extracts and have identified active ingredients, offering scientific support to the therapeutic or

28

Chemistry, Biological Activity, and Uses of Clusia Latex

725

prophylactic use of these plants in folk medicine for the treatment of illnesses that affect humans and animals (Table 1).

4.1

Antitumoral Activity

Medicinal plants with recurrent use in different traditional medicine systems have served as a source of various bioactive molecules in modern medicine or for the development of new drugs for the cure of various diseases, such as malignant tumors, which are the second most frequent cause of death throughout the world [110]. The development of anticancer medications is directly related to natural products, and much of this therapeutic arsenal is of a plant origin (i.e., vinblastine, vinorelbine, etoposide, and teniposide) [111]. Despite not finding any record of species of Clusia in folk medicine specifically for the treatment of cancer, several research groups have been dedicated to the discovery of novel anticancer agents, prioritizing phytochemical investigations, and the antitumoral activity of some species of the genus. The justification is that there is a greater chance of finding an anticancer drug by investigating plants based on ethnobotanical knowledge than through random screening [112]. In vitro and in vivo studies conducted with Clusia extracts and isolated chemical constituents belonging to the chemical classes of prenylated biphenyls, triterpenes, phytosteroids, prenylated benzophenones, and flavonoids have demonstrated promising results regarding various human cancer cell lines. Bailón-Moscoso et al. [113] reported the in vitro antiproliferative activity of the hexanic extracts EtOAc and MeOH from the leaves of C. latipes against four human cancer cell lines (PC-3 [prostate], RKO [colon], D-384 [astrocytoma], and MCF-7 [breast]). The antitumoral activity was attributed to the extract constituents friedelin (1), friedelin-3-ol (2), and hesperidin (3), as previous studies found that friedelin and friedolan-3-ol also have anti-proliferative effects in human T4 lymphoblastoid and human cervical cancer cells [114] and hesperidin was found to be cytotoxic to other tumor cells, including breast [115] and colon cancer [116].

The hexanic extracts ethyl acetate and methanol from the leaves of C. minor collected in Cuba exhibited cytotoxic activity against three tumor cell lines: CT26-WT (murine colon cancer), 4 T1 (mouse metastatic mammary

726

C. A. G. da Camara et al.

adenocarcinoma), and EAHy926 (human endothelial). The viability of CT26-WT was the least affected, and ethyl acetate seems to be more cytotoxic [117]. The chemical analysis of the extracts revealed the presence of the sterols and triterpenes stigmasterol (4), β-sitosterol (5) [118], lupeol (6) [119], α-amyrin (7), and β-amyrin (8) [120], which exhibited cytotoxic activity and the capacity to inhibit tumor promotion in cells.

Ribeiro et al. (2020) [121] evaluated the cytotoxic potential of the ethanolic extract from the stems and leaves of C. grandiflora collected in the state of Rio de Janeiro (southeastern Brazil) in the presence of four tumor cell lines (HCT-116 [human colon], AGP-01 [malignant gastric ascites], MCF7 [human breast]), and a human fibroblast cell line (MRC5). Promising results were found for the stem and leaf extracts regarding the human colon and gastric ascites lines, respectively. No phytochemical study was performed to correlate cytotoxicity with the constituents of the extract, but the histochemical analysis enabled the determination of phenolic compounds in the leaves and stems of C. grandiflora. Studies have demonstrated that plants rich in phenolic compounds, such as flavonoids, have antioxidant properties, reducing the incidence of oxidative stress and preventing associated diseases, such as cancer. The literature also reports the antiproliferative or antitumoral properties of this class of compounds [122]. Isolation and purification using conventional chromatographic methods of the hexanic extract from the shoots of C. studartiana collected in the state of Rio de Janeiro (Brazil) revealed three pentacyclic triterpenes: friedelin (1), friedelin-3β-ol (2), and 3-oxo-olean-12-en-28-oic-acid (9). Methyl olean-12-en-3-oxo-28oate (10) was obtained by the derivatization of 3-oxo-olean-12-en-28-oic-acid (9) with diazomethane. These compounds exhibited an inhibitory effect on human myeloid leukemia cells (K562); 3-oxo-olean-12-en-28-oic-acid (9) in particular was able to induce apoptosis and promoted the discrete inhibition of P-glycoprotein activity, which is an important aspect of the multidrug resistance phenotype [123]. Betulinic acid (11) is a pentacyclic triterpene found in several species of Clusia, such as the leaves [124] and roots of C. nemorosa [125], and has been extensively

28

Chemistry, Biological Activity, and Uses of Clusia Latex

727

studied with regards to its cytotoxicity to a large variety of cancer cell lines, primary tumor samples, and xenograft mouse models [126].

Seo et al. [127] found that the chloroform extract from the roots of C. paralicola collected in a fragment of the Atlantic Forest in the city of Recife (northeastern Brazil) exhibited DNA strand-scission activity, and moderate cytotoxicity to a human oral epidermoid carcinoma cell line (KB). Bioassay-guided fractionation was carried out on this extract involving an in vitro DNA strand scission assay, which led to the isolation of three biphenyl compounds: clusiparalicoline A-C (12–14).

Clusiparalicoline A (12) and clusiparalicoline B (13) were found to be active in a DNA strand-scission assay, whereas all three compounds exhibited moderate cytotoxicity against the KB cell line. Moreover, Takaoka et al. [128] found that clusiparalicoline A (12) had neurite outgrowth-promoting activity in a primary culture of rat cortical neurons. Besides flavonoids, biphenols, triterpenes, and sterols with antitumoral activity, species of Clusia have another prominent chemical class of bioactive compounds: oxidized benzophenones, generally substituted by cyclic or non-cyclic prenyl or geranyl groups. These compounds are denominated by polyprenylated benzophenones (PPBs), some of which are structurally complex, the biological properties of which have attracted the interest of research groups. More than 231 benzophenones have been isolated from the family Clusiaceae and 64.9% are PPBs [129]. To date, 66 PPBs have been isolated from species of the genus Clusia. The phytochemical investigation of floral resins from these plants revealed that the exudates are composed basically of PPBs. However, these constituents are found throughout different parts of the plant, with reports of their isolation from fruits, flowers, and stems. Moreover, this chemical class is part of the pool of substances that constitute latex

728

C. A. G. da Camara et al.

[130, 131]. Substances with this type of carbon skeleton have been the object of biological activity studies and have demonstrated considerable potential, especially with regards to the search for novel anticancer agents. Nemorosone (15) is one of the most widely investigated PPBs for its pharmacological potential and was the major component identified as a methyl derivative in the floral resin of the species C. nemorosa (38%), C. insignis (43%), C. rosea (48%), and C. grandiflora (69%) [132]. However, this compound was isolated without derivatization from the fruits of C. torresii [133] and C. rosea as well as the latex from the trunk of C. grandiflora [130, 134].

Studies on the biological potential of nemorosone (15) have demonstrated cytotoxicity to tumor cells as well as high chemoresistance, proving to be a potent cytotoxic agent. This compound exhibited cytotoxic activity in vitro against several types of tumor cell lines, such as HeLa (human cervix), Hep-2 (human larynx), PC-3 (prostate), U251 (central nervous system), LAN-1, NB69 (neuroblastoma), HepG2 (liver carcinoma), and breast cancer [135–138]. Nemorosone (15) is also a potent protonophoric mitochondrial uncoupler, which may form the basis of its cytotoxicity to cancer cells [139]. Camargo et al. [140] found that this PPB (13) did not exhibit genotoxic activity, but exhibited antiestrogenic action, reducing cell proliferation in the MCF-7 line (breast cancer). Nemorosone (15) has also exhibited cytotoxicity to the leukemia cell lines HL60 WT, HL60 ADR, MDR1+ CEM WT, CEM VBL, MDR1+ Jurkat WT, Tanoue WT, Kasumi WT, and K-562 WT. Antiproliferative and apoptotic effects on the Jurkat and K-562 lines were found through the inhibition of the enzyme Akt/PKB, interrupting the cell cycle [141]. Surprising results were also obtained with nemorosone (15) in an in vivo test, revealing a growth inhibition effect on pancreas cancer with few side effects, making this constituent a promising anticancer agent with considerable potential for use in combined therapies [142]. Antitumoral action has also been found for other PPBs, such as 7-epi-nemorosone (16), which is a diastereomer in the C-7 position of nemorosone (15) isolated from the floral resin of C. rosea and is also found in the floral resin of C. grandiflora, C. insignis, C. nemorosa, and C. renggerioides. This compound (16) exhibited

28

Chemistry, Biological Activity, and Uses of Clusia Latex

729

cytotoxicity to the androgen-dependent prostate carcinoma cell lines DU-145, PC-3, and LNCaP by targeting the MEK1/2 signal transducer [143]. The compounds burlemarxione A methyl derivative (17) and sampsonine N (18) isolated from the hexanic extract from the trunk of Clusia burle-marxii collected in the city of Mucugê in the state of Bahia, Brazil, exhibited strongly in vitro cytotoxic activity against the GL-15 glioblastoma-derived human cell line [144]. Other PPBs have also exhibited cytotoxic activity, such as xanthochymol (19) and its double-bond isomer guttiferone E (20). Xanthochymol (19) has been isolated from several species of Garcinia, but was also isolated together with guttiferone E from the leaves of C. rosea [145]. Xanthochymol (19) and guttiferone E (20) were found to exhibit activity against KB cells in the tubulin/microtubule system [146]. In other studies, this compound promoted growth inhibition in four human leukemia (NB4, HL-60, U937, and K562) and four human colon (COLO-320-DM, HCT116, HT29, and SW480) cell lines as well as breast (MCF-7) and liver (WRL-68) cell lines [147–149]. Moreover, guttiferone E (20) exhibited cytotoxicity to three human colon cancer cell lines (HCT116, HT29, and SW480) and a human ovarian cell line (A2780) [148, 150]. Clusionone A (21) was first isolated from the bark and broken twigs of C. congestiflora and is a regioisomer of nemorosone (15) [151]. This compound has also been reported in the fruit of C. sandiensis [152] and as the main component of the floral resin from C. spiritu-sanctensis [132]. Clusianone (21) inhibited the proliferation of HeLa (cervix carcinoma), MIA-PaCa-2 (pancreatic carcinoma), MCF7 (mamma carcinoma) and conjunctival melanoma cells lines (CRMM-1 and CRMM-2) [153, 154]. This compound also exhibited a cytotoxic effect on HepG2 (hepatocarcinoma) and is a mitochondrial uncoupler [155].

4.2

Anti-Inflammatory and Antinociceptive Activity

Inflammation is a natural response to an injury induced by numerous agents, including pathogens. Chronic inflammation is associated with different diseases,

730

C. A. G. da Camara et al.

such as arthritis, allergies, atherosclerosis, and cancer [156]. Among studies that have evaluated the anti-inflammatory potential of species of Clusia, the hexanic extract from the flowers of C. nemorosa collected in the Murici Biological Reserve in the state of Alagoas, Brazil, exhibited strong anti-inflammatory activity in carrageenan-induced mice pleurisy and cotton pellet-induced mice granuloma models, and the effect was partially mediated by the inhibition of neutrophil responsiveness [157]. This anti-inflammatory activity was confirmed in another study evaluating the antinociceptive effect of C. nemorosa leaf extract in mice using the formalin test, which is a model of inflammatory pain [158]. The pharmacological investigation of constituents isolated from the leaves and bark of C. nemorosa collected in the Murici Reserve [124] revealed that betulinic acid (11) [159, 160], kaempferol (22) [161], and β-sitosterol-β-D-glucoside (23) [162] have antiinflammatory activity that may be related to this phytochemical complex.

An antinociceptive effect has also been reported for the ethanolic extract from the leaves of C. minor collected in the National Botanical Garden in Cuba [163] and 13, II8-binarigenin (24), which is a biflavonoid isolated from C. columnaris collected in Puerto Ayacucho in the Venezuelan Amazon [164]. Chemical analysis by gas chromatography-mass spectrometry (GC-MS) of the ethanolic extract from the leaves of C. minor identified phytosterols and triterpenes as the major constituents. The most abundant sterol was β-sitosterol (5) (14.04%), followed by the triterpenes α-amyrin (7) (11.94%) and β-amyrin (8) (7.82%). In another study, the pharmacological evaluation of β-sitosterol (5) [165, 166], α-amyrin (7), and β-amyrin (8) [167, 168] revealed that these constituents have antinociceptive and antiinflammatory properties. Other triterpenes, such asfriedelin (1) and lupeol (6), were also found in significant quantities in the leaves of C. minor. Several in vivo and in vitro pharmacological studies of lupeol (6) have demonstrated that this triterpene is promising in the treatment of inflammation, cancer, arthritis, diabetes, heart disease, nephrotoxicity, and hepatotoxicity [169]. In vitro and in vivo tests of anti-inflammatory activity have been conducted with flavonoids isolated from different parts of Clusia. For instance, apigenin (25) is one of the most widely distributed in the plant kingdom and is found in considerable quantities in the fruit of C. nemorosa, which is a common plant in the municipality of Cabo de Santo Agostinho on the coast of the state of Pernambuco (northeastern Brazil), where it is locally known as orelha-de-burro [donkey ear] and apuí [170]. This flavonoid (25) has exhibited potent anti-inflammatory activity with

28

Chemistry, Biological Activity, and Uses of Clusia Latex

731

different modes of action, including p38/MAPK and PI3K/Akt, as well as the prevention of IKB degradation and the nuclear translocation of the NF-κB and a reduction in COX-2 activity [171]. Indigenous people of the Patamona and Palikur groups in the Guianas make use of the stems, stem bark, and latex as an antiseptic for the treatment of dermatosis and persistent wounds. A poultice prepared with the leaves of C. nemorosa is used in folk medicine for acute inflammation caused by organic pathogens or trauma. A phytochemical study of the volatile components in the leaves of this species, which grows in sandy areas on the coast of the state of Pernambuco, revealed that the major constituents of the essential oil are α-humulene (26) (16.5–12.1%) and β-caryophyllene (27) (48.6–37.3%) [172]. These compounds exhibited strong anti-inflammatory activity as oral treatment in experimental models with mice and rats [173], which lends scientific support to the use of this plant in folk medicine as an anti-inflammatory agent. Morelloflavone (28), also known as fukugetin, is a biflavonoid consisting of two covalently bonded flavones (apigenin and luteolin) isolated from the MeOH extract from leafed branches of C. columnaris in Venezuela [174]. This biflavonoid (28) exhibited anti-inflammatory effects in LPS-induced RAW 264.7 macrophages with the inhibition of nitrite concentration as compared to the positive control [175]. In another study, the compound (28) was also found to exert an inhibitory effect on human secretory phospholipase A2 as well as ameliorate 12-otetradecanoylphorbol-13-acetate – induced ear inflammation and carrageenan – induced paw edema in mice [176].

El-Sakhawy et al. [177] reported the anti-inflammatory activity of the crude ethanolic extract from the leaves of C. fluminensis from Shebein El-Kanater in Qalyubia, Egypt, and the ethyl acetate fraction (EtOAc) obtained by the partition

732

C. A. G. da Camara et al.

of the crude ethanolic extract. The extract exhibited greater anti-inflammatory activity compared to the EtOAc fraction, corresponding to 82% of the potency of indomethacin used as the positive control. According to the authors [177], the antiinflammatory activity is attributed to the C-glycosylflavones isolated and identified as binary blends of isoorientin (29) + orientin (30) and isovitexin (31) + vitexin (32).

The pharmacological properties found for these organic extracts and their chemical constituents lend scientific support to the therapeutic strategies used by traditional people involving species of Clusia described in Table 1 with the aim of reducing inflammatory processes, such as tendinitis, back pain, and muscle pain in general. However, other inflammatory processes are associated with respiratory/ pulmonary diseases and skin infections caused by viruses, fungi, and bacteria, for which phytotherapeutic agents are prepared with the aqueous or organic extracts from different parts of the plant, including latex from species of Clusia, can serve anti-inflammatory agents. For instance, indigenous people of the Shuar group in Ecuador inhale an infusion of the leaves of C. trochiformis to treat respiratory diseases [80]. The Marudá people in the state of Pará in northern Brazil and indigenous people of Guyana use the flowers of C. grandiflora and C. rosea, respectively, to treat coughs [73, 76].

4.3

Antiviral Activity

In the search for novel drugs for the treatment of human immunodeficiency virus (HIV), Gustafson et al. [145] found that the organic extract (EtOAc) from the leaves of C. rosea collected in the Dominican Republic inhibited the cytopathic effects of in vitro HIV infection. The bioassay-guided fractionation of this extract led to the isolation of xanthochymol (19) and guttiferone E (20) as the major active

28

Chemistry, Biological Activity, and Uses of Clusia Latex

733

ingredients. Five PPBs were isolated from the fruit of C. torresii collected in Turrialba, Costa Rica, without any previous treatment with diazomethane and were investigated for their activity against HIV infection in C8166 cells. All compounds inhibited infection, with selectivity index values ranging from 2.25 to 15.6 μM. The most promising compound was propolone A (33). Nemorosone (15) and 7-epi-clusianone (34) exhibited relatively potent anti-HIV activity. Clusianone (21) was active at very low concentrations but also exhibited increased cytotoxicity. 18,19-Dihydroxyclusianone (35) had the lowest activity [133].

The dichloromethane (DCM)/MetOH (1:1) extract from the leaves of ten species of Clusia collected in Mexico was investigated with regards to anti-HIV-1 reverse transcriptase activity in a nonradioactive colorimetric immunoassay. Two species (C. massoniana and C. guatemalensis) exhibited high anti-HIV-1 RT activity (
70% inhibition), while two other species (C. quadrangular and C. minor) were moderately active (65.6 and 56.1% inhibition, respectively), and six species exhibited less than 50% inhibition. Although the organic extract from C. quadrangula was not toxic to the MT2 cell line (human lymphocyte), the inhibition of HIV-1 IIIb/LAV replication was less than 52%. The excellent response found for C. quadrangula in the HIV-1 RT assay suggests that it may contain HIV-1 inhibitory substances [178]. To date, however, no phytochemical study has been conducted on this species. Another virus that served as a biological model for the evaluation of the antiviral potential of Clusia derivative was Epstein-Barr or human herpesvirus 4, one of the most widely disseminated viruses in the world and responsible for herpes simplex. This condition can cause infectious mononucleosis in the lytic phase of the life cycle of the virus. An in vitro test showed that clusionone (21) promoted a significant inhibitory effect on the early activation antigen induced by 12-O-tetradecanoylphorbol-13-acetate of the Epstein-Barr virus in Raji cells [179]. No references were found on the use of species of Clusia in folk medicine for the treatment of infection by HIV or human herpes virus 4. However, traditional people of the rural zone of Valle de la Cruz in Venezuela use the latex from C. minor, locally known as quiripiti, copei, or matapalo, in the treatment of warts, which are benign proliferations of the skin caused by the human papillomavirus (HPV) [84]. No phytochemical studies of the latex from C. minor have been conducted, but the presence of monoterpenes, sesquiterpenes, sterols, pentacyclic triterpenes, tocopherols, and polyprenylated benzophenones have been reported in various species of Clusia [130, 131]. A recent phytochemical study of the hexanic/ethanolic extracts

734

C. A. G. da Camara et al.

(EtOH) from C. minor revealed the presence of β-sitosterol (5) (14.04%/17.77%), followed by the triterpenes α-amyrin (7) (11.94%/9.39%), β-amyrin (8) (7.82%/ 3.85%), and lupeol (6) (13.70% in the hexanic extract) as the main constituents [117, 180]. The popular use of C. minor in the treatment of warts may be justified by the known antiviral properties of sterols and triterpenes, including for HPV. For instance, Cheng et al. [181] reported the effect of β-sitosterol on the expression of HPV E6 and p53 in cervical carcinoma cells. Moreover, pentacyclic triterpenes have been shown to have antiviral properties against herpes simplex virus (HSV) [182], hepatitis B virus (HBV) [183], and HIV [184]. β-Amyrin (8) has been shown to have antiviral efficacy against influenza A and HSV [185]. Volkensiflavone (36), which is a biflavonoid isolated from C. columnaris [174], exhibited good activity against influenza B [186]. Morelloflavone (28), which is another biflavonoid isolated from C. columnaris, exhibited significant antiviral activity against HIV-1 in phytohemagglutinin-stimulated primary human peripheral blood mononuclear cells [187].

4.4

Anti-obesity and Antidiabetic Activity

The search for novel inhibitors of α- and β-glucosidase is of considerable relevance due to the broad therapeutic potential, with possible antiviral and antidiabetic activity as well as activity in combating Gaucher disease and osteoarthritis [188– 190]. Pharmacological studies with species of Clusia have been conducted to evaluate the glucosidase-inhibiting potential. Among the crude extracts from plants of the Amazon, the EtOH extract from the stems of C. venusta occurring in the Napo Province of Ecuador exhibited fairly good inhibition activity for β-glucosidase (70.9%) compared to the positive control (1-deoxynojirimycin: 80.19%) [191]. Recently, Silva-Rivas et al. [192] found that greater inhibition of α-glucosidase (half maximal inhibitory concentration (IC50): 0.90 μg ml1) was detected in the

28

Chemistry, Biological Activity, and Uses of Clusia Latex

735

EtOAc fraction rich in isoquercetin (37) obtained from the methanolic extract from the leaves of C. latipes collected in the Loja Province of Ecuador. A previous investigation of the inhibitory activity of isoquercetin (37) (IC50 ¼ 0.185 mM) against α-glucosidase suggested that this flavonoid glycoside is promising for the prevention of diabetes [193]. The biflavonoid morelloflavone (28) promoted a significant decrease in lipid accumulation in a dose-dependent manner. The diminished effect of adipogenesis of α-humulene (26) suggests that this biflavonoid potentially exhibits anti-obesity properties at higher concentrations [175]. The anti-obesity activity of betulinic acid (11) isolated from the bark of C. nemorosa [124] was also investigated using mice on a fat-rich diet, revealing that this triterpene can act in the treatment of obesity through the modulation of the metabolism of fats and carbohydrates [125].

4.5

Antioxidant Activity

Among the medicinal uses described for species of Clusia, the treatment of wounds is one of the most widely cited by traditional people. There are records of the use of different parts of the plant and derivatives (latex) as an antiseptic and for wound healing (Table 1). The wound healing process involves the phases of inflammation, proliferation, and remodeling and proceeds with an interaction between tissues and cells. As oxidizing agents reduce the adverse effects of wounds and remove the products of inflammation, substances with antioxidant potential play a fundamental role in the healing of wounds [194]. Through phytochemical studies, it is currently known that species of Clusia used medicinally by different indigenous people of the New World

736

C. A. G. da Camara et al.

are composed of substances capable of producing a protective effect on biological systems and can assist in avoiding various diseases related to oxidative stress, such as cardiovascular disease, diabetes, atherosclerosis, asthma, etc. [195]. As reactive oxygen species produced during the inflammatory process exert a negative impact on tissues, it has been speculated that substances with antioxidant properties contribute favorably to the wound healing process [196]. Based on phytochemical investigations, plants of the genus Clusia contain flavonoids, which are recognized for their antioxidant properties and can therefore assist in the treatment of wounds. Thus, species of Clusia have been investigated for the determination of such properties. Using the colorimetric method with 2, 2-diphenyl-1-picrylhydrazyl (DPPH), the EtOH extract from the leaves of C. venusta collected in the Napo Province of Ecuador exhibited strong antioxidant activity, with a half-maximal effective concentration of 3.61 μg mL1 required to reduce DPPH [191]. Using the same method, methanol (MeOH) extracts from the leaves (EC50 ¼ 3.48  0.13), fruit (EC50 ¼ 4.84  0.40 μg mL1), and stems (EC50 ¼ 3.28  0.20 μg mL1) and acetonic extract from the mature fruit (EC50 ¼ 2.71  0.34 μg mL1) and stems (EC50 ¼ 4.56  0.26 μg mL1) of C. fluminensis collected in the city of Niterói (state of Rio de Janeiro, Brazil) exhibited significant antioxidant activity, which was related to the quantity of flavonoids in the extract. A greater percentage of flavonoids was determined for the acetonic and methanolic extracts from the fruit [197]. In vivo tests involving the determination of glutathione in the blood of alloxaninduced diabetic rats using vitamin E as the reference drug revealed significant antioxidant activity for the EtOH extract from the leaves of C. fluminensis collected in Shebein El-Kanater, Qalyubi (Egypt) [177]. A phytochemical study of the ethanolic extract enabled the determination of two blends rich in C-glycosylflavones: isoorientin (29) + orientin (30) and isovitexin (31) + vitexin (32), with the former exhibiting greater antioxidant activity than the latter. Armijos et al. [198] reported moderate antioxidant activity for the MeOH extract from the leaves of C. alata collected in the Zamora-Chinchipe Province of Ecuador using the DPPH (IC50 ¼ 90 μg mL1) and 2,2-azinobis (3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) (IC50 ¼ 80 μg mL1) methods. These activities are related to the high content of phenolic compounds determined by the Folin-Ciocalteu colorimetric method (991.1  34 mg of gallic acid equivalents per gram of extract). However, an investigation of the capacity of the EtOH extracts from the leaves of C. alata to induce genotoxicity and mutagenicity using the comet and chromosome aberration assays revealed that this extract has a mutagenic effect on peripheral leukocytes and bone marrow cells in mice [199]. The hexanic and EtOH extracts from different organs (leaves, pericarp, and seeds) of C. criuva collected in the Tijuca National Forest (Rio de Janeiro, Brazil) exhibited antioxidant activity using the DPPH method. The most active were the MeOH extracts from the seeds (EC50 ¼ 4.06  1.12 g extract/g DPPH) and pericarp (EC50 ¼ 5.01  0.16 g extract/g DPPH), followed by the hexanic extract from the seeds (EC50 ¼ 8.32  0.30 g extract/g DPPH) [200].

28

Chemistry, Biological Activity, and Uses of Clusia Latex

737

The antioxidant properties of the extracts (hexane, ethyl acetate, and methanol) from the leaves and stems of C. latipes collected in the Loja Province of Ecuador were also evaluated using stable free radicals of DPPH and ABTS. The most active were the MeOH extracts from the stems (drug concentration eliciting 50% of maximum stimulation, SC50 ¼ 6.77 μg mL1  0.59 μg mL1 with DPPH and 4.59  0.34 μg mL1 with ABTS) and leaves (SC50 ¼ 6.44  0.52 μg mL1with DPPH and 5.43  0.30 μg mL1with ABTS) [192]. An investigation of antioxidant activity using the DPPH and ABTS radical scavenging methods as well as β-carotene/linoleic acid of the EtOH, n-hexane, and EtOAc extracts from the green fruit of C. paralicola collected in the city of Santa Rita in the state of Paraíba, Brazil, revealed similar activity for these extracts with all methods tested. A phytochemical study of the EtOH extract led to the isolation of the bioflavonoids GB1-70 -O-beta-glucoside (38) and 3,8”-binaringenin-70 -O-beta-glucoside (39), which exhibited moderate activity in the three bioassays [201]. The antioxidant potential of the MeOH extract and the isolated flavonoid vitexin (32) from the shoots of C. paralicola collected in the city of Cruz do Espírito Santo in the state of Paraíba, Brazil, were also evaluated using the DPPH, ABTS radical scavenging, and β-carotene/linoleic acid methods. The antioxidant activity of vitexin (32) determined using the DPPH method was 4.7-fold greater than that found for the MeOH extract [202].

Based on the DPPH method, Ferreira et al. [203] found that the EtOH extract from the leaves of C. lanceolata collected in the Barra de Maricá sandbar in the state of Rio de Janeiro, Brazil, had a greater antioxidant activity with galls than without galls, but was significantly lower than the ascorbic acid standard. In contrast, the β-carotene/linoleic acid assay revealed that the antioxidant activities of the galled and non-galled leaves in this study were similar and significantly higher than the trolox standard. A chemical analysis of the extract using HPLC/DAD and LC-ESI-MS revealed the presence of flavonoids and tannins and that the antioxidant activity

738

C. A. G. da Camara et al.

could be partially attributed to four flavone C-glycosides identified in both extracts: isoorientin (28), orientin (30), vitexin-20 -O-rhamnoside (40), and isovitexin-20 -Orhamnoside (41).

In another evaluation of the antioxidant potential of constituents isolated from organic extracts (MeOH and DCM) from the leaves of C. lanceolata collected at the Grumari sandbar in the state of Rio de Janeiro, Brazil, the flavonoid vitexin (32) and a blend containing vitexin-20 -O-α-L-rhamnopyranoside (40) and isovitexin-20 -O-α-L-rhamnopyranoside (41) exhibited antioxidant activity in vivo when employing the yeast Saccharomyces cerevisiae as a biological system model, protecting the cells from the action of hydrogen peroxide to the same degree as the control treatment [204]. Besides the studies with crude extracts and isolated chemical constituents cited above, compounds identified in congener species of Clusia have also been evaluated but exhibited low to moderate DPPH radical scavenging activity, such as the PPBs clusianone (21) – first isolated from the roots of Clusia congestiflora followed by the fruit of Clusia andiensis and floral resin of Clusia spiritu-sanctensis (IC50 > 100 μM) [181, 205] – as well as xanthochymol (19) (IC50 ¼ 53  1.0 μM) and guttiferone E (20) (IC50 ¼ 68  0.33 μM) previously isolated from the leaves of C. rosea [145.206]. Baggett et al. [206] also found the same level of activity against for the bioflavonoids isolated from C. columnaris: morelloflavone (28) (IC50 ¼ 62  5.1 μM), volkensiflavone (36) (IC50 ¼ 298  13.8 μM) and fukugiside (42) (IC50 ¼ 116  9.0 μM) [174]. The antioxidant activity of these three biflavonoids (28, 36, and 42) was also reported by Panthong et al. [207] using DPPH, hydroxyl radical scavenging, and superoxide anion assays. Only the compounds morelloflavone (28) and fukugiside (42) were active, exhibiting the same degree of antioxidant activity for DPPH (IC50 ¼ 18 μmol L1) and both were approximately 7.5-fold more antioxidant than butylated hydroxytoluene used as the positive control. With lower activity compared to the positive control (tannin, IC50 ¼ 0.12 mmol L1), the biflavonoids (28 and 42) exerted inhibitory effects on hydroxyl radicals, with IC50 of 0.74 mmol L1 and 0.56, respectively. In the superoxide anion assay, these biflavonoids (28 and 42) were approximately 1.5-fold and 3.7-fold more antioxidant, respectively, than the positive control (trolox: IC50 1.36 mmol L1).

28

4.6

Chemistry, Biological Activity, and Uses of Clusia Latex

739

Antimicrobial and Antiparasitic Activity

The main medicinal uses of species of Clusia are for the treatment of wounds, dermatological conditions, and gastrointestinal disorders caused by bacteria, fungi, and protozoan parasites. However, besides C. venusta, among the species listed in Table 1, only C. nemorosa, C. grandiflora, C. rosea, C. columnaris, and C. burlemarxii have been investigated pharmacologically with regards to antimicrobial potential. The antimicrobial activity of crude extracts prepared from the leaves, flowers, stems, twigs, or floral resin and chemical constituents has been investigated using the main methods described in the literature, such as agar-well diffusion or disc diffusion, macro-dilution/micro-dilution methods performed in broth, and the thin-layer chromatography (TLC) bioassay (bioautography test). The main microorganisms selected for the assessment of the antibacterial and antifungal potential of these extracts and their respective constituents are those that cause dermatological and gastrointestinal disorders. In general, Gram-positive bacteria were more susceptible than Gram-negative bacteria and the fungi tested were generally more resistant than the bacteria. The antimicrobial activity of extracts and chemical constituents of Clusia varies according to the type of microorganism, type of extract/part of the plant, and a chemical class of the compounds analyzed. The EtOH extract prepared from the bark of the twigs, branches, and roots of C. amazonica collected in the Loreto District of the Peruvian Amazon exhibited week antimicrobial activity against 13 pathogenic and multi-resistant microbes. Regarding Gram-negative bacteria, minimum inhibitory concentration (MIC) values ranged from 1.2 mg mL1 for Klebsiella pneumoniae and Pseudomonas aeruginosa to 0.6 mg mL1 for Stentrophomonas maltophilia. Among Gram-positive bacteria, these values ranged from 1.2 mg mL1 for Enterococcus sp. to 0.6 mg mL1 for Staphylococcus aureus, S. lugdunensis, S. warneri, Streptococcus agalactiae, and

740

C. A. G. da Camara et al.

S. dysgalactiae and 0.3 mg mL1 for Staphylococcus epidermidis (8157). Regarding miscellaneous strains, the MIC ranged from 0.6 mg mL1 for Corynebacterium striatum and Mycobacterium smegmatis to 1.2 mg mL1 for Candida albicans [67]. All MIC values obtained for the EtOH extract from C. amazonica against the 13 pathogenic microbes are within the range accepted by the Clinical and Laboratory Standards Institute (512 μg mL1 > MIC >0.25 μg mL1) [208] and are therefore important and promising results. Honorio de Oliveira et al. [209] reported low activity of the EtOH extract from the leaves of C. nemorosa collected in the Araripe National Forest in the state of Ceará, Brazil, for the multi-resistant Gram-negative bacteria Escherichia coli and Pseudomonas aeruginosa and the Gram-positive Staphylococcus aureus (CIM
1024 μg mL1). However, this extract acted synergically with commercial antibiotics, reducing the minimal concentrations of amikacin, neomycin, and gentamycin fourfold in the presence of these microorganisms. The aqueous and EtOH extracts from the leaves of C. rosea collected in Odo, Ado and Government Reserve Areas of Ado-Ekiti in Nigeria inhibited the growth of some bacteria. At the highest concentration tested (2.5 mg mL1), the aqueous extract was more efficient (inhibition halo: 12–15 mm) than the ethanolic abstract (10–14.5 mm). S. aureus (inhibition halo: 15/15 mm for aqueous/EtOH extract) and Salmonella typhi (15/14.8 mm) were the most susceptible bacteria to the extracts [210]. Using the agar diffusion method, the EtOH extract (100 μg) from the stems of C. venusta collected in Ecuador inhibited the growth of Staphylococcus aureus (11 mm) and Corynebacterium diphtheriae (24 mm) [191]. Ethanolic extracts from different organs (flowers, stems, adventitious roots, and leaves) of C. grandiflora in Rio de Janeiro, Brazil, exhibited antimicrobial activity against Pseudomonas aeruginosa and Escherichia coli, with better results achieved using the adventitious roots (MIC ¼ 32 μg mL1 and 16 μg mL1, respectively), stems (64 μg mL1 and 32 μg mL1, respectively), and leaves (64 μg mL1 and 32 μg mL1, respectively) [121]. A phytochemical study and antimicrobial evaluation of extracts and constituents from C. burle-marxii collected in the state of Bahia, Brazil, revealed activity only against Gram-negative bacteria, and no activity was found against the fungi tested (Aspergillus niger and Cladosporium cladosporioides). The EtOH extract from the leaves of C. burle-marxii exhibited activity against Gram-positive bacteria (MIC ¼ 31.25 μg mL1 for Bacillus subtilis and 62.50 μg mL1 for Staphylococcus aureus), whereas the MeOH extract from the trunk inhibited the growth of B. subtilis (62.50 μg mL1), Streptococcus mutans (62.50 μg mL1), and Micrococcus luteus (31.25 μg mL1). In the same study, the compounds 2,2-dimethyl-3,5-dihydroxy-7(4-hydroxyphenyl)chromane (43) and lyoniresinol (44) were isolated from the trunk, whereas kaempferol-3-O-alpha-L-rhamnoside (45) and quercetin 3-O-α-Lrhamnopyranosyl (46) were isolated from the leaves. The compounds (43) exhibited significant activity against all Gram-positive bacteria tested and was stronger against

28

Chemistry, Biological Activity, and Uses of Clusia Latex

741

M. luteus (25 μg mL1) and S. aureus (50 μg mL1), whereas compounds (44) and (45) were more selective and exhibited strong activity against S. aureus (25 μg mL1). Quercetin 3-O-α-L-rhamnopyranoside (46) exhibited moderate activity against B. subtilis (50 μg mL1) [211].

De Souza et al. [212] found that the floral resin of Clusia sp. grown on Santa Elisa Farm in Campinas (state of São Paulo, Brazil) exhibited strong antimicrobial activity against the vector of tuberculosis, Mycobacterium tuberculosis (MIC ¼ 20 μg mL1). Moreover, floral resins from several Clusia species, also cultivated in the state of São Paulo, Brazil, exhibited antimicrobial activity against Staphylococcus aureus, Bacillus subtilis, and Candida albicans in a bioautography test [213]. Another species with antibacterial activity is C. columnaris, which grows in terra firme forests in the central Amazon of Brazil and Columbia. The methanol/ dichloromethane (DCM) (1:1) extract exhibited significant activity against the Gram-negative bacteria Enterococcus faecalis (MIC ¼ 180 μg mL1 and minimal bactericidal concentration [MBC] ¼ 270 μg mL1) and Pseudomonas aeruginosa (MIC ¼ 140 μg mL1 and MBC > 200 μg mL1). S. aureus, and E. faecalis are important bacterial species related to infectious diseases in humans [214]. Lokvam and Braddock [215] reported the activity of the floral resin from C. grandiflora collected in Canaima National Park in Venezuela against the bee pathogens, Paenibacillus larvae and P. alvei. Lokvam et al. [130] found that nemorosone II (47), which is a constituent of the flower resin, and chamone I (48) isolated from the latex of the trunk of C. grandiflora exhibited potent antibacterial activity against two bee pathogens using the bioautography test. epi-7-Clusianone (49) found in the fruit of C. torresii collected in Costa Rica exhibited antimicrobial activity against Gram-positive bacteria (MIC ¼ 1.2 μg mL1 for Staphylococcus aureus and 0.6 μg mL1 for Bacillus cereus) [216]. Rojas et al. [217] reported the antibacterial activity of nemorosone (15) against Salmonella typhi, Proteus mirabilis, Shigella sonnei, and Streptococcus faecalis. Nemorosone (15) exhibited moderate activity (growth inhibition) against the Gram-positive bacterium S. aureus (IC50 ¼ 16.1  0.1 μg mL1), whereas no activity was found against E. coli or the fungi T. rubrum and C. albicans. Nemorosone (15) also strongly inhibited the growth of P. falciparum (IC50 ¼ 0.4  0.2 μM), which is a protozoan that causes deadly parasitic diseases, namely malaria [218].

742

C. A. G. da Camara et al.

Xantochymol (19) found in the fruit of C. rosea collected in the Dominican Republic exhibited antibacterial activity against methicillin-resistant Staphylococcus aureus at a concentration (3.1–12.5 μ mL1) nearly equal to that of the antibiotic vancomycin [219]. β-Sitosterol glucoside (23) isolated from the leaves of C. nemorosa occurring in the state of Alagoas, Brazil [124], exhibited potent inhibitory action against the formation and motility of the biofilm of Escherichia coli without affecting cell viability [220]. The antimicrobial potential of the bioflavonoids morelloflavone (28), volkensiflavone (36), and fukugiside (42), initially isolated from Rheedia gardneriana but also found in C. columnaris [174], was investigated, revealing a MIC that varied from 0.12 to 1.0 mg mL1 for Bacilli cereus and 0.09 to 1.0 mg mL1 for Staphylococcus aureus. The lowest MIC was found for morelloflavone (28). The three bioflavonoids exhibited the same inhibition potential for Escherichia coli and Pseudomonas aeruginosa (MIC ¼ 1.0 mg mL1) [221]. Fukugiside (42) also exhibited antibiofilm and anti-virulence potential against Streptococcus pyogenes [222]. The minimum biofilm inhibitory concentration was 80 μg mL1 of compound (38), achieving 91% biofilm inhibition. This biflavonoid also proved more effective against the reference Helicobacter pylori (MIC ¼ 10.8 μM) than the control metronidazole (MIC ¼ 11.1 μM). Volkesiflavone (36) was another biflavonoid isolated from C. columnaris with strong activity against the same strain (MIC ¼ 14.4 μM) [223]. Infections caused by protozoans of the genera Plasmodium and Leishmania and diseases caused by arboviruses, especially malaria, are significant public health concerns in the Americas. For traditional communities in these regions, the only way to treat these infections or attenuate the symptoms is through plant-based remedies [105, 224–225]. Despite having references of the medicinal use of species belonging to different genera and families for the treatment of these types of infections, only two citations of plants from the genus Clusia were found in the literature consulted – one for C. nemorosa, the stem latex of which is used in the form of a poultice on wounds caused by cutaneous leishmaniasis, and one for C. hoffmannseggiana (C. palmicida), the roots of which are used to prepare a decoction mixed with the leaves of Stigmaphyllon sinatum (DC.) A. Juss. and ingested to treat symptoms of malaria [73, 105] (Table 1).

28

Chemistry, Biological Activity, and Uses of Clusia Latex

743

On the other hand, the species C. spathulifolia (cupi or apui in Brazil), C. huberi (tari-yekin Venezuela), and C. obovata (apui in Brazil and mode in Guyana) are used as vermifuges (antiparasitic or anthelmintic) by indigenous people of the Taiwano group (Brazil and Colombia) and Pemon group (Venezuela) of the Amazon. To date, these species have not been the object of investigation regarding their pharmacological properties or the determination of their chemical constituents to confirm or attribute the strong antiparasitic activity indicated by the traditional uses of these plants. In contrast, crude extracts, fractions, and chemical constituents from other species of Clusia have been studied for their antileishmanial and antimalarial potential. A preliminary investigation of the methanolic extract from C. rosea and DCM extract from C. coclensis collected in Panama exhibited antimalarial activity against Trypanosoma cruzi. In particular, the C. rosea extract had cytotoxicity below 25% for mammalian cells, and trypanocidal activity of
75% at 100 mg mL1 [226]. In another study, the methanolic extract from the leaves of C. flava occurring in Mexico exhibited good inhibitory activity regarding the growth of promastigotes of L. mexicana LV-4 (IC50 ¼ 32 μg mL1) [75]. The EtOAc extract from the stem bark of C. aff. pernambucensis collected in the state of Goiás, Brazil, exhibited an IC50 ¼ 65.0 μg mL1 against Leishmania (Leishmania) amazonensis promastigotes. The phytochemical analysis of this organic extract and the evaluation of the antileishmanial activity of isolated chemical constituents revealed moderate activity against L. (L.) amazonensis for clusiaxanthone (IC50 ¼ 66.9  6.1 μM) and low activity for Z-δ-tocotrienoloic acid (50) (IC50 ¼ 181.0 μM). The other compounds, δ-tocotrienol (51), δ-tocotrienolic alcohol (52), δ-tocotrienol methyl ester (53), and betulinic acid (9) – exhibited little inhibitory activity against L. (L.) amazonensis (IC50 > 200.00 μM) [227].

Three novel polycyclic phloroglucine derivatives were isolated from the MeOH extract of C. gundlachii A. Stahl. collected in Puerto Rico, denominated gundlachiione A–C (54–56), demonstrated antileishmanial activity against Leishmania donovani promastigotes and amastigotes in THP1 cultures. The compounds were more active against amastigotes, with the IC50values of gundlachiione A (54) (0.84 μg mL1) and gundlachiione C (56) (2.32 μg mL1) comparable to that of the standard drug pentamidine (0.77 μg mL1). Weak activity against L. donovani promastigotes was found for the three compounds, with IC50 values of 11.30, 30.12, and 9.63 μg mL1for gundlanchiione A (54), B (55), and C (56), respectively [228].

744

C. A. G. da Camara et al.

The biflavonoids fukugiside (42) (IC50 ¼ 0.0446 mM) and morelloflavone (28) (IC50 ¼ 0.1390 mM) exhibited considerable leishmanicidal activity against Leishmania amazonensis promastigotes. Morelloflavone (28) also exhibited highly inhibitory activity against the r-CPB2.8 isoform, with an IC50 of 0.4200 mM. These compounds were also evaluated regarding antiplasmodial activity, but none was active against P. falciparum when tested up to a concentration of 4.5 μg mL1 [229].

4.7

Antivenom and Antihemorrhagic Activity

Natives of the Patamona group in Guyana use the latex from the stems or prepare a drink from the stem bark of C. fockeana, locally known as Mang-yik, as antivenom for snakebites. No phytochemical or pharmacological study has yet been conducted on this plant. However, the literature reports that congeners of Clusia have been evaluated with regards to the neutralization of the hemorrhagic effect induced by snakebites. Hydroalcoholic and EtOAc extract from the fruit and flowers of C. torresii and C. palmana collected in Costa Rica were incubated with the venom of Bothrops asper at at a ratio of 1 mg/20 μg and neutralized 100% of the venom. The phytochemical analysis of these extracts identified the presence of condensed tannins, along with the isolation of the flavonoids vitexin (32) and epicatechin (57), which suggests that the antihemorrhagic activity found in the extract may be attributed to these phenolic compounds [230]. Hexanic extract from different parts of C. fluminensis (leaves, stems, fruit, and flowers) collected in the municipality of Niterói in the State of Rio de Janeiro, Brazil, inhibited proteolysis and hemolysis induced by the venom of Bothrops jararaca. The stem extract exhibited anticoagulant activity and the acetonic extract from the fruit exhibited antihemorrhagic activity. Clusianone (58) and lanosta8,24-dien-3β-ol (lanosterol) (59) isolated from the hexanic extract of the flowers and fruit, respectively, had no anti-coagulant or antihemorrhagic activity. However, lanosterol (59) -inhibited proteolysis, and clusianone (58) -inhibited hemolysis [231].

28

Chemistry, Biological Activity, and Uses of Clusia Latex

745

In a recent study investigating aqueous extracts from the leaves, stems, and fruit of the same species of Clusia, all extracts inhibited the activity against the venom from B. jararaca and B. jararacuçu in vitro (anticoagulant and anti-proteolytic) and in vivo (antihemorrhagic, anti-myotoxic, and anti-edematogenic). Particularly, a gel solution prepared from the fruit extract inhibited hemorrhage induced by the snake venom. Chemical prospecting of the extracts revealed the presence of tannins, flavonoids, and saponins [232]. Besides the occurrence of PPBs as major constituents of the floral resin, species of Clusia are sources of flavonoids, biflavonoids, catechins, flavones, anthocyanins, and condensed tannins found in different organs of the plant. The phyotherapeutic use of these plants is a valid alternative for the treatment of diseases and symptoms caused by snakebites due to the antihemorrhagic activity of phenolic compounds that serve as zinc-chelating agents, which is a requirement for the enzymatic activity of hemorrhagic metalloproteins [230].

4.8

Antihypertensive Activity

In traditional medicine of Panama, Peru, and Costa Rica, the species C. coclensis, C. minor, C. palmana, and C. rotundata are widely used for the treatment of arterial hypertension. In different regions of Colombia, an infusion of the latex from the fruit of C. octopetala is used for its hypotensive property. The species C. hoffmannseggiana (C. palmicida, C. cf. palmicida) and C. grandiflora are traditionally used in Guyana due to their aphrodisiac properties, suggesting an antihypertensive effect (Table 1). Concerning the pharmacological investigation of the hypotensive and aphrodisiac properties of these species, only C. coclensis was studied with regards to its therapeutic effect described in traditional medicine in Costa Rica. The hypotensive effect of the aqueous extract from the leaves was demonstrated through in vivo experiments with dogs by Villalobos and Hasbun [233] and rats by González and Matamoros [234]. Hasbún-Pacheco et al. [235] investigated the chemical profile of the leaves of various species of Clusia occurring in Costa Rica, some of which are indicated in folk medicine for the treatment of arterial hypertension, and identified friedelin (1) in C. coclensis, C. flava, C. major, C. minor, C. palmana, C. rotundata, C. stenophylla, and C. torresii. In another investigation, the same authors isolated β-sitosterol (5),

746

C. A. G. da Camara et al.

friedelin-3-β-ol (2), (-)-epicatechin(57), and friedelan-3-one (60) from the leaves of C. coclensis [236]. Studying the taxonomic significance of the chemical composition of the epicuticular wax from species of Clusia occurring in Panama, Medina et al. [237] identified friedelin (1) by GC-MS in several species, including C. coclensis, demonstrating that phytotherapeutic remedies prepared from the leaves of this species have significant quantities of triterpenes.

Many of the compounds identified in C. coclensis have relevant biological activities that justify their use in folk medicine. Triterpenes and phytosterols (4–5) are classes of chemical compounds that draw considerable interest due to their biological activities and pharmacological properties, many of which, such as lanostane, ursane, lupane, and friedelane, have been identified in the genus Clusia. β-Sitosterol (5) has been associated with cardiovascular protection, exerting its effect mainly through the increase in the antioxidant defense system and an effective reduction in serum cholesterol levels in humans [165]. Flavonoids are another chemical class that occurs in the genus, such as epicatechin (57) identified in the shoots of C. coclensis [236]. Bioassays performed with MeOH/DCM and aqueous extracts from the twigs of this species inhibited the [H-3]-AT-II binding (angiotensin II AT(1) receptor) by more than 50% [238]. Besides exerting beneficial effects due to their antioxidant properties, flavonoids also have a positive effect on the cardiovascular system, producing vasodilatation and regulating apoptotic processes in the endothelium. These phenolic compounds also have the capacity to bond to G protein-coupled receptors and are therefore promising agents for the treatment of cardiovascular disease, arterial hypertension, and mental disorders [238]. There is evidence to support several mechanisms by which flavonoids can diminish blood pressure and attenuate the severity of hypertension in animals and humans. For instance, the flavonoids found in C. nemorosa – kaempferol (22) and quercetin (61) [170, 124] – modulate the renin-angiotensin-aldosterone system through an improvement in endothelial dysfunction and the regulation of smooth muscle contractions in vessels [239].

28

Chemistry, Biological Activity, and Uses of Clusia Latex

747

Epicatechin (57), which is found in the fruit of C. paralicola [201], also exhibited hypotensive activity in rats with hypertension. The suggested mechanism of action of the flavonoid is based on the reduction of superoxide production in the aorta and the left ventricle, but also the increase in NO-synthase activity [240]. Apigenin (25) isolated from the fruit of C. nemorosa [170] is another promising agent for the treatment of cardiovascular disease, inhibiting angiotensin-converting enzyme activity, with an IC50 value of 280 μM [241]. Morelloflavone (28), which was first isolated from G. morella [242], is also found in the shoots of C. columnaris [174]. A pharmacological study of this biflavonoid revealed a pronounced in vivo hypotensive and diuretic effect (28) in anesthetized normotensive and 2K1C hypertensive rats [243]. In another study, morelloflavone (28) and fukugiside (42), also found in C. columnaris [174], were evaluated for aphrodisiac activity; only the compound (28) exhibited hypotensive activity, and induced the relaxation of aorta rings, with an EC50 of 42.76 μg mL1. The activity of fukugiside (42) was only found at the highest concentration, but this compound was the most active constituent with regards to aphrodisiac activity [244]. Among the classes of substances isolated from Clusia, benzophenones and flavonoids attract the most interest and have considerable structural diversity, giving them a broad spectrum of biological activity. Considering the significant number of species of Clusia already identified (> 450), few of which have been exhaustively investigated with regards to their chemical profile, one may expect more bioactive benzophenones and flavonoids to be discovered in the near future. The chemical and biological investigation of the pharmacological properties of extracts and chemical constituents from species of Clusia are most often directed at the discovery of a drug for the determination and validation of biological target rather than validating the plant product in natura or processed in the form of an infusion, decoction, or poultice, as used by traditional people for the cure of the different categories and subcategories of diseases listed in Table 1. In some cases, pharmacological investigations testing crude extracts with subsequent fractionation and the isolation of the active compound have revealed that the activity of the crude extract is greater than that of the active constituent (201, 228, and 177). This type of ethnopharmacological approach with a focus on Western medicine, which prioritizes the search for a single active compound with a defined pharmacological effect,

748

C. A. G. da Camara et al.

reveals a large number of species of Clusia that are used in traditional medicine, the phytotherapeutic action of which has not yet been validated.

5

Chemical Constituents and Biological Properties of Clusia Latex

Although the function of plant latex has not been fully clarified, this milky fluid with minuscule droplets of organic matter forming a colloidal aqueous suspension has the function of distributing nutrients to different parts of the plant, conferring protection from herbivores and providing antimicrobial and healing effects, which enable the closure of wounds on the plant surface [12, 101]. This defensive property inherent to latex is likely what aroused the interest in humans for use in the cure of different diseases. For traditional communities of South America, Clusia latex is an important phytotherapeutic resource, the importance of which can currently be attributed to the chemical diversity found in the substance. The use of this exudate is often associated with the sociocultural context in hunting activities and religious rituals. While there are few reports of chemical or pharmacological studies directed specifically at Clusia latex, plants of the genus are recognized for the production of terpenes, flavonoids, and PPBs. The few phytochemical studies of the latex conducted to date have revealed the presence of terpenes (phytosterols, triterpenes, monoterpenes, and sesquiterpenes), tocotrienolic acid derivatives, and prenylated benzophenones. Dreyer [245] reported the isolation of the yellow pigment xanthochymol (19) from the yellow latex taken from the fruit of C. rosea collected in Hilo, Hawaii. Besides the antioxidant activity and antitumoral activity reported for different cell lines [145, 206], this PPB (also isolated from the EtOAc extract from the leaves of C. rosea) was one of the active ingredients responsible for inhibiting the cytopathic effects of HIV infection in vitro [145]. The PPBs chamone I (48) and chamone II (62) were isolated from the latex of the trunk of C. grandiflora collected in Canaima National Park in southeastern Venezuela. As mentioned above, chamone I (48) exhibited pronounced antibacterial activity against bee pathogens in a thin-layer chromatography bioassay [130].

28

Chemistry, Biological Activity, and Uses of Clusia Latex

749

Fig. 5 First generation artificial hybrids attacked by fungi. Leaf and stem of (a) C. paralicola C. fluminensis; (b) C. lanceolata  C. nemorosa

Based on field observations, the artificial hybrid species of Clusia proved to be more susceptible to attacks from microorganisms than the parent species (Fig. 5). Based on this observation, da Camara et al. [21] initially investigated the chemical profile and antimicrobial activity of the latex from the twigs of the hybrids C. paralicola C. nemorosa and C. lanceolata  C.nemorosa and the parents (C. nemorosa, C. paralicola, and C. lanceolata). The twig latex was collected with the aid of a scalpel and placed directly into a beaker with MeOH, which promoted the formation of a water-soluble precipitate (polysaccharide). The sampling procedure was performed for the latex from the fruit of ten other species of Clusia. The qualitative chemical analysis (thin-layer chromatography) of the MeOH-soluble fraction of the latex from the twigs and fruit enabled the separation of the constituents into three main ranges denominated non-polar (Rf ¼ 0.90–0.55), intermediate (R f ¼ 0.50–0.45), and polar (Rf < 0.40), which were then isolated and the chemical constituents were identified. Table 2 shows the color of the latex, quantities of the MeOH-soluble fraction, the polysaccharide, and triterpenes characterized in the latex from 14 species of Clusia. The coloration of the latex varied from species to species, with a predominance between beige and greenish-yellow. The beige color of the latex from C. nemorosa and C. lanceolata was predominant in the hybrid species. Regarding the quantity of latex, only one of the hybrids (C. paralicolaC. nemorosa) had a larger amount than the parent species. In another study, da Camara et al. [246] reported the partial characterization of the polysaccharide obtained through precipitation of the latex solubilized in MeOH (Table 2). The polysaccharide from the fruit of twelve species of Clusia displayed

750

C. A. G. da Camara et al.

Table 2 Amount of methanol extract from twigs and fruit latices (MeOH extract in mg g1 of twigs or mg g1 of fruit), polysaccharide (PS in mg g1 of twigs), and triterpenes (Tri in mg g1 of MeOH extract) Species or hybrid C. nemorosa C. paralicola C. lanceolata C. paralicola  C. nemorosa C. lanceolata  C. nemorosa Species C. nemorosa C. rosea C. grandiflora C. criuva ssp. parviflora C. criuva ssp. criuva C. hilariana C. lanceolata C. paralicola C. weddelliana C. fluminensis C. panapanari C. spiritu-sanctensis

Latex color (twigs) Beige Green yellow Beige Beige Beige Latex color (fruit) Beige Green yellow White Green yellow Beige White Beige Green yellow Green yellow White Beige White

Twigs MeOH extract 0.24 0.41 0.31 0.51 0.10 Fruit MeOH extract 6.6 8.6 1.0 29.7 21.4 5.0 4.5 9.3 3.6 6.9 5.1 4.5

PS 0.15 0.32 0.24 0.40 0.10 PS 2.1 2.8 0.2 10.0 8.91 1.6 1.5 3.6 1.0 3.7 1.6 1.5

Tri 26.3 34.2 48.6 62.3 54.1 Tri 40.3 55.8 33.3 70.2 78.1 38.0 115.4 56.3 105.1 114.5 26.9 84.4

similar characteristics, the molecular weight of about 50,000 daltons and several anomeric 13C NMR signals with chemical shifts ranging from 109 to 96.3 ppm. The protein content was low and varied among the species, with the highest proportion found in C. paralícola (3.0%) and the lowest found in C. criuva (0.3%). The percentage of sugar was highest for the polysaccharide obtained from the latex of C. hilariana (93%) and lowest for that obtained from C. paralicola (56%). GC-MS analysis of the hexose residues was performed with trimethylsilylation (TMS) derivatives of the methyl glycosides and methyl ester glycosides obtained via methanolysis MeOH/HCl followed by TMS. The sugar residue composition of all samples was similar, consisting of arabinose (29.82 to 59.15%), 6-deoxy-galactose (4.81 to 9.75%), mannose (7.44 to 12.65%), galactose (26.27 to 44.24%), and glucuronic acid (2.07 to 4.24%). The 13C NMR analysis and comparison of the data obtained for this polysaccharide to others reported in the literature suggests a principal β-galactose chain (1 ! 3) with β-galactose branching (1 ! 6), whereas other monosaccharides compose the extremity of the polysaccharide (63).

28

Chemistry, Biological Activity, and Uses of Clusia Latex

751

Isolation of the intermediate fraction using preparative TLC and subsequent GC-MS analysis of the latex from the fruit of the 12 species of Clusia furnished chromatograms that were similar in the region with a retention time of 55–65 min. The type of fragmentation of the peaks of this region of the chromatogram suggests the presence of a mixture of the triterpenes lanostane, euphane, and oleane [21]. The identification of triterpenes in the latex from the fruit of the species C. paralicola, C. weddelliana, C. fluminensis, C. spiritu-sanctensis, C. rosea, and C. lanceolata was performed using the method described by Olea and Roque [247], which consists of the analysis of 13C NMR spectra with the complete decoupling of the protons and a DEPT 90 and 135, in which the signals of quaternary carbons are eliminated and methylene groups appear with an inverted phase in relation to the methynic and methyl groups (Table 3). Table 3 Triterpenes identification from an intermediate fraction of MeOH extract of fruit Clusia species Triterpene Lanost-7-en-3-β-ol (64) Lanosta-7,24-dien-3-β-ol (65) Lanost-8-en-3-β-ol (66) Lanosta-8,24-dien-3-β-ol (59) Eufa-8-en-3-β-ol (67) Eufa-8,24-dien-3-β-ol (68) Olean-12-en-3-β-ol (8) a

Fruit latexa Para Wedd X X X X X X X X

Flum

X X X X

Spiri

Rose X X

Lance X X

X

X

X X

Mixture of triterpenes from the intermediate fraction of the methanolic extract of the latex of the fruits. Para C. paralicola, Wedd C. weddelliana, Flum C. fluminensis, Spiri C. spiritu-sanctensis, Rosea C.rosea e Lance C. lanceolata

752

C. A. G. da Camara et al.

The presence of large quantities of triterpenes in the latex could partially be related to the pharmacological effects observed in folk medicine for diseases in which the immune system is compromised, justifying its use for the treatment of rheumatism, diabetes, etc. [248]. The GC-MS analysis of the nonpolar fraction of the latex from the twigs of the hybrid and parental species revealed that C. paralicolaC. nemorosa inherited a larger number of compounds identified in C. paralicola than C. nemorosa. Among the seven sesquiterpenes identified in C. lanceolata C. nemorosa, the compounds δ-elemene (69) (1.25%), β-elemene (70) (0.80%), γ-elemene (71) (0.66%) and α-humulene (26) (1.31%) were not found in the parent species. Besides these differences, the hybrids did not produce oxygenated sesquiterpenes [21].

Da Camara et al. [249] reported a different chemical composition for the nonpolar fraction of the latex from the fruit of the 12 species of Clusia compared to the twig latex. The chemical profile of these latices was characterized by the presence of fatty acid derivatives, benzenoids, and sesquiterpenes, the latter of which was the predominant class (98.34%). Among the sesquiterpenes identified in the fruit latices, α-humulene (26) and β-caryophyllene (27) were found in significant quantities in C. hilariana (18.27 and 58.11%), C. lanceolata (7.81 and 36.39%), and C. weddelliana (5.28 and 24.05%). β-Caryophyllene (27) was also the major constituent of the latex from C. nemorosa (21.10%) and C. fluminensis (35.61%). Despite the abundance of sesquiterpenes, considerable qualitative and quantitative differences were found among the nonpolar fractions of the fruit latices. After isolation

28

Chemistry, Biological Activity, and Uses of Clusia Latex

753

of the polar fraction (Rf < 0.40) of the MeOH extract from the latex of the fruit of C. grandiflora, C. paralicola, C. criuva ssp. parviflora, and C. hilariana through preparative TLC, the respective extracts were derivatized with an ether solution saturated with diazomethane. GC-MS analysis of the methylated polar fractions enabled the identification of fatty acid derivatives, polyprenylated benzophenones, grandone (72), olean-3-oxo-28-oic acid (73), olean-12-en-3-oxo-28-oic acid (74), tocotrienolic acid derivative, (Z)-δ-tocotrienolic acid (50), (Z)-γ-tocotrienolic acid (75), and 5,8-diidroxi-(Z)-γ-tocotrienolic acid (76). Compounds (50) and (75) were isolated without derivatization with diazomethane, whereas compounds (75) and (76) were isolated as methyl esters of the respective tocotrienolic acids. The derivatives of γ-tocotrienolic acid – compounds (75) and (76) – were isolated for the first time from the latex of C. grandiflora as previously unknown natural products [122].

Only compounds (50), (75), and (76) were found in all species, with proportions ranging from 10 μM; HeLa >10 μM [96]; A549 0.347 μM; HeLa 0.663 μM [94] Antiarigenin [(3β,5β,12β)-3,5,12,14-tetrahydroxy-19-oxocard-20(22)-enolide] (24) isolated from C. procera [97] Asclepin (25) isolated from C. gigantea [95] in Thailand [95]. IC50 against tested cancer cell lines: MCF-7 30.5  1.2 nM [95] Asclepioside [(3β,5α)-3-[(6-deoxy-α-D-allopyranosyl)oxy]-14-hydroxycard-20(22)-enolide] (26) isolated from C. procera [98] in Puerto Rico Calactin (10) isolated from the latex of C. procera [94, 97, 99] in Egypt [94] and USA (greenhouse) [99]; the whole plant (C. procera) in Puerto Rico [98] and the latex of C. gigantea [100] in Thailand. IC50 against tested cancer cell lines: A549 22  2 nM; HeLa 28  3 nM [96]; A549 0.985 μM; HeLa 0.083 μM [94]; MCF-7 45.2  6.1 nM [95]; T47D 8.58  0.68 nM [100] Calactinic acid (20) isolated from C. procera [97]. IC50 against tested cancer cell lines: KB 31.28 μM; MCF-7 inactive; NCI-H187 inactive [101] Calactinic acid methyl ester (27) isolated from C. procera [97] and C. gigantea in Thailand [95, 102] Calactoprocin (28) isolated from C. procera in Egypt [94] IC50 against tested cancer cell lines: A549 0.079 μM; HeLa 0.128 μM [94] Caloproside (29) isolated from C. procera in Egypt [94] IC50 against tested cancer cell lines: A549 0.065 μM; HeLa 0.104 μM [94] Calotoxin (12) isolated from the latex of C. procera [94, 97, 99] in Egypt; the whole plant (C. procera) [96] in Puerto Rico; and the latex of C. gigantea [100] IC50 against tested cancer cell lines: A549 67  8 nM; HeLa 87  10 nM [96]; KB 3 nM; MCF-7 5.95 μM; NCI-H187 3 nM [100]; A549 0.549 μM; HeLa 0.863 μM [94]; BT-549 0.049  0.002 μM; Hs578T 0.12  0.05 μM; MDA-MB-231 0.63  0.04 μM [103]; T47D 348.53  24.14 nM [104] Calotropagenin (21) isolated from the latex of C. procera [97, 99] in the USA (greenhouse) [99]; the whole plant (C. procera) [98] in Puerto Rico; and the latex of C. gigantea [100]. IC50 against tested cancer cell lines: KB 6.33 μM; MCF-7 106.06 μM; NCI-H187 48.04 μM [101] T47D 6836.67  355.10 nM [100] Calotropagenin diacetate (30) isolated from C. procera [97] Calotropin (9) isolated from the latex of C. procera [97]; the whole plant (C. procera) [98] in Puerto Rico; and the latex of C. gigantea [95, 100] in Thailand. IC50 against tested cancer cell lines: A549 29  3 nM; HeLa 46  5 nM [96]; KB 0.015 μM; Colo 320 DM 0.0086 μM; DLD-1 0.052 μM; HT-1080 0.030 μM; KKLS 0.011 μM; MKN-28 0.022 μM; MKN-45 0.055 μM; HLE 0.012 μM; Hep 3B 0.021 μM; Hep G2 0.094 μM; Hu H7 0.030 μM; SK-Hep-1 0.016 μM; PC-9 0.040 μM; QG-56 0.025 μM; G-292 0.0072 μM; KHOS/NP 0.0065 μM; MNNG/HOS 0.011 μM; OST 0.044 μM; LNCap 0.043 μM; PC-3 0.011 μM; also of mouse origin: Colon 26; L1210; L5178Y; FM3A; B16-F10, all: >2 μM [104]; BT-549 0.030  0.002 μM; Hs578T 0.06  0.01 μM; MDA-MB-231 0.44  0.08 μM [103]; MCF-7 59.8  6.3 nM [93]; T47D 27.92  2.76 nM [100] Coroglaucigenin (31) isolated from the whole plant (C. procera) [98] in Puerto Rico [98]. IC50 against tested cancer cell lines: KB 1.0 μM; Colo 320 DM 0.71 μM; DLD-1 > 2 μM; HT-1080 1.5 μM; KKLS 0.88 μM; MKN-28 1.1 μM; MKN-45 > 2 μM; HLE 0.70 μM; Hep 3B 1.9 μM; Hep G2 > 2 μM; Hu H7 > 2 μM; SK-Hep-1 1.3 μM; PC-9 > 2 μM; QG-56 1.7 μM; G-292 0.31 μM; KHOS/NP 0.27 μM; MNNG/HOS 0.73 μM; OST >2 μM; LNCap>2 μM; PC-3 0.74 μM; also of mouse origin: Colon 26; L1210; L5178Y; FM3A; B16-F10, all: >2 μM [104]; BT-549 2.3  0.3 μM; Hs578T 1.8  0.3 μM; MDA-MB-231 20  4 μM [103] (continued)

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

777

Table 1 (continued) Deglucoerycordin (tentative) (32) isolated from the whole plant (C. gigantea) in China [105] 19-Deoxy-15β-hydroxyuscharin (33) isolated from C. gigantea in Thailand [95]. IC50 against tested cancer cell lines: MCF-7 68.8  7.0 nM 12β,16α-Dihydroxycalotropin (34) isolated from C. gigantea in Thailand [100]. IC50 against tested cancer cell lines: T47D 4686.00  380.56 nM [100] 30 -Epi-afroside (35) isolated from C. gigantea [95, 100] in Thailand [95]. IC50 against tested cancer cell lines: T47D 438.03  40.49 nM [100] 30 -Epi-afroside acetate (36) isolated from C. gigantea from Thailand [100]. IC50 against tested cancer cell lines: T47D 764.73  63.92 nM [100] 30 -Epi-gomphoside (37) isolated from C. gigantea in Thailand [95] 20 -Epiuscharin (38) isolated from C. gigantea in Thailand [106] Frugoside (39) isolated from C. gigantea in Thailand [95]. IC50 against tested cancer cell lines: A549 187  11 nM; HeLa 858  67 nM [96]; KB 30 nM; MCF-7 3.65 μM; NCI-H187 0.20 μM [101]; KB 0.15 μM; Colo 320 DM 0.061 μM; DLD-1 0.51 μM; HT-1080 0.20 μM; KKLS 0.14 μM; MKN-28 0.23 μM; MKN-45 0.40 μM; HLE 0.096 μM; Hep 3B 0.10 μM; Hep G2 1.1 μM; Hu H7 0.22 μM; SK-Hep-1 0.16 μM; PC-9 0.32 μM; QG-56 0.26 μM; G-292 0.030 μM; KHOS/NP 0.034 μM; MNNG/HOS 0.088 μM; OST 0.44 μM; LNCap 0.70 μM; PC-3 0.11 μM; also of mouse origin: Colon 26; L1210; L5178Y; FM3A; B16-F10, all >2 μM [104]; BT-549 0.121  0.007 μM; Hs578T 0.38  0.06 μM; MDA-MB-231 1.25  0.09 μM [103]; T47D 230.07  9.29 nM [100]. An X-ray crystal structure is known of the tris(bromobenzoyl derivative [103] Gomphoside (40) isolated from C. gigantea in Thailand [95]. IC50 against tested cancer cell lines: MCF-7 42.0  5.6 nM [95] 15β-Hydroxyasclepin (41) isolated from C. gigantea in Thailand [100]. IC50 against tested cancer cell lines: T47D 329.03  11.94 nM [100] 15β-Hydroxycalactin (42) isolated from C. procera in Egypt [94] and from C. gigantea [95, 100] in Thailand. IC50 against tested cancer cell lines: A549 107  12 nM; HeLa > 10 μM [96]; A549 0.079 μM; HeLa 0.128 μM [92]; T47D 605.23  36.38 nM [100] 15β-Hydroxycalotropin (43) isolated from the latex and the whole plant (C. gigantea) in Thailand [100]. IC50 against tested cancer cell lines: A549 > 10 μM; HeLa >10 μM [94]; 241.17  13.74 nM [100] 16α-Hydroxycalotropin (44) isolated from C. gigantea [95, 100] in Thailand. IC50 against tested cancer cell lines: T47D 5766.67  207.47 nM [100] 12β-Hydroxycoroglaucigenin (45) isolated from C. gigantea in Thailand [100]. IC50 against tested cancer cell lines: KB 1.67 μM; MCF-7 84.55 μM; NCI-H187 15.36 μM [101] 15β-Hydroxyuscharin (46) isolated from C. procera in Thailand [93] and Egypt [94]. IC50 against tested cancer cell lines: A549 60  7 nM; HeLa 86  9 nM [96]; A549 0.157 μM; HeLa 0.318 μM [94];MCF-7 40.1  3.1 nM [95] 16α-Hydroxyuscharin (47) isolated from C. gigantea in Thailand [95] 19-Nor-10β-hydroxycalactin (48) isolated from C. gigantea in Thailand [100]. IC50 against tested cancer cell lines: T47D 4628.33  201.31 nM [100] 2”-Oxovoruscharin [UNBS 1244] (49) isolated from C. gigantea in Thailand [95, 100]. IC50 against tested cancer cell lines: MCF-7 32.9  2.4 nM [95]; Hs-683 8 nM; U-373 15 nM; HCT-15 16  5 nM; LoVo 10 nM; A-549 74 nM [107]; T47D 8.24  0.24 nM [100] Procegenin A (50) isolated from C. procera in Egypt [94]. IC50 against tested cancer cell lines: A549 0.604 μM; HeLa 1.151 μM [94] Procegenin B (51) isolated from C. procera in Egypt [94]. IC50 against tested cancer cell lines: A549 1.106 μM; HeLa 1.434 μM [94] (continued)

778

A. A. Bankole and T. Thiemann

Table 1 (continued) Proceroside (2α,3β)-14-hydroxy-19-oxo-2,3-[(tetrahydro-3,4-dihydroxy-6-methyl-2H-pyran-3,2diyl)bis(oxy)]card-20(22)-enolide (52) isolated from the latex and the whole plant of C. procera [97, 98] in Puerto Rico [98] Syriogenin (53) isolated from C. procera [97] Syriogenin 3,12-diacetate (54) isolated from C. procera [97] Uscharidin (11) isolated from the latex of C. procera) [97, 99, 108]; whole plant (C. procera) [98] in Puerto Rico [98], and the latex of C. gigantea in Thailand [95] Uscharin (13) isolated from C. procera [94, 96, 99, 109] in Egypt [94] and the USA (greenhouse) [99]; C. gigantea [95]. IC50 against tested cancer cell lines: Hs-683 4 nM; U-373 40 nM; HCT-15 28 nM; LoVo 10 nM; A549 25 nM [107]; A549 122  13 nM; HeLa 385  36 nM [96]; A549 3 ng/mL; HCT-116 13 ng/mL; Hep-G2 20 ng/mL [110]; A549 0.104 μM; HeLa 0.275 μM [94]; 0.0146  0.0001 μM; 0.034  0.003 μM; 0.102  0.004 μM [103]; MCF-7 33.2  2.6 nM [95] T47D 10.55  1.23 nM [100]. An X-ray crystal structure is known [95, 100] Uzarigenin (55) isolated from the latex [97] and whole plant of C. procera [98] in Puerto Rico [98]. IC50 against tested cancer cell lines: BT-549 3.9  0.4 μM; Hs578T 3.6  0.1 μM; MDA-MB 231 > 30 μM [103]; HT29: 50 μM leads to 59% metabolic activity reduction; HepG2: 50 μM leads to 35% metabolic activity reduction [111] Voruscharin (14) isolated from C. procera [84, 97, 99] in USA (greenhouse) [99]. IC50 against tested cancer cell lines: Hs-683 4 nM; U-373 32 nM; HCT-15 27 nM; LoVo 17 nM; A549 5 nM [107] Nature of the cell lines used: A172: brain cancer cell line; A549: adenocarcinomic human alveolar basal epithelial cells (nonsmall cell lung carcinoma); B-16: melanoma cell line; BT-549: triple negative cancer cell line; Caco-2: human colorectal adenocarcinoma; CEM: leukemia cell line; Colo 320 DM: colon adenocarcinoma; DLD-1: colon adenocarcinoma; EAC: Ehrlich ascites carcinoma; G-292: osteosarcoma; HeLa: human cervical carcinoma cell line; HCT-8: colon carcinoma; HCT-15 human colon cancer cell line; HCT 116: colon carcinoma; Hep G2: hepatocellular carcinoma; HLE: hepatoma; Hs578T: triple negative cancer cell line; Hs683: brain cancer cell line; HT-29: colon adenocarcinoma; HT-1080: fibrosarcoma; Hu H7: hepatoma; K562: human chronic myelogenous leukemia cell line; KB: cervical adenocarcinoma cell line; KHOS/NP: osteosarcoma; KKLS: gastric adenocarcinoma; LNCap: prostate adenocarcinoma; MCF-7: breast cancer line; MDA-MB-231: triple negative cancer cell line; MKN-28: gastric adenocarcinoma; MKN-45: gastric adenocarcinoma; MNNG/HOS: osteosarcoma; NCI-H187: small lung cancer cell line; 549 NSCLC nonsmall cell lung cancer; OST: osteosarcoma; P388: murine leukemia cell line; PANC-1: human pancreatic carcinoma cell line; PC-3: prostate adenocarcinoma; PC-9: lung adenocarcinoma; QG-56: lung squamous carcinoma; RPMI: head-and-neck cancer cell line; SGC-7901: human gastric cancer cell line; SK-Hep-1: hepatoma; SKOV-3: human ovarian cancer cell line; U373 GBM: glioblastoma; WiDR: colon cancer cell line

stability was investigated [119]. Subsequently, a second cysteine protease was purified and isolated from the latex of C. procera and named as procerain B [118, 119]. As proteases have several applications in the food, dairy, and detergent industries as well as in the pharmaceutical industry, procerain B has been prepared in an immobilized form on Amberlite MB-150 beads, using Schiff base linkage [120] to increase its potential industrial application. Overall, C. D. Freitas et al. have been able to distinguish among four cysteine proteinases in C. procera, which were separated by gel filtration chromatography [121]. Proteins of C. procera have been studied by 1D and 2D electrophoresis and characterized by MALDI-TOF [122]. Proteins from the latex have been separated by centrifugation, where the supernatant is subjected to dialysis with a cutoff at 8000 DA, leading to a dialyzed fraction with relatively low-weight molecules (DL) and a nondialyzed fraction (NDL) containing

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

779

Fig. 3 Structures of cardenolides found in the latex of Calotropis plants

concentrated proteins. An osmotin (CpOsm) as a laticifer protein has been crystallized and analyzed by X-ray diffraction [123]. Cysteine proteases found in C. gigantea [126] have been evaluated to exhibit thrombin and plasmin-like activities [124]. The molecular structure of the sulfhydryl protease calotropin I, isolated from C. gigantea [127], has been determined by X-ray crystal structural analysis [128] at 3.2 Å resolution [129]. The peptide backbone was found to be organized in

780

A. A. Bankole and T. Thiemann

Fig. 4 Structures of cardenolide glycosides and uscharin-type cardenolides from Calotropis latex

Fig. 5 Structures of steroids and triterpenoids isolated from Calotropis latex

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

781

Fig. 6 Structure of flavonoids and lignans isolated from Calotropis latex

two distinct lobes, one with mostly alpha-helical structures and one with antiparallel pleated sheets. Overall, calotropin I was found to resemble papain and actinidin [129]. U. Heinemann et al. also pointed out differences in the structure of these three sulfhydryl proteases, which may be responsible for the inability of calotropin I to hydrolyze certain substrates both papain and actinidin can hydrolyze [129]. With calotropain FII, DI, and DII, further proteases have been found in C. gigantea [126]. While flavonoids have been found mostly in the leaves of Calotropis plants, high concentrations of rutin (67) were also found in the latex of the plant [130]. Also, other phenolic compounds were isolated from the latex of C. procera and C. gigantea. These were identified as lignin glycosides, identified as (+)-pinoresinol (68), (+)-pinoresinol4-O-β-D-glucopyranoside (69) [131], (+)-pinoresinol-4-O-[600 -O-vanillyl]-β-D-glucopyranoside (70), pinoresinol-40 -O-[600 -O-(E)–feruloyl]-β-D-glucopyranoside (71) [132], (+)-medioresinol-4-O-β-D-glucopyranoside (72, Eucommin A) [133], 60 -Ovanilloyltachioside (73), and 60 -O-vanilloylisotachiode (74) [134] (Fig. 6).

3

Biological Activities and Uses of Calotropis Latex

3.1

Insecticidal, Nematicidal, and Molluscicidal Uses of Calotropis Latex Extracts

The latex from the green parts of the Calotropis plant represents an effective system of defense against insects [64, 78, 135]. The latex affects the larvae development and mortality in the mosquito Aedes aegypti, a vector of the Dengue

782

A. A. Bankole and T. Thiemann

virus, and suppresses its egg hatching [136]. Also, aq. latex extracts lead to diminished ovipositioning in gravid A. aegypti females [137], where the ovipositioning female can distinguish among the latex extract concentrations to lay its eggs in the medium with the least larvicidal concentration [137]. Aq. latex extracts have been shown to also have a larvacidal effect on the mosquitoes Anopheles labranchiae [138] and Culex qinquefasciatus [139, 140]. Methanolic latex extracts of C. procera have been proven to be even more effective as a larvacide against A. aegypti. C. quinquefasciatus, and Anopholes stephensi as shown in a field study by Singhi et al. in Jodphur City, India, where an aq. solution of a dried methanolic extract of C. procera latex was dispersed in water tanks normally functioning as breeding grounds for different mosquito species. A 100% larval mortality was noted when a solution of the dried latex extract was used at a concentration of 100 ppm [141]. Latex extracts of both C. procera and C. gigantea were found to be effective against the desert locust Schistocerca gregaria [142]. For C. gigantea a nonprotein amino acid was forwarded as an antifeedant [143] and thought to be the active principle. However, the structure of the amino acid could not be confirmed [144]. Cardiac glycosides in the extracts of C. procera are the active principles according to the work by D. H. Al-Rajhy et al. on the efficacy of Calotropis extracts on the camel tick Hyalomma dromedarii (Acari: Ixodidae) [145]. Not all insects are affected negatively by the Calotropis plants. The African monarch, Danaus chrysippus, a butterfly common to many regions in Africa and Asia, prospers on Calotropis and its caterpillars (first to fifth instar) use some of the latex proteins in their diet. There is the suggestion that the caterpillars’ proteolytic digestive system destroys the toxic proteins of the Calotropis latex, including the peptidases. So, caterpillars become immune to the toxic principles of the plant [64, 146]. Danaus chrysippus caterpillars, especially the young instars, maintain a fine equilibrium in their feeding behavior where the need for nourishment is balanced against the exposure to de facto poisonous cardenolides in the latex. Caterpillars cut the leaves, wait for the exuded latex to dry, and only then start feeding off the leaves while avoiding the latex [64, 146]. Latex extract of C. gigantea has been used to control the plant-pathogenic nematode Meloidogyne incognita and the cowpea cyst nematode Heterodera cajani [147]. Ethyl acetate solutions of lyophilized C. procera latex have been found to inhibit egg hatching of Haemonchus contortas, one of the most important pathogenic nematodes infecting ruminants. Here, the latex showed a pronounced larvicidal effect (EC50 ¼ 0.22 mg/mL) and inhibited the motility of the parasites by over 80% after a 6 h contact time [148]. Much of the above mentioned activity of Calotropis latex extracts can be attributed to their cardenolide content. Studies on the molluscicidal activity of C. procera extracts against the land snail Monacha cantania [149] and single-compound toxicity studies of uscharin (13) in the snail Thepapisana [150] have clearly shown the molluscicidal activity of cardenolides found in the latex. Thus, uscharin (13) has been found to be 128 more toxic against the land snail Thepapisana [150] than carbamate methomyl (75) (Fig. 7), a

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

783

Fig. 7 Structures of methomyl (75), rofecoxib (76), diclofenac (77), and melatonin (79)

well-known broad-spectrum, systemic, anticholinesterase carbamate insecticide, which is also used against snails.

3.2

Use of C. procera and C. gigantea Latex Extracts as Snake Venom Antidote

According to the World Health Organization (WHO), there are about five million cases of snakebite annually, where the areas most affected are rural, agricultural areas in the intertropical zone [151]. Snake venoms contain strong cardiac or neurologically active compounds and various enzymes which result in inflammatory reactions, hemorrhage, and local tissue necrosis. Phospholipase A2 (PLA2), proteases, and hyaluronidase are hydrolytic enzymes found in snake venoms that induce the local effect and help to spread the toxins in the system of the victim. Extracts of medicinal plants have been utilized as so-called snake venom antidotes and especially for the treatment of local tissue damage by snake venoms [152, 153], where the constituents of the plant extract inhibit the above named hydrolytic enzymes. Traditional healers from the Central Indian Chhattisgarh area use both the aqueous extracts of roots and the leaves and latex of C. gigantea, from which a paste is formed [154]. Also, among the Bagata tribe of the Eastern Ghats, Andra Pradesh, India, the use of C. gigantea and C. procera (roots and leaf latex) against snake bite has been noted [155]. In the Namal valley, Punjab, Pakistan, the leaves of C. procera are eaten raw as an antidote [156]. Also, the latex of C. procera is applied along with a paste made of the leaves of Mexican cotton (Gossypium hirsutum) to the bitten skin [156]. The anticoagulant activity especially of the latex extracts may well result from an interaction with the protease coagulative activity discussed below. Again, the extracts can act in different ways and are differently effective, depending on the snake venom present. Thus, M. Molander et al. [157] showed that aq. extracts of C. procera exhibit only a very weak hyaluronidase inhibitory effect toward the venom of the black-necked spitting cobra (Naja nigricollis) and a very weak phospholipase A2 inhibitory effect toward the venom of puff adder (Bitis arietans). Also, there are clear indications that reports of successful treatment of snake bites with C. procera extracts should be treated with extreme caution. There are accounts of Calotropis poisoning upon ingestion of Calotropis extracts [158, 159], some of the cases being severe, with cardiovascular collapse ([69], see also Sect. 1.2).

784

3.3

A. A. Bankole and T. Thiemann

Anti-Inflammatory and Antinociceptive Properties of the Calotropis Latex

The proinflammatory characteristics of the latex of C. procera have been well documented [160]. Accidental exposure to C. procera latex can cause contact dermatitis [161], keratitis [72, 162, 163], and toxic iridocyclitis [72, 163, 164], where the contact of plant latex with the human eye has been found to cause a temporary acute, inflammatory reaction and intense photophobia [163], which subsides with medical treatment (see also Sect. 1.2). Thus, frequently, local application of the latex of C. procera has been reported to lead to an inflammatory response, especially to skin and mucous membranes [165], which is thought to be mediated by histamine and prostaglandins ([160, 166–168], see also above). Studies have shown that the early phase of this response is mediated partly by the histamine present in the latex and partly by the release of histamine from mast cells [166]. In addition, the synthesis and release of prostaglandins through induction of COX-2 also contributes to the overall inflammatory process [168]. The associated inflammation can be ameliorated by cyproheptadine (76) as an antiserotonergic and antihistaminic drug and by rofecoxib (77) and diclofenac (78) [169] (Fig. 7), while the associated hyperalgesia can also be lessened by treatment with oxytocin and melatonin (79), as could be shown in the rat edema model [165]. Interestingly, oral administration of Calotropis latex has been practiced in Indian traditional medicine to treat rheumatism and various aches. When administered orally, the latex has been reported to exhibit anti-inflammatory and analgesic properties [40, 170–177]. Both latex granules of aerial parts of C. procera and methanolic extracts thereof showed a strong anti-inflammatory response in male Wistar rats with pedal edema induced through injection with carrageenan, histamine (80), serotonin (81), compound 40/80 (82), prostaglandin E2 (83, PGE2), or bradykinin (84, BK) [174] (Fig. 8). Latex granules were found to be more effective in carrageenininduced edema, but both the methanolic extracts and the granules were found to be more effective than the standard anti-inflammatory drug phenylbutazone (85, PBZ) in inhibiting inflammatory cellular infiltration [174]. Methanolic extracts of C. procera latex (MeDL) have been shown to be effective against ulcerative colitis, an inflammatory condition of the colon [178]. Wistar rats with acetic acid– induced colitis were fed 50 mg/kg–150 mg/kg MeDL, and it was found that there was a marked reduction in colonic mucosal damage as well as a restorative effect on tissue histology and tissue levels of cyclooxygenase-2 (COX-2), inducible nitric oxide (iNOS), and nuclear factor kappa beta (NFκB) subunit p65 [178]. The oral administration of polar extracts of C. procera latex at 200 mg/kg has been found more effective than prednisolone at 50 mg/kg to manage colitis in Wistar rats [179]. Colitis laticifer proteins of C. procera are deemed to be responsible for the anti-inflammatory [180–182] and antinociceptive activity [183] observed in the test animals, although nonprotein constituents soluble in polar solvents are also held to be partly responsible, especially antioxidant flavonoids [169]. Recently, there has been an effort to work with tissue cultures of C. procera to produce pharmacologically active proteins from the plant latex [184].

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

785

Fig. 8 Structures of histamine (80), serotonin (81), compound 40/80 (82), prostaglandin-E2 (PGE2, 83), bradykin (84), and phenylbutazone (85)

3.4

Wound Healing: Use of Calotropis Extracts for Treating Skin and Wound Infections: Antimicrobial and Fungicidal Activity of Calotropis Extracts

In traditional medicine, extracts of different parts of C. procera and C. gigantea have been used in wound treatment [185]. This includes the roots and latex of C. gigantea and C. procera [186, 187]. Recently, it has been reported that the topical application of an ethanolic extract of C. gigantea led to a higher percentage of wound extraction with lower resultant scarring and an acceleration in wound healing [188]. Also, both latex extracts of C. gigantea and C. procera have been ascribed wound healing activity [189, 190] and are also used traditionally to stop bleeding of fresh cuts [191]. The interest in the use of Calotropis extracts in wound treatment stems from their blood clotting ability and their anti-inflammatory, antimicrobial, and antifungal activity. Although latex extracts from a number of plants have been used to staunch bleeding in traditional medicines [192], the utilization of plant-derived topical hemostatic agents is becoming more important in wound care [193]. The blood clotting ability of the Calotropis extracts is associated with cysteine proteases found in the latex, which exhibit thrombin-like, but also plasmin-like activities [194, 195]. These latex thrombin-like proteases (PTLPs) act directly on fibrinogen to form fibrin clots and stop the bleeding. In vivo tail bleeding tests have been performed with Swiss albino mice, where latex extracts of C. gigantea significantly reduced bleeding time and blood volume upon topical application in mice [196]. This was also true for factor VIII deficient plasma, a factor that hemophilia A patients lack [196]. However, the study also showed that the administration of PTLPs from C. gigantea at 25 μg per test animal led to a hemorrhage of the skin with extensive damage to the dermis and basement membrane surrounding blood vessels,

786

A. A. Bankole and T. Thiemann

and led to massive infiltration of inflammatory cells [196]. When a homogeneous hydrogel from extracted hemicellulose of the seeds of the peacock flower (Caesalpinia pulcherrima), impregnated with the water-soluble protein fraction from C. procera latex, was topically used on excisional wounds in Swiss mice, the hydrogel enhanced healing by wound contraction [197]. It was suggested that the inflammatory phase of the healing process was intensified, stimulating fibroplasia and neovascularization (proliferative phase) and tissue remodeling by increasing new collagen fiber deposition [197]. The wound-healing ability of the latex extracts of the Calotropis plants has been partly ascribed to the pronounced antimicrobial activity of the extracts [198], which may well be connected to the presence of latex proteins, although C. procera cardenolides [94, 199] and C. procera flavonoids [200], present in the latex, have antimicrobial activity, see also [201]. O. O. Shobowale et al. have tested latex extracts of C. procera, harvested in Nigeria, for their antimicrobial activity and have found them to be active against Escherichia coli, Salmonella typhi, and Bacillus subtilis. Here, ethanolic extracts were found to be more effective than aq. extracts [202]. Also, it has been reported that the inhibitory effect of latex extracts on E. coli was more pronounced than that of leaf extracts [203]. Sampling sites and seasonal variations in which the plant was harvested as well as the extract preparation play a significant role in the antimicrobial properties of the plants.

3.5

Antiprotozoal Activity of Calotropis Latex Extracts

Malaria remains a deadly parasitic disease in sub-Saharan Africa, areas of South America, India, as well as parts of Southeast Asia. In some of these areas, it has a high rate of incidence and high mortality rates. There are five kinds of malaria parasites that infect humans, Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. While the first four are transmitted from mosquitoes to humans, the last is transmitted from macaques to humans. Traditionally, C. procera [19] as well as C. gigantea plant extracts [204] have been used as an antimalarial remedy. However, the antiplasmodial activity of Calotropis latex has only been studied sparingly [205]. This may also be due to the fact that leaf and flower extracts, which have been studied extensively in this regard, have for the most part few side effects than root or latex extracts. Thus, K. Samuel and Y.I. Sudi showed that albino rats upon ingestion of latex extract exhibited appreciably changed hematological parameters. At an ingestion of 0.6 mL latex/kg, the animals showed a reduced packed cell volume (31.33  1.76% vs. 37.67  0.67%), a reduced white (4.10  0.15  103 cells/mm3 vs. 5.47  0.24  103 cells/mm3) and red (3.90  0.06  1012/L vs. 4.73  0.03  1012/L) blood count, and a diminished hemoglobin level (10.43  0.59 g/dL vs. 12.43  0.29 g/dL) [206]. Freeze-dried acetone extract exhibits acute toxicity with a median lethal dose (LD50) of 745 mg/kg body weight in mice [205]. In rats, LD50 for C. procera latex was recorded to be 1 mL/kg addition [207]. On a molecular level, the reason for the antiplasmodial activity of Calotropis has not been made out. Abdulkadir et al. attributed the antiplasmodial

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

787

activity of C. procera to cysteine protease inhibitors [208]. One would expect to find cysteine protease inhibitors mostly in C. procera latex, and Abdulkadir et al. have noted that cysteine protease inhibitor fractions of C. procera latex led to an appreciable suppression (48%, at 50 mg/kg [bw].day ingestion rate) of P. berghei in the mouse model [208].

3.6

Antiviral Activity of Calotropis Latex Extracts

Not much is known about the potential antiviral activity of Calotropis latex extracts. Nevertheless, early work from Khurana et al. found that aq. extracts of C. procera latex, applied to leaves’ surfaces, act as inhibitors of the tobacco mosaic virus, a virus that infects tobacco and other members of the family Solanaceae [209]. Also, it could be shown that the lignin glucoside (+)-pinoresinol 4-O-[600 -O-vanilloyl]-β-Dglucopyranoside (70), isolated from the latex of C. gigantea, has inhibitory activity against A/PR/8/34 (H1N1). Subsequently, it was found to be active against human influenza viruses, both subtype A and B (IC50 values: 13.4–39.8 μM). The vanilloyl unit within the molecule is of importance for its inhibitory activity as (+)-pinoresinol 4-O-β-D-glucopyranoside (69) itself was found to be inactive [210]. There has already been some effort to screen the suitability of metabolites of the Calotropis plants as therapeutic agents against COVID-19. Thus, A.D. Sharma and I. Kaur have looked at possible interactions of calotropin and the main protease Mpro of SARSCoV-2 via in silico molecular docking experiments, finding that it might bind to the S1 pocket and might serve as an inhibitor of the protein [211].

3.7

Antitumor Activity of Calotropis Extracts

Calotropis latex exhibits a larger number of compounds that have antitumor activity in pure and isolated form. These include cardenolides [95, 101, 102, 105, 107, 212–215] and other steroids [110, 216], triterpenoids [216], flavonoids [186], and proteins [187, 188], including a number of chitinase isoforms present especially in the latex of C. procera. Most of the mechanisms that lead many of these molecules to be antitumor agents are not yet known. Highlighted, however, should be the action of cardenolides (Table 1), which are natural ligands of Na+/K+-ATPase, the abnormal expression of which has been reported in various cancers. The sodium pump interacts with neighboring membrane proteins and is intricately linked to different signaling pathways in the cells, which certain cardenolides can influence. For instance, calotropin suppresses tumor growth by inhibiting Wnt signaling. Also, it has been seen that Calotropis extracts induce apoptosis of cancer cells through reactive oxygen species generation. This was found for C. gigantea extract which induced apoptosis in A549 and NCI-H1299 nonsmall cell lung cancer cells [105]. Thus, 48 h treatment of A549 with ethanolic C. gigantea whole plant extracts at 7.5 μg/mL led to cell viability of 68%; the same treatment at 15 μg/mL (48 h) reduced the number of viable cells to 50%. The same treatment of H1299 led to a cell viability of 48% (at 7.5 μg/mL 48 h)

788

A. A. Bankole and T. Thiemann

and 45% (at 15 μg/mL, 48 h). Latex proteins have been noted to be effective against MDA-MB-435, HL-60, HCT-8, and SF-295 cell lines [184]. As for latex extracts, N.H. Mohamed et al. [94] showed that C. procera latex extract has a significant effect on A549 and HeLa cells, while T.L. Jucá et al. [80] found a significant effect of C. procera latex on HL-60, Ovcar-8, HCT-116, and SF-295 cells.

3.8

Uses of Metal Nanoparticles Employing Calotropis Extracts

Metal nanoparticles have been prepared in the presence of latex extracts, where constituents of the extracts can adsorb to the nanoparticles. These particles have been screened for their antimicrobial, antifungal, and antitumor properties. Thus, recently, monodisperse copper nanoparticles have been prepared by mixing aqueous latex extract with copper acetate, leading to an instantaneous reduction of Cu(II) to Cu(0). FT-IR measurements of these nanoparticles led the authors to believe that antioxidant enzymes cysteine protease, and tryptophan are adsorbed on the copper particles. These latex end-capped copper nanoparticles showed no appreciable toxicity toward HeLa, A549, and BHK21 cells, indicating their biocompatibility [217]. Similarly, gold nanoparticles were formed from aq. latex extract and chlorauric acid (HAuCl4). Again, no appreciable toxicity toward HeLa, A549, and BHK21 cells was observed [218]. C. procera latex has been used to produce AgNPs from AgNO3 [130]. AgNPs produced in the presence of C. procera latex were found to inhibit the growth of bacteria E.coli, P. aeruginosa, and Serratia sp., and the fungus C. albicans [219]. Lastly, zinc oxide nanoparticles have been formed from aqueous zinc acetate upon the addition of C. procera latex [220].

3.9

Miscellaneous Uses

While the Calotropis plant, especially its stem and seed pods, has found its application in material uses [1], the material uses of its latex are much more limited. During the World War I, there was some rubber production from C. procera latex, especially in Northeast Africa [79]. Up to 25–35% of the latex by dry weight can be composed of natural rubber [poly(cis-1,4-isoprene, 1) [221]. This polyisoprene has coagulative-like properties that lend an increased adhesiveness to the latex, e.g., when secreted as a response to herbivory [64]. An interesting application of Calotropis latex comes from the food industry. Due to a rise in cheese production worldwide, as well as a decrease in calf rennet availability and rising pricing, researchers are looking for alternative milk clotting enzymes as rennet replacements [222]. In this regard, a cysteine protease (CpCP3) isolated from C. procera latex has biotechnological potential for cheese making. It has several characteristics that make it suitable for commercial use in cheese making: It is resistant to a variety of metal ions. In a similar way to chymosin, it hydrolyzes κ-casein and causes casein micelle aggregation. Indeed, it generates cheeses that are comparable in productivity, protein, fat, and ash content to those prepared with

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

789

chymosin. Cheeses produced with CpCP3 exhibit a high acceptability index for the parameters color, smell, texture, look, taste, and overall impression, according to the sensory studies. The process using CpCP3 has limited potential to produce allergens and toxins. The cysteine protease remains completely active after 96 h at 25
C. Furthermore, it can be effectively expressed in E. coli cells, allowing for large-scale production [125, 223].

4

Conclusion

The latex of both C. procera and C. gigantea has been found to be the source of a plethora of physiologically active chemicals, including strongly antitumor active cardenolides and proteins. Frequently, Calotropis plants grow in profusion on degraded, arid lands without human intervention. Studies have been conducted to evaluate the possibility of increasing farmers’ incomes by the extensive cultivation of Calotropis plants, where the plants are harvested periodically but propagate naturally without the need of external input of water and fertilizer. Little has been openly disclosed of the cultivation of Calotropis for targeted harvesting of constituents of medicinal value, although efforts have been articulated to induce an increased production in the plants of compounds of medicinal value such as cardenolides. While Calotropis extracts are commercially available as insecticides or for medicinal purposes, a large-scale extraction and purification of individual plant constituents still pose significant problems. In this regard, much work is left to be done.

References 1. Al Sulaibi M, Thiemann C, Thiemann T (2020) Chemical constituents and uses of Calotropis procera and Calotropis gigantea – a review (part I – the plants as material and energy resources). Open Chem J (Bentham) 7:1–15 2. Little EL Jr, Woodbury RO, Wadsworth FH (1974) Trees of Puerto Rico and the Virgin Islands, vol 2. U.S. Department of Agriculture, Washington, DC, p 1024 3. Forster PI, Little DJ, Nicholas A (1996) Asclepiadaceae. In: Flora of Australia, vol 8. Australian Government Publishing Service, Canberra, p 214 4. Jagtap VA, Usman MRM, Salunkhe PS, Gagrani MB (2010) Anti-inflammatory activity of Calotropis gigantea Linn. leaves extract on in-vitro models. Int J Curr Pharm Rev Res 1:1–5 5. Space JC, Lorence DH, LaRosa AM (2009) Report to the Republic of Palau: 2008 update on invasive plant species. USDA Forest Service, Hilo, Hawai‘i, p 18 6. Hancock IR, Henderson CP (1988) Flora of the Solomon Islands. Research bulletin no. 7. Ministry of Agriculture and Lands, Honiara, p 54 7. Howard RA (1989) Flora of the Lesser Antilles, Leeward and Windward Islands. Havard University, Jamaica Plain, p 6 8. Krings A, Areces Berazain F, Lazcano Lara JC (2005) New and rediscovered milkweeds from Cuba: Calotropis gigantea and Gonolobus stephanotrichus. Willdenowia 35:315–318 9. Cavalcante A, Major I (2006) Invasion of alien plants in the Caatinga biome. Ambio 35:141–143

790

A. A. Bankole and T. Thiemann

10. Silva MCC, da Silva AB, Texeira FM, de Sousa PCP, Rondon RMM, Honorio JER Jr, Sampaio LRL, Oliveira SL, Holonda ANM, de Vasconcelos SMM (2010) Therapeutic and biological activities of Calotropis procera (Ait.) R. Br. Asian Pac J Trop Med 3:332–336 11. Gracia CA, Rangel-Buitrago N, Castro-Barros J-D (2019) Non-native plant species in the Atlantico Department Coastal Dune Systems, Caribbean of Colombia: a new management challenge. Mar Pollut Bull 141:603–610 12. Ibrahim AH (2013) Tolerance and avoidance responses to salinity and water stresses in Calotropis procera and Suaeda aegyptiaca. Turk J Agric For 37:352–360 13. Al-Zahrani HS (2002) Effects on salinity stress on growth of Calotropis procera seedlings. Bull Pure Appl Sci 21:109–122 14. Cumo C (2015) Plants and people: origin and development of human--plant science relationships, 1st edn. CRC Press, Boca Raton, FL 15. Mulugeta M, Fazlurrahman K, Gizachew M, Archana P (2020) Phytochemical profile and antimicrobial effects of different medicinal plants: current knowledge and future perspectives. Curr Tradit Med 6:24–42 16. Amini MH, Ahmady A, Zhakfar AM, Sediqi MN, Babak G (2019) Preliminary phytochemical profile, in vitro antioxidant and sun protective activities of Alhagi pseudalhagi and Elaeagnus angustifolia L. J Pharm Res Int 31:1–13 17. Fatima A, Ahmad M, Zafar M, Yaseen G, Zada Khan MP, Butt MA et al (2018) Ethnopharmacological relevance of medicinal plants used for the treatment of oral diseases in Central Punjab-Pakistan. J Herb Med 12:88–110 18. Jamshidi-Kia F, Lorigooini Z, Amini-Khoei H (2018) Medicinal plants: past history and future perspective. J Herb Med Pharmacol 7:1–7 19. Verma R, Satsangi GP, Shrivastava JN (2010) Ethno-medicinal profile of different plant parts of Calotropis procera (Ait.) R. Br. Ethnobot Leaflets 14:721–742 20. Ayoub SMH, Kingston DBI (1981) Screening of plants used in Sudan folk medicine for anticancer activity (I). Fitoterapia 52:281–284 21. Ayoub SMH, Svendson AB (1981) Medicinal and aromatic plants in Sudan: usage and exploration. Fitoterapia LII 66:243–246 22. Fleurentin J, Pelt MJ (1982) Repertory of drugs and medicinal plants of Yemen. J Ethnopharmcol 6:85–108 23. Ali NA, Julich WD, Kusnick C, Lindequist U (2001) Screening of Yemeni medicinal plants for antibacterial and cytotoxic activities. J Ethnopharmacol 74:173–179 24. Schopen A (1983) Traditionelle Heilmittel in Jemen. Franz Steiner Verlag GmbH, Wiesbaden 25. Balkrishna A, Misra L (2018) Chemo-botanical and neurological accounts of some Ayurvedic plants useful in mental health. Nat Prod J 8:14–31 26. Ranade AV, Acharya R (2015) Arka and its pharmaceutical attributes in Indian alchemy (Rasashastra): a comprehensive review. Int J Ayurv Med 6:280–288 27. Ranade AV, Acharya R (2015) Arka and its botanical equivalents: a critical analysis. Ayurpharm Int J Ayur Alli Sci 4:60–68 28. Ranade AV, Acharya R (2014) An appraisal on ethno-medicinal claims of Calotropis procera Ait. and Calotropis gigantea (Linn.) R. Br. – two source drugs of Ayurvedic medicinal plant “arka”. Glob J Res Med Plants Indigen Med 3:475–488 29. Chitme HR, Chandra R, Kaushik S (2005) Evaluation of antipyretic activity of Calotropis gigantea (Asclepiadiaceae) in experimental animals. Phytother Res 19:454–456 30. Parhira S, Zhu G-Y, Li T, Liu L, Bai L-P, Jiang Z-H (2016) Inhibition of IKK-β by epidiooxysterols from the flowers of Calotropis procera (Niujiaogua). Chin Med 11:9 31. Nagaty HF, Rifaat MA, Morsy TA (1959) The latex of Calotropis procera (family: Asclepiadaceae), a new substance having anascaricidal effect in-vitro. J Egypt Med Assoc 42:563–566 32. Sharma P, Sharma JD (2000) In-vitro schizonticidal screening of Calotropis procera. Fitoterapia 71:77–79

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

791

33. Larhsini M, Oumoulid L, Lazrek HB, Wataleb S, Bousaid M, Bekkouche K, Jana M (2001) Antibacterial activity of some Moroccan medicinal plants. Phytother Res 15:250–252 34. Olaitan OJ, Wasagu SUR, Adepoju-Bello AA, Nwaeze KU, Olufunsho A (2013) Preliminary anti-fungal activity of the aqueous bark extract of Calotropis procera (Asclepiaceae). Nig Q J Hosp Med 23:338–341 35. Olaitan O (2000) Preliminary study on the phytochemical and antifungal properties of Calotropis procera. Usmanu Danfodiyo University, Sokoto 36. Kumar S, Dewan S, Sangraula H, Kumar VL (2001) Antidiarrhoeal activity of the latex of Calotropis procera. J Ethnopharmacol 76:115–118 37. Das A, Dutta AK, Razzaque S, Saha B, Gope PS, Choudhury N (2011) Analgesic and antidiarrhoel properties of the latex of Calotropis procera. Int J Pharm Biol Arch 2:521–525 38. Rahman R, Rahman F, Shashank B, Rajasshekar S, Gagadhar B, Chandrasekhar S (2012) Evaluation of Calotropis gigantea root in experimental diarrhea. Int J Pharm Ind Res 2:10–15 39. Murti Y, Singh SP, Devender P (2012) Comparison of anti-diarrheal activity of hydroethanolic extract of Calotropis procera and Calotropis gigantea leaves. J Pharm Sci Innov 1:32–33 40. Dewan S, Sangraula H, Kumar VL (2000) Preliminary studies on the analgesic activity of latex of Calotropis procera. J Ethnopharmacol 73:307–311 41. Kirtikar KR, Basu BD (1935) Indian medicinal plants. Sudhindhra Nath Basu, Allahabad 3:1609 42. Aliyu IM, Zezi AU, Magaji MG, Abdu-Aguye I, Ibrahim ZYY, Atiku I, Muntaka A (2017) Anti-histaminic and bronchodilatory activities of aqueous and methanol extracts of Calotropis procera (Ait) R.Br. root bark on allergic asthma in rodents. J Pharm Bioresour 14. https://doi. org/10.4314/jpb.v14i2.4 43. Warrier PK, Nambiar VPK, Ramankutty C (1994) Indian medicinal plants, vol 1. Orient Longman Ltd., Hyderabad, pp 431–435 44. Mhaskar KS, Blatter E, Caius JF (2000) Kirtikar and Basu’s illustrated Indian medicinal plants. Sri Satguru Publication, Dehli, pp 2217–2219 45. Samvatsar S, Diwanji VB (2000) Plant sources for the treatment of jaundice in the tribals of Western Madhya Pradesh of India. J Ethnopharmcol 73:313–316 46. Ebbell B (1935) A contribution to the earliest history of leprosy. Int J Leprosy 3:257–263 47. de Wildeman E (1949) Médicaments antilépreux d’origine végétale. Inst Roy Col Belge Memoire 18:40–44 48. Ba O (1969) Traitement de la lèpre chez les Toucouleurs. Notes africaines 124:126 49. Bacou P (1944) Traitement de la lèpre chez un Bambara de Kouliloro. Notes africaines 22:10 50. Rahimi M (2015) Pharmacognostical aspects and pharmacological activities of Calotropis procera. Bull Environ Pharmacol Life Sci 4:156–162 51. Gautam AK, Bhadauria R (2009) A preliminary survey on ethnomedicinal flora of Bilaspur district, Himachal Pradesh (India). Ethnobot Leaflets 13:123–130 52. Nandkarni AK (1996) Indian materia medica, vol 1. Popular Prakashan, Bombay, p 246 53. Al-Snafi AE (2016) Antiparasitic effects of medicinal plants (part 1) – a review. IOSR J Pharm 6:51–66 54. Asolkar LV, Kakkar KK, Chakre OJ (2005) Glossary of Indian medicinal plants with active principles (second supplement). Part-1. (A-K), (1965–1981). National Institute of Science Communication and Information Resources (CSIR), New Delhi, p 157 55. Kanchan T, Atreya A (2016) Calotropis gigantea. Wilderness Environ Med 27:350–351 56. Ramos MV, Grangeiro TB, Freire EA, Sales MP, Souza DP, Araujo ES, Freitas CDT (2010) The defensive role of latex in plants: detrimental effects on insects. Arthropod-Plant Interact 4:57–66 57. Olaitan OJ, Wasagu SUR, Adepoju-Bello AA, Nwaeze KU, Olufunsho A (2013) Preliminary anti-fungal activity of the aqueous bark extract of Calotropis procera (Asclepiadaceae). Nig Q J Hosp Med 23:338–341 58. Kwon CW, Yang H, Yeo SB, Park K-M, Jeong AJ, Lee KW, Ye S-K, Chang P-S (2018) Molecular cloning and anti-invasive activity of cathepsin L propeptide-like protein from Calotropis procera R. Br. against cancer cells. J Enzyme Inhib Med Chem 33:657–664

792

A. A. Bankole and T. Thiemann

59. Konno KP (2011) Plant latex and other exudates as plant defense systems: roles of various defense chemicals and proteins contained therein. Phytochemistry 72:1510–1530 60. Datta SK, De S (1986) Laticifer differentiation of Calotropis gigantea R. Br. ex Ait. in cultures. Ann Bot 57:403–406 61. Roy AT, De DN (1992) Studies on differentiation of laticifers through light and electron microscopy in Calotropis gigantea (Linn.) R. Br. Ann Bot 70:443–449 62. Waikar S, Srivastava VK (2015) Calotropis induced ocular toxicity. Med J Armed Forces India 71:92–94 63. Ramos MV, Araújo ES, Jucá TL, Monteiro-Moreira ACO, Vasconcelos IM, Moreira RA et al (2013) New insights into the complex mixture of latex cysteine peptidases in Calotropis procera. Int J Biol Macromol 58:211–219 64. Ramos MV, Demarco D, da Costa Souza IC, de Freitas CDT (2019) Laticifers, latex, and their role in plant defense. Trends Plant Sci 24:553–567 65. Kwon CW, Park K-M, Kang B-C, Kweon D-H, Kim M-D, Shin SW et al (2015) Cysteine protease profiles of the medicinal plant Calotropis procera R. Br. revealed by de novo transcriptome analysis. PLoS One 10:e0119328 66. Ahmed OM, Fahim HI, Boules MW, Ahmed HY (2016) Cardiac and testicular toxicity effects of the latex and ethanolic leaf extract of Calotropis procera on male albino rats in comparison to abamectin. SpringerPlus 5:1644 67. Tossou ML, Ballogou V, Maina J, Gicheha M (2018) Effect of Calotropis procera on the proximate composition and potential toxicity of Wagashi (traditional cheese) in Benin. Food Sci Qual Manage 74:30 68. Bezerra CF, Mota ÉF, Silva ACM, Tomé AR, Silva MZR, de Brito D et al (2017) Latex proteins from Calotropis procera: toxicity and immunological tolerance revisited. Chem Biol Interact 274:138–149 69. Iyadurai R, Gunasekaran K, Jose A, Pitchaimuthu K (2020) Calotropis poisoning with severe cardiac toxicity a case report. J Fam Med Prim Care 9:4444–4447 70. Sehgal R, Kumar VL (2005) Calotropis procera latex-induced inflammatory hyperalgesia – effect of anti-inflammatory drugs. Mediat Inflamm 2005:216–220 71. Basak SK, Bhaumik A, Mohanta A, Singhal P (2009) Ocular toxicity by latex of Calotropis procera (Sodom apple). Indian J Ophthalmol 57:232–234 72. Al-Mezaine HS, Al-Amry MA, Al-Assiri A, Fadel TS, Tabbara KF, Al-Rajhi AA (2008) Corneal endothelial cytotoxicity of the Calotropis procera (ushaar) plant. Cornea 27:504–506 73. Khan AQ (1989) Studies in the chemical constituents of Euphorbia tirucalli and Calotropis procera. Dissertation, University of Karachi 74. Thakur S, Das P, Itoh T, Imai K, Matsumoto T (1984) Latex extractables of Calotropis gigantea. Phytochemistry 23:2085–2087 75. Girdhar G, Deval K, Mittal PK, Vasudevan P (1984) Mosquito control by Calotropis latex. Pesticides 18:26–29 76. Ramos MV, Freitas CDT, Staniscuaski F, Macedo LLP, Sales MP, Sousa DP, Carlini CR (2007) Performance of distinct crop pests reared on diets enriched with latex proteins from Calotropis procera: role of laticifer proteins in plant defense. Plant Sci 173:349–357 77. Konno K (2011) Plant latex and other exudates as plant defense systems: roles of various defense chemicals and proteins therein. Phytochemistry 72:1510–1530 78. Juncker T, Schuhmacher M, Dicato M, Diederich M (2009) UNBS1450 from Calotropis procera as a regulator of signaling pathways involved in proliferation and cell death. Biochem Pharmacol 78:1–10 79. Neuwinger HD (1994) Afrikanische Arzneipflanzen und Jagdgifte. Wissenschaftliche Verlagsgesellschaft mbH, Stuttgart, p 224 80. Jucá TL, Ramos MV, Moreno FBMB, Matos MPV, Marinho-Filho JDB, Moreira RA, Monteiro-Moreira ACO (2013) Insights on the phytochemical profile (cyclopeptides) and biological activities of Calotropis procera latex organic fractions. Sci World J. Article ID 615454

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

793

81. Rani R, Sharma D, Chaturvedi M, Yadav JP (2019) Phytochemical analysis, antibacterial and antioxidant activity of Calotropis procera and Calotropis gigantea. Nat Prod J 9:47–60 82. Lewin L (1913) Calotropis procera, einneuesdigitalisartigwirkendes Herzmittel. Arch Exp Path Pharmakol 71:142–156 83. Hesse G, Reicheneder F (1936) Über das afrikanische Pflanzengift Calotropin. Annalen 526: 252–272 84. Hesse G, Lettenbauer G (1957) Ein zweiterschwefelhaltiger Stoff aus dem Milchsaft von Calotropis procera. Angew Chem 69:392–392 85. Hesse G, Ludwig G (1960) Voruscharin, ein zweites schwefelhaltiges Herzgift aus Calotropis procera. Liebigs Ann Chem 632:158–171 86. Mahran GH, Rizkallah MM, Saber AH (1971) A phytochemical study of Calotropis procera (Ait.) R. Br. growing in Egypt. Bull Fac Pharm Cairo Univ 10(1):1–10 87. Hesse G, Hertel H (1957) Herzgift-Methylreduktinsäure. Angew Chem 69:61–61 88. Hesse G, Hertel H, Mix K (1959) Reduktinsäuren und verwandteStoffeausHerzgiften von Calotropis procera. Ann Chem 625:174–183 89. Heusser H (1950) Konstitution, Konfiguration und Synthese digitaloider Aglykone und Glykoside. Fortschr Chem Org Naturst 7:87–166 90. Thieme PC, Engelhardt H (2000) Gerhard Hesse (1908–1997) in memoriam. Eur J Org Chem 2677–2688 91. Hassall CH, Reyle K (1959) Cardenolides. III. The constitution of calotropagenin. J Chem Soc 85–89 92. Cheung HTA, Watson TR (1980) Stereochemistry of the hexosulose in cardenolide glycosides of the asclepiadaceae. J Chem Soc Perkin Trans 1:2162–2168 93. Parihar G, Balekar N (2017) Isolation and characterisation of stigmast-5-en-3-ol (β-sitosterol) from Calotropis procera latex ethyl acetate fraction for immunomodulatory activity. Int J Pharm Sci Res 8:1375–1380 94. Mohamed NH, Liu M, Abdel-Mageed WM, Alwahibi LH, Dai H, Ismail MA, Badr G, Quinn RJ, Liu X, Zhang L, Shoreit AMM (2015) Cytotoxic cardenolides from the latex of Calotropis procera. Bioorg Med Chem Lett 25:4615–4620 95. Parhira S, Zhu GY, Chen M, Bai LP, Jiang ZH (2016) Cardenolides from Calotropis gigantea as potent inhibitors of hypoxia inducible factor-1 transcriptional activity. J Ethnopharmacol 194:930–936 96. You H, Lei M, Song W, Chen H, Meng Y, Guo D, Liu X, Hu L (2013) Cytotoxic cardenolides from the root bark of Calotropis gigantea. Steroids 78:1029–1034 97. Brüschweiler F, Stoecklin W, Stoeckel K, Reichstein T (1969) Die Glykoside von Calotropis procera R. BR. Helv Chim Acta 52:2086–2106 98. Erdman MD (1983) Nutrient and cardenolide composition of unextracted and solventextracted Calotropis procera. J Agric Food Chem 31:513–516 99. Seiber JN, Nelson CJ, Lee SM (1982) Cardenolides in the latex and leaves of seven Asclepias species and Calotropis procera. Phytochemistry 21:2343–2348 100. Zheng Z, Zhou Z, Zhang Q, Zhou X, Yang J, Yang M-R, Zhu G-Y, Jiang Z-H, Li T, Lin Q, Bai L-P (2021) Non-classical cardenolides from Calotropis gigantea exhibit anticancer effect as HIF-1 inhibitors. Bioorg Chem 109:104740 101. Seeka S, Sutthivaiyakit S (2010) Cytotoxic cardenolides from the leaves of Calotropis gigantea. Chem Pharm Bull 58:725–728 102. Lhinhatrakool T, Sutthivaiyakit S (2006) 19-Nor- and 18,20-epoxy-cardenolides from the leaves of Calotropis gigantea. J Nat Prod 69:1249–1251 103. Pederson PJ, Cai S, Carver C, Powell DR, Risinger AL, Grkovic T, O’Keefe BR, Mooberry SL, Cichewicz RH (2020) Triple-negative breast cancer cells exhibit differential sensitivity to cardenolides from Calotropis gigantea. J Nat Prod 83:2269–2280 104. Kiuchi F, Fukao Y, Maruyama T, Obata T, Tanaka M, Sasaki T, Mikage M, Haque ME, Tsuda Y (1998) Cytotoxic principles of a Bangladeshi crude drug, akondmul (roots of Calotropis gigantea L.). Chem Pharm Bull 46:528–530

794

A. A. Bankole and T. Thiemann

105. Lee J, Jang H-J, Chun H, Pham T-H, Bak Y, Shin J-W, Jin H, Kim Y-I, Ryu HW, Oh SR, Yoon DY (2019) Calotropis gigantea extract induces apoptosis through extrinsic/intrinsic pathways and reactive oxygen species generation in A549 and NCI-H1299 non-small cell lung cancer cells. BMC Compl Med Ther 19:134 106. Parhira S, Zhu G-Y, Jiang R-W, Liu L, Bai L-P, Jiang Z-H (2014) 20 -Epi-uscharin from the latex of Calotropis gigantea with HIF-1 inhibitory activity. Sci Rep 4:4748 107. Van Quaquebeke E, Simon G, André A, Dewelle J, El Yazidi M, Bruyneel F, Tuti J, Nacoulma O, Guissou P, Decaestecker C, Braekman J-C, Kiss R, Darro F (2005) Identification of a novel cardenolide (20 -oxovoruscharin) from Calotropis procera and the hemisynthesis of novel derivatives displaying potent in vitro antitumor activities and high in vivo tolerance: structureactivity relationship analyses. J Med Chem 48:849–856 108. Kanojiya S, Madhusudanan P (2012) Rapid identification of Calotropagenin glycosides using high-performance liquid chromatography electrospray ionisation tandem mass spectrometry. Phytochem Anal 23:117–125 109. Hesse G, Heuser LJ, Hütz E, Reicheneder F (1950) Zusammenhänge zwischen den wichtigsten Giftstoffen der Calotropis procera V. Mitteilung über afrikanische Pfeilgifte. Justus Liebigs Ann Chem 566:130–139 110. Jacinto SD, Chun EAC, Montuno AS, Shen C-C, Espineli DL, Ragasa CY (2011) Cytotoxic cardenolide and sterols from Calotropis gigantea. Nat Prod Commun 6:803–806 111. Shaker KH, Morsy N, Zinecker H, Imhoff JF, Schneider B (2010) Secondary metabolites from Calotropis procera (Aiton). Phytochem Lett 3:212–216 112. Hesse G, Eilbracht H, Reicheneder F (1941) Das krystallisierte Calotropis-Harz. Liebigs Ann Chem 546:233–252 113. Murti PBR, Seshadri TR (1943) Chemical composition of Calotropis gigantea. Proc Indian Acad Sci A18:145–159 114. Pant R, Chaturvedi K (1989) Chemical analysis of Calotropis procera latex. Curr Sci 58:740– 742 115. Pant R, Chaturvedi K (1989) Occurrence of lupeol in Calotropis procera latex. Curr Sci 58: 302–303 116. Khastgir HN, Pradhan BP, Duffield AM, Durham LJ (1967) Identification of a new terpene, 3-epimoretenol, from the bark of Sapium sebiferum Roxb. J Chem Soc Chem Commun 1217–1218 117. Wagh SJ, Gujar JG, Gaikar VG (2012) Experimental and modeling studies on extraction of amyrins from latex of mandar (Calotropis gigantea). Ind J Chem Technol 19:427–433 118. Dubey VK, Jagannadham MV (2003) Procerain, a stable cysteine protease from the latex of C. procera. Phytochemistry 62:1057–1071 119. Dubey VK, Jagannadham MV (2003) Differences in the unfolding of procerain induced by pH, guanidine hydrochloride, urea, and temperature. Biochemist 42:12287–12297 120. Singh AN, Shukla AK, Jagannadham MV, Dubey VK (2010) Purification of a novel cysteine protease, procerain B, from Calotropis procera with distinct characteristics compared to procerain. Process Biochem 45:399–406 121. Singh AN, Dubey VK (2011) Exploring applications of procerain B, a novel protease from Calotropis procera, and characterization by N-terminal sequencing as well as peptide mass fingerprinting. Appl Biochem Biotechnol 164:573–580 122. Singh AN, Singh S, Dubey VK (2013) Immobilization of procerain B, a cysteine endopeptidase, on amberlite MB-150 beads. PLoS One 8:e66000 123. Freitas CDT, Oliveira JS, Miranda MR, Macedo NM, Sales MP, Villas-Boas LA, Ramos MV (2007) Enzymatic activities and protein profile of latex from Calotropis procera. Plant Physiol Biochem 45:781–789 124. Bruno-Moreno F, de Oliveira RSB, Moreira RD, Lobo MDP, de Freitas CDT, Ramos MV, Grangeiro TB, Monteiro-Moreira ACO (2013) Crystallization and X-ray diffraction analysis of an antifungal laticifer protein. Acta Cryst Sect F 69:646–649

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

795

125. Abraham KI, Joshi PN (1979) Studies on proteinases from Calotropis gigantea latex, I. Purification and some properties of two proteinases containing carbohydrate. Biochim Biophys Acta 568:111–119 126. Freitas CDT, Leite HB, Oliveira JPB, Amaral JL, Egito AS, Vairo-Cavalli S et al (2016) Insights into milk-clotting activity of latex peptidases from Calotropis procera and Cryptostegia grandiflora. Food Res Int 87:50–59 127. Pal GP, Sinha NK (1980) Isolation, crystallization and properties of calotropins DI and DII from Calotropis gigantea. Arch Biochem Biophys 202:321–329 128. Pal GP, Sinha NK, Saenger W (1981) Crystallizations and preliminary x-ray studies of calotropins DI and DII. J Mol Biol 153:1157–1159 129. Heinemann U, Pal GP, Hilgenfeld R, Saenger W (1982) Crystal and molecular structure of the sulfhydryl protease calotropin DI at 3.2 Åresolution. J Mol Biol 161:591–606 130. Mondal AK, Mondal S, Samanta S, Mallick S (2011) Synthesis of ecofriendly silver nanoparticle from plant latex used as an important taxonomic tool for phylogenetic interrelationship. Adv Biores 2:122–133 131. Wang D-M, Pu W-J, Wang Y-H, Zhang Y-J, Wang S-S (2012) A new isorhamnetin glycoside and other phenolic compounds from Callianthemum taipaicum. Molecules 17:4595–4603 132. Ouyang M-A, Wein Y-S, Zhang Z-K, Kuo Y-H (2007) Inhibitory activity against tobacco mosaic virus (TMV) replication of pinoresinol and syringaresinol lignans and their glycosides from the root of Rhus javanica var. roxburghiana. J Agric Food Chem 55:6460–6465 133. Deyama T, Ikawa T, Nishibe S (1985) The constituents of Eucommia ulmoides OLIV. II. Isolation and structures of three new lignan glycosides. Chem Pharm Bull 33:3651–3657 134. Parhira S, Yang Z-F, Zhu G-Y, Chen Q-L, Zhou B-X, Wang Y-T et al (2014) In vitro antiinfluenza virus activities of a new lignan glycoside from the latex of Calotropis gigantea. PLoS One 9:e104544 135. Larhsini M, Lazrek HB, Bousaid M, Jana M, Amarouch H (1997) Evaluation of antifungal and molluscicidal properties of extracts of Calotropis procera. Fitoterapia 68:371–373 136. Ramos MV, Bandeira GP, de Freitas CD, Nogueira NAP, Alencar NMN, de Sousa PA, Carvalho AFU (2006) Latex constituents from Calotropis procera (R. Br.) display toxicity upon egg hatching and larvae of Aedes aegypti (Linn.). Mem Inst Oswaldo Cruz 101:503–510 137. Singhi M, Joshi V, Sharma RC, Sharma K (2004) Ovipositioning behavior of Aedes aegypti in different concentrations of latex of Calotropis procera: studies on refractory behavior and its sustenance across genotrophic cycles. Dengue Bull 28:184–188 138. Markouk M, Bekkouche K, Larhsini M, Bousaid M, Lazrek HB, Jana M (2000) Evaluation of some Moroccan medicinal plant extracts for larvicidal activity. J Ethnopharmacol 73:293–297 139. Shahi M, Hanafi-Bojd AA, Iranshahi M, Vatandoost H, Hanafi-Bojd MY (2010) Larvicidal efficacy of latex and extract of Calotropis procera (Gentianales: Asclepiadaceae) against Culex quinquefasciatus and Anopheles stephensi (Diptera: Culicidae). J Vector Borne Dis 47:185–188 140. Tahir HM, Ishaq T, Mukhtar MK, Khan SY, Ahmed L (2013) Potential use of Calotropis procera (milk weed) to control Culex quinquefasciatus (Diptera: culicidae). Pak J Zool 45: 615–621 141. Singhi M, Purohit A, Chattopadhyay S (2015) Effectiveness and feasibility of methanol extracted latex of Calotropis procera as larvicide against dengue vectors of western Rajasthan, India. J Vector Borne Dis 52:142–146 142. Al Robai AA (1997) Toxicological studies on the latex of the uscher plant C. procera (Ait) in Saudi Arabia. IV. Effects of partly purified uscher latex and of the poison gland secretion of the uscherhopper; Poekilocerus bufonius Klug on the desert locust, Schistocerca gregaria Forskal. (Orthoptera: Acrididae). Arab Gulf J Sci Res 15:709–716 143. Pari K, Rao PJ, Devakumar C, Rastogi JN (1998) A novel insect antifeedant nonprotein amino acid from Calotropis gigantea. J Nat Prod 61:102–104 144. Suparpprom C, Vilaivan T (2001) Synthesis of 2-[40 - (ethylcarbamoyl)phenyl]-Nacetylglycine, the proposed structure for giganticine. J Nat Prod 64:1114–1116

796

A. A. Bankole and T. Thiemann

145. Al-Rajhy DH, Alahmed AM, Hussein HI, Kheir SM (2003) Acaricidal effects of cardiac glycosides, azadirachtin and neem oil against the camel tick, Hyalomma dromedarii (Acari: Ixodidae). Pest Manag Sci 59:1250–1254 146. Pereira DA, Ramos MV, Souza DP, Portela TCL, Guimarȁes JA, Madeira SVF, de Freitas CDT (2010) Digestibility of defense proteins in latex of milkweeds by digestive proteases of Monarch butterflies, Danaus plexippus L.: a potential determinant of plantherbivoreinteractions. Plant Sci 179:348–355 147. Devi LS, Gupta P (2000) Evaluation of some plant lattices against Heterodera cajani in cowpea (Vigna sinensis). Natl Acad Sci Lett 23:65–67 148. Cavalcante GS, de Morais SM, Andre WPP, Ribeiro WLC, Rodrigues ALM, De Lira FC, Viana JM, Bevilaqua CML (2016) Chemical composition and in vitro activity of Calotropis procera (Ait.) latex on Haemonchus contortus. Vet Parasitol 226:22–25 149. Al-Sarar A, Hussein H, Abobakr Y, Bayoumi A (2012) Molluscicidal activity of methomyl and cardenolide extracts from Calotropis procera and Adenium arabicum against the land snail Monachacantiana. Molecules 17:5310–5318 150. Hussein HI, Kamel A, Abou-Zeid M, Abdel-Khalek, El-Sebae H, Saleh MA (1994) Uscharin, the most potent molluscicidal compound tested against land snails. J Chem Ecol 20:135–140 151. Gutiérez JM, Warrell DA, Williams DJ, Jensen S, Brown N, Calvete JJ (2013) Global snakebite initiative. The need for full integration of snakebite envenoming within a global strategy to combat the neglected tropical diseases: the way forward. PLoS Negl Trop Dis 7: e2162 152. Félix-Silva J, Silva-Junior AA, Zucolotto SM, de Freitas Fernandes-Pedrosa M (2017) Medicinal plants for the treatment of local tissue damage induced by snake venoms: an overview from traditional use to pharmacological evidence. Evid-Based Compl Altern Med 2017: 5748256 153. Upasani SV, Beldar VG, Tatiy AU, Upasani MC, Surana SS, Patil DS (2017) Ethnomedicinal plants used for snakebite in India: a brief overview. Integr Med Res 6:114–130 154. Oudhia P. Traditional medicinal knowledge about common herbs used in treatment of snakebite: the result of recent ethnobotanical surveys in Chhattisgarh, India. http://botanical.com/ site/column_poudhia/285_snakebite.html. Accessed 1 June 2020 155. Sri BS, Reddi TVVS (2011) Traditional phyto-antidotes used for snakebite by Bagata tribe of Eastern Ghats, Visakhapatnam district, Andhra Pradesh. Int Multidiscpl Res J 1:42–45 156. Shah A, Sarvat R, Shoaib S, Ayodele AE, Nadeem M, Qureshi TM, Ishitiaq M, Abbas A (2018) An ethnobotanical survey of medicinal plants used for the treatment of snakebite and scorpion sting among the people of Namal Valley, Mianwali District, Punjab, Pakistan. Appl Ecol Environ Res 16:111–143 157. Molander M, Nielsen L, Søgaard S, Staerk D, Rønsted N, Diallo D, Chifundera KZ, van Staden J, Jäger AK (2014) Hyaluronidase, phospholipase A2 and protease inhibitory activity of plants used in traditional treatment of snakebite-induced tissue necrosis in Mali, DR Congo and South Africa. J Ethnopharmacol 157:171–180 158. Mishra A, George A, Samson N, Sathyendra DS (2015) A rare case of Calotropis poisoning. Indian J Forensic Med Toxicol 9:62–64 159. Reddy CY (2019) Clinical manifestations in Calotropis poisoning: a prospective study in Government General Hospital Nalgonda, India. Int J Adv Med 6:1314–1316 160. Singh H, Kumar S, Dewan S, Kumar VL (2000) Inflammation induced by latex of Calotropis procera – a new model to evaluate anti-inflammatory drugs. J Pharmcol Toxicol Methods 43: 219–224 161. Handa F, Sadana JK, Sharma PK (1984) Allergic dermatitis due to the plant Calotropis procera (Vern: AK). A case report. Indian J Dermatol 39:27–29 162. Al-Mezaine HS, Al-Rajhi AA, Al-Assiri A, Wagoner MD (2005) Calotropis procera (ushaar) keratitis. Am J Ophthalomol 139:199–202 163. Biedner B, Rothkoff L, Witzum A (1977) Calotropis procera (Sodom apple) latex keratoconjuctivitis. Isr J Med Sci 13:914–916

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

797

164. Tomar VPS, Agarwal PK, Agarwal BL (1970) Toxic iridocyclitis caused by calotropis. Indian J Ophathmol 18:15–16 165. Padhy BM, Kumar VL (2005) Inhibition of Calotropis procera latex-induced inflammatory hyperalgesia by oxytocin and melatonin. Mediat Inflamm 6:360–365 166. Shivkar YM, Kumar VL (2003) Histamine mediates the pro-inflammatory effect of latex of Calotropis procera in rats. Mediat Inflamm 4:299–302 167. Shivkar YM, Kumar VL (2004) Effect of anti-inflammatory drugs on pleurisy induced by latex of Calotropis procera in rats. Pharmacol Res 50:335–340 168. Kumar VL, Shivkar YM (2004) Involvement of prostaglandins in inflammation induced by latex of Calotropis procera. Mediat Inflamm 5:151–155 169. Sehgal R, Kumar VL (2005) Calotropis procera latex-induced inflammatory hyperalgesiaeffect of anti-inflammatory drugs. Mediat Inflamm 6:216–220 170. Kumar VL, Basu N (1994) Anti-inflammatory activity of the latex of Calotropis procera. J Ethnopharmcol 44:123–125 171. Sangraula H, Dewan S, Kumar VL (2002) Evaluation of anti-inflammatory activity of latex of Calotropis procera in different models of inflammation. Inflammopharmacol 9:257–264 172. Dewan S, Kumar S, Kumar VL (2000) Antipyretic effect of latex of Calotropis procera. Indian J Pharmacol 32:252–252 173. Arya S, Kumar VL (2005) Antiinflammatory efficacy of extracts of latex of Calotropis procera against different mediators of inflammation. Mediat Inflamm 2005:228–232 174. Awasthi S, Irshad M, Das MK, Ganti SS, Rizvi MA (2009) Anti-inflammatory activity of Calotropis gigantea and Tridax procumbens on carrageenin-induced paw edema in rats. Ethnobot Leaflets 13:568 175. Basu A, Chaudhuri AK (1991) Preliminary studies on the antiinflammatory and analgesic activities of Calotropis procera root extract. J Ethnopharmacol 31:319–332 176. Kumar VL, Basu N (1994) Anti-inflammatory activity of the latex of Calotropis procera. J Ethnopharmacol 44:123–125 177. Obese E, Ameyaw EO, Biney RP, Henneh IT, Edzeamey FJ, Woode E (2018) Phytochemical screening and anti-inflammatory properties of the hydroethanolic leaf extract of Calotropis procera (Ait). R. Br. (Apocynaceae). J Pharm Res Int 23:1–11 178. Kumar VL, Pandey A, Verma S, Das P (2019) Protection afforded by methanol extract of Calotropis procera latex in experimental model of colitis is mediated through inhibition of oxidative stress and pro-inflammatory signaling. Biomed Pharmacother 109:1602–1609 179. Awaad AA, Alkanhal HF, El-Meligy RM, Zain GM, Sesh Adri VD, Hassan DA, Alqasoumi SI (2018) Anti-ulcerative colitis activity of Calotropis procera Linn. Saudi Pharm J 26:75–78 180. Alencar NMN, Figueiredo IST, Vale MR, Bitencurt FS, Oliveira JS, Ribiro RA, Ramos MV (2004) Anti-inflammatory effect of the latex from Calotropis procera in three different experimental models: peritonitis, paw edema and hemorrhagic cystitis. Planta Med 70:1144–1149 181. Alencar NMN, Oliveira JS, Mesquita RO, Lima MW, Vale MR, Etchells JP, Freitas CDT, Ramos MV (2006) Pro- and anti-inflammatory activities of the latex of Calotropis procera (Ait.) R. Br. are triggered by compounds fractionated by dialysis. Inflamm Res 55:559–564 182. Kumar VL, Chaudhary P, Ramos MV, Mohan M, Matos MPV (2011) Protective effect of proteins derived from the latex of Calotropis procera against inflammatory hyperalgesia in monoarthritic rats. Phytother Res 25:1336–1341 183. Soares PM, Lima SR, Matos SG, Andrade MM, Patrocinio CA, de Freitas CDT, Ramos MV, Criddle DN, Cardi BA, Carvalho KM, Assreuy AMS, Vasconcelos MMS (2005) Antinociceptive activity of C. procera latex in mice. J Ethnopharmcol 99:125–129 184. Texeira FM, Ramos MV, Soares AA, Oliveira RSB, Almeida-Filho LCP, Oliveira JS, Marinho-Filho JDB, Carvalho CPS (2011) In vitro tissue culture of the medicinal shrub Calotropis procera to produce pharmacologically active proteins from plant latex. Process Biochem 46:1118–1124 185. Ali-Seyed M, Siddiqua A (2020) Calotropis – a multi-potential plant to humankind: special focus on its wound healing efficacy. Biocat Agric Biotechn 28:101725

798

A. A. Bankole and T. Thiemann

186. Roy S, Uddin MZ, Hassan A, Rahman MM (2008) Medico-botanical report on the Chakma community of Bangladesh. J Plant Taxon 15:67–72 187. Biswas TK, Mukherjee B (2003) Plant medicines of Indian origin for wound healing activity, a review. Int J Lower Extrem Wound 2:25–39 188. Deshmukh PT, Fernandes J, Atul A, Toppo E (2009) Wound healing activity of Calotropis gigantea root bark in rats. J Ethnopharmcol 125:178–181 189. Nalwaya N, Pokharna G, Deb L, Jain NK (2009) Wound healing activity of latex of Calotropis gigantea. Int J Pharm Pharm Sci 1:176–182 190. Aderounmu AO, Omonisi AE, Akingbasote JA, Makanjuola M, Bejide RA, Orafidiya LO, Adelusola KA (2013) Wound-healing and potential anti-keloidal properties of the latex of Calotropis procera (Aiton) Asclepiadaceae in rabbits. Afr J Tradit Complement Altern Med 10:574–579 191. Rajesh R, Raghavendra Gowda CD, Nataraju A, Dhananjaya BL, Kemparaju K, Vishwanath BS (2005) Procoagulant activity of Calotropis gigantea latex associated with fibrin (ogen) olyticactivity. Toxicon 46:84–92 192. Urs AP, Manjuprasanna V, Rudresha G, Yariswamy M, Vishwanath B (2017) Plant latex proteases: natural wound healers. In: Proteases in physiology and pathology. Springer, Singapore, pp 297–323 193. Samudrala S (2008) Topical hemostatic agents in surgery: a surgeon’s perspective. AORN J 88:S2–S11 194. Shivaprasad HV, Riyaz M, Kumar RV, Dharmappa KK, Tarannum S, Siddesha JM, Rajesh R, Vishwanath BS (2009) Cysteine proteases from the Asclepiadeceae plants latex exhibited thrombin and plasmin like activities. J Thromb Thrombolysis 28:304–308 195. Ramos MV, Viana CA, Silva AFB, Freitas CDT, Figueiredo IST, Oliveira RSB, Alencar NMN, Lima JVM, Kumar VL (2012) Proteins derived from latex of C. procera maintain coagulation homeostasis in septic mice and exhibit thrombin- and plasmin-like activities. Naunyn Schmiedeberg's Arch Pharmacol 385:455–463 196. Urs AP, Rudresha GV, Manjuprasanna VN, Suvilesh KN, Milan Gowda MD, Yariswamy M, Hiremath V, Ramakrishnan C, Savitha MN, Jayachandra K, Sharanappa P, Vishwanath BS (2019) Plant latex thrombin-like cysteine proteases alleviates bleeding by bypassing factor VIII in murine model. J Cell Biochem 120:12843–12858 197. Vasconcelos MMS, Souza TFG, Figueiredo IS, Sousa ET, Sousa FD, Moreira RA, Alencar NMN, Lima-Filho JV, Ramos MV (2018) A phytomodulatory hydrogel with enhanced healing effects. Phytother Res 32:688–697 198. Samy RP, VTK C (2012) Pilot study with regard to the wound healing activity of protein from Calotropis procera (Ait.) R. Br. Evid-Based Compl Altern Med 2012:294528 199. Akhtar N, Malik A, Ali SN, Kazmit SU (1992) Proceragenin, an antibacterial cardenolide from Calotropis procera. Phytochemistry 31:2821–2824 200. Neenah G (2013) Antimicrobial activity of Calotropis procera Ait. (Asclepiadaceae) and isolation of four flavonoid glycosides as the active constituents. World J Microbiol Biotechnol 29:1255–1262 201. Amini MH, Ashraf K, Salim F, Lim SM, Ramasamy K, Manshoor N, Sultan S, Ahmad W (2021) Important insights from the antimicrobial activity of Calotropis procera. Arab J Chem 14:103181 202. Shobowale OO, Ogbulie NJ, Itoandon EE, Oresegun MO, Olatope SOA (2013) Phytochemical and antimicrobial evaluation of aqueous and organic extracts of Calotropis procera Ait leaf and latex. Nig Food J 31:77–82 203. Kareem SO, Akpan I, Ojo OP (2008) Antimicrobial activities of Calotropis procera on selected pathogenic microorganisms. Afr J Biomed Res 11:105–110 204. Taek MM, Tukan GD, Prajogo BEW, Agil M (2021) Antiplasmodial activity and phytochemical constituents of the selected antimalarial plants used by native people in West Timor Indonesia. Turk J Pharm Sci 18:80–90

29

Chemistry, Biological Activities, and Uses of Calotropis Latex

799

205. Adejoh J, Inyang BA, Egua MO, Nwachukwu KC, Alli LA, Okoh MP (2021) In-vivo antiplasmodial activity of phosphate buffer extract of Calotropis procera latex in mice infected with Plasmodium berghei. J Ethnopharmacol 277:114237 206. Samuel K, Sudi YI (2020) Effects of Calotropis procera latex on biochemical and hematological parameters in albino rats. Nig J Biotech 37:94–100 207. Simonsen HT, Nordskjold JB, Smitt UW, Nyman U, Palpu P, Joshi P, Varughese G (2001) In vitro screening of Indian medicinal plants for antiplasmodialactivity. J Ethnopharmacol 74: 195–204 208. Abdulkadir A, Umar I, Ibrahim S, Onyike E, Kabiru A (2006) Cysteine protease inhibitors from Calotropis procera with antiplasmodial potential in mice. J Adv Med Pharm Sci 6:1–13 209. Khurana SMP, Singh S (1972) Studies on Calotropis procera latex as inhibitor of tobacco mosaic virus. J Phytopathol 73:341–346 210. Mamidala E, Gujjeti RP, Namthabad S (2014) Calotropis gigantea flowers extracts with HIV-1 reverse transcriptase (RT) inhibitory activity. World J Pharm Pharmaceut Sci 3: 1016–1022 211. Sharma AD, Kaur I (2020) Calotropin from milk of Calotropis gigantea a potent inhibitor of COVID 19 corona virus infection by Molecular docking studies. arXiv:2012.06139 [q-bio.BM] 212. Hasballah K, Sarong M, Rusly R, Fitria H, Maida DR, Iqhrammullah M (2021) Antiproliferative activity of triterpenoid and steroid compounds from ethyl acetate extract of Calotropis gigantea root bark against P388 murine leukemia cell lines. Sci Pharm 89:21 213. Mutiah R, Widyawaruyanti A, Sukardiman S (2018) Calotropis gigantea leaf extract increases the efficacy of 5-fluorouracil and decreases the efficacy of doxorubicin in Widr colon cancer cell culture. J Appl Pharm Sci 8:51–56 214. Nguyen MTT, Nguyen KDH, Dang PH, Nguyen HX, Awale S, Nguyen NT (2020) A new cytotoxic cardenolide from the roots of Calotropis gigantea. Nat Prod Res. https://doi.org/10. 1080/14786419.2020.1781114 215. Khang PV, Zhang Z-G, Meng Y-H, Guo DA, Liu X, Hu LH, Ma L (2014) Cardenolides from the bark of Calotropis gigantea. J Nat Res 28:1191–1196 216. Ibrahim SRM, Mohamed GA, Shaala LA, Banuls LMY, van Goietsenoven G, Kiss R, Youssef DTA (2012) Newursane-type triterpenes from the root bark of Calotropis procera. Phytochem Lett 5:490–495 217. Harne S, Sharma A, Dhaygude M, Joglekar S, Kodam K, Hudlikar M (2012) Novel route for rapid biosynthesis of copper nanoparticles using aqueous extract of Calotropis procera L. latex and their cytotoxicity on tumor cells. Colloids Surf 95:284–288 218. Das RK, Sharma P, Nahar P, Bora U (2011) Synthesis of gold nanoparticles using aqueous extract of Calotropis procera latex. Mat Lett 65:610–613 219. Mohamed NH, Ismail MA, Abdel-Mageed WM, Shoreti AAM (2014) Antimicrobial activity of latex silver nanoparticles using Calotropis procera. Asian Pac J Trop Biomed 4:876–883 220. Singh RP, Shukla VK, Yadav RS, Sharma PK, Singh PK, Pandey AC (2011) Biological approach of zinc oxide nanoparticle formation and its characterization. Adv Mater Lett 2: 313–317 221. Mohamed NH, Ismail MA, Abdel-Mageed WM, Shoreit AAM (2017) Biodegradation of natural rubber latex of Calotropis procera by two endophytic fungal species. J Bioremed Biodegr 8:1–5 222. Anusha R, Singh MK, Bindhu OS (2014) Characterisation of potential milk coagulants from Calotropis gigantea plant parts and their hydrolytic pattern of bovine casein. Eur Food Res Technol 238:997–1006 223. Silva MZR, Oliveira JPB, Ramos MV, Farias DF, de Sá CA, Ribeiro JAC et al (2020) Biotechnological potential of a cysteine protease (CpCP3) from Calotropis procera latex for cheesemaking. Food Chem 307:125574

Chemistry, Biological Activities, and Uses of Ficus carica Latex

30

María Victoria Castelli and Silvia Noelí Lo´pez

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Chemical Composition of F. carica Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Volatile Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Triterpenoids, Phytosterols, and Fatty Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Organic Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Amino Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Gum or Natural Rubber . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6 Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Ethnopharmacological Uses of F. carica Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Biological Activities of F. carica Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Antimicrobial Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Acetylcholinesterase Inhibition . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Cytotoxicity and Antiviral Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Toxicology . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Economic Importance . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

802 803 803 805 807 808 808 808 814 815 815 816 817 817 818 818 818 819

Abstract

Ficus carica L. (Moraceae), also known as the common fig, is the most relevant fig species. It is valued both as food and as medicine. Fig contains milky latex in all parenchymatous tissues, which consists of the cytoplasmic content of laticifers and is leaked in response to physical damage. In this book chapter, aspects of the chemical composition of latex from the common fig are reviewed, including proteins with enzymatic activity, fatty acids, amino acids, volatile and nonvolatile low molecular weight molecules (secondary metabolites), and rubber particles. M. V. Castelli · S. N. López (*) Farmacognosia, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario – CONICET, Rosario, Argentina e-mail: [email protected]; [email protected] © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_34

801

M. V. Castelli and S. N. Lo´pez

802

Biological activity, ethnopharmacological uses, and commercial aspects of fig latex and enzymes with high economic value purified from F. carica latex are also discussed. Keywords

Ethnopharmacology · Ficin · Ficus carica · Latex · Rubber · Warts List of Abbreviations

GC-IT-MS HPLC-DAD HPLC-UV HPLC-UV-MS/MS HPLC-UV/Vis HS-SPME/GC-IT-MS TLC

1

Gas Chromatography-Ion Trap-Mass Spectrometry High-Performance Liquid Chromatography-Diode Array Detector High-Performance Liquid Chromatography-Ultraviolet High-Performance Liquid Chromatography- Ultraviolet-Mass/Mass High-Performance Liquid Chromatography-Ultraviolet/ Visible Headspace Solid-Phase Microextraction/Gas Chromatography-Ion Trap-Mass Spectrometry Thin Layer Chromatography

Introduction

Latex is a biological sticky fluid produced by laticifers, a specialized type of secretory cells that are peculiar in phenotype, differentiation, and physiological role found in a wide variety of plants. Laticifers are long branched or tubular structures distributed throughout the plant body. The stored latex consists of the cytoplasmic content of laticifers and is leaked at the wound site in response to physical damage. When these cells are injured, the latex is distributed to any damaged plant tissue [1]. A complex mixture of molecules and plant cell organelles, such as nuclei, mitochondria, vacuoles, ribosomes, and others have been described in latex [2]. Most of the described metabolites are biosynthesized and/or accumulated in the organelles (plastids, endoplasmic reticulum) and transferred to the central vacuole where an emulsion (the latex) is formed with the lipophilic and hydrophilic compounds [3]. In some plant species, the latex serves as storage for food, while in other plants, it contains specific metabolites such as cardiac glycosides, alkaloids, tannins, terpenoids, and cannabinoids [4]. Proteins with enzymatic activity such as lipases and peptidases, involved in the antioxidative metabolism among other functions, are also commonly found in various latex samples [3]. Gum or natural rubber is a biopolymeric component (cis1,4-polyisoprene) found in some plant latexes and is of great importance in human society. It is amply employed in the production of industrial and medicinal products that require elasticity and flexibility. Natural rubber was historically obtained from Hevea brasiliensis (also known as rubber tree) latex. Due to its high rubber content and quality, it is the only commercial source [5].

30

Chemistry, Biological Activities, and Uses of Ficus carica Latex

803

Latexes and laticifers appear to have an extraordinary combination of tools that plants use to defend themselves against predators, infectious agents, etc., beyond their biological identity [3]. The laticiferous network is strategically distributed throughout the plant tissue. In this context, peptidases, which are already present in appreciable amounts, acquire a major protagonism, being the cutting edge of defense when the latex is released after an injury, accompanied by the release of bioactive, probably toxic, secondary metabolites [3]. After contact with the air, latex acts as a physical defense by forming a sticky barrier that seals wounds, immobilizes insects’ mouthparts, and even traps small insects [6]. To date, at least 43 families of vascular plants are known to contain laticifers, with angiosperms being the largest group with 41 families. Laticifers have been described either in the basal clades, basal eudicots, magnoliids, monocots, asterids, or rosids [7]. Ficus L. genus includes more than 800 species and belongs to the angiosperm family Moraceae, which currently consists of about 40 genera [8]. The mulberry family contains numerous edible plants characterized by the presence of milky latex in all the parenchyma, and reproductive organs (unisexual flowers, anatropous ovules, achenes, or aggregated drupes) [9]. In addition to the fig (Ficus spp.), laticifers have been described in several species of Moraceae, including Sorocea bonplandii (Baill.) W.C. Burger, Lanj. & de Boer, Morus L. spp., Castilla elastica Serv., Broussonetia L’Hér. ex Vent. spp., Brosimum gaudichaudii Trécul, Dorstenia cayapia Vell., Maclura tinctoria (L.) D.Don. ex Steud, and Artocarpus heterophyllus Lam [7]. Ficus carica L. (common fig) is the fig species with the highest commercial value and comprises various genetically diverse varieties [9, 10]. Other remarkable species include Ficus benghalensis L. (the banyan tree), Ficus elastica Roxb. ex Hornem. (the Indian rubber tree), Ficus racemosa L. (syn. glomerata, the giant cluster tree), and Ficus religiosa L. (the Bo tree) [11]. In F. carica, the latex is accumulated in branched non-articulated laticifers [12]. With few exceptions (H. brasiliensis, Papaver somniferum, or F. elastica), the latex is produced in very small quantities in plant tissues and is usually collected by dripping [13–15]. In F. carica, any organ of the plant can exude latex [16]. However, the amount may vary according to the physiological conditions of the plant [5]. In this book chapter, aspects of the chemical composition of the latex of the common fig are reviewed, including proteins, low molecular weight molecules (secondary metabolites), and rubber particles. In addition, the biological activity, ethnopharmacology, and commercial aspects of fig latex are also discussed.

2

Chemical Composition of F. carica Latex

2.1

Volatile Compounds

The qualitative volatile composition of the latex of F. carica from unripe green fruits from the Mirandela region (Northeast Portugal) was studied by Oliveira et al. (2010) using HS-SPME/GC-IT-MS (Headspace Solid-Phase Microextraction/ Gas Chromatography-Ion Trap-Mass Spectrometry). Thirty-four compounds were

M. V. Castelli and S. N. Lo´pez

804

Table 1 Volatile compounds characterized from F. carica latex samples by HS-SPME/GC-IT-MS [17] Volatile compounds detected in F. carica latex Aliphatic short-chain alkanes/alkenes Terpenoids Aldehydes Alcohols Ketones Monoterpenes 1 Pentanal 5 10 11 1-Butanol- 6-Methylα-Thujene 3-methyl 5-hepten2-one 2 Hexanal 6 12 1-Butanolα-Pinene 2-methyl 3 Heptanal 7 13 1-Pentanol β-Pinene 4 Octanal 8 14 1-Hexanol Limonene 9 15 1Eucalyptol Heptanol 16 Terpinolene 17 cis-Linalool oxide 18 Linalool 19 Epoxylinalool

Sesquiterpenes 20 α-Guaiene

Shikimic acid derivatives 29 Methyl salicylate

21 α-Bourbonene

30 Quinoline

22 β-Caryophyllene

31 Psoralen 23 32 Trans-α-bergamotene Benzaldehyde 24 33 α-Caryophyllene Phenylethyl alcohol 25 34 τ-Muurolene Phenylpropyl alcohol 26 Germacrene D 27 Cadinene 28 α-Calacorene

identified (Table 1, Fig. 1); sesquiterpenes were the most abundant (ca. 91%), followed by aliphatic short-chain compounds containing alcohols (ca. 4%), aldehydes or ketones; monoterpenes and shikimic acid derivatives were also identified. The qualitative volatile profile detected in fig latex was comparable to that of fruit pulp, peels, or leaves [17]. Volatile compounds, mostly monoterpene or sesquiterpene (C10 or C15) aldehydes and alcohols are biosynthesized and accumulated by plants as a defense to wounding and play an important role in plant defense, as tools for pest resistance, and protection against microbial attack. In addition, they can also act as potent insect attractants (e.g., phenyl ethyl alcohol 33) [17]. Monoterpenes (e.g., linalool 18, α-pinene 12, β-pinene 13, limonene 14), and sesquiterpenes such as germacrene D 26 characterized in this latex can alter insect behavior and play a role in attracting pollinators, and many of them also act as antimicrobial agents [3]. Benzaldehyde 32, the major aldehyde detected in the latex of the unripe fig fruits, is used as an ingredient for industrial production related to perfumes, pharmaceuticals, or agrochemicals. In addition, benzaldehyde 32 has been used in the treatment of human terminal carcinomas, and as an antimicrobial agent [17, 18]. Psoralen 31 is a small

30

Chemistry, Biological Activities, and Uses of Ficus carica Latex

805

Fig. 1 Volatile compounds characterized in F. carica latex

molecule with well-characterized photodynamic properties, isolated from the aerial parts of F. carica, along with other furanocoumarins: bergapten 35, marmesin 36, umbelliferone 37, and 40 ,50 -dihydropsolaren 38 (Fig. 1) [17, 19, 20].

2.2

Triterpenoids, Phytosterols, and Fatty Acids

Triterpenoids (C30) and phytosterols are formed by the mevalonate biosynthetic pathway, through an extensive series of cyclizations and Wagner–Meerwein

806

M. V. Castelli and S. N. Lo´pez

rearrangements on squalene epoxide catalyzed by the enzyme squalene epoxidase. Phytosterols are present in most plant-based foods, especially in vegetable oils [21]. Oliveira et al. (2010) conducted a comprehensive study of fatty acid and phytosterol content in latex samples obtained by the incision of stalks of unripe fruits of F. carica (Mirandela region, Portugal) using HPLC-DAD (High-Performance Liquid Chromatography-Diode Array Detector) and GC-IT-MS. In addition to the most abundant phytosterol β-sitosterol 45, the authors informed the triterpenoids betulin 39, lupeol 40, lanosterol 41, lupeol acetate 42, β-amyrin 43, and α-amyrin 44 (Fig. 2) [22]. The isolation of a cytotoxic mixture of sterylglycosides identified as 6-Oacyl-β-D-glucosyl-β-sitosterols (6-AGS, 46 R1–4) from the latex of F. carica was described in 2001 by Rubnov et al. Raji, T-cell leukemia, Burkitt B lymphoma cells, prostate cancer, and breast cancer cells were tested against the 6-AGS, with over 50% (up to 87%) inhibition at 25–50 μg/well; the 6-O-palmitoyl-β-D-glucosyl-β-sitosterol derivative 46 R3 showed the best activity. Acylglucosylsterols have been reported in plants that are important food sources worldwide (soybean and chickpea) and in the common fig. In addition, this class of compounds has also been isolated from snakes and the epidermis of chickens (Fig. 2) [13]. The evaluation of the fatty acid composition of F. carica latex from unripe fruits has shown that it consists mainly of saturated fatty acids (ca. 86.4%), in contrast to fresh and dried ripe fruits, which contain mainly polyunsaturated fatty acids (ca. 69% and 84% respectively) [23, 24]. As for the fatty acid composition determined in the latex, 14 saturated fatty acids were detected [Palmitic (C16:0), stearic (C18:0),

Fig. 2 Triterpenoids, sterols, and acylsterylglucosides (6-AGS) characterized in F. carica latex

30

Chemistry, Biological Activities, and Uses of Ficus carica Latex

807

arachidic (C20:0), and behenic (C22:0)]; meanwhile, oleic (C18:1n9) and linoleic (C18:2, ca. 9.9% of the total) acids were the main mono- and polyunsaturated fatty acids identified [22]. Oleic acid is known to lower plasmatic cholesterol levels, which promotes the reduction of cardiovascular disease risk, and for its anti-inflammatory and antidiabetic properties [22, 25, 26]. On the other hand, linoleic acid is an essential fatty acid that serves as a substrate for ω-6 fatty acids, including arachidonic and γ-linolenic acids, and can be converted into eicosanoids, a group of hormone-like molecules that affect physiological responses covering from blood coagulation up to immune response [23, 27].

2.3

Organic Acids

This group of molecules has the property of adding acidity and affecting the organoleptic properties of plant tissues, such as flavor [17]. Based on HPLC-UV analysis performed on acidified latex samples of immature green fruits of F. carica (Mirandela region, Portugal), several organic acids were detected and quantified. The qualitative profile of organic acids in the latex was analogous to that of the other fig tissues analyzed, such as peels, pulp, and leaves, with some differences at a quantitative level. Malic acid 47 and shikimic acid 48 were the most abundant (808.4 and 817.5 mg/kg respectively), each accounting for about 26%, followed by quinic acid 49 (751.1 mg/kg, ca. 24%) [17]. Aref et al. (2011) reported other phenolic acids (caffeic acid 50, 3,4-dihydroxybenzoic acid 51, p-coumaric acid 52, p-OHphenylacetic acid 53, and ferulic acid 54, Fig. 3) in the analysis of organic extracts Fig. 3 Major organic acids characterized in F. carica latex

M. V. Castelli and S. N. Lo´pez

808

from latex samples of unripe fruits by HPLC-UV-MS/MS (High-Performance Liquid Chromatography-Ultraviolet-Mass/Mass), however, the authors did not provide information on the quantification of these phenolic acids [28].

2.4

Amino Acids

The profile of free amino acids of F. carica latex obtained from the stalk of green fruits (Mirandela region, Northeast Portugal) was characterized by HPLC-UV/Vis (High-Performance Liquid Chromatography-Ultraviolet/Visible) and showed the presence of essential (tryptophan, histidine, lysine, phenylalanine, leucine) and nonessential (glutamine, asparagine, alanine, tyrosine, serine, glycine, cysteine, ornithine) amino acids. Although the content of amino acids in the latex is reduced (7.2 mg/g latex), its extraction and pre-concentration may yield a product useful for topical or oral application in health-promoting formulations [22].

2.5

Gum or Natural Rubber

Gum is an isoprenoid secondary metabolite whose basic skeleton contains exclusively 1,4-polymers of isoprene (C5H8) units with a cis-double bond, and MW between 104 and > 106 [29]. In latex, the hydrophobic rubber polymer is circumscribed by a monolayer membrane containing proteins, lipids, and other constituents to form the rubber particles [29, 30]. It is assumed that rubber is compartmentalized within the rubber particle as a final product that cannot be catabolized during the life of the plant [31]. Ficus carica is one of the approximately 2,000 rubber-producing plant species described up to date. Studies with Korean F. carica revealed that the rubber content in the bark is 0.3%, in the leaves and fruits is 0.1%, and the content in the latex is 4% w/v [5]. Moreover, the syconium bleeds a large amount of latex [16]. In Ficus spp. rubber polymers are packed in subcellular globular particles of 0.2–6.5 μm [5, 32, 33]. Rubber is a secondary metabolite with unknown functions produced with a high-energy cost. Although rubber biosynthesis has been shown in other species to occur by rubber transferase enzymes anchored in the monolayer membrane of rubber particles, the two major proteins characterized on the membrane of F. carica rubber particles have not been shown to be associated with another proposed rubber transferase. In addition, both proteins were characterized as peroxidase and trypsin inhibitors, stress-related proteins involved in plant defense strategy rather than rubber biosynthesis [30, 34, 35].

2.6

Proteins

As in other Ficus species (F. glabrata, F. elastica), the latex of this plant is a rich source of hydrolytic enzymes [21]. It is a distinctive character when compared to

30

Chemistry, Biological Activities, and Uses of Ficus carica Latex

809

latex-producing plant species that accumulate low molecular weight secondary metabolites, e.g., vindoline in vinca latex (Catharanthus roseus, Apocynaceae) or morphine in poppy latex (P. somniferum) [27]. Proteases of plant origin have been used since remote times. Homeric writings such as the Íliad describe the use of fig latex for milk curdling and cheese making. Nowadays, the number of proteases of plant origin used industrially is small [36]. However, in recent years, plant proteases have attracted renewed interest from the biotechnology and pharmaceutical industry, because of their proteolytic activity on different types of proteins and because they remain active across a range of pHs and temperatures [36].

2.6.1 Ficin The major protein component of the latex of F. carica is ficin, a papain-like cysteine protease (PLCP) that occurs in multiple isoforms [37]. Ficin and other PLCPs such as papain (Carica papaya L., Caricaceae) and bromelain (Ananas comosus (L.) Merr., Bromeliaceae) have potent proteolytic activity and broad substrate specificity, justifying high commercial value in the pharmaceutical and food industries [36, 37]. In plants, cysteine proteases (CPs) are involved in plant development, biotic/ abiotic stress responses, and in senescence and programmed cell death [37]; meanwhile, in plant latex, they are involved in the defense actions to protect fruits during ripening from pathogens such as insects or fungi. Cysteine proteases can directly attack the invading organisms, e.g., insects, by degrading their protective cuticle or peritrophic matrix [38, 39]. In addition, CPs are also involved in latex coagulation after abiotic or biotic injuries. This wound-healing property is an efficient strategy to protect plants from the invasion and further spread of pathogens [39]. Ficin or ficain (EC 3.4.22.3; CAS 9001-33-6) is a group of glycoproteins with cysteine endopeptidase activity belonging to the C1 peptidase family, with a molecular weight of c.a. 25,000 Da, a pH activity range of 6.5–8.5 [40, 41]. The separation of multiple ficin forms on cationic gel media was reported as early as 1964 [42, 43]. Currently, there are at least five isoforms (A, B, C, D, and S) of ficin in protein databases [39, 44, 45]. However, different nomenclatures are used for the characterized ficin isoforms. Some authors name the set of enzymes simply as ficin, others discriminate the isoforms as ficin A, B, C to S, while others refer to them as ficin I, II to V, according to the order of elution observed in molecular exclusion chromatography experiments on sepharose gel. A new isoform of ficin was reported by Milošević et al. in 2020. Isoform 1c was characterized from transcriptomic data as a single alkaline isoform, with proteolytic and gelatinolytic activity. This new isoform contains β-sheets (25.6%) and α-helices (23.4%), and its secondary structure is related to other CPs, such as caricain and papain. The stability of this isoform 1c was lower than that of ficin, suggesting that isoenzyme diversity contained in ficin is related to the stability of the protease [46]. Recently, the fig genome was published, providing the necessary information for several bioinformatics analyzes [47]. A combined study of the PLCP family involving genomics, transcriptomics, and proteomics, provided information on this family in fig. Seventy-four proteins (MW range 8.9–206.1 kDa; pI range 4.84–10.78) were

810

M. V. Castelli and S. N. Lo´pez

identified in latex obtained from fruits at the commercial-ripe stage. Ficin 1A (8.04%), ficin 1B (8.63%), ficin D (1.50%), ficin 4 (14.93%), and cysteine proteinase RD21a (5.82%) were the characterized PLCPs, accounting for 38.93% of the total [37]. Ficin, along with papain and bromelain, is used in a variety of processes including the pharmaceutical industry, the manufacturing of bioactive peptides, and the production of Fab fragments from IgG antibodies by specific hydrolysis [36]. It is also traditionally used in food processing, for example, to tenderize meat, in the brewing industry to avoid turbidity due to better colloidal properties at lower temperatures, in the production of a fish protein hydrolysate, and in the cheese industry to achieve coagulation of milk [48]. In addition, purified ficin is offered as a laboratory reagent by leading companies, such as Thermo Scientific® (http://www.piercenet.com/ product/immobilized-ficin) or Sigma-Aldrich ® (http://www.sigmaaldrich.com), in solution, immobilized on agarose resin, or a fine powder [49, 50]. In addition to proteases, the latex of F. carica contains several other enzyme activities, namely prenyltransferase, lipase, amylase, peroxidase, collagenase, and fibrinolytic activity, among others [21]. Table 2 summarizes the information on enzymes present in F. carica latex.

2.6.2 Fibrinolytic Activity In a recent publication, Hamed et al. (2020) reported serine protease activity in F. carica latex able to degrade fibrinogen (α, β, and γ chains) and fibrin clots, thus possibly acting as an anticoagulant. The observation of the anticoagulant behavior could counteract the procoagulant activity of the latex due to ficin activity. However, the anticoagulant effect of the latex observed at a higher protein concentration suggests that ficin might be inhibited by other small anti-protease peptides [51]. The fact that the latex of F. carica has simultaneous procoagulant and anticoagulant properties is not surprising, since plants normally contain a combination of constituents with opposite effects. Moreover, the same factor can act as a pro-coagulant or anticoagulant under different conditions [51]. 2.6.3 Collagenase Activity Collagenases are a group of enzymes that hydrolyze native collagen and can be classified as metallo- or serine-collagenases. Serine collagenases have been described in crustaceans, especially crab species, and fish, and are involved in the physiological food digestion process [52]. Metallo-collagenases contain zinc but usually also require calcium for optimal stability and activity [52]. Unlike bacterial and mammalian metallo-collagenases, which have substrate specificity for collagen, serine collagenases have proteolytic activity in addition to collagenolytic activity [53]. The first collagenase activity described in F. carica is a serine protease that is specific for gelatin and collagen, is pH- and temperature-stable, and has very low nonspecific protease activity, obtained from fresh latex obtained from unripe green fruits of F. carica var. Brown Turkey (Montenegro, Europe). It was purified and characterized as a monomer with an MW of 41  9 kDa (ficin has an MW of 24 kDa)

30

Chemistry, Biological Activities, and Uses of Ficus carica Latex

811

Table 2 Enzymatic activities isolated and characterized from F. carica latex Name Ficin 1a (A0A2Z6DRL4)b Ficin 1b (A0A2Z6DRT1)b Ficin 1c (A0A2Z6DRL5)b Ficin 2a (A0A2Z6DRL9)b Ficin 2b (A0A2Z6DRP9)b Ficin 2c (A0A2Z6DRM5)b Ficin 3 (A0A2Z6DRN1)b Ficin 4 (A0A2Z6DRL6)b Ficin 5 (A0A2Z6DRM9)b Ficin 6a (A0A2Z6DRW8)b Ficin 6b (A0A2Z6DRN0)b Ficin isoform A (A0A182DW06)a/b Ficin isoform B (A0A182DW08)a/b Ficin C (A0A182DW09)a/b Ficin D (A0A182DW11)a/b Collagenase Amylase Fibrinolysine

Peroxidase (EC 1.11.1.7) isoform FC1 Peroxidase (EC 1.11.1.7) isoform FC2 Peroxidase (EC 1.11.1.7) isoform FC3

Activity Peptidase

MW 23.64

pI 6.89

Ref. [46, 61]

23.57

8.42

[46, 61]

23.59

8.64

[46, 61]

23.28

5.39

[46, 61]

23.25

5.39

[46, 61]

23.25

5.39

[46, 61]

23.70

9.50

[46, 61]

23.29

8.88

[46, 61]

23.81

8.85

[46, 61]

24.05

7.70

[46, 61]

24.05

7.70

[46, 61]

23.53

8.94

[46, 61]

24.11

7.69

[46, 61]

24.17

8.10

[46, 61]

23.65

4.87

[46, 61]

41  9 kDa

5

[55]

– 48 kDa

– n.d.

[28] [62]

Oxidase

30 kDa

–

[4]

H2O2 hydrolysis

Oxidase

–

–

[4]

H2O2 hydrolysis

Oxidase

–

–

[4]

Peptidase Peptidase Peptidase Peptidase Peptidase Peptidase Peptidase Peptidase Peptidase Peptidase Peptidase Peptidase Peptidase Peptidase Collagenase Starch hydrolysis Fibrinogen hydrolysis (gelatin > fibrin > albumin > hemoglobin > casein > collagen) H2O2 hydrolysis

Type Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Cysteine protease Serine protease – Serine protease

(continued)

M. V. Castelli and S. N. Lo´pez

812 Table 2 (continued) Name Prenyltransferase

Activity Rubber cis-polyprenyltransferase

Type Transferase

MW –

pI –

Ref. [30]

a

Isoforms A, B, C, D (https://www.brenda-enzymes.org/literature.php?e¼3.4.22.3&r¼733039; https://www.uniprot.org/uniprot/?query¼ec%3A3.4.22.3&sort¼score) (Accessed on 19 July 2021) b Source: https://www.uniprot.org/uniprot/?query¼ficin&sort¼score (Accessed on 19 July 2021)

and a pI of 5, with maximum activity at pH 8.0–8.5 and 60  C. After pre-incubation in the range of pH 4–9 and 20–80  C it retained more than 80% of activity [53]. There is evidence that supports the association among the highest collagenolytic activity in fig latex with the starting of the fruit ripening [52]. Some of the uses of fig latex in ancient and modern ethnomedicine that can be related to collagenase effects include the removal of scars, the treatment of warts, debridement, and healing of ulcers. Current conventional treatment of conditions such as scar tissue and wound healing, as well as other fibroproliferative diseases, involves the use of commercial bacterial collagenase. The collagenolytic protease of fig latex is appropriate for the restructuring of connective tissue because it facilitates the diffusion of active small molecules through the skin and internal soft tissue [52]. Cancer therapy is often compromised by a failure in the delivery to and uptake at the tumor tissue of the targeted drug, mainly caused by the increased pressure of the interstitial fluid in solid tumors [54]. The concomitant use of collagenase has improved the delivery of both small and relatively large drugs (e.g., nanoparticles) to solid tumors [52, 55]. Studies have shown that fig latex collagenase facilitates the migration of a set of low molecular weight molecules through a model of gelatin hydrogel, suggesting that collagenase activity enhances the availability of small antiproliferative drugs in anticancer therapies for the treatment of tissue-embedded tumors. Fig latex collagenase resists gastric digestion, suggesting that it should be considered for oral administration [52].

2.6.4 Amylase Activity Amylase enzyme (EC3.2.1.1) catalyzes the endo hydrolysis of (1 ! 4)-α-D-glucosidic linkages in polysaccharides that contain three or more (1 ! 4)-α-linked D-glucose units [40]. The amylolytic activity of latex obtained from Bidhi and Kahli varieties of F. carica (Tunisia, Africa) was studied by Aref et al. [56]. Both latexes showed amylase activity, which was optimal at pH 6.5 and 7 (45  C), the half-life was 85 and 60 min (80  C) respectively, with a wide stability range from pH 4 to 12. The analysis of metal ions showed that 106 mM Mg2+ increased Kahli amylase activity, but strongly inhibited Bidhi amylase activity. However, both enzymes increased their activity (2.5-fold) when tested with 106 and 105 mM Ca2+. These results are consistent with previous reports of animal and plant α-amylases, which contain a Ca2+-binding domain necessary to stabilize the tertiary structure. The addition of 103 mM Fe2+ or 102 mM Cu2+ increased the amylase activity of Bidhi var. to

30

Chemistry, Biological Activities, and Uses of Ficus carica Latex

813

260%, whereas it was inhibited by EDTA and Mg2+. The amylase activity of Kahli var. fig was not affected by Cu2+ or Fe2+. Based on the analysis of reaction products performed by HPLC and TLC (Thin Layer Chromatography), the amylase from Kahli var. fig was characterized as amyloglucosidase, while the endo-amylolytic character of Bidhi var. amylase was on β-fructose and α(1–4)-glucose [56]. The amylase activity of fig latex differs according to fig variety or stage of ripeness and is increased in the immature stage. This is in agreement with the main role of amylase in the metabolism of carbohydrates in different plant tissues, resulting in a net loss of starch when the fruit ripens [57]. Amylases have important applications in biotechnology, especially in processes involving starch hydrolysis. Along with amylases from plants, they can be obtained from various other sources such as microorganisms and animals. Microbial amylases are of greater importance in terms of commercial availability due to having advantageous properties such as thermal stability and resistance to product inhibition, providing a better strategy to obtain glucose from starch [28].

2.6.5 Peroxidase Activity Peroxidase (EC 1.11.1.7) is a hemoprotein that catalyzes the oxidation of a variety of inorganic and organic substrates, using hydrogen peroxide as an electron acceptor [58]. As described above (gum or natural rubber section), peroxidases have been characterized on the membrane of rubber particles from F. carica latex [34]. The physiological role of latex peroxidases seems related to being protective barriers [4, 58] ready to react after the plant tissues are injured [34, 59]. Three peroxidase isoenzymes (FP1–3) were isolated from F. carica latex by Elsayed et al. [60]. Complete purification of FP1 showed that it is a monomeric protein (MW 30 kDa). The FP1 and FP3 isoenzymes had the same temperature (40  C) and optimal pH (¼5.5), whereas the optimal values for FP2 were 30  C and pH 7.0. FP1 was stable at 50  C and pH 5.0 and 7.5; FP2 was stable at 40  C and pH 4.0 and 8.0, while FP3 was stable at 30  C and pH 4.5 and 5.5. The adding of Ca2+ (10 mM) increased the activity of FP1 and FP2 [63]; moreover, the three isoenzymes showed broad specificity to phenolic substrates such as O-phenylenediamine, guaiacol, and O-dianisidine among others. In addition, peroxidase isoenzymes of F. carica latex were effective in decolorizing synthetic dyes (e.g., methyl green, methyl blue, indigo carmine, fuchsin, and methyl violet). Despite the differences reported for each isoform, properties such as broad pH stability, thermal stability, and affinity for structurally diverse substrates make them useful for biomedical, industrial, environmental, and food processing applications [60]. 2.6.6 Prenyltransferase Activity The study of prenyltransferase activity in F. carica latex has been developed by several authors. Rubber biosynthesis activity was tested in vitro following the amounts of radiolabeled isoprenyl pyrophosphate ([14C]-IPP) added to the newly synthesized rubber chains [59]. However, isolation and characterization attempts of prenyltransferase enzyme(s) have so far failed. Kim et al. [34] analyzed washed rubber particles of F. carica latex

814

M. V. Castelli and S. N. Lo´pez

by gel electrophoresis. The two major proteins tightly associated with the particles (approximately 25 and 48 kDa) were partially sequenced and immunochemical analyzes of these proteins revealed that they were not related to any other proposed rubber transferase, but were related to peroxidase and trypsin inhibitor proteins, as mentioned previously [34]. Rubber transferase (EC 2.5.1.20) or rubber polymerase requires a divalent ion for its activity, and the concentration of Mg2+in the latex can affect rubber transferase activity. Experiments conducted in vitro with washed rubber particles from F. carica latex showed that the optimal Mg2+ concentration for incorporation of [14C]-IPP into rubber was 1 mM, similar to that of H. brasiliensis (2 mM). The addition of up to 15–20 mM EDTA to washed rubber particles significantly increased the incorporation of [14C]-IPP into rubber. Since Mg2+ concentration in F. carica latex is 3,000 ppm, the effect of low EDTA concentrations in promoting rubber biosynthesis might be due to the removal of excess magnesium ions [34].

3

Ethnopharmacological Uses of F. carica Latex

Preparations from various parts of F. carica have been used by people since ancient times to cure various ailments. Fresh or dried fig fruits, unripe or ripe, decocted or crude, alone or in combinations, preparations with leaves, etc. have been prescribed to treat several ailment stages [11]. In Central and South America, the latex of Ficus spp. (Moraceae) is traditionally used as a vermifuge. Latex activity against the cestode Vampirolepis nana and oxyurids (Syphacia obvelata and Aspiculuris tetraptera) was studied in experiments on naturally infected mice treated with diluted samples of Ficus insipida and F. carica latex by the intragastric route. Compared to the control group, the percentages of elimination of worms were not pronounced in the treated group. In addition, treated mice exhibited hemorrhagic microfoci in the gastrointestinal mucosa after necropsy. Therefore, the use of these products should not be recommended in traditional medicine for the treatment of intestinal helminthiasis [63]. In the Middle East, the latex released when the fruit is peaked is used to treat warts and skin tumors. Ullman et al. conducted the first scientific study on the effects of fig latex in the 1940s. In experiments on rats, injections of high doses of latex proved lethal. Smaller doses injected into mice with benzopyrene-induced sarcoma resulted in inhibition of tumor growth and even disappearance of small tumors [11, 13]. The latex obtained from young leaves and fruits has been used both fresh and after drying in the shade. Lansky et al. [11] conducted a comprehensive review focusing on ancient preparations in which F. carica and other species of Ficus were used to treat inflammation and cancer. Poultices, liniments, ointments, or drinking preparations formulated with the milk of the fig tree were used, either alone or in combination with almonds, egg yolk, starch, etc. These preparations were indicated to dissolve or burst hard tumors, splenomegaly, for splenic and liver hardness, open ulcers, spreading wounds, and gout (Table 3) [11].

30

Chemistry, Biological Activities, and Uses of Ficus carica Latex

815

Table 3 Ancient medications using F. carica latex. (Modified from Ref. [11]) Medicament Milk (latex), especially from tree bark at beginning of spring Boiled milk (latex) with almond (or starch) Milk (latex), barley flour (or barley mush or wheat flour or cornflour) Milk (latex), egg yolk Milk (latex), egg yolk, dried milk Milk (latex), starch Milk (latex), fenugreek flour (+/vinegar)

Indications Tumors, hard tumors (to dissolve or cause to burst), spleen/liver hardness, splenomegaly, head ulcers Hard Hard tumors, ulcers, tumors of the uterus

Route of administration Poultice/ ointment, drink (often together) Poultice Drink

Running head ulcers, spreading sores, tetter

Poultice

Ulcers (to open) Ulcers (to open)

Poultice Liniment

Ulcers (to open) Gout

Drink Poultice, ointment

Currently, the latex of the common fig continues to be used to treat inflammatory diseases and tumors. Fresh latex mixed with vegetable oil or egg yolk is used in Iran to treat warts, wounds, and ulcers [11]; decoctions of fresh latex and fresh latex are used externally for warts and verrucas in Italy, Tunisia, and Turkey [64–66]. It is also used topically to treat pain from scorpion bites and bee stings in Turkey and for boils and eruptions in India [11, 67, 68].

4

Biological Activities of F. carica Latex

4.1

Antioxidant Activity

The antioxidant capacity of latex obtained from unripe fruits of the F. carica cultivar Pingo de Mel (Northeast Portugal) was investigated by De Oliveira et al. (2010). The 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay showed an IC25 ¼ 1049 μg mL1, the superoxide radical assay showed an IC25 ¼ 291 μg mL1, and nitric oxide scavenging capacity showed an IC25 ¼ 1768 μg mL1. In all cases, a concentration-dependent behavior was shown. Based on the scavenging capacity of the latex observed for nitric oxide and superoxide radicals, the latex could also prevent the formation of other biologically important oxidative species such as peroxynitrite and hydroxyl radicals resulting from the reaction of these two [17]. In a later work, Shahinuzzaman et al. (2020) evaluated the in vitro antioxidant activity of latex from leaves of eighteen cultivars of F. carica using standard methods, i.e., Folin–Ciocalteu assay for the determination of total phenolic content (TPC), DPPH, 2,20 -azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and ferric ion reducing antioxidant power (FRAP). The latex samples were collected during the daytime in Bangi, Selangor, Malaysia. In this work, the authors concluded

M. V. Castelli and S. N. Lo´pez

816

that the best extraction methods were maceration and ultrasound-assisted extraction (UAE) with 75% ethanol and that the latex of cultivar White Genoa had the highest antioxidant activity of 65.91%  1.73% and 61.07%  1.65% in DPPH, 98.96%  1.06% and 83.04%  2.16% in ABTS, and 27.08  0.34 and 24.94  0.84 mg Trolox equivalents (TE)/g latex in FRAP assay by maceration and UAE, respectively. The TPC of White Genoa was 315.26  6.14 and 298.52  9.20 μg gallic acid equivalents mL1 over the two extraction methods, respectively. The latex of the White Genoa cultivar was more viscous, sticky, and concentrated than that of the other cultivars studied. The authors concluded that the latex of F. carica is a potential natural source of antioxidants for food additives, dietary supplements, and drug synthesis [69].

4.2

Antimicrobial Activity

Lazreg Aref et al. (2010) studied the antimicrobial activity of F. carica latexes from Tunisia. Latex from immature fig fruits growing in Chott Mariem Sousse (Tunisia) was lyophilized, powdered, and then repeatedly macerated in methanol. The concentrated residue was partitioned with hexane, ethyl acetate, and chloroform. The extracts were then tested against seven fungal strains including three dermatophytes (Trichophyton soudanense, Microsporum canis, and Trichophyton rubrum), two hyphomycetes (Aspergillus fumigatus and Scopulariopsis brevicaulis), and two opportunistic pathogenic yeasts (Candida albicans and Cryptococcus neoformans). Six bacterial strains were tested, including three Gram-positive bacteria, Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, and Citrobacter freundii (clinical isolate), and three Gram-negative bacteria, Pseudomonas aeruginosa ATCC27853, Proteus mirabilis (clinical isolate), and Escherichia coli ATCC25922. In vitro antimicrobial properties were evaluated using disk diffusion assays, minimum inhibitory concentration (MIC) in microwells, and calculation of percent inhibition (1%) of fungal growth. The ethyl acetate extract showed antimicrobial activity against five bacterial species (E. faecalis, E. coli, C. freundii, P. aeruginosa, and P. mirabilis). Methanol, ethyl acetate, and chloroform extracts showed good antifungal activity (96–100% inhibition) against the tested yeasts at 500 μg mL1, while hexane extract was less active (25% inhibition). For filamentous fungi, extracts showed good antifungal activity against M. canis and A. fumigatus, with the ethyl acetate extract being the most active (80–86% inhibition at 500 μg mL1) [70]. The antibacterial activity of the hexane extract of the latex of caprifig Jrani latex obtained from unripe inedible fruits from Mesjed Aissa, Tunisia, was tested against ten ATCC cultures and clinical isolates. The highest zones of inhibition recorded in the agar diffusion test were observed against S. aureus ATCC 25923, Staphylococcus saprophyticus, Staphylococcus epidermidis (26–28 mm), while lower zones of inhibition were observed against Pseudomonas aeruginosa ATCC 27950 and ATCC 2783, and Enterococcus faecalis ATCC 29212 (14–15 mm). MIC values ranged from 19 (S. aureus ATCC 25923) to 312 μg mL1 (P. aeruginosa ATCC 27950 and

30

Chemistry, Biological Activities, and Uses of Ficus carica Latex

817

ATCC 2783, and E. faecalis ATCC 29212) indicating that the extract is an effective antimicrobial agent [71].

4.3

Acetylcholinesterase Inhibition

Alzheimer’s disease (AD) causes the degeneration of brain cells and is the main cause of dementia. Currently, there are about 50 million AD patients worldwide and this number is expected to reach 152 million by 2050 [72]. The cholinergic hypothesis postulates that a deficit in cholinergic function in the brain leads to memory impairment, and one of the most promising treatment approaches is to increase acetylcholine levels in the brain by acetylcholinesterase inhibitors [27]. When the effect of F. carica latex on acetylcholinesterase activity was tested, the latex showed low inhibitory properties, and the inhibition was less than 10% at the highest concentration tested (5317 μg mL1) [17, 73].

4.4

Cytotoxicity and Antiviral Activity

Fig latex has been shown to be a potential antiviral agent against skin warts caused by human papillomavirus (HPV) and warts caused by bovine papillomavirus (BPV), without unavoidable tissue damage and treatment complications [17, 74, 75]. A comprehensive study conducted with latex collected from immature fruits of F. carica trees in Tehran, Iran, showed that it effectively inhibited HPV-positive cervical cancer cells (CaSki and HeLa), without a cytotoxic effect on the human immortalized keratinocyte cell line (HaCaT). Latex exhibited anticancer effects by inducing apoptosis and inhibiting cell transformation, colony formation, cell proliferation, migration, and invasion. In addition, latex influenced the deregulation of HPV oncoproteins (E6 and E7) and the HPV diagnostic marker protein (p16) and initiated the reactivation of tumor suppressor proteins Rb and p53 [75]. The cytotoxicity and antiviral properties of the latex of F. carica collected from unripe fig fruits in Tunisia, Africa, were evaluated. The latex was macerated in methanol to obtain extract P1, which was fractionated by silica gel chromatography with hexane (extract P2), hexane–ethyl acetate 5:5 (product P3), and ethyl acetate (product P4). The final elution fraction was performed with methanol-water, and this phase was then extracted with chloroform (product P5). The extracts were evaluated in vitro for their cytotoxicity on kidney cells of the African green monkey Cercopithecus aethiops (Vero cell line ATCC CCL-81), and for their antiviral potential against adenovirus (ADV), echovirus type 11 (ECV-11), and herpes simplex type 1 (HSV-1). At the concentrations tested, extracts showed no cytotoxic effect on Vero cells but they did exhibit antiviral activity. The extracts showed virucidal activity by affecting the integrity of each virus and preventing them from infecting cells. In addition, the tested fractions prevented the adsorption and penetration of each virus into the cells by acting on the cellular receptors, and they were also able to inhibit viral intracellular replication at 78 μg mL1 [56].

M. V. Castelli and S. N. Lo´pez

818

5

Toxicology

Figs are one of the oldest known fruits consumed by humans and have a very high safety profile. However, the toxicological evaluation of other fig products remains to be investigated. Latex can cause allergic reactions such as asthma, dermatitis, and anaphylaxis after skin contact and can cause hallucinosis when administered orally [76–78]. Experimental treatment with fig latex was evaluated to determine anthelmintic activity as described above (see Ethnopharmacological Uses). Hemorrhagic microfoci were observed in the mucosa of the gastrointestinal tract of mice treated with latex [63].

6

Economic Importance

Latex is used by several indigenous communities as a coagulant in the production of cheese [21]. Enzymes from fig latex can be used in combination with papain for tissue dissociation and bacterial cell detachment in meat products replacing trypsin. The use of fig latex enzymes to tenderize fermented sausages increased the release of Listeria monocytogenes and improved the sensitivity of tests to detect this bacterial agent, which is a ubiquitous intracellular pathogen that can contaminate raw or minimally processed foods [61]. Ficin is suitable as a proteolytic enzyme for the production of certain types of cheese, particularly those made from sheep’s milk. Ficin could also be used in the production of cheese based on ultrafiltered cow’s milk. In addition, it could be successfully used for the production of milk protein hydrolysates to obtain ingredients with lower allergenicity and better bioavailability for applications in infant formula and geriatric nutrition [48]. As stated before, purified ficin can be purchased in solution, as a fine powder, or immobilized on agarose resin, and is marketed by Sigma Aldrich and Thermo Scientific among others [49, 50].

7

Conclusions

Ficus carica latex is a very rich source of proteins with enzymatic activity and of primary (fatty acids or amino acids) and secondary metabolites (gums, phenolic acids, triterpenes, sterols, etc.). Most of the studies included in this revision were conducted with latex obtained from cultivars from Asia, North Africa, and Europe. The Mediterranean region contains the largest number of studies, as do the regions in Asia. Most of the studies use latex obtained from immature fruits. Further studies are needed to determine how the extracted latex varies from one organ to another of the same individual and between individuals considering an organ other than the fruit.

30

Chemistry, Biological Activities, and Uses of Ficus carica Latex

819

The crude latex is used in folk medicine mainly to treat warts or as a vermifuge to eradicate helminths. It is also used in the preparation of foods, especially in the curdling of milk to make cheese or to tenderize meat. There is a relationship between the uses and the enzyme composition, especially the proteolytic activity. Ficin is the best-studied group of fig latex proteolytic isoenzymes, and its commercial value and potential for industrial applications are promising. Purified ficin can be purchased with high-quality standards. In addition, several other enzymes have been described in F. carica latex, e.g., amylase, collagenase, peroxidase, and prenyltransferase. Despite efforts to characterize the prenyltransferase activity of F. carica latex, questions related to the biosynthesis of rubber within the rubber particles or the identification and localization of prenyltransferases involved in the elongation of isoprene chains remain unanswered. In addition to its antioxidant, antiviral, and wound-healing properties, fig latex may play a role in preventing the progression of cervical cancer. These new findings once again highlight the importance of the fig tree as a food and as a remedy for curing diseases. Acknowledgments This work was supported by grants from Universidad Nacional de Rosario (UNR, Grant 80020180300045UR). MVC and SNL are members of CONICET.

References 1. Agrawal AA, Konno K (2009) Latex: a model for understanding mechanisms, ecology, and evolution of plant defense against herbivory. Annu Rev Ecol Evol Syst 40:311–331 2. Kim YS, Park SJ, Lee EJ et al (2008) Antibacterial compounds from rose bengal-sensitized photooxidation of β-Caryophyllene. J Food Sci 73:C540–C545 3. Ramos MV, Demarco D, da Costa Souza IC, de Freitas CDT (2019) Laticifers, latex, and their role in plant defense. Trends Plant Sci 24:553–567 4. Mohamed SA, Abdel-Aty AM, Hamed MB, El-Badry MO, Fahmy AS (2011) Ficus sycomorus latex: a thermostable peroxidase. Afr J Biotechnol 10:17532–17545 5. Kang H, Soo Kim Y, Chung GC (2000) Characterization of natural rubber biosynthesis in Ficus benghalensis. Plant Physiol Biochem 38:979–987 6. Villard C, Larbat R, Munakata R, Hehn A (2019) Defence mechanisms of Ficus: pyramiding strategies to cope with pests and pathogens. Planta 249:617–633 7. Teixeira SP, Marinho CR, Leme FM (2020) Structural diversity and distribution of laticifers. Adv Bot Res 93:27–54 8. Woodland DW (1997) Contemporary plant systematics, 2nd edn. Andrews University Press, Michigan 9. Barolo MI, Ruiz Mostacero N, López SN (2014) Ficus carica L. (Moraceae): an ancient source of food and health. Food Chem 164:119–127 10. Salhi-Hannachi A, Chatti K, Saddoud O, Mars M, Rhouma A, Marrakchi M, Trifi M (2006) Genetic diversity of different Tunisian fig (Ficus carica L.) collections revealed by RAPD fingerprints. Hereditas 143:15–22 11. Lansky EP, Paavilainen HM, Pawlus AD, Newman RA (2008) Ficus spp. (fig): ethnobotany and potential as anticancer and anti-inflammatory agents. J Ethnopharmacol 119:195–213 12. Marinho CR, Teixeira SP (2019) Novel reports of laticifers in Moraceae and Urticaceae: revisiting synapomorphies. Plant Syst Evol 305:13–31

820

M. V. Castelli and S. N. Lo´pez

13. Rubnov S, Kashman Y, Rabinowitz R, Schlesinger M, Mechoulam R (2001) Suppressors of cancer cell proliferation from fig (Ficus carica) resin: isolation and structure elucidation. J Nat Prod 64:993–996 14. Paşayeva L, Özalp B, Fatullayev H (2020) Potential enzyme inhibitory properties of extracts and fractions from fruit latex of Ficus carica-based on inhibition of α-amylase and α-glucosidase. J Food Meas Charact 14:2819–2827 15. Boyacıoğlu O, Kara B, Tecimen S et al (2021) Antiproliferative effect of Ficus carica latex on cancer cell lines is not solely linked to peroxidase-like activity of ficin. Eur J Integr Med 45: 101348 16. Kitajima S, Aoki W, Shibata D et al (2018) Comparative multi-omics analysis reveals diverse latex-based defense strategies against pests among latex-producing organs of the fig tree (Ficus carica). Planta 247:1423–1438 17. Oliveira AP, Silva LR, Ferreres F et al (2010) Chemical assessment and in vitro antioxidant capacity of Ficus carica latex. J Agric Food Chem 58:3393–3398 18. Sakagami H, Sugimoto M, Kanda Y, Murakami Y, Amano O, Saitoh J, Kochi A (2018) Medicines changes in metabolic profiles of human oral cells by benzylidene ascorbates and eugenol. Medicine 5:116 19. Song P-S, Tapley KJ (1979) Photochemistry and photobiology of psoralens. Photochem Photobiol 29:1177–1197 20. Petruccelli R, Ieri F, Ciaccheri L, Bonetti A (2018) Polyphenolic profiling and chemometric analysis of leaves from Italian Ficus carica L. varieties. Polyphenol compounds in common fig. Eur J Hortic Sci 83:94–103 21. Badgujar SB, Patel VV, Bandivdekar AH, Mahajan RT (2014) Traditional uses, phytochemistry and pharmacology of Ficus carica: a review. Pharm Biol 52:1487–1503 22. Oliveira AP, Silva LR, Andrade PB et al (2010) Further insight into the latex metabolite profile of Ficus carica. J Agric Food Chem 58:10855–10863 23. Jeong WS, Lachance PA (2001) Phytosterols and fatty acids in fig (Ficus carica var. Mission) fruit and tree components. J Food Sci 66:278–281 24. Pande G, Akoh CC (2009) Organic acids, antioxidant capacity, phenolic content and lipid characterisation of Georgia-grown underutilized fruit crops. Food Chem 120:1067–1075 25. Ryan M, Mcinerney D, Owens D, Collins P, Johnson A, Tomkin GH (2000) Diabetes and the Mediterranean diet: a beneficial effect of oleic acid on insulin sensitivity, adipocyte glucose transport and endothelium-dependent vasoreactivity. Q J Med 93:85–91 26. Rees K, Takeda A, Martin N et al (2020) Mediterranean-style diet for the primary and secondary prevention of cardiovascular disease: a Cochrane review. Glob Heart 15:56 27. Dewick P (2009) Medicinal natural products. A biosynthetic approach. Wiley, London 28. Aref HL, Mosbah H, Louati H, Said K, Selmi B (2011) Partial characterization of a novel amylase activity isolated from Tunisian Ficus carica latex. Pharm Biol 49:1158–1166 29. Yamashita S, Takahashi S (2020) Molecular mechanisms of natural rubber biosynthesis. Annu Rev Biochem 89:821–851 30. Singh AP, Wi SG, Chung GC, Kim YS, Kang H (2003) The micromorphology and protein characterization of rubber particles in Ficus carica, Ficus benghalensis and Hevea brasiliensis. J Exp Bot 54:985–992 31. Cornish K (2001) Similarities and differences in rubber biochemistry among plant species. Phytochemistry 57:1123–1134 32. Cornish K, Siler DJ (1996) Characterization of cis-prenyl transferase activity localised in a buoyant fraction of rubber particles from Ficus elastica latex. Plant Physiol Biochem 34: 377–384 33. Cherian S, Ryu SB, Cornish K (2019) Natural rubber biosynthesis in plants, the rubber transferase complex, and metabolic engineering progress and prospects. Plant Biotechnol J 17:2041–2061

30

Chemistry, Biological Activities, and Uses of Ficus carica Latex

821

34. Kim JS, Kim YO, Ryu HJ, Kwak YS, Lee JY, Kang H (2003) Isolation of stress-related genes of rubber particles and latex in fig tree (Ficus carica) and their expressions by abiotic stress or plant hormone treatments. Plant Cell Physiol 44:412–419 35. Men X, Wang F, Chen GQ, Zhang H-B, Xian M (2019) Biosynthesis of natural rubber: current state and perspectives. Int J Mol Sci 20:50 36. Feijoo-Siota L, Villa TG (2011) Native and biotechnologically engineered plant proteases with industrial applications. Food Bioprocess Technol 4:1066–1088 37. Zhai Y, Cui Y, Song M, Vainstein A, Chen S, Ma H (2021) Papain-like cysteine protease gene family in fig (Ficus carica L.): genome-wide analysis and expression patterns. Front Plant Sci 12:1–14 38. Konno K, Hirayama H, Nakamura M, Tateishi K, Tamura Y, Hattori M, Kohno K (2004) Papain protects papaya trees from herbivorous insects: role of cysteine proteases in latex. Plant J 37: 370–378 39. Azarkan M, Matagne A, Wattiez R, Bolle L, Vandenameele J, Baeyens-Volant D (2011) Selective and reversible thiol-pegylation, an effective approach for purification and characterization of five fully active ficin (iso)forms from Ficus carica latex. Phytochemistry 72: 1718–1731 40. https://www.brenda-enzymes.org/literature.php?e¼3.4.22.3&r¼733039 41. Chemical Abstract Service. https://www.chemicalbook.com/ProdSupplierGWCB4261869_ EN.htm 42. Kramer DE, Whitaker JR (1964) Ficus enzymes. II. Properties of the proteolytic enzymes from the latex. J Biol Chem 239:2178–2183 43. Sgarbieri VC, Gupte SM, Kramer DE, Whitaker JR (1964) Ficus enzymes. I. Separation of the proteolytic enzymes of Ficus carica. J Biol Chem 239:2170–2177 44. Devaraj KB, Kumar PR, Prakash V (2008) Purification, characterization, and solvent-induced thermal stabilization of ficin from Ficus carica. J Agric Food Chem 56:11417–11423 45. Richter G, Schwarz HP, Dorner F, Turecek PL (2002) Activation and inactivation of human factor X by proteases derived from Ficus carica. British J Haematol 119:1042–1051 46. Milošević J, Vrhovac L, Đurković F, Janković B, Malkov S, Lah J, Polović ND (2020) Isolation, identification, and stability of Ficin 1c isoform from fig latex. New J Chem 44:15716–15723 47. Usai G, Mascagni F, Giordani T et al (2019) Epigenetic patterns within the haplotype phased fig (Ficus carica L.) genome. Plant J 102:600–614 48. Aider M (2021) Potential applications of ficin in the production of traditional cheeses and protein hydrolysates. JDS Commun 2. 10.3168/jdsc.2020-.0073. https://doi.org/10.3168/jdsc. 2020-0073 49. https://www.sigmaaldrich.com/US/en 50. https://www.thermofisher.com/home.html 51. Hamed MB, El-Badry MO, Kandil EI, Borai IH, Fahmy AS (2020) A contradictory action of procoagulant ficin by a fibrinolytic serine protease from Egyptian Ficus carica latex. Biotechnol Rep 27:e00492 52. Raskovic BG, Polovic ND (2016) Collegenase activity in fig latex could contribute to its efficacy in ethnomedicinal preparations. J Herb Med 6:73–78 53. Raskovic B, Bozovic O, Prodanovic R, Niketic V, Polovic N (2014) Identification, purification and characterization of a novel collagenolytic serine protease from fig (Ficus carica var. Brown Turkey) latex. J Biosci Bioeng 118:622–627 54. Boucher Y, Baxter LT, Jain RK (1990) Interstitial pressure gradients in tissue-isolated and subcutaneous tumors: implications for therapy. Cancer Res 50:4478–4484 55. Goodman TT, Olive PL, Pun SH (2007) Increased nanoparticle penetration in collagenasetreated multicellular spheroids. Int J Nanomedicine 2:265–274 56. Aref HL, Gaaliche B, Fekih A, Mars M, Aouni M, Chaumon JP, Said K (2011) In vitro cytotoxic and antiviral activities of Ficus carica latex extracts. Nat Prod Res 25:310–319

822

M. V. Castelli and S. N. Lo´pez

57. Aref HL, Gaaliche B, Ladhari A, Hammami M, Hammami SO (2018) Co-evolution of enzyme activities and latex in fig (Ficus carica L.) during fruit maturity process. South Afr J Bot 115: 143–152 58. Elsayed AM, Hegazy UM, Hegazy MGA, Abdel-Ghany SS, Salama WH, Salem AMH, Fahmy AS (2018) Purification and biochemical characterization of peroxidase isoenzymes from Ficus carica latex. Biocatal Agric Biotechnol 16:1–9 59. Kang H, Kang M, Han K (2000) Identification of natural rubber and characterization of rubber biosynthetic activity in fig tree. Plant Physiol 123:1133–1142 60. Elsayed AM, Hegazy UM, Hegazy MGA, Abdel-Ghany SS, Salama WH, Salem AMH, Fahmy AS (2018) Decolorization of synthetic dyes by Ficus carica latex peroxidase isoenzymes. Biotechnol J Int 21:1–14 61. Vatić S, Mirković N, Milošević JR, Jovčić B, Polović ND (2020) Broad range of substrate specificities in papain and fig latex enzymes preparations improve enumeration of Listeria monocytogenes. Int J Food Microbiol 334:108851 62. Altaf F, Wu S, Kasim V (2021) Role of fibrinolytic enzymes in anti-thrombosis therapy. Front Mol Biosci 8:1–17 63. De Amorin A, Borba HR, Carauta JPP, Lopes D, Kaplan MAC (1999) Anthelmintic activity of the latex of Ficus species. J Ethnopharmacol 64:255–258 64. De Feo V, Aquino R, Menghini A, Ramundo E, Senatore F (1992) Traditional phytotherapy in the peninsula Sorrentina, Campania, Southern Italy. J Ethnopharmacol 36:113–125 65. Yeşilada E, Honda G, Sezik E et al (1995) Traditional medicine in Turkey. V. Folk medicine in the inner Taurus Mountains. J Ethnopharmacol 46:133–152 66. Lokar LC, Poldini L (1988) Herbal remedies in the traditional medicine of the Venezia Giulia region (North East Italy). J Ethnopharmacol 22:231–279 67. Fujita T, Sezik E, Tabata M et al (1995) Traditional medicine in Turkey VII. Folk medicine in middle and West Black Sea regions. Econ Bot 49:406–422 68. Sebastian MK, Bhandari MM (1984) Medico-ethno botany of mount Abu, Rajasthan, India. J Ethnopharmacol 12:223–230 69. Shahinuzzaman M, Yaakob Z, Anuar FH et al (2020) In vitro antioxidant activity of Ficus carica L. latex from 18 different cultivars. Sci Rep 10:10852 70. Aref HL, Salah KBH, Chaumont JP, Fekih AW, Aouni M, Said K (2010) In vitro antimicrobial activity of four Ficus carica latex fractions against resistant human pathogens (antimicrobial activity of Ficus carica latex). Pak J Pharm Sci 23:53–58 71. Aref HL, Mars M, Fekih A, Aouni M, Said K (2012) Chemical composition and antibacterial activity of a hexane extract of Tunisian caprifig latex from the unripe fruit of Ficus carica. Pharm Biol 50:407–412 72. Breijyeh Z, Karaman R (2020) Comprehensive review on Alzheimer’s disease: causes and treatment. Molecules 25:5789 73. Oliveira AP, Valentão P, Pereira JA, Silva BM, Tavares F, Andrade PB (2009) Ficus carica L.: metabolic and biological screening. Food Chem Toxicol 47:2841–2846 74. Hemmatzadeh F, Fatemi A, Amini F (2003) Therapeutic effects of fig tree latex on bovine papillomatosis. J Veterinary Med Ser B 50:473–476 75. Ghanbari A, Le Gresley A, Naughton D, Kuhnert N, Sirbu D, Ashraf GH (2019) Biological activities of Ficus carica latex for potential therapeutics in human papillomavirus (HPV) related cervical cancers. Sci Rep 9:1–11 76. Luna LE (1984) The concept of plants as teachers among four mestizo shamans of Iquitos, Northeastern Peru. J Ethnopharmacol 11:135–156 77. Luna LE (1984) The healing practices of a Peruvian shaman. J Ethnopharmacol 13:123–133 78. Marin FA, Peres SPBA, Zuliani A (2002) Alergia látex-fruta. Rev Nutr 15:95–103

Chemistry, Biological Activities, and Uses of Jatropha Latex

31

R. Vijayalakshmi, A. Vetriselvi, Eli Jose´ Miranda Ribeiro Junior, and Patrícia de Arau´jo Rodrigues

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Bioactive Compounds Isolated from the Latex of Jatropha curcas . . . . . . . . . . . . . . . . . . . . . . . 2.1 Alkaloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Terpenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Flavonoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Phenolic Acids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Defense Proteins in the Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 The Pharmacological Activity of Jatropha Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Antifungal Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Antibacterial Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Antiviral Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Cytotoxic Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5 Collagenase Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6 Mutagenic and Antimutagenic Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7 Angiogenesis Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8 Wound Healing Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9 Hemostatic Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.10 Hunting Poison . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.11 Antioxidant Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Other Uses of Jatropha curcas . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Alternative Biodiesel Feedstock Systems . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Synthesis of Green Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

825 827 827 827 828 829 829 830 830 830 831 831 832 832 833 833 833 834 834 834 834 836 837 837

R. Vijayalakshmi (*) · A. Vetriselvi Department of Botany, Queen Mary’s College, Chennai, India E. J. Miranda Ribeiro Junior Faculty of Inhumas (FacMais), Inhumas, Goiás, Brazil P. de Araújo Rodrigues Post-Graduate Programme in Medical Sciences, Department of Medicine, Faculty of Medicine, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Ceará, Brazil © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_35

823

824

R. Vijayalakshmi et al.

Abstract

Jatropha curcas is an evergreen small tree that belongs to the family Euphorbiaceae. The plant is a rich source of latex that has a wide range of uses in the medicinal field. Latex is an excellent source of various bioactive compounds such as gallic acid, isoflavonoids, jatrophine, jatropham, phenolic acids, vanillic acid, free amino acids, organic acids, terpenoids, curcacycline B, curcin, tannin, saponin, and wax. Scientific evidence from various studies proved the antifungal, antibacterial, anticancer, antiviral, antioxidant, and larvicidal activities of latex. These studies provide information on the phytochemicals and biological activities of latex and its active constituents. Keywords

Curcin · Gallic acid · Jatropham · Jatrophine · Latex · Vanillic acid Abbreviations

Al ANP BLAST CaO Cas9 CD34 COD Cr CRISPR CuNPs DJW FASTA Fe2O3 FeTiO3 GC-MS GHGs HC HPLC HT KOH La2O3 Mg MgO MNPCE NaFeTiO4 NCTC NOx.

Aluminum The National Agency for Petroleum, Natural Gas and Biofuels Basic Local Alignment Search Tool Calcium oxide CRISPR associated protein 9 Transmembrane phosphoglycoprotein Chemical oxygen demand Chromium Clustered regularly interspaced short palindromic repeats Copper nanoparticles De-Oiled Jatropha waste Fast-All or FastA Iron(III) oxide or ferric oxide Iron titanate Gas chromatography-mass spectrometry Greenhouse gas Hydrocarbons High-performance liquid chromatography Hydrotalcite Potassium hydroxide Lanthanum oxide Magnesium Magnesium oxide Micronucleated polychromatic erythrocytes Stoichiometric sodium iron titanate National collection of type cultures Nitrogen oxides

31

Chemistry, Biological Activities, and Uses of Jatropha Latex

NP TCA TiO2 NPs TWW ZnO

1

825

Nanoparticles Trichloroacetic acid Titanium dioxide nanoparticles Tannery waste water Zinc oxide

Introduction

Latex is a translucent white milky fluid that flows out from all the plant parts when injured. The latex extracted from Jatropha curcas is not taken to generate rubber but rather the bioactive compounds possess potent medicinal applications. Jatropha curcas, popularly known as physic nut, is a monoecious perennial, lactiferous tree [1, 2]. Latex production is strongly influenced by the various environmental conditions, photosynthetic activity, and endogenous hormonal level which directly correlate the primary and secondary metabolism of the plant. The secondary metabolites isolated from the crude latex possess various activities such as wound healing, anticancer, antiviral, antioxidant, antimicrobial, anticoagulant, and procoagulant activities. J. curcas latex also possesses nanotechnological potential. Latex possesses the capacity of reducing activity and prevent the aggregation of nanoparticles. The laticiferous plant has received significant interest lately owing to its tremendous economic potential. The latex produced from the plant has been used in traditional medicine to treat different illnesses such as burns, hemorrhoids, mycoses, ulcers, and anticoagulant activities [3, 4]. The phytochemical investigations show that the latex includes different natural components with cytotoxic potential. Essential secondary metabolite compounds present in the latex are curcacyclins A and B and curcusomes A, B, C, and D, curcin anticancerous protein, jatrophine, and jatropham, alkaloids, curcacyclins A, B, and jatrophidin antibactericidal and antimalarial compounds [5–8]. Latex secretion depends on the availability of carbohydrates, nutritional status, the morphology of laticiferous vessels, biosynthesis of amino acids, and reserve proteins. Environmental factors such as seasonal climate changes, light, temperature, and humidity have a strong influence on latex production. These factors also affect photosynthetic activity, change plant metabolism, and ultimately reduce latex production [9]. Literature data strongly support the direct correlation between the environmental condition and latex production. Changes in climatic conditions interfere with latex production and in turn, affect the flowering and uneven fruit maturation [10]. J. curcas plant is highly sensitive to low temperatures which in turn leads to change in the plant metabolism. After the fruit harvest, the plant growth declines and followed by more leaf fall which in turn leads to greater production of latex. Thus, the low temperatures and leaf aging are linked directly to latex production and potentially correlated with the storage of carbohydrates and remobilization of nutrients from leaves to stem [11]. According to Liang et al., low temperatures induce plant stress, which in turn impacts numerous physiochemical processes and has a significant impact on latex production [12]. Similarly, according to Matos et al.

826

R. Vijayalakshmi et al.

[13], a succulent stem filled with latex acts as a water reservoir and delays dehydration even in the summer months. Increasing the water retaining cells and maintaining leaf hydration is an essential step in the formation of leaf chlorophyll. The chlorophyll and carotenoids concentration shows a lack of abiotic stress. Since these pigments act as a photoprotection in photosynthetic apparatus and strongly influence latex production. As a consequence, climate changes such as rainfall, moisture, low temperatures, chlorophyll, and the concentration of carotenoids affect latex production. Latex contains many biobased products but still little is explored in the scientific investigation. It is necessary to investigate and record the scientific data which will add more commercial value to this crop. Hence, this review mainly focuses on active chemical constituents and medicinal applications of the J. curcas latex [14] (Fig. 1).

Fig. 1 Jatropha curcas (a) Tree; (b) small seedling; (c) inflorescence; (d) fruits; (e) seeds

31

2

Chemistry, Biological Activities, and Uses of Jatropha Latex

827

Bioactive Compounds Isolated from the Latex of Jatropha curcas

Bioactive compounds isolated from Latex of J. curcas have been reported to contain unique secondary metabolites. These bioactive compounds include curcacycline A, curcain, lignans and coumarins, flavonoids, diterpenes, triterpenes phytosterols, saponins, and phenolic compounds [15]. A previous study on latex using the IR spectrum of ethyl acetate extract reported the presence of aromatic phenolic compounds [16]. Suhaili et al. [17] reported saponin and tannin as major compounds in the crude latex of J. curcas.

2.1

Alkaloids

Alkaloids commonly found in angiosperms exhibit numerous biological activities with remarkable functional and structural diversity. They are rarely nontoxic to humans and broad spectrums of microorganisms mainly due to their spectacular physiological and neurological activities. The latex of Jatropha contains major alkaloids including jatropham, jatrophine, and curcain [18]. The two major biologically active alkaloids such as 5-hydroxypyrrolidin, pyrimidine-2, 4-dione have been reported from J. curcas [19] in earlier studies. Further from the Jatropha genus, six alkaloids were reported [20]. However, this compound was isolated from the Nigerian medicinal plant J. podagrica and showed antibronchoconstrictor and antiarrhythmic activity [21]. Jatrodein, Jatrophan, Jatropholone A (https://doi.org/10.1021/jo00217a054), Jatropholone B, and Jatrophone are also isolated from J. macrorhiza, and J. gossypiifolia [22, 23] (Fig. 2), lignans such as gossypifan, gossypilingossypidien [24], gadain, jatroiden [25]. Dipankar Das et al. isolated a new alkaloid antherospermidine in ethyl acetate extract of J. curcas stem bark and latex [26].

2.2

Terpenoids

Species of Jatropha are an important source of terpenoid compounds. Among the terpenes, diterpenoid chemicals play a major role in these species with regard to their unique chemical structures and therapeutic benefits. Jatropha-isolated diterpenes are used for rhamnofolane, lathyrane, deoxy-preussomerin, dinorditerpene, pimarane, daphnane, and tigliane. Rakshit Devappa et al. identified nine diterpenes from Jatropha species [27]. Phytosterols are waxy, soluble in polar solvents, however insoluble, and as an active group includes alcohol (OH). Sterol is composed of three fused cyclohexane skeletons and hydro phenanthrene rings with varying side chains. Stigmasterol exhibited a significant anti-inflammatory effect when administered topically in J. curcas latex. Stigmasterol minimizes tetra decanoyl phorbol acetateinduced edema and inhibits metallo peroxidase activity and reduces inflammation [28]. Two dinorditerpenoids, four podocarpane diterpenoids, two lathyrane-type

828

R. Vijayalakshmi et al.

Fig. 2 Alkaloids from Jatropha curcas L.

diterpenoids, jatromulone A, and nine diterpenoids were extracted from J. multifida latex [27]. The other diterpenes isolated from latex include 15-O-acetyl japodagrone, jatrogrossidentadione, jatrogrosidentadione acetate, multifidone, multifolone, and multidione [29]. Terpenoids constitute the largest class of natural compounds. A tale noncyanogenic cyanoglucoside, 1-cyano-3-β-D-glucopyranoside, was secluded from the latex of Jatropha multifida [30].

2.3

Flavonoids

Flavonoids comprise an assortment of polyphenolic compounds with a benzo-γ-pyrone ring structure. The major classes of flavonoids include significant organic molecules with a broad variety of biological and medicinal activities. Polyphenolic compounds include flavanones, flavones, isoflavones, anthocyanins, and flavonols. Claudemir de Carvalho et al. [29] analyzed the protein content and flavonoids content in the latex. They found more amount of total phenol [4.808%]

31

Chemistry, Biological Activities, and Uses of Jatropha Latex

829

and less amount of flavonoid. But in leaves extract, more flavonoids [2.322%] and less amount of total flavonoid content were recorded. Rampadarath et al. screened the qualitative and quantitative assay of phenol and flavonoid compounds in latex and leaves extract of J. multifida and found the same result in concordance with the above work [31, 32]. Similarly in J. curcas leaves were reported to contain a greater number of flavones [6:90 to 8:85 mg/g dry weight] and less amount of phenol [33].

2.4

Phenolic Acids

Phenolic acids are widely used natural bioactive agents often involved in a wide range of bio-activities such as antimicrobial, antioxidants, anticancer, diabetics, and hepatoprotective activities [34]. Phenolic acids, namely, cinnamic acids, protocatechuic acid, caffeic acid, ferulic acid, and vanillic acid, were commonly reported from the latex of J. curcas [35]. High-performance liquid chromatography (HPLC) analyses in the hot water latex extract confirmed the presence of pyrogallol, rutin, myricetin, gallic acid, and daidzein compounds. The hot water latex extract also showed 3.0
0.1 mg/g of phorbol esters. GC-MS analysis also detected the following compounds 2 nitro-1, 3-propanediol, β-sitosterol, 2-furancarboxaldehyde, 5-(hydroxymethyl)-2 hydroxymethyl and acetic acid in the methanol leaf extract, 2-furancarboxaldehyde, 5-(hydroxymethyl), acetic acid, and furfural (2-furancarboxaldehyde) in the hot water latex extract [36].

2.5

Defense Proteins in the Latex

Approximately 10% of all angiosperms plants contain white sticky sap called latex [37]. The defense mechanism in plant latex and its physiological and biochemical role is poorly understood [38]. A variety of secondary metabolites, such as terpenoids, cardenolides, isoprenoids, [39], phenolics, alkaloids, and proteins, such as peptides [40, 41], protease inhibitors, chitinases, proteases, oxidases, and lectins [42], are commonly reported from latex. Analyzing these enzymes, proteins, hydrocarbons, and peptides in the latex is the primary step in pharmaceutical development [43]. Plant tests are destitute in proteins and wealthy in oxidative proteins, proteases, auxiliary metabolites, and saccharides. Proteomic analysis is an effective technique used to identify and describe the properties and functionalities of individual proteins from latex. The most popular method to extract protein from latex is phenol extraction method and acetone/TCA extraction method. Proteomic data of J. curcas latex showed the presence of hundreds of proteins with various isoelectric points. Bioinformatics analysis such as BLAST and FASTA was also performed in the latex of J. curcas [44]. Van den Berg et al. extracted a novel cyclic octapeptide from the latex of J. curcas and named the compound curcacycline A. The compound was found to contain four leucine one threonine, two glycines, and one valine residue [45].

830

R. Vijayalakshmi et al.

3

The Pharmacological Activity of Jatropha Latex

3.1

Antifungal Activities

Latex is also used as a good antifungal agent; Schmook and Serralta-Peraza used latex to treat fungal infections in the mouth, bee, wasp stings infections, and digestive problems of children in Mexico [46]. Henning et al. reported the unique alkaloid jatrophine isolated from branches of J. curcas which is believed to be having anticancerous properties [47]. According to Nath and Dutta, aproteolytic enzyme named curcain from the latex of J. curcas was found to have a wound-healing effect in mice [48]. Irvine reported that the latex mixed with the dry powdered leaves when applied to sluggish wounds found to cure the infections. Dried latex powder when formulated as an enema is used in the treatment of gonorrhea [49]. The latex is also used in styptic cuts, refractory ulcers healing of wounds, septic gums, and bruises. The stability studies were also carried out in J. curcas latex in 14 weeks under different storage conditions. The infra-red spectral analysis of all the samples was recorded from two to four weeks to elucidate the effect of light and moisture levels in inducing the activity. Exposed light reduces the antibacterial activity with a reduction in the width of the inhibition zone. The reduction was as high as 10 mm during 98 days of storage. The liquid latex lost its antifungal action after 2 days [50]. Watt and Breyer-Brandwijk used J. curcas latex as an antifungal agent [51].

3.2

Antibacterial Activities

Preliminary antibacterial screening of the dry latex powder and ethylacetate leaf extract of J. curcas was carried out by Oyi et al. (2007). The latex that was screened displays the wide spectrum of antibacterial activity against Escherichia coli NCTC 10418, Staphylococcus aureus NCTC6571, Streptococcus pyogenes NCTC8198, Bacillus subtilis NCTC 8326, and Pseudomonas aureus NCTC 6750. The zone of inhibition was maximum in E. coli compared to other strains [52]. Kumar Arun et al. [53] carried out antibacterial screening in J. curcas latex along with methanol and ethanolic leaf extract against the E. coli and S. aureus by utilizing the disc diffusion technique. The magnitude of antibacterial activity towards E. coli and S. aureus was observed to be significantly greater in latex comparing to leaf extracts. The maximum antibacterial activity was also reported in the latex when compared to the standard tetra cyclin discs. Thomas et al. [54] also reported the antibacterial activity against S. aureus by spreading the latex of J. curcas. Heyne and Suwondo et al. [55] proved the antibacterial activity of J. curcas latex. Latex when applied on absorbent cotton and placed over the decaying cavities relive the toothache [Table 1].

31

Chemistry, Biological Activities, and Uses of Jatropha Latex

831

Table 1 Medicinal uses of latex in Jatropha curcas Plant source Latex

Pharmacological activity Anticoagulant and procoagulant in blood

Latex

Topical wound healing

Latex Latex Latex

Anticancer activity Rotamase activity of cyclophilin B Fungal infections in the mouth, wasp and bee stings, and digestive troubles in children Prevent inflammation

Latex Latex

Gum bleeding, toothache, soothe baby’s inflamed tongue

Latex

Antibacterial activity against Staphylococcus aureus

3.3

Plant part used Reduce the blood clotting time in human Protease curcain induces the proliferation of human T-cells Curcacycline A Curcacycline B Application of latex to the infected regions

References [51]

Massaging the latex to the traumatic area Mouth rinse solution Latex applied on absorbent cotton to relieve toothache Spreading of latex

[66]

[41]

[45] [40] [46]

[54, 59]

[53]

Antiviral Activity

Some Jatropha species such as J. curcas, J. gossypiifolia, J. multifida, J. gaumeri, J. unicostata, and J. nana were reported to possess antiviral activities. Tewari and Shukla et al. demonstrated the antiviral actions of J. curcas latex toward watermelon mosaic virus. Latex of J. curcas possesses strong inhibitory properties against the watermelon mosaic virus on Cucurbitaceae members [56].

3.4

Cytotoxic Activities

Latex of J. curcas contains various proteins such as curcain, curcacycline A, curcacycline B, and jatrophidin I. Among these, curcacycline A and B showed cytotoxicity and antiproliferative activity in tumor cells [58]. Catherine et al. [57] studied the trans isomerase activity of cyclophilin B in latex of J. curcas Cytotoxic activity of extracted latex of J. curcas in epithelial and fibroblast cells was reported by Hitesh Kumar Parmar et al. [59]. The cells were developed in 96-well plates and permitted to attach for 120 h before treatment with a serial concentration of J. Curcas latex for 24 h. The cytotoxicity test of epithelial and fibroblast cells had been conducted using MTT assay to evaluate inhibitory concentration at 50 percent IC50 value. In both instance, cell’s toxicity was found dose-dependent, and IC50 value for epithelial and fibroblast cells was 4339 mg/ml and 3876 mg/ml accordingly. When treated cells and control cells were observed morphologically, the control cells were normal in size to compare to treated cells which are smaller in

832

R. Vijayalakshmi et al.

size. Thus, J. curcas latex was toxic to both epithelial and fibroblast cells and exhibited strong cytotoxic activity. The latex obtained from J. curcas is used in traditional medicine to treat a variety of diseases [60]. Latex contains natural compounds with therapeutic potential. 50% of diluted latex on Allium cepa root cells proved cytotoxic and genotoxic effects. Thus, the above study revealed the cytotoxic and genotoxic effect of latex on Allium cepa meristematic root cells [61].

3.5

Collagenase Activities

Collagenase has become a neutralized protease involved in cell macrophages and fibroblasts. Fazwishni Siregar evaluated the effect of J. curcas latex on collagenase released by the fibroblast cells. Four doses of latex from 375 to 300 μg/ml were added to three human gingival primary fibroblast cell cultures. After 24 h to 96 h of incubation, collagenase release was recorded in the supernatant solution and was assayed with standard collagen. Jatropha curcas latex lowered collagenase secreted by human gingival fibroblast cells. Thus, the latex of J. curcas inhibits the release of collagenase by human gingival fibroblast cells [62].

3.6

Mutagenic and Antimutagenic Activities

Mutagenic and antimutagenic activity of J. curcas latex was demonstrated by measuring the frequency of micronuclei in mouse bone marrow cells. To determine the mutagenic activity, the animals were treated with 10, 30, 50, and 100 (mg/kg body weight) doses of latex intraperitoneally. The negative control group was treated with 1 ml of sterile water. To examine the antimutagenic activity, the animals are sequentially treated with latex and mitomycin C (4 mg/kg). Latex was co-administrated with a mutagenic drug doxorubicin ®, and it showed an antimutagenic effect. The experimental findings revealed a substantial increase in the frequency of micronucleated polychromatic erythrocytes (MNPCE) compared to the negative control group in a dose-dependent manner. To test the antimutagenicity, the dosages of 10 and 30 mg/kg co-administered with mitomycin C revealed a substantial reduction in micronucleated polychromatic erythrocytes frequency compared to the positive control group. However, no significant decrease in micronucleated polychromatic erythrocytes frequency was observed at the dosages of 50 and 100 mg/kg. Polyphenols present in the latex are responsible for both antimutagenic and mutagenic activity. Polyphenol can act as a mutagen by directly binding to DNA molecules. It also generates free radicles and inhibits topoisomerase enzymes. At the same time, polyphenols can also act as antimutagens by interfering with cytochrome P450-mediated metabolism. Polyphenols also exhibit antioxidant potential and interact with mutagen metabolites. The above experimental results suggest that J. curcas latex can play a dual role in mutagenic and antimutagenic activity [63–66].

31

3.7

Chemistry, Biological Activities, and Uses of Jatropha Latex

833

Angiogenesis Activities

Ummu Balqis demonstrated the angiogenesis activity of J. curcas latex in cream formulation on wound healing mice; 10 to 15% creamy latex showed a significant immune response to CD34 macrophage on the third and seventh day in wound healing of mice skin. The creamy latex of J. curcas shows considerable potential for angiogenesis capacity in mice skin wound healing [67].

3.8

Wound Healing Activities

Jatropha curcas latex may function as a natural wound healing agent owing to the presence of flavonoids and saponins. Macrophages serve a crucial part in the wound healing process. Macrophage promotes cell proliferation and improves tissue reclamation taking after injury. Flavonoids collected in the latex play a significant role in the inflammatory phase by boosting interleukin-2, the proliferation of macrophages, and lymphocytes. Saponins in the latex may also enhance the proliferation of monocytes and also raise the number of macrophages that release the growth factor that is essential for the wound healing process [68]. The latex may also use it as a remedy for inflammation, yellow fever, eczema, paralysis, dropsy, and burns [69]. The latex cream of J. curcas has anti-inflammatory activities in the wound healing process of mice skin. De Feo et al. [70] reported the anti-inflammatory activity of J. curcas latex. Latex has a tremendous effect when massaged on the traumatic area to prevent inflammation.

3.9

Hemostatic Activities

Latex of Jatropha contains alkaloids such as jatrophine, jatrophen, jatrophore, and curcain which are anticarcinogenic and traditionally also used as a hemostatic agent. The hemostatic activity of J. curcas latex was tested using several groups of Wistar albino rats utilizing varying dosages of latex. Incisions were created on the thighs of various groups of animals and varying dosages of the stem latex were applied. The experiment was performed daily for a couple of weeks. The control group was not incised. The animals were killed and the impact of the stem latex on blood biochemistry and hematological parameters was evaluated using current techniques. There were no statistically substantial changes (P > 0.05) in the outcome of biochemical and hematological parameters obtained for the control and experimental animals. These results revealed that the stem latex of J. curcas has no negative consequences [71]. Southern Nigerian people used the stem latex of J. grossypifolia to prevent nose bleeding, gum bleeding, and injuries in the skin [72]. Jatropha curcas latex possesses both coagulant and anticoagulant activities on plasma cells. Ethyl acetate and butanol fraction of latex of J. curcas showed strong

834

R. Vijayalakshmi et al.

coagulant and anticoagulant activity in a lower concentration. The prothrombin time and enacted partial thromboplastin time tests on plasma support these results. Dissolvable dividing of the latex with ethyl acetate and butanol led to a partial partition of components at low concentrations. The proportion of ethylacetate exhibited a procoagulant impact, whereas the fraction of butanol showed the most evident activity of anticoagulants. The residual aqueous fraction did not affect blood coagulation time and the prothrombin time test and delayed the enacted partial thromboplastin time test slightly. All latex significantly reduces the coagulation period of blood samples. Diluted latex increased the clotting time, and at severe dispersion, the blood did not coagulate even really. This reveals that the J. curcas latex has both anticoagulant and coagulant properties. Omolaja and Funmi et al. studied the anticoagulant and coagulant properties of J. curcas latex [73].

3.10

Hunting Poison

In some parts of Africa and the Philippines, people used stem bark or latex of J. curcas as fishing poison. Nigerians used J. curcas seeds mixed with latex of Euphorbia poisonii and coated with corn. The latex-coated corn was being used as bait for hunting guineafowl. Nigerian tribes generate arrow poison from the seed oil of J. curcas and Strophanthus spp. Seeds grated with palm oil are used to kill rats in Gabon [74]. Such historic applications as hunting poison are linked to the extreme toxicity of the seed and latex of J. curcas.

3.11

Antioxidant Activities

The antioxidant assay was carried out in J. curcas latex using DPPH radical scavenging method. A good antioxidant potential was reported at IC50 value 0.87 mg/ml. Ascorbic acid and tannic acid were treated as a positive control group. The experimental studies demonstrated that latex acts as free radical scavengers [75, 76].

4

Other Uses of Jatropha curcas

4.1

Alternative Biodiesel Feedstock Systems

Biodiesel is a typical plant-based renewable energy and makes it renewable and friendly to the environment. The rising cost of manufacturing biodiesel from edible oils has prompted researchers to look for nonedible oil feedstocks. Biodiesel is produced by transesterifying vegetable oils, animal fats, or residual cooking oil with low-density alcohol and a catalyst to generate mono-alkyl esters of longchain fatty acids [77, 78]. Jatropha curcas has been identified as a potential recurring

31

Chemistry, Biological Activities, and Uses of Jatropha Latex

835

energy crop for biodiesel generation in the tropical and temperate regions (primarily in India, Mexico, China, and Brazil). Biodiesel processing of J. curcas was assessed in relation to other edible and nonedible feedstocks as economically viable and environmentally sustainable [79]. Jatropha curcas biodiesel was recently demonstrated without significant modifications as engine fuel on numerous diesel engines [80, 81]. There are currently several technologies available for the processing of biodiesel including super-critical fluid extraction, ultrasonic extraction, organic solvent extraction, and mechanical screw press [82–84]. In addition, various methods are available to improve biodiesel production such as blending, thermal cracking, microemulsification, transesterification [85, 86]. Among them, the most common and mature method is transesterification. The acid acts as a catalyst in the esterification process. Transesterification reactions usually involve three types of catalysts: alkali catalysts, enzymatic catalysts, and acid catalysts, depending on the form of catalyst used [87]. However, it is critically important to select and explore catalysts for biodiesel production by esterification and transesterification. Mostly, different types of catalysts are used in biodiesel production such as calcium oxide-based metals [88, 89]; calcium oxide with magnesium oxide [90]; MgO-ZnO mixed metal oxide [91]; CaO–La2O3 calcium to lanthanum metal oxide [92]; hydrotalcite (HT) [93]; hydrotalcite with Mg/Al ([94]; acid heterogeneous catalysts montmorillonite clay [95]; and calcined waste animal bones [96]. In addition, Jatropha biodiesel-regulated engine emission is lower than the diesel engine net greenhouse gas (GHGs). Global warming potential Jatropha biodiesel dependent on the quantity of fertilizer utilized in the harvest, the amount of diesel irrigation fuel used, and the technique utilized to produce the biodiesel [97]. Research also indicated that 23 percent of diesel fuel has the ability to generate global warming from the processing and use of Jatropha biodiesel. Other emissions, such as NOx and HC, are mostly engine load based. Likewise, the amount of HC emitted by the increased combustion of Jatropha biodiesel is reduced to diesel fuel [98, 99]. Additionally, the relevance of producing biofuels utilizing renewable crops and the need of proposing innovative catalytic components that may be synthesized in a sustainable approach are discussed. Recently, Adriana et al. [100] performed biodiesel production using J. curcas L. oil, a sustainable NaFeTiO4/Fe2O3–FeTiO3 catalyst that was fabricated using a solid-state process. The advantages of this composite are to improve the magnetic activity, low cost, and availability of the precursor materials. However, the biodiesel quality varies, which were obtained from different genotypes of J. curcas in terms of saponification number and ester number [101]. Likewise, Nisar et al. [102] focused on the analysis of potassium hydroxide transformed animal bones (KOH) for the transesterification of nonedible Jatropha oil as a heterogeneous solid basis catalyst. Different studies have also established J. curcas oil’s suitability for biodiesel production by the reaction to transesterification [101–103]. Brazil has a major presence and tremendous capacity to produce produce electricity from agriculture and organic waste, and it is recognized as a great important country of the world biomass market owing to its extensive production of crops like

836

R. Vijayalakshmi et al.

sugar cane and soya and other forms of agriculture [104]. Brazil’s diverse national biodiversity provides several promising oilseed species for biodiesel processing. Brazil is the world’s second largest ethanol industry with the highest sustainable biofuel growth and manufacturing process. However, soybeans constitute the majority of the raw materials used in biofuel processing, accounting for 79.1% on average, thanks to well-managed farming that ensures a consistent supply of oil. In order to strengthen the domestic production process and adapt to changing global supply for biodiesel, it is also necessary to focus on the development of oilseeds that are suitable for various edapho-climatic conditions to expand the production facility and eliminate the scarcity of conventional raw materials and the high costs associated with them. Furthermore, genomics provides a broad variety of techniques used to collect genetic information that may be integrated with several crop genetic improvement schemes to aid the creation of cultivars with an exceptional production of biodiesel efficiency [105, 106]. Jatropha curcas has been emphasized in this scenario of exploring for raw materials appropriate for the production of biodiesel because (i) its seeds contain high-quality oil, (ii) it matures quickly, (iii) it has a long production period, (iv) it sustains drought, and (v) its genetic diversity allows genetic manipulation. Peixoto et al. [107] examined 179 Jatropha half-sib families and discovered a low heritability to seed productivity (0.35) and oil yield (0.24). Diana and coauthors [108] studied the degumming mechanism and oxidative stability assessment for J. curcas L. methyl and ethyl biodiesel. The results showed physicochemical characteristics consistent with ANP resolution limits (ANP – National Agency of Petroleum, Natural Gas and Biofuels from Brazil).

4.2

Synthesis of Green Nanoparticles

Green synthesis is an easy, eco-friendly, and emergent method and less toxic to nanoparticles synthesis (NPs) from biodegradable materials such as microbes, enzymes, and plant extracts [109]. Interestingly, plant extract synthesis seems to be the most viable technique, since it reduces the chance of related pollution while decreasing the response time and preserving the structure of the cell. Though J. curcas leaves are generally considered waste material, they are environmentally sustainable and readily available and indeed useful in TiO2 NPs (titanium dioxide nanoparticles) green synthesis. In addition, the green synthesized nanoparticles were for the first time introduced to test their ability for simultaneous elimination from the secondary treatment of chemical oxygen (COD) and chromium (Cr) ions 82.26% and 76.46%, respectively, in 5 h from tannery wastewater (TWW) [110]. In addition, the spherical shape (size 25–50 nm) of TiO2 NPs was prepared from the latex of J. curcas [111]. The presence of peptides is the key constituent of J. curcas’s latex for the synthesis of lead nanoparticles in the range of 10 to 12.5 nm [113]. Suriyaprabha and co-workers synthesized Zinc oxide (ZnO) green NPs from J. curcas shells. This research first reports the toxicological evaluations for multifunctional biomedical applications and the prepared NPs are high purity (100%), with a hexagonalized structure and an average particle size of 53 nm

31

Chemistry, Biological Activities, and Uses of Jatropha Latex

837

[112]. Harekrishna et al. reported the quick synthesis of silver nanoparticles from the aqueous seed extract of J. curcas, an eco-friendly method. The resulting silver particles mostly provide spherical particles of 15 to 50 nm in diameter [114] as well as the same group synthesized silver nanoparticles from latex J. curcas as a capping agent which is 10–20 nm in diameter [115]. In addition, Ag-based nanoparticles from J. Curcas leaf extracts were synthesized and their antibacterial activity was investigated and documented by Chauhan et al. [116]. Suvardhan and co-workers [117] reported the formation of gold nanoparticles by de-oiled Jatropha waste (DJW) as a natural source of renewable energy waste with an average 14 nm particle size. Copper nanoparticles (CuNPs) were synthesized by Mithunkumar et al. [118] by using J. Curcas leaf extracts and its photo catalytical properties were investigated.

5

Conclusion

Jatropha curcas has been shown to be environmentally friendly for long-term application, with the potential to solve economic development concerns. Many valid concerns about different crop strengths and weaknesses derive from the need to produce marginalized and polluted lands to prevent competitive land on crop production. The detailed pharmacological, such as anticancer, antimicrobial, antidiabetic, anticoagulant, and antiviral, and phytochemical research findings presented in this study provide realistic paperwork for J. curcas traditional usage and confirm that this plant may be regarded as a superior source for medicinal molecules. Acknowledgments My sincere thanks to the all mighty for giving me the strength and opportunity to carry out my work in a unique way.

References 1. Ma J, Waxman DJ (2008) Modulation of the antitumor activity of metronomic cyclophosphamide by the angiogenesis inhibitor axitinib. Mol Cancer Ther 7:79–89. https://doi.org/10. 1158/1535-7163.MCT-07-0584 2. Yang W-H, Xu J, Mu J-B, Xie J (2017) Revision of the concept of anti-angiogenesis and its applications in tumor treatment. CDTM 3:33–40. https://doi.org/10.1016/j.cdtm.2017.01.002 3. Ribeiro S, de Jesus A, dos Anjos C et al (2012) Evaluation of the cytotoxic activity of some Brazilian medicinal plants. Planta Med 78:1601–1606. https://doi.org/10.1055/s-00321315043 4. de Almeida M, do Prado DL, D’Abadia L et al (2016) The state-of-art in angiogenic properties of latex from different plant species. Curr Angiogenes 4:10–23. https://doi.org/10.2174/ 221155280401160517164531 5. Diéguez MC, Cerecedo I, Muriel A et al (2011) Adaptation and validation of the Spanish version of the Quality Of Life in Latex Allergy questionnaire (QOLLA). J Investig Allergol Clin Immunol 21:283–289. PMID: 21721374 6. Matos FS, Ciappina AL, Rocha EC, Almeida LM (2017) Factors that influence in Jatropha curcas L. latex production. Bragantia 77:74–82. https://doi.org/10.1590/1678-4499.2016468

838

R. Vijayalakshmi et al.

7. Pereira IR, D’Abadia PL, Prado do ADL et al (2018) Trends and gaps in the global scientific literature about Jatropha curcas L. (Euphorbiaceae), a tropical plant of economic importance. Semin Cienc Agrar 39:7. https://doi.org/10.5433/1679-0359.2018v39n1p7 8. Debnath M, Bisen P (2008) Jatropha curcas L., a multipurpose stress resistant plant with a potential for Ethnomedicine and renewable energy. Curr Pharm Biotechnol 9:288–306. https:// doi.org/10.2174/138920108785161541 9. Oskoueian E, Abdullah N, Saad WZ et al (2011) Antioxidant, anti-inflammatory and anticancer activities of methanolic extracts from Jatropha curcas Linn. J Med Plant Res 5(1):49–57 10. Insanu M, Anggadiredja J, Kayser O (2012) Curcacycline A and B – new pharmacological insights to an old drug. Int J Appl Res Nat Prod 5(2). https://www.researchgate.net/publication/ 266226063_Curcacycline_A_and_B_-_New_pharmacological_insights_to_an_old_drug 11. Nowak-Sliwinska P, Segura T, Iruela-Arispe ML (2014) The chicken chorioallantoic membrane model in biology, medicine, and bioengineering. Angiogenesis 17:779–804. https://doi. org/10.1007/s10456-014-9440-7 12. Liang Y, Chen H, Tang MJ, Yang PF, Shen SH (2007) Responses of Jatropha curcas seedlings to cold stress: photosynthesis-related proteins and chlorophyll fluorescence characteristics. Physiol Plant 131:508–517. https://doi.org/10.1111/j.1399-3054.2007.00974.x 13. Matos FS, Ciappina AL, Rocha EC, Almeida LM (2018) Factors that influence in Jatropha curcas L. latex production. Bragantia 77(1):74–82. https://doi.org/10.1590/1678-4499. 201646814 14. Aleksandrowicz E (2015) Ethical euthanasia and short-term anesthesia of the chick embryo. ALTEX 143–147. https://doi.org/10.14573/altex.1410031 15. Zhang XP, Zhang ML, Su XH et al (2009) Chemical constituents of the plants from genus Jatropha. Chem Biodivers 6(12):2166–2183. https://doi.org/10.1002/cbdv.200700461 16. Filler R (1978) Textbook of organic medicinal and pharmaceutical chemistry, 7th edition (Wilson, Charles O.). J Chem Educ 55:A244. https://doi.org/10.1021/ed055pA244.2 17. Suhaili Z (2011) Antibacterial profile of Jatropha curcas latex extracts against selected human pathogenic bacteria. Afr J Microbiol Res 5. https://doi.org/10.5897/ajmr11.663 18. Thomas R, Sah NK, Sharma PB (2008) Therapeutic biology of Jatropha curcas: a mini review. Curr Pharm Biotechnol Aug 9(4):315–324. https://doi.org/10.2174/ 138920108785161505 19. Staubmann R, Schubert-Zsilavecz M, Hiermann A, Kartnig T (1999) A complex of 5-hydroxypyrrolidin-2-one and pyrimidine-2,4-dione isolated from Jatropha curcas. Phytochemistry 50. https://doi.org/10.1016/S0031-9422(98)00531-7 20. Aiyelaagbe OO, Adesogan K, Ekundayo O, Gloer JB (2007) Antibacterial diterpenoids from Jatropha podagrica Hook. Phytochemistry 68. https://doi.org/10.1016/j.phytochem.2007. 05.021 21. Félix-Silva J, Giordani RB, da Silva-Jr AA, Zucolotto SM, de Freitas Fernandes-Pedrosa M (2014) Jatropha gossypiifolia L. (Euphorbiaceae): a review of traditional uses, phytochemistry, pharmacology, and toxicology of this medicinal plant. J Evid Based Complement Altern Med 32, article id 369204. https://doi.org/10.1155/2014/369204 22. Rajic A, Kweifio-Okai G, Macrides T et al (2000) Inhibition of serine proteases by antiinflammatory triterpenoids. Planta Med 66. https://doi.org/10.1055/s-2000-8657 23. García MD, Sáenz MT, Gómez MA, Fernández MA (1999) Topical antiinflammatory activity of phytosterols isolated from Eryngium foetidum on chronic and acute inflammation models. Phytother Res 13. https://doi.org/10.1002/(SICI)1099-1573(199902)13:13.0.CO;2-F 24. Das B, Anjani G (1999) Gossypidien, a lignan from stems of Jatropha gossypifollia 1Part 29 in the series studies on phytochemicals. For Part 28 see Das, B., and Venkataiah, B. (1998). Biochemical Systematics and Ecology in press. Iict Communication No. 4148. Phytochemistry 51:115–117. https://doi.org/10.1016/S0031-9422(98)00727-4 25. Oduola T, Adeosun GO, Oduola TA et al (2005) Mechanism of action of Jatropha gossypifolia stem latex as a haemostatic agent. Electron J Gen Med 2. https://doi.org/10.29333/ejgm/82329

31

Chemistry, Biological Activities, and Uses of Jatropha Latex

839

26. Das Gupta D, Haque ME, Islam MN et al (2011) Alkaloid and steroid from the stem bark of Jatropha curcas (Euphorbiaceae). Dhaka Univ J Pharm Sci 10. https://doi.org/10.3329/dujps. v10i1.10009 27. Devappa RK, Makkar HPS, Becker K (2011) Jatropha diterpenes: a review. JAOCS J Am Oil Chem Soc 88:3. https://doi.org/10.1007/s11746-010-1720-9 28. Zhu JY, Zhang CY, Dai JJ et al (2017) Diterpenoids with thioredoxin reductase inhibitory activities from Jatropha multifida. Nat Prod Res 31. https://doi.org/10.1080/14786419.2017. 1297441 29. de Carvalho C, Vieira Mariano L, Negrão VS et al (2018) Phenols, flavonoids and antioxidant activity of Jatropha multifida L. collected in Pindamonhangaba, Sao Paulo State, Brazil. J Anal Pharmaceut Res 7. https://doi.org/10.15406/japlr.2018.07.00286 30. van den Berg AJJ, Horsten SFAJ, Kettenes-van den Bosch JJ et al (1995) Multifidin-A cyanoglucoside in the latex of Jatropha multifida. Phytochemistry 40:597–598. https://doi. org/10.1016/0031-9422(95)93759-9 31. Rampadarath S, Puchooa D, Ranghoo-Sanmukhiya VM (2014) Antimicrobial, phytochemical and larvicidal properties of Jatropha multifida Linn. Asian Pac J Trop Med 7. https://doi.org/ 10.1016/S1995-7645(14)60262-5 32. Ebuehi OA, Okorie NA (2009) Phytochemical screening and quantification of flavonoids from leaf extract of Jatropha curcas Linn. Nig Q J Hosp Med 19. https://doi.org/10.4314/nqjhm. v19i4.54526 33. Li S, Cheng X, Wang C (2017) A review on traditional uses, phytochemistry, pharmacology, pharmacokinetics, and toxicology of the genus Peganum. J Ethnopharmacol 203:127–162. https://doi.org/10.1016/j.jep.2017.03.049 34. Saibabu V, Fatima Z, Khan LA, Hameed S (2015) Therapeutic potential of dietary phenolic acids. Adv Pharmacol Sci 823539. https://doi.org/10.1155/2015/823539 35. Xu J-J, Tan N-H (2012) Phenolic compounds from Jatropha curcas. Zhongguo Zhong Yao Za Zhi 37(20):3074–3077. 23311156 36. Oskoueian E, Abdullah N, Ahmad S et al (2011) Bioactive compounds and biological activities of Jatropha curcas L. kernel meal extract. Int J Mol Sci 12:5955–5970. https://doi. org/10.3390/ijms12095955 37. Konno K (2011) Plant latex and other exudates as plant defense systems: roles of various defense chemicals and proteins contained therein. Phytochemistry 72(13):1510–1530. https:// doi.org/10.1016/j.phytochem.2011.02.016 38. Agrawal AA, Konno K (2009) Latex: a model for understanding mechanisms, ecology, and evolution of plant defense against herbivory. Annu Rev Ecol Evol Syst 40. https://doi.org/10. 1146/annurev.ecolsys.110308.120307 39. Heldt H-W, Piechulla B (2011) A large diversity of isoprenoids has multiple functions in plant metabolism. In: Plant biochemistry, 4th ed. Academic Press, pp 409–429. https://doi.org/10. 1016/B978-0-12-384986-1.00017-X 40. Auvin C, Baraguey C, Blond A et al (1997) Curcacycline B, a cyclic nonapeptide from Jatropha curcas enhancing rotamase activity of cyclophilin. Tetrahedron Lett 38. https://doi. org/10.1016/S0040-4039(97)00495-4 41. Nath LK, Dutta SK (1991) Extraction and purification of curcain, a protease from the latex of Jatropha curcas Linn. J Pharm Pharmacol 43. https://doi.org/10.1111/j.2042-7158.1991. tb06642.x 42. Upadhyay RK (2011) Plant latex: a natural source of pharmaceuticals and pesticides. Int J Green Pharm 5(3):169–180. https://doi.org/10.4103/0973-8258.91222 43. Brenan JPM, Irvine FR (1962) Woody plants of Ghana and their uses woody plants of Ghana, with special reference to their uses. Kew Bull 16:2. https://doi.org/10.2307/4118826 44. Yang S, Ding MM, Chen F, Xu Y (2017) Proteomic analysis of latex from Jatropha curcas L stems and comparison of two classic proteomic sample isolation methods: the phenol extraction and the TCA/acetone extraction. Electron J Biotechnol 27. https://doi.org/10.1016/j.ejbt. 2017.01.006

840

R. Vijayalakshmi et al.

45. van den Berg AJJ, Horsten SFAJ, Kettenes-van den Bosch JJ et al (1995) Curcacycline a – a novel cyclic octapeptide isolated from the latex of Jatropha curcas L. FEBS Lett 358(3):215– 218. https://doi.org/10.1016/0014-5793(94)01405-P 46. Schmook B, Serralta-Peraza L (1997) Jatropha curcas: distribution and uses in Yucatan Peninsula of Mexico. In: Gubitz GM, Mittelbach M, Trabi M (eds) Biofuels and Industrial Products from Jatropha curcas. DBV Graz, pp 53–57 47. Henning RK (1998) Use of Jatropha curcas L. (JCL): a household perspective and its contribution to rural employment creation – experiences of the Jatropha project in Mali, West Africa, 1987 to 1997. Presentation: Regional Workshop on the Potential of Jatrophacurcas in Rural Development and Environmental Protection, Harare, Zimbabwe. http://www.Jatropha.de/harare98.htm 48. Nath LK, Dutta SK (1991) Extraction and purification of curcain, a protease from the latex of Jatropha curcas Linn. J Pharm Pharmacol 43(2):111–114. https://doi.org/10.1111/j.20427158.1991.tb06642.x 49. Irvine FR (1961) Woody plants of Ghana: with special reference to their uses. Oxford University Press, London 50. Osoniyi O, Onajobi F (2003) Coagulant and anticoagulant activities in Jatropha curcas latex. J Ethnopharmacol 89. https://doi.org/10.1016/S0378-8741(03)00263-0 51. Watt JM, Breyer-Brandwijk MG (1933) The medicinal and poisonous plants of southern Africa: being an account of their medicinal uses, chemical composition, pharmacological effects and toxicology in man and animal. Nature 132:336. https://doi.org/10.1038/ 132336a0 52. Oyi AR, Onaolapo JA, Haruna AK, Morah CO (2007) Antimicrobial screening and stability studies of the crude extract of Jatropha curcas Linn latex (Euphorbiaceae). Nig J Pharm Sci 6(2):14–20. https://njps.abu.edu.ng/pdf/23.pdf 53. Arun K, Anu B, Ruchika G (2013) A comparative study of antibacterial activity of leaves and latex of Jatropha curcas L. Int J Pharmacogn Phytochem Res 4(4):190–194. http:// impactfactor.org/PDF/IJPPR/4/IJPPR,Vol4,Issue4,Article4.pdf 54. Thomas OO (1989) Re-examination of the antimicrobial activities of Xylopia aethiopica, Carica papaya, Ocimum gratissimum, and Jatropha curcas. Fitoterapia 60:147–155 55. Heyne K, Indonesia., Kehutanan. BP dan P (1988) Tumbuhan berguna Indonesia. 1180–1182. https://doi.org/10.1007/978-3-319-49653-5 56. Tewari JP, Shukla IK (1982) Inhibition of infectivity of two strains of watermelon mosaic virus by latex of some angiosperms. Geobios 9(3):124–126 57. Catherine A, Carine B, Alain B, Francoise L, Jean-Louis P, Bernard B (1997) Curcacycline B, a cyclic nonapeptide from Jatropha curcas enhancing rotamase activity of cyclophilin. Tetrahedron Lett 38(16):2845–2848. https://doi.org/10.1016/S0040-4039(97)00495-4 58. Nucera S, Biziato D, de Palma M (2011) The interplay between macrophages and angiogenesis in development, tissue injury and regeneration. Int J Dev Biol 55(4–5):495–503. https://doi. org/10.1387/ijdb.103227sn 59. Parmar HK A review on pharmacological activity of Jatropha curcas latex. J Herbal Biol Res 1(1):13–15 60. Watt JM, Breyer Kimura Y, Sumiyoshi M, Kawahira K, Sakanaka M (2006) Effects of ginseng saponins isolated from red ginseng roots on burn wound healing in mice. Br J Pharmacol 148: 860–870. https://doi.org/10.1038/sj.bjp.0706794 61. Ciappina AL, Ferreira FA, Pereira IR et al (2017) Toxicity of Jatropha curcas L. latex in Allium cepa test. J Biosci 33(5):1295–1304. https://doi.org/10.14393/bj-v33n5a2017-33835 62. Siregar F, Akbar SMS (2007) Jatropha curcas latex inhibits the release of collagenase by gingival fibroblast. Med J Indones 16:4; 219–223. https://doi.org/10.13181/mji.v16i4.282 63. Kristiani FS (2007) Mutagenicity activity of Jatropha curcas L. (Euphorbiaceae) latex. Berkala Ilmu Kedokteran 39(1):23–26. https://journal.ugm.ac.id/bik/article/view/3039 64. Kumar A, Tewari SK (2015) Origin, distribution, ethnobotany and pharmacology of Jatropha curcas. Res J Med Plant 9:48–59. https://doi.org/10.3923/rjmp.2015.48.59

31

Chemistry, Biological Activities, and Uses of Jatropha Latex

841

65. Marnewick JL, Gelderblom WCA, Joubert E (2000) An investigation on the antimutagenic properties of south African herbal teas. Mutat Res Genet Toxicol Environ Mutagen 471(1–2): 157–166. https://doi.org/10.1016/S1383-5718(00)00128-5 66. Bekalu Y (2020) Review on the economic importance of Jatropha apart from its use as a biofuel. EPRA IJRD 5(1):24–33. https://eprajournals.com/jpanel/upload/859pm_6.EPRA% 20JOURNALS-3898.pdf 67. Balqis U, Darmawi, Iskandar CD, Salim MN (2018) Angiogenesis activity of Jatropha curcas L. latex in cream formulation on wound healing in mice. Vet World 11:939–943. https://doi. org/10.14202/vetworld.2018.939-943 68. Bailão EFLC, Pereira IR, Silva JGV et al (2019) The mitigating effect of Jatropha curcas L. latex against genotoxicity induced by doxorubicin. European J Med Plants 30:1–9. https:// doi.org/10.9734/ejmp/2019/v30i130166 69. Heller J (1996) Physic nut. Jatropha curcas L. promoting the conservation and use of underutilized and neglected crops. 1. Institute of Plant Genetics and Crop Plant Research, Gatersleben/international plant genetic resources institute, Rome, 66 p. https://www. bioversityinternational.org/fileadmin/_migrated/uploads/tx_news/Physic_nut__Jatropha_ curcas_L._161.pdf 70. De Feo V (1989) Use of plant action antiinflammatoria upper Ucayall, eastern Peru. Fitoterapia 481–494 71. Oduola T, Popoola GB, Avwioro OG, Oduola TA, Ademosun AA, Lawa MO (2007) Use of Jatropha gossypifolia stem latex as a hemostatic agent: how safe is it? J Med Plant Res 1(1): 014–017. https://citeseerx.ist.psu.edu/viewdoc/download?doi¼10.1.1.964.7465&rep¼rep1& type¼pdf 72. T. O, O. GA, T. BA (2005) Suitability of the leaf extract of Jatropha gossypifolia as an anticoagulant for biochemical and hematological analyses. Afr J Biotechnol 4:679–681. https://doi.org/10.5897/AJB2005.000-3125 73. Osoniyi O, Onajobi F (2003) Coagulant and anticoagulant activities in Jatropha curcas latex. J Ethnopharmacol 89:101–105. https://doi.org/10.1016/S0378-8741(03)00263-0 74. Evans Schultes R (1980) Medicinal plants of east and Southeast Asia: attributed properties. Econ Bot 34:361–361. https://doi.org/10.1007/BF02858311 75. Neuwinger HD (1996, 1997) African ethnobotany: poisons and drugs: chemistry, pharmacology, toxicology. Chapman & Hall. Weinheim, Germany. J Nat Prod 60(8):864–865. https:// doi.org/10.1021/np960638h 76. Anani K, Adjrah Y, Ameyapoh Y et al (2016) Antimicrobial, Anti-inflammatory and antioxidant activities of Jatropha multifida L. (Euphorbiaceae). Pharmacogn Res 8:142. https://doi. org/10.4103/0974-8490.172657 77. Alaba PA, Sani YM, Ashri Wan Daud WM (2016) Efficient biodiesel production: Via solid superacid catalysis: a critical review on recent breakthrough. RSC Adv 6:78351–78368. https://doi.org/10.1039/C6RA08399D 78. Raja S, Smart D, Lee C (2011) Biodiesel production from Jatropha oil and its characterization. Res J Chem Sci 1(1):81–87. http://www.isca.in/rjcs/Archives/v1/i1/13.pdf 79. Jonas M, Ketlogetswe C, Gandure J (2020) Variation of Jatropha curcas seed oil content and fatty acid composition with fruit maturity stage. Heliyon 6:1. https://doi.org/10.1016/j.heliyon. 2020.e03285 80. Singh D, Sharma D, Soni SL et al (2021) A comprehensive review of physicochemical properties, production process, performance and emissions characteristics of 2nd generation biodiesel feedstock: Jatropha curcas. Fuel 285. https://doi.org/10.1016/j.fuel.2020.119110 81. Ganapathy T, Gakkhar RP, Murugesan K (2011) Influence of injection timing on performance, combustion and emission characteristics of Jatropha biodiesel engine. Appl Energy 88. https:// doi.org/10.1016/j.apenergy.2011.05.016 82. Amalia Kartika I, Yani M, Ariono D et al (2013) Biodiesel production from Jatropha seeds: solvent extraction and in situ transesterification in a single step. Fuel 106:111–117. https://doi. org/10.1016/j.fuel.2013.01.021

842

R. Vijayalakshmi et al.

83. Ali M, Watson IA (2014) Comparison of oil extraction methods, energy analysis and biodiesel production from flax seeds. Int J Energy Res 38:5. https://doi.org/10.1002/er.3066 84. Kumar M, Sharma MP (2015) Assessment of the potential of oils for biodiesel production. Renew Sustain Energy Rev 44:814–823. https://doi.org/10.1016/j.rser.2015.01.013 85. Farobie O, Matsumura Y (2017) State of the art of biodiesel production under supercritical conditions. Prog Energy Combust Sci 63:173–203. https://doi.org/10.1016/j.pecs.2017.08.001 86. Jain S, Sharma MP (2010) Prospects of biodiesel from Jatropha in India: a review. Renew Sustain Energy Rev 14:2; 763–771. https://doi.org/10.1016/j.rser.2009.10.005 87. Leung DYC, Wu X, Leung MKH (2010) A review on biodiesel production using catalyzed transesterification. Appl Energy 87(4):1083–1095. https://doi.org/10.1016/j.apenergy.2009.10.006 88. Islam A, Taufiq-Yap YH, Chu CM et al (2013) Studies on the design of heterogeneous catalysts for biodiesel production. Process Saf Environ Prot 91(1):131–144. https://doi.org/ 10.1016/j.psep.2012.01.002 89. Teo SH, Goto M, Taufiq-Yap YH (2015) Biodiesel production from Jatropha curcas L. oil with ca and La mixed oxide catalyst in near supercritical methanol conditions. J Supercrit Fluids 104:243–250. https://doi.org/10.1016/j.supflu.2015.06.023 90. Teo SH, Rashid U, Taufiq-Yap YH (2014) Biodiesel production from crude Jatropha curcas oil using calcium-based mixed oxide catalysts. Fuel 136:244–252. https://doi.org/10.1016/j. fuel.2014.07.062 91. Taufiq-Yap YH, Lee HV, Yunus R, Juan JC (2011) Transesterification of non-edible Jatropha curcas oil to biodiesel using binary ca-mg mixed oxide catalyst: effect of stoichiometric composition. Chem Eng J 178:342–347. https://doi.org/10.1016/j.cej.2011.10.019 92. Lee HV, Taufiq-Yap YH, Hussein MZ, Yunus R (2013) Transesterification of Jatropha oil with methanol over Mg-Zn mixed metal oxide catalysts. Energy 49. https://doi.org/10.1016/j. energy.2012.09.053 93. Helwani Z, Aziz N, Bakar MZA et al (2013) Conversion of Jatropha curcas oil into biodiesel using re-crystallized hydrotalcite. Energy Convers Manag 73:128–134. https://doi.org/10. 1016/j.enconman.2013.04.004 94. Deng X, Fang Z, Liu YH, Yu CL (2011) Production of biodiesel from Jatropha oil catalyzed by the nanosized solid basic catalyst. Energy 36(2):777–784. https://doi.org/10.1016/j.energy. 2010.12.043 95. Negm NA, Sayed GH, Yehia FZ et al (2017) Biodiesel production from the one-step heterogeneous catalyzed process of castor oil and Jatropha oil using novel sulphonated phenyl silane montmorillonite catalyst. J Mol Liq 234:157–163. https://doi.org/10.1016/j.molliq.2017.03.043 96. Nisar J, Razaq R, Farooq M et al (2017) Enhanced biodiesel production from Jatropha oil using calcined waste animal bones as a catalyst. Renew Energy 101:111–119. https://doi.org/ 10.1016/j.renene.2016.08.048 97. Prueksakorn K, Gheewala SH (2006) Energy and greenhouse gas implications of biodiesel production from Jatropha curcas L. the 2nd joint international conference on “sustainable energy and environment (SEE 2006)”. https://pdfs.semanticscholar.org/d2e7/ bde1a3fd29ae389fa3179be8e78a45bc2785.pdf 98. Achten WMJ, Verchot LV (2011) Implications of biodiesel-induced land-use changes for CO2 emissions: case studies in tropical America, Africa, and Southeast Asia. Ecol Soc 16:4. https:// doi.org/10.5751/ES-04403-160414 99. Patel PD, Lakdawala A, Chourasia S, Patel RN (2016) Biofuels for compression ignition engine: a review on engine performance, emission and life cycle analysis. Renew Sust Energ Rev 65(C):24–43. https://doi.org/10.1016/j.rser.2016.06.010 100. Gutiérrez-López AN, Mena-Cervantes VY, García-Solares SM et al (2021) NaFeTiO4/Fe2O3FeTiO3 as heterogeneous catalyst towards a cleaner and sustainable biodiesel production from Jatropha curcas L. oil. J Clean Prod 304:127106. https://doi.org/10.1016/j.jclepro.2021.127106 101. Maftuchah ZA, Winaya A, Rahmadesi Y (2020) Biodiesel generated from Jatropha (Jatropha curcas Linn.) seeds selected based on various genotypes crossbred. Energy Rep 6:345–350. https://doi.org/10.1016/j.egyr.2020.11.160

31

Chemistry, Biological Activities, and Uses of Jatropha Latex

843

102. Hashimoto N, Nishida H, Kimoto M et al (2018) Effects of Jatropha oil blending with C-heavy oil on soot emissions and heat absorption balance characteristics for boiler combustion. Renew Energy 126:924–932. https://doi.org/10.1016/j.renene.2018.04.018 103. Keneni YG, Hvoslef-Eide AK (Trine), Marchetti JM (2020) Optimization of the production of biofuel from Jatropha oil using a recyclable anion-exchange resin. Fuel 278. https://doi.org/ 10.1016/j.fuel.2020.118253 104. Zhu T, Zhang L, Li Z et al (2021) Partial hydrogenation of Jatropha oil biodiesel catalyzed by nickel/bentonite catalyst. Waste Biomass Valori 12:465–474. https://doi.org/10.1007/s12649020-00977-8 105. Welfle A (2017) Balancing growing global bioenergy resource demands – Brazil’s biomass potential and the availability of the resource for trade. Biomass Bioenergy 105:83–95. https:// doi.org/10.1016/j.biombioe.2017.06.011 106. de Paula NQ, Biscola PHN, Figueiredo JC de et al (2017) Network and innovation at the Brazilian agricultural research corporation. OrganizaçõesRurais&Agroindustriais 19. https:// doi.org/10.21714/2238-68902017v19n3p192 107. de Azevedo PL, Laviola BG, Bhering LL et al (2016) Oil content increase and toxicity reduction in Jatropha seeds through family selection. In. J. Ind Crop Prod 80:70–76. https:// doi.org/10.1016/j.indcrop.2015.10.034 108. Diana da Silva Araújo F, Araújo IC, Costa ICG et al (2014) Study of degumming process and evaluation of oxidative stability of methyl and ethyl biodiesel of Jatropha curcas L. oil from three different Brazilian states. Renew Energy 71:495–501. https://doi.org/10.1016/j.renene. 2014.06.001 109. Devatha CP, Thalla AK, Katte SY (2016) Green synthesis of iron nanoparticles using different leaf extracts for treatment of domestic wastewater. J Clean Prod 139:1425–1435. https://doi. org/10.1016/j.jclepro.2016.09.019 110. Goutam SP, Saxena G, Singh V et al (2018) Green synthesis of TiO2 nanoparticles using leaf extract of Jatropha curcas L. for photocatalytic degradation of tannery wastewater. Chem Eng J 336:386–396. https://doi.org/10.1016/j.cej.2017.12.029 111. Hudlikar M, Joglekar S, Dhaygude M, Kodam K (2012) Green synthesis of TiO2 nanoparticles by using aqueous extract of Jatropha curcas L. latex. Mater Lett 75:196–199. https://doi.org/ 10.1016/j.matlet.2012.02.018 112. Suriyaprabha R, Balu KS, Karthik S et al (2019) A sensitive refining of in vitro and in vivo toxicological behavior of green synthesized ZnO nanoparticles from the shells of Jatropha curcas for multifunctional biomaterials development. Ecotoxicol Environ Saf 184:109621. https://doi.org/10.1016/j.ecoenv.2019.109621 113. Joglekar S, Kodam K, Dhaygude M, Hudlikar M (2011) Novel route for rapid biosynthesis of lead nanoparticles using aqueous extract of Jatropha curcas L. latex. Mater Lett 65:3170– 3172. https://doi.org/10.1016/j.matlet.2011.06.075 114. Bar H, Bhui D, Sahoo G, Sarkar P, Pyne S, Misra A (2009) Green synthesis of silver nanoparticles using seed extract of Jatropha curcas. Colloids surf. A Physicochem. Eng Asp 348:212–216. https://doi.org/10.1016/j.colsurfa.2009.07.021 115. Chauhan N, Tyagi AK, Kumar P, Malik A (2016) Antibacterial potential of Jatropha curcas synthesized silver nanoparticles against food-borne pathogens. Front Microbiol 7:1748. https://doi.org/10.3389/fmicb.2016.01748 116. Kanchi S, Kumar G, Lo A-Y et al (2018) Exploitation of de-oiled Jatropha waste for gold nanoparticles synthesis: a green approach. Arab J Chem 11:247–255. https://doi.org/10.1016/j. arabjc.2014.08.006 117. Kanchi S, Kumar G, Lo A-Y, Tseng C-M, Chen S-K, Lin C-Y, Chin T-S (2018) Exploitation of de-oiled Jatropha waste for gold nanoparticles synthesis: a green approach. Arab J Chem 11(2):247–255. https://doi.org/10.1016/j.arabjc.2014.08.006 118. Ghosh MK, Sahu S, Gupta I, Ghorai TK (2020) Green synthesis of copper nanoparticles from an extract of Jatropha curcas leaves: characterization, optical properties, CT-DNA binding, and photocatalytic activity. RSC Adv 10:22027–22035. https://doi.org/10.1039/D0RA03186K

Chemistry, Biological Activities, and Uses of Latex from Selected Species of Apocynaceae

32

Clarissa Marcelle Naidoo, Ashlin Munsamy, Yougasphree Naidoo, and Yaser Hassan Dewir

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Chemical Composition of Latex . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Alkaloids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Flavonoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 Cardenolides . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 Latex Proteins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Bioactive Compounds and Biological Activities of Selected Apocynaceae Species . . . . . . 4.1 Tabernaemontana ventricosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Calotropis gigantea . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Alstonia scholaris . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 Hancornia speciosa . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Gomphocarpus physocarpus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Future Perspective . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

846 847 848 848 849 849 850 850 850 855 857 858 858 860 860 860

Abstract

Latex is a complex phytochemical that is mainly involved in the plant defense system. Several species belonging to the Apocynaceae family produce latex that is composed of diverse classes of phytochemicals including proteins, alkaloids, Clarissa Marcelle Naidoo and Ashlin Munsamy contributed equally with all other contributors. C. M. Naidoo · A. Munsamy · Y. Naidoo School of Life Sciences, Westville Campus, University of KwaZulu-Natal, Durban, South Africa Y. H. Dewir (*) Plant Production Department, College of Food and Agriculture Sciences, King Saud University, Riyadh, Saudi Arabia Department of Horticulture, Faculty of Agriculture, Kafrelsheikh University, Kafr El-Sheikh, Egypt e-mail: [email protected] © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_36

845

846

C. M. Naidoo et al.

glycolipids, glycosides, acids, sterols, fatty acids, tannins, resins, oils, terpenoids/ flavonoids, acetogenins, saponins, and allergens. These phytochemicals contain bioactive compounds with various biological activities such as antibacterial, antifungal, antiviral, antiamebic, anti-inflammatory, anticancer, antioxidant, and antivenom properties. Additionally, species within the Apocynaceae have palliative effects, which frequently promotes the usage of latex-bearing species in traditional and contemporary medical systems. This chapter addresses the chemical composition of latex and provides a summary of its biological activities in selected species of Apocynaceae. Keywords

Apocynaceae · Alkaloids · Biological activity · Chemistry · Latex

1

Introduction

The substantial appreciation of plants from primitive humanity has paved a distinctive pathway towards traditional medicine’s contemporary practice [1]. Traditional healers have exclusively and largely subsidized a range of plant-based health care necessities, including the prevention, management, and treatment of noncommunicable diseases, and psychological and gerontological well-being concerns [2]. Numerous ailments have been cured or treated by traditional healers using the accumulated wealth of knowledge on herbal medicine [3]. The utilization of herbal remedies in various forms is generally preferred due to their effectiveness, affordability, and reduced side effects when compared to modern medicine [3]. The World Health Organization (WHO) [4] has reported an exponential demand for traditional medicine in Europe, Asia, America, and the Western Pacific [2]. Approximately 40–60% of people utilize plants to treat numerous illnesses [2]. It has been noted that nearly 60% of the population in Hong Kong habitually depend on traditional health practitioners [5], and a large percentage of the inhabitants from Australia (46%), France (49%), and Canada (70%), although regarded as developed nations, frequently use complementary and alternative medicine [5]. In African countries, a single traditional healer is often allocated to treat approximately 500 people in rural areas to overcome the lack of access to modern medical resources [6]. Despite the increased acceptance of conventional medicine, by indigenous communities, there is still a large part in support of traditional medical systems [1–3, 7]. This will systematically lead to the overexploitation of medicinal plants, especially in the plant family, Apocynaceae, which is regularly used for its analgesic effects [1]. The Apocynaceae (Dogbane family) belongs to the order Gentianales which consists of five families, namely, Apocynaceae, Gelsemiaceae, Gentianaceae, Loganiaceae, and Rubiaceae [8–10]. Comprised of approximately 5100 species and 375 genera, the Apocynaceae is one of the 10 largest angiosperm families [10], including 5 subfamilies: Apocynoideae, Asclepiadoideae, Periplocoideae, Rauvolfioideae, and Secamonoideae [8]. Species within this family display variable habitable forms, from trees to vines,

32

Chemistry, Biological Activities, and Uses of Latex from Selected Species. . .

847

small herbs, and also a few succulents [10]. One of the distinctive features of the Dogbane family is a milky white fluid-like substance called “latex” [11, 12]. Latex is present in a majority of Apocynaceae species and is often used for its healing properties and health benefits [13]. Several members within Apocynaceae contribute primarily to the economy as they are crucial in the medicinal industry [14]. A prominent case within the Apocynaceae is the essential herb Catharanthus roseus, also known as “Madagascar periwinkle,” is a source of several indolomonoterpenic alkaloids [15]. Various plant parts and latex of C. roseus contain an array of bioactive compounds [15]. A few of these compounds include vinblastine and vincristine and are utilized in modern medicine to treat Hodgkin’s disease, lymphocytic leukemia, and neuroblastoma, respectively [14, 16]. The species Alstonia scholaris (L.) R. Br. and Alstonia macrophylla Wall. ex G. Don. are frequently used in traditional medicine in countries like India, Thailand, and China [17]. In Africa, these species are used to treat malaria, jaundice, gastrointestinal issues, and cancer [18]. Major chemical constituents responsible for the biological activity of the species include alkaloids, phenolics, steroids, iridoids, and terpenoids [18]. Despite the biological importance of compounds found in latex and many species within the Apocynaceae, there remains a vast variety of species that are yet to be considered or investigated. Regarding the recent publications, in this chapter, we describe the updated chemical analyses, biological activities, and general medicinal uses of latex from selected Apocynaceae species. This chapter will elaborate on species within Apocynaceae, emphasizing the pharmacological aspects that have been recently published.

2

Latex

Latex-bearing plants are estimated to be found in 12,500–20,000 species in over 40 families which include monocotyledonous and eudicotyledonous plants [19, 20]. Latex-producing cells called laticifers are a type of internal secretory structure that consists of an extensive cellular network found throughout the plant [21–24]. These cells are characterized as articulated when distinct rows of cells are interconnected after anastomosis of adjacent cell walls [20–24]. The non-articulated form develops from primordial initials present at the embryo stage and may continue to traverse the plant body via intrusive growth, forming branched or unbranched networks [20, 23, 24]. The widespread distribution of the different types of laticifers has suggested that these secretory structures are of polyphyletic origin since these are often found dispersed throughout unrelated plant orders [21]. Latex is described as a suspension of numerous tiny particles in sap of unspecified composition with various refractive indices [11, 12]. According to van Die [22], the distinct cytoplasm within laticifers identified as latex consists of several components which may be divided into various groups such as polyisoprene hydrocarbons, triterphenols and sterols, fatty acids, and aromatic acids (esterified), carotenes, phospholipids, proteins, and inorganic constituents [11]. Moreover, Heinrich [23] reported that the latex of certain plants may contain specific substances such as composite sugars, variously shaped

848

C. M. Naidoo et al.

starch grains, tannins, and alkaloids. Despite the common milky white color often observed in several latex-bearing plants, the color often varies in many plant species as it may appear yellow, orange, red, brown, or even colorless [12]. Since the discovery of latex, there have been plentiful suggestions regarding its functions [11, 24]. According to Fahn [11], the most probable function of latex is protection. Several decades later, studies conducted by Hagel [24] and Konno [25] supported this assumption. These authors suggested that latex contains numerous concentrated specialized metabolites that are potentially cytotoxic. Ramos [26] investigated the toxicity of the defensive roles of latex against certain larvae and insects using a direct observation approach. In the study, Calotropis procera latex fractions were tested against the larvae of Anticarsia gemmatalis and Callosobruchus maculatus. The findings suggested that the presence of protease inhibitors, chitinase and cysteine protease activities are possibly responsible for the toxicities against insects and larvae. Herbivorous insects that feed on latex-bearing plants are often deterred by the high concentrations of defense substances within the latex, rather than the lower concentrations contained in leaves since relatively large droplets of latex often emerge at a site of puncture on plant organs [25]. Insects are often immediately trapped due to the stickiness of the latex and are shortly poisoned from the large dosages of secondary metabolites within the latex which accumulates at the point of plant injury [25, 27].

3

Chemical Composition of Latex

Latex composition differs among different taxonomic levels. The basic constitution of latex compounds is carbon, hydrogen, and nitrogen [19]. Latexes consist of a mixture of low-molecular-weight compounds and high-molecular-weight compounds, a category mainly reserved for latex proteins [28]. This emulsion of secondary metabolites can have a complex phytoprofile containing proteins, alkaloids, glycolipids, glycosides, acids, sterols, fatty acids, tannins, resins, oils, terpenoids/flavonoids, acetogenins, saponins, and allergens [19, 25, 28]. Some of the major compound classes will be highlighted.

3.1

Alkaloids

Alkaloids are one of the most common classes of bioactive compounds found in plants belonging to Apocynaceae, Papaveraceae, Moraceae, and Euphorbiaceae families [19]. These are a diverse group of important compounds that function in plant defense against herbivory, insects, fungi, and other microorganisms [28, 29]. Alkaloids are synthesized from the decarboxylation of amino acids to amines through a series of enzymatic reactions, resulting in alkaline compounds with nitrogenous ring structures [19]. There are more than 15 subtypes of alkaloids characterized by the chemical structure, origin, and bioactivity. Alkaloids have various pharmacological activities such as antimicrobial, antihypertensive,

32

Chemistry, Biological Activities, and Uses of Latex from Selected Species. . .

849

antimalarial, and antitumor activities [15, 16, 18]. The alkaloids, vincristine, and vinblastine, extracted from C. roseus, are used to treat acute lymphocytic leukemia [30]. Monoterpenoid indole alkaloids (MIAs) were extracted from the latex of Tabernaemontana catharinensis using mass spectrometry techniques. Ten known and three novel MIAs, known for their analgesic, anti-inflammatory, bactericidal, and antitumor properties, as well as cholinesterase inhibitor activity were identified [31].

3.2

Flavonoids

Flavonoids are a diverse class of plant metabolites that are important in plant defense and cellular protection [32]. These are structurally small compounds and are further divided into two subclasses based on the presence of a side sugar moiety (called glycoside flavonoids) or absence (called aglycones) [32, 33]. These function in UV protection and is needed to provide color and aroma, making these chemicals important for signaling during pollination [34]. Flavonoids have a wide range of biological activities such as anticancer, antioxidant, and antimicrobial activities. These metabolites can promote decreased proliferation of tumor cells and initiate signaling cascade pathways leading to apoptosis [34–36]. Flavonoids were also tested for anticancer properties in breast, colon, lung, and liver, and prostate cell lines [32, 34, 35]. The flavonoids identified in Calotropis procera: quercetin3-O-rutinosides, kaempferol-3-O-rutinoside, isorhamnetin-3-O-rutinoside, and 5hydroxy-3,7-dimethoxyflavone-4-O-D-glucopyranoside are some of the compounds that contribute to the potent biological activities identified [26, 36]. Flavonoids, quercetin glycosides, and 3-O-rutinoside were identified in Gomphocarpus sinaicus and Gomphocarpus fruticosus. These flavonoid compounds have potent anticancer and antioxidant activities [36–38].

3.3

Cardenolides

Cardenolides are a subclass of plant-derived steroidal compounds found within the class of cardiac glycosides. Historically, this class of toxic compounds has been used by native Amazonian and African communities as arrow poisons during hunting and as weapons during civil unrest [39, 40]. Cardenolides are a 23-carbon molecule composed of three parts: (I) a steroidal backbone of four fused carbon rings, (II) a lactone group, and (III) a sugar moiety is located on the first carbon ring. The focal enzymatic target of cardenolides in the ubiquitous Na+/K+-ATPase [29, 41]. This enzyme, located on the cell membrane of animal cells, is active in maintaining the Na+ and K+ ions balance of the cytoplasm with the extracellular fluid [41–43]. This is especially important in cardiac myocytes, as the balance of Na+ and K+ ions is coupled with intracellular calcium ions which is important in regulating contractility [41, 42, 44, 45]. Cardenolides inhibit Na+/K+-ATPase, resulting in altered cardiac activity. Cardenolides are also part of the plant’s defense against herbivory. Many

850

C. M. Naidoo et al.

genera such as Nerium, Asclepias, Thevetia, Cerbera, and Apocynum, within Apocynaceae, are known to contain cardenolides. Over 200 different cardenolides were identified from Asclepias species (milkweeds) [46–50]. The cardenolides calactin, calotropin, and voruscharin, identified in milkweeds, are active in plant defense and are primarily responsible for anticancer, antimicrobial, antiviral, and anti-inflammatory pharmacological activities [46, 47, 49].

3.4

Latex Proteins

Latex proteins are macromolecular compounds used in primary plant metabolism and processes. The composition is diverse, and the main function is in plant defense [51]. Several proteins accumulate in laticifers within the latex mixture in response to increased herbivory and microbial pathogen encounters. Proteases found in latex are a class with diverse forms characterized by their different catalytic amino acid composition [51]. For example, cysteine, serine, and aspartate proteases are enzymatic active proteins used in cell wall remodeling, and eventually, as plant wound coagulants and insect deterrents [51]. The proteins cysteine proteases, chitinases, peroxidases, and osmotin-like proteins have been identified and isolated from C. procera (Table 1) [52–58]. These latex proteins showed increased antiinflammatory activity and therapeutic significance in a study performed on rats that focused on reducing adverse effects of colorectal cancer treatment regimens. Rats supplemented with C. procera latex proteins during cancer treatment displayed fewer side effects and improved quality of life [54]. Over 17 classes of pathogenrelated (PR) proteins, characterized by structure and function, were found in plant latex [54–56]. These act as food allergens and in turn as insect deterrents [56–58].

4

Bioactive Compounds and Biological Activities of Selected Apocynaceae Species

4.1

Tabernaemontana ventricosa

Tabernaemontana ventricosa is an evergreen, small to medium-sized latex bearing tree (Fig. 1) belonging to the Apocynaceae [59]. This species is commonly known as the “Forest toad tree” or “Small-fruited toad tree” due to the green wart-like appearance of the skin on its fruit [59]. Tabernaemontana ventricosa species often appear in a scattered distribution along with eastern Nigeria, Ghana, the Democratic Republic of Congo, Kenya, and the northern and southern regions of Africa [59, 60]. These species flourish in disturbed shady habitats such as open forests and thickets [59, 60]. All plant parts of T. ventricosa contain a milky white latex. It is suggested that the chemical constituents found within that latex function to deter herbivores and microorganisms and may contain medicinal value [59, 60]. All parts of T. ventricosa are often used in ethnobotany for the treatment of many ailments which include reduction of blood pressure, fever, pain, and relief of neurological

Blackboard tree or devil’s tree

Moth plant/vine, white bladder flower, cruel vine Bastard ipecacuanha; cotton bush; milky cotton bush; red-cotton; redhead Giant milkweed or crown flower

Apple of Sodom or rubber bush and rubber tree

Alstonia scholaris

Araujia sericifera

Calotropis procera

Calotropis gigantea

Asclepias curassavica

Common name Golden trumpet. Common trumpet vine, yellow allamanda

Species Allamanda cathartica

Fresh latex+ distilled water Hexane, dichloromethane,

Fresh latex+ distilled water

Fresh latex+ phosphate buffer

Fresh latex was extracted with 95% ethanol: liquidliquid partition with dichloromethane, ethanolwater Fresh latex+ methanol Fresh fruit latex + distilled water

Solvent and extraction method Fresh latex + distilled water; silver nanoparticle synthesis with silver nitrate

Germin-like proteins, proteases

Lignan glycoside, 20 -epi-uscharin, cardenolides, lupeol

Cysteine proteases

Lipase

Triterpenoids, phenolics, flavonoids, and proanthocyanidins

Bioactive compound Allamanda cathartica silver nanoparticles

Antiviral, antitumor, inflammatory, diabetic, cytotoxic, and antimicrobial activities Oxalate oxidase activity and antioxidant activity,

Biological activity Cytotoxic and genotoxic to human peripheral blood mononuclear cells (possible antitumor activity) Antioxidant activity Antibacterial activity against Bacillus subtilis, Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa Biocatalyst for biotechnological applications Thrombin-like activity and pro-coagulation

Table 1 Significant bioactive compounds of latex and their biological activities in selected species of Apocynaceae

Chemistry, Biological Activities, and Uses of Latex from Selected Species. . . (continued)

[26, 28, 36, 39, 53, 54, 57, 115–118]

[64, 65, 112– 114]

[111]

[110]

[86, 87]

References [108, 109]

32 851

Indian rubber vine

Balloon plant

Jungle dragon

Cryptostegia grandiflora

Gomphocarpus physocarpus

Gomphocarpus sinaicus Hancornia speciosa Gomes

Janaguba, sucuuba, and bellaco-Caspi

Oleander and rosebay

Amapa and amapazeiro

Nerium oleander

Parahancornia amapa

Janaguba

Himatanthus drasticus Mart. Himatanthus sucuuba

Mangaba tree

Common name

Species

Table 1 (continued)

Latex+ phosphate buffer/ casein Diluted with distilled water Maceration (hexane, dichloromethane, methanol)

Coagulated by n-butanol, evaporated, suspend in bi-distilled water, and filtered Hexane fractionation

ethyl acetate, n-butanol, and aqueous fractions. Distilled water-ionexchange chromatography Reverse-phase HPLC Fresh latex+ distilled water, and methanolic extract Powdered dry latex extracted in methanol Fresh latex+ distilled water, biomembrane synthesis Fresh latex+ distilled water

Solvent and extraction method

Lyophilized latex, methylmyoinositol, and cornoside

Cyclopeptides and amino acids Latex proteins (proteolytic and nonproteolytic) Cysteine peptidase Cardiac glycosides, phenolic compounds, terpenoids Flavonoids and cardenolides glycosides Chlorogenic acid, naringenin-7-O-glucoside, catechin, and procyanidin Phenols, flavonols, lupeol, α-amyrin, and β-amyrin Lyophilized latex + lipopolysaccharide, cinnamates, plumericin, isoplumericin, lupeol acetate, α-amyrin, lupeol cinnamates, fresh latex Fresh latex

Bioactive compound

Morphological alterations in postembryonic development, mortality

Antioxidant and protease

Anti-inflammatory and wound healing (angiogenesis) Anticancer and antioxidant activities Antileishmanial, antiinflammatory, analgesic, antifungal, antibacterial, cytotoxicity, wound healing

Cytotoxicity against cancer cell lines and antioxidant activity Antioxidant and anticancer

anti-inflammatory and toxicity activity; anticancer Pro-inflammatory, proteolytic, procoagulant

Biological activity

[129, 130]

[128]

[123–127]

[122]

[88–90, 98, 100]

[38, 44]

[Unpublished results]

[26, 58, 119– 121]

References

852 C. M. Naidoo et al.

Frangipani

Bridal bouquet

Katha Champa and jasmine

Snakeskin and jasmine

Plumeria pudica

Plumeria rubra

Tabernaemontana catherinensis

Sarcostemma gilliesii

Bou Hliba

Plumeria alba

Pergularia tomentosa Philibertia gilliesii Hook.

Water-soluble fraction

Fresh latex, distilled waterion-exchange chromatography, latex+ phosphate buffer/casein, acetone precipitation

Fresh latex, latex-water dialysis, latexchromatography with distilled water.

Fresh latex, dewax latexchromatography

Fresh latex + distilled water Ion-exchange chromatography

Crude latex, ibogamine, affinisine, 16-epi-affinine, 16-epi-affinine, voachalotine, 10-hydroxyNa-methyl vellosimine, voacamine

Plumerin R, fresh latex, latex proteins (proteolytic and nonproteolytic), purified protease, protein fraction

Fresh/freeze-dried latex, proteolytic latex, watersoluble proteins, latex proteins

Proteolytic latex, papainlike cysteine peptidase, Philibertain g II Fresh latex, cysteine protease

Fresh latex + distilled water

Purgative, cardiotonic, hypotensive, diuretic; platelet aggregation, procoagulant, fibrinolytic, thrombin, and plasmin-like activities Anti-inflammatory, antinociceptive, myeloperoxidase, antidiarrheal, antioxidant, antiperiodontitis Anti-inflammatory, silver nanoparticle synthesis, larvicidal, fibrinolytic, procoagulant. Proteolytic, antioxidant, anti-gastric lesions Anti-inflammatory, snake antidote, proteolytic, anticancer, antimicrobial

Proteolytic, caseinolytic

Insecticidal and toxicity

(continued)

[31]

[142–145]

[137–141]

[134–136]

[132, 133]

[131]

32 Chemistry, Biological Activities, and Uses of Latex from Selected Species. . . 853

Common name “Pinwheel flower” and “crape jasmine”

Forest toad tree

Yellow oleander

Species Tabernaemontana divaricata

Tabernaemontana ventricosa

Thevetia peruviana

Table 1 (continued) Solvent and extraction method Latex-chromatography with distilled water, latex dialysis Fresh latex+ distilled water, and methanolic extract Latex dialysis with distilled water, latex filtration with distilled water, oven-dried latex extracted with petroleum ether, chloroform, ethyl acetate, acetone, methanol, and aqueous Alkaloids, cardiac glycosides, phenolic compounds, terpenoids Latex extracts, latex proteins, peruvianin I

Bioactive compound Latex solution, latex extract, latex proteases

Biological activity Local anesthetic, hemostatic potential, proteolytic Antibacterial, antioxidant, cytotoxicity, silver nanoparticle synthesis Proteolytic, biocontrol agent, silver nanoparticle synthesis, antifungal activity

[154–158]

[Unpublished results]

References [146–153]

854 C. M. Naidoo et al.

32

Chemistry, Biological Activities, and Uses of Latex from Selected Species. . .

855

Fig. 1 Tabernaemontana ventricosa tree growing in KwaZulu-Natal, South Africa (Unpublished photograph; inset leaf, inflorescence, and fruits)

issues. In addition, the latex is often applied onto sores eyes, or wounds to stimulate healing [59]. According to Schmelzer and Gurib-Fakim [59], the leaves contain high amebic activity and are regularly used to reduce the growth of the amoeba protist. There is a profuse number of alkaloids, cardiac glycosides, phenolic compounds, terpenoids within T. Ventricosa species that are responsible for the antibacterial, antioxidant, and cytotoxic properties of this species (unpublished results) (Table 1; Fig. 2a). However, Schripsema [61] reported the presence of conopharyngine, which is an indole alkaloid commonly used to heal wounds [62]. Additionally, large quantities of a rare compound identified as a strychnine alkaloid were observed within T. ventricosa crude extracts [61]. Furthermore, several alkaloids such as 10-hydroxyheyneanine, 16-epi-isositsirikine, apparicine, tubotaiwine, norfluorocurarine, and akuammicine have been found within this species [61, 62].

4.2

Calotropis gigantea

Calotropis gigantea (L.) R. Br., commonly known as the “crown flower” or “giant milkweed,” is a medium-sized xerophytic woody shrub that usually thrives in warm climatic regions exhibiting sandy, alkaline, and dry soil-like environments [63]. This aromatic species are native to Asia, Africa, China, India, Sri Lanka, Vietnam,

856

C. M. Naidoo et al.

Fig. 2 Chemical structure and molecular formula of significant bioactive compounds from Tabernaemontana ventricosa (a) (akuammicine, conopharyngine, ibogamine, tubotaiwine, voacristine, and vobasine); Calotropis gigantea (b) (calotropin and ψ-taraxasterol); Alstonia scholaris (alstonine and villalstonine) (c); Hancornia speciosa (d) (chlorogenic acid and lupeol); and Gomphocarpus physocarpus (e) (betulinic acid, gomphoside, and taraxerol acetate)

Thailand, and Malaysia [64, 65]. In traditional medicine, the entire plant including the milky white latex is utilized to treat skin diseases, scabies, ringworm, pneumonia, and leprosy [13, 66, 67]. Pharmacologically, the species is used for several healing properties such as hepatoprotective, antidiarrheal, analgesic, antiinflammatory, antitumor, anti-ulcer, and anti-asthmatic properties [13, 67]. Recently, Calotropis species have been frequently investigated due to the presence of large quantities of milky white latex [68, 69]. The latex reportedly contains cardiac poisons, calcium oxalate, and resins; however, despite the presence of the potentially lethal compounds, the latex was discovered to exhibit several important biological activities such as purgative, procoagulant, wound healing, anti-inflammatory, and antimicrobial activities [13, 63]. The bioactivities of the latex are directly related to

32

Chemistry, Biological Activities, and Uses of Latex from Selected Species. . .

857

the presence of biologically active chemical compounds, such as cardiac glycosides, triterpenoids, proteases, flavonoids, alkaloids, phenolics, resins, proteins, and sterols [67, 69]. A few of the reported chemical constituents from the latex of C. gigantea are calotropain-F1, calotropain-FII, 30 -methylbutanoate, ψ-taraxasterol, calotropins DI, calotropins DII, giganteol, and lupeol (Fig. 2b) [13, 70–72]. The abovementioned compounds showed promising results for several pharmacological activities [49, 65, 73–80]. Giganteol, belonging to the chemical class triterpene alcohol is a major compound extracted from species within Calotropis [65]. It is often used in the treatment of stings, toothaches, tumors, rheumatism, and sepsis [65]. Recently, lupeol, a pentacyclic triterpene, was isolated, extracted, and characterized by the latex of C. gigantea. The latex was reported to contain anti-inflammatory, anti-diabetic, cytotoxic, and antimicrobial activities (Table 1) [64]. Due to the copious amounts of lupeol within Calotropis species, it has been suggested that this compound can be utilized as a supporting compound during drug formulation [13, 64, 65, 79]. The GC-MS analysis performed by Sharma [80] reported several bioactive compounds in the latex extracts of C. gigantea. Compounds such as D-mannose-1-phosphate, 5-Nonadecen-1-ol, campesterol, and D-mannose possess a range of pharmacological activities [80].

4.3

Alstonia scholaris

Alstonia scholaris, also known as the devil tree or dita bark, is an evergreen tree that often inhabits deciduous forests and plains [81–83]. The plant is distributed throughout India, particularly in the sub-Himalayan regions from the Yamuna and West Bengal. The species also appears dispersed in the localities of Pakistan, Sri Lanka, and South Asia [82]. Due to the abundant source of alkaloids within A. scholaris, the bark, leaves, flowers, roots, and milky white latex of this species are often used for its curative properties in India [82]. Traditionally, the bark is used as a stimulant, carminative, stomachic, bitter tonic, astringent, aphrodisiac, expectorant, febrifuge, gastrointestinal sedative, and antiperiodic [82]. The leaves are often used to treat ulcers, snake bites, rheumatism, asthma, and diabetes; the flowers are used to assist with respiratory complications; and the roots promote pain relief [82]. Furthermore, the milky white latex is used in the treatment of dental issues, ulcers, rheumatic pains, tuberculosis, asthma, and earache pains [82, 84, 85]. It has been reported that the pharmacological properties of A. scholaris are due to the occurrence of several classes of chemical compounds such as iridoids, coumarins, flavonoids, terpenoids, alkaloids, phenolics, steroids, saponins, and tannins [18, 82]. Despite the variety of chemical compounds present within this species, alkaloids remain a significant compound often responsible for several properties [18]. For example, alstonine, echiamine chloride, and villalstonine (Fig. 2c) were identified as indole alkaloids and subsequently isolated from Alstonia species [82]. These compounds exhibit a variety of biological properties which includes antimalarial, anxiolytic, schizophrenia, antipsychotic, and anticancer, antiamebic, and antiplasmodial activities (Table 1) [80, 84–87].

858

4.4

C. M. Naidoo et al.

Hancornia speciosa

Hancornia speciosa Gomes is a fruit-bearing tree, commonly known as the Mangaba tree. It is a monophyletic species that grows to 5–10 m in height and is native to Brazil. All parts of the tree exude a sticky white latex upon mechanical damage [88, 89]. The tree is a source of edible fruit and is used in many food products, slowly becoming more commercially successful each year. The latex has been traditionally used to treat skin diseases, acne, warts, microbial diseases, tuberculosis, stimulate hepatic function, bone fractures, and wounds [88–92]. Phytochemical profiling of the latex by Sampaio [93] identified seven 3-β-O-acyl lupeol esters, triterpenes α-amyrin, β-amyrin, lupeol, and one 3-βO-30 ,50 -dihydroxy eicosanoic lupeol. Bioactive latex is also used in the production of biomembranes. These membranes are used as temporary regeneration and replacement tissue to promote wound healing [93]. The natural rubber latex material conventionally used in biomembrane synthesis comes from Hevea brasiliensis; however, some individuals display allergic reactions to some of these latex components [94]. Hancornia speciosa latex is used as an alternate material to produce biomembranes and was found to be effective in wound healing [95, 96]. The membrane displayed favorable adherence properties, is nontoxic to fibroblast cells, and stimulates inflammatory cells and angiogenesis (Table 1) [95, 96]. Chlorogenic acid (Fig. 2d) was also found in the serum latex extract of H. speciosa and promotes angiogenesis during the tissue repair phase of wound healing [95, 97–101]. In addition, H. speciosa latex displays anti-inflammatory activity by inhibiting nitric oxide and cytokine production [98]. Naringenin-7-O-glucoside, catechin, and procyanidin are also found in latex produced by H. speciosa and were suggested to be responsible for promoting bone formation through osteogenic stimulation and enhanced cell proliferation in rats [98–101].

4.5

Gomphocarpus physocarpus

Gomphocarpus physocarpus also known as Asclepias physocarpus, generally known as balloon plant (Fig. 3), belongs to the Asclepiadoideae subfamily within Apocynaceae. It is regarded as a milkweed species which is native to South Africa, Mozambique, and Swaziland. It grows easily in disturbed regions along roadsides, bushlands, and grasslands [102]. Phytochemical screening conducted in our laboratory revealed that G. physocarpus extracts are rich in cardiac glycosides, terpenoids, alkaloids, and phenols (unpublished data). It is a weed that is poisonous to livestock and other herbivores that consume the leaves. The latex also causes edema and swelling of the eyes of humans and animals upon contact [103]. The plant exudes a milky white latex from all plant parts when punctured. In South Africa, all parts of the plant are traditionally used to treat headaches, and latex is applied to treat warts [102]. The potential bioactive compounds and biological activities of G. physocarpus are under investigations and yet to be elucidated. Studies have been conducted on closely related species, Gomphocarpus fruticosus. Marzouk [104, 105] identified

32

Chemistry, Biological Activities, and Uses of Latex from Selected Species. . .

859

Fig. 3 Gomphocarpus physocarpus shrub growing in KwaZulu-Natal, South Africa (Unpublished photograph; inset inflorescence)

triterpenoids: 3β-taraxerol acetate, 3β-taraxerol, and betulinic acid; cardenolide aglycone uzarigenin; cardenolide glycosides gomphoside; calotropin and pregnane glycoside lineolon-3O-[β-D-oleandropyranosyl-(1–4)-β-D-cymaropyranosyl-(1–4)β-D-cymaropyranoside. These compounds have anti-asthmatic, hepatoprotective, anticancer, and antioxidant properties [104–107] (Table 1; Fig. 2e). In G. sinaicus, six cardenolides: 7,8-dehydrocalotropin, calotropin, coroglaucigenin 3-(6-deoxyb-allopyranoside)-19-acetate (frugoside 19-acetate), coroglaucigenin, and 16aacetoxycalotropin were identified [38, 44]. These compounds were identified as deterrents of plant-insect pests confirming the important function it offers in plant defense [44].

860

5

C. M. Naidoo et al.

Conclusion

For centuries, traditional healers have relied on medicinal plants for their therapeutic benefits. Among these medicinal plants, species within the family Apocynaceae are often utilized for broad range of beneficial properties. It has been proposed that the “milky white” substance, commonly known as latex, found within numerous species belonging to the Apocynaceae is primarily responsible for its healing and health properties. A few of the most commons latex-bearing species include Catharanthus roseus, Alstonia scholaris, Calotropis gigantea, Gomphocarpus physocarpus, and Hancornia speciosa Gomes that are known/used in traditional medicine. The phytochemical compound classes such as proteins, alkaloids, glycolipids, glycosides, acids, sterols, fatty acids, tannins, resins, oils, terpenoids/flavonoids, acetogenins, saponins, and allergens detected within the latex of these species have been reported to contain several pharmacological properties. These include hepatoprotective, antidiarrheal, analgesic, anti-inflammatory, antitumor, anti-ulcer, anti-asthmatic, antimicrobial, antimalarial, antiemetic properties, and many more. However, despite the well-evaluated compound reported in this chapter and the associated biological activity, several latex-bearing plants that are used traditionally are yet to be assessed for their pharmacological potential. It is imperative that latex of species such as T. ventricosa and G. physocarpus are considered for their biological activity to deduce the comprehensive functions of latex.

6

Future Perspective

Latex-containing plants are a valuable resource that is largely underutilized. Although the phytochemical profiles of economically and medicinally popular plant species have been known and well established for centuries, much remains unknown about numerous species within Apocynaceae. Fewer studies focus solely on the latex component of plants. Research efforts toward a better understanding of laticifers, the biochemical pathways and processes for latex synthesis, and potential medicinal benefits should be ongoing and active. The presence of latex in hundreds of plant species within Apocynaceae and other angiosperm families offers much potential for future research to uncover novel useful compounds.

References 1. Šantić Ž, Pravdić N, Bevanda M, Galić K (2017) The historical use of medicinal plants in traditional and scientific medicine. Psychiatr Danub 29:787–792 2. AbdullahiAA (2011) Trends and challenges of traditional medicine in Africa. Afr JTradit Complement Altern Med 8:115–123 3. Shakya AK (2016) Medicinal plants: future source of new drugs. Int J Herb Med 4:59–64 4. World Health Organization. Available online https://www.who.int/data/gho/data/themes/ topics/topic-details/GHO/worldhealth-statistics. Accessed 17 Sep 2018

32

Chemistry, Biological Activities, and Uses of Latex from Selected Species. . .

861

5. Amzat J, Abdullahi AA (2008) Roles of traditional healers in the fight against HIV/AIDS. Stud Ethno Med 2:153–159 6. Endress ME, Liede-Schumann S, Merve U (2014) An updated classification for Apocynaceae. Phytotaxa 159:175–194 7. Chatora R (2003) An overview of the traditional medicine situation in the African region. Afr Health Mon 4:4–7 8. Endress ME (2004) Apocynaceae: brown and now. Telopea 10:525–541 9. Angiosperm Phylogeny Group (2009) An update of the angiosperm phylogeny group classification for the orders and families of flowering plants. APG III Bot J Linn Soc 161:105–121 10. Rapini A (2012) Taxonomy “under construction”: advances in the systematics of Apocynaceae, with emphasis on the Brazilian Asclepiadoideae. Rodriguésia 63:075–088 11. Fahn A (1979) Secretory tissues in plants. Academic Press, London 12. Pickard WF (2008) Laticifers and secretory ducts: two other tube systems in plants. New Phytol 177:877–888 13. Kumar G, Karthik L, Rao KVB (2011) A review on pharmacological and phytochemical profile of Calotropis gigantea Linn. Pharmacol Online 1:1–8 14. Nazar N, Goyder DJ, Clarkson JJ, Mahmood T, Chase MW (2013) The taxonomy and systematics of Apocynaceae: where we stand in 2012. Bot J Linn Soc 171:482–490 15. Pereira DM, Ferreres F, Oliveira JM, Gaspar L, Faria J, Valentão P, Sottomayor M, Andrade PB (2010) Pharmacological effects of Catharanthus roseus root alkaloids in acetylcholinesterase inhibition and cholinergic neurotransmission. Phytomedicine 17:646–652 16. Alan CA, Wilkes B (1964) Studies on the suppression of immune responses by the periwinkle alkaloids vincristine and vinblastine. J Clin Investig 43:2394–2403 17. Changwichit K, Khorana N, Suwanborirux K, Waranuch N, Limpeanchob N, Wisuitiprot W, Suphrom N, Ingkaninan K (2011) Bisindole alkaloids and secoiridoids from Alstonia macrophylla Wall. ex G. Don. Fitoterapia 82:798–804 18. Khyade MS, Kasote DM, Vaikos NP (2014) Alstonia scholaris (L.) R. Br. and Alstonia macrophylla Wall. ex G. Don: a comparative review on traditional uses, phytochemistry, and pharmacology. J Ethnopharmacol 153:1–18 19. Evert RF (2006) Esau’s plant anatomy. John Wiley & Sons, New York 20. Lewinsohn TM (1991) The geographical distribution of plant latex. Chemoecology 2:64–68 21. Keating RC (2003) Leaf anatomical characters and their value in understanding morphoclines in the Araceae. Bot Rev 68:510–523 22. Van Die J (1955) A comparative study of the particle fractions from Apocynaceae latices. Ann Bot Gard 2:1–124 23. Heinrich G (1969) Elektronenmikroskopische beobachtungen zur entstehungsweise der exkretbehalter von Ruta graveolens, Citrus limon und Poncirus trifolialiata. Ost Bot 3:97–403 24. Hagel JM, Yeung EC, Facchini PJ (2008) Got milk? The secret life of laticifers. Trends Plant Sci 13:631–639 25. Konno K (2011) Plant latex and other exudates as plant defense systems: roles of various defence chemicals and proteins contained therein. Phytochemistry 72:1510–1530 26. Ramos MV, Aguiar VC, Melo VMM, Mesquita RO, Silvestre PP, Oliveira JS, Oliveira RSB, Macedo NMR, Alencar NMN (2007) Immunological and allergenic responses induced by latex fractions of Calotropis procera (Ait.) R. Br. J Ethnopharmacol 111:115–122 27. Dussourd DE (1995) Entrapment of aphids and whiteflies in lettuce latex. Ecol Popul Biol 88: 163–172 28. Macel M (2011) Attract and deter: a dual role for pyrrolizidine alkaloids in plant-insect interactions. Phytochem Rev 10:75–82 29. Hansen I, Brimer L, Molgaard P (2003) Herbivore-deterring secondary compounds in heterophyllous woody species of the Mascarene Islands. Perspect Plant Ecol Evol Syst 6:187–203 30. El-Sayed A, Handy GA, Cordell GA (1983) Catharanthus alkaloids XXXVIII. Confirming structural evidence and antineoplastic activity of the bisindole alkaloids leurosine-N’b-oxide (pleurosine) roseadine and vindolicine from Catharanthus roseus. J Nat Prod Res 46:517–527

862

C. M. Naidoo et al.

31. Higashia B, De Almeidab R, Pilauc EJ, Gonçalvesd J, Gonçalvesae RAC, Braz de Oliveira AJ (2021) Metabolic profiling of monoterpenoid indole alkaloids from Tabernaemontana catharinensis (A. DC) latex by GC-MS. Phytochem Lett 41:6–13 32. Panche AN, Diwan AD, Chandra SR (2016) Flavonoids: an overview. J Nutr Sci 5:1–15 33. Takshak S (2018) Bioactive compounds in medicinal plants: a condensed review. SEJ Pharm Nat Med 1:1–35 34. Abotaleb M, Samuel SM, Varghese E, Varghese S, Kubatka P, Liskova A, Büsselberg D (2019) Flavonoids in cancer and apoptosis. Cancers 11:1–39 35. Upadhyay RK (2011) Plant latex: a natural source of pharmaceuticals and pesticides. Int J Green Pharm 5:1–12 36. Nenaah GE (2013) Potential of using flavonoids, latex, and extracts from Calotropis procera (Ait.) as grain protectants against two coleopteran pests of stored rice. Ind Crop Prod 45:327–334 37. Kopustinskiene DM, Jakstas V, Savickas ABernatoniene J (2020) Flavonoids as anticancer agents. Nutrients 12:1–25 38. Sarg T (1993) Chemical constituents of Gomphocarpus sinaicus (Asclepiadaceae). Egypt J Pharm Sci 34:577–585 39. Samy RP, Rajendran P, Li F, Anandi NM, Stiles BG, Ignacimuthu S, Sethi G, Chow VT (2012) Identification of a novel Calotropis procera protein that can suppress tumor growth in breast cancer through the suppression of NF-κB pathway. PLoS One 7:e48514 40. Wen S, Chen Y, Lu Y, Wang Y, Ding L, Jiang M (2016) Cardenolides from the Apocynaceae family and their anticancer activity. Fitoterapia 112:74–84 41. Malcolm SB (1991) Cardenolide-mediated interactions between plants and herbivores. Herbivores: their interactions with secondary plant metabolites, vol 1, 1st edn. Academic Press, San Diego, pp 251–296 42. Glynn IM (1957) The action of cardiac glycosides on sodium and potassium movements in human red cells. J Physiol 136:148–173 43. Repke KRH (1985) New developments in cardiac glycoside structure-activity relationships. Trends Pharmacol Sci 6:275–278 44. Green PW, Veitch NC, Stevenson PC, Simmonds MS (2011) Cardenolides from Gomphocarpus sinaicus and Pergularia tomentosa (Apocynaceae: Asclepiadoideae) deter the feeding of Spodoptera littoralis. Arthropod-Plant Inter 5:219–255 45. Carter CA, Forney RW, Gray EA, Gehring AM, Schneider TL, Young DB, Lovett CM Jr, Scott L, Messer AC, Richardson DP (1997) Toxicarioside A. A new cardenolide isolated from Antiaris toxicaria latex-derived dart poison. Assignment of the 1H-and 13C-NMR shifts for an antiarigenin aglycone. Tetrahedron 53:13557–13566 46. Züst T, Petschenka G, Hastings AP, Agrawal AA (2019) Toxicity of milkweed leaves and latex: chromatographic quantification versus biological activity of cardenolides in 16 Asclepias species. J Chem Ecol 45:50–60 47. Petschenka G, Fandrich S, Sander N, Wagschal V, Boppré M, Dobler S (2013) Stepwise evolution of resistance to toxic cardenolides via genetic substitutions in the Na+/K+-ATPase of milkweed butterflies (Lepidoptera: Danaini). Evolution 67:2753–2761 48. Agrawal AA, Petschenka G, Bingham RA, Weber MG, Rasmann S (2012) Toxic cardenolides: chemical ecology and coevolution of specialized plant-herbivore interactions. New Phytol 194:28–45 49. Agrawal AA, Patrick ET, Hastings AP (2014) Tests of the coupled expression of latex and cardenolide plant defense in common milkweed (Asclepias syriaca). Ecosphere 5:1–11 50. Konno K (2011) Plant latex and other exudates as plant defense systems: roles of various defense chemicals and proteins contained therein. Phytochemistry 72:1510–1530 51. Hou S, Jamieson P, He P (2018) The cloak, dagger, and shield: proteases in plant-pathogen interactions. Biochem J 475:2491–2509 52. Freitas AP, Bitencourt FS, Brito GA, de Alencar NM, Ribeiro RA, Lima-Júnior RC, Ramos MV, Vale ML (2012) Protein fraction of Calotropis procera latex protects against

32

Chemistry, Biological Activities, and Uses of Latex from Selected Species. . .

863

5-fluorouracil-induced oral mucositis associated with downregulation of pivotal pro-inflammatory mediators. Naunyn Schmiedeberg’s Arch Pharmacol 385:981–990 53. Freitas CD, Oliveira JS, Miranda MR, Macedo NM, Sales MP, Villas-Boas LA, Ramos MV (2007) Enzymatic activities and protein profile of latex from Calotropis procera. Plant Physiol Biochem 45:781–789 54. de Alencar NM, da Silveira BF, de Figueiredo IS, Luz PB, Lima-Júnior RC, Aragão KS, Magalhães PJ, de Castro Brito GA, Ribeiro RA, de Freitas AP, Ramos MV (2017) Side-effects of Irinotecan (CPT-11), the clinically used drug for colon cancer therapy, are eliminated in experimental animals treated with latex proteins from Calotropis procera (Apocynaceae). Phytother Res 31:312–320 55. van Loon LC, Rep M, Pieterse CMJ (2006) Significance of inducible defense-related proteins in infected plants. Annu Rev Phytopathol 44:135–162 56. Sinha M, Singh RP, Singh TP (2014) Current overview of allergens of plant pathogenesis related protein families. Sci World J 2014:1–17 57. Jucá TL, Ramos MV, Moreno FB, Viana de Matos MP, Marinho-Filho JD, Moreira RA, Monteiro-Moreira AC (2013) Insights on the phytochemical profile (cyclopeptides) and biological activities of Calotropis procera latex organic fractions. Sci World J 2013:1–10 58. Ramos MV, de Oliveira RS, Pereira HM, Moreno FB, Lobo MD, Rebelo LM, Brandão-Neto J, de Sousa JS, Monteiro-Moreira AC, Freitas CD, Grangeiro TB (2015) Crystal structure of an antifungal osmotin-like protein from Calotropis procera and its effects on Fusarium solani spores, as revealed by atomic force microscopy: insights into the mechanism of action. Phytochemistry 119:5–18 59. Schmelzer GB, Gurib-Fakim A (2008) Medicinal plants. Backhuys Publishers, Netherlands 60. Naidoo CM, Naidoo Y, Dewir YH (2020) The secretory apparatus of Tabernaemontana ventricosa Hochst. ex A. DC. (Apocynaceae): laticifer identification, characterization, and distribution. Plan Theory 9:686–702 61. Schripsema J, Hermans-Lokkerbol A, Van der Heijden R, Verpoorte R, Svendsen AB, Van Beek TA (1986) Alkaloids of Tabernaemontana ventricosa. J Nat Prod 49:733–735 62. Kokwaro JO (1976) Medicinal plants of East Africa. East African Literature. Kampala, Nairobi, Dar-es-Salaam 63. Merzaia AB, Riaz H, Rehman R, Nisar S, Azeem MW (2017) A review of toxicity, therapeutic and biological activities of Calotropis. Int J Chem Bio Sci 11:58–64 64. Saratha V, Pillai SI, Subramanian S (2011) Isolation and characterization of lupeol, a triterpenoid from Calotropis gigantea latex. Int J Pharm Sci Rev Res 10:54–57 65. Kadiyala M, Ponnusankar S, Elango K (2013) Calotropis gigantea (L.) R. Br (Apocynaceae): a phytochemical and pharmacological review. J Ethnopharmacol 150:32–50 66. Kirtikar KR, Basu BD (1999) Indian medicinal plants. International Book Distributor, Dehrandun 67. Kshirsagar A, Ingawale D, Ashok P, Vyawahare N (2009) Calotropis gigantea: a comprehensive review. Pharmacol Online 2:229–239 68. Gharge VG, Ghadge DM, Shelar PA, Yadav AV (2017) Importance of Pharmacognostic study of medicinal plants Calotropis gigantea (Linn.): a review. Int J Pharmacognosy 4:363–371 69. Kumari A, Sood N (2020) A comparative study of traditional knowledge of Calotropis procera and Calotropis gigantea among four villages of Jaipur district of Rajasthan. J Med Plants 8:16–20 70. Abraham KI, Joshi PN (1979) Studies on proteinases from Calotropis gigantea latex. 1. Purification and some properties of two proteinases containing carbohydrate. Biochim Biophys Acta 568:111–119 71. Pal G, Sinha NK (1980) Isolation, crystallization, and properties of calotropins DI and DI from Calotropis gigantea. Arch Biochem Biophys 202:321–329 72. Thakur S, Das P, Itoh T, Imai K, Matsumoto T (1984) Latex extractable of Calotropis gigantea. Phytochemistry 23:2085–2087

864

C. M. Naidoo et al.

73. Chitme HR, Chandra M, Kaushi S (2004) Studies on anti-diarrhoeal activity of Calotropis gigantea R. Br. in experimental animals. J Pharm Sci 7:70–75 74. Wang M, Mei W, Deng Y, Liu S, Wang Z, Dai H (2008) Cytotoxic cardenolides from the roots of Calotropis gigantea. Mod Pharma Res 1:4–9 75. Mahatma OP, Singhvi I, ShirsatMrunal SK, Dwivedi J, Vaya R (2010) Anti-inflammatory and antipyretic activities leaves of Calotropis gigantea (Linn). J Glob Pharma Tech 2:75–78 76. Bharathi P, Alex T, Ansa T, Krishnan S, Ravi TK (2011) Antibacterial activity of leaf extracts of Calotropis gigantea Linn against certain gram-negative and gram-positive bacteria. Int J Chem Sci 9:919–923 77. Rathod NR, Chitme HR, Irchhaiya R, Chandra R (2011) Hypoglycaemia effect of Calotropis gigantea Linn leaves and flowers in streptozotocin-induced diabetic rats. Oman Med J 26: 104–110 78. Prabhu S, Veeravel R (2015) Effect of dust formulation of milkweed (Calotropis gigantea R. Br.) different plant parts against Helicoverpa armigera (Hubner). III Int Symp Underutilized Plant Species 1241:537–540 79. Chan EWC, Sweidan NI, Wong SK, Chan HT (2017) Cytotoxic cardenolides from Calotropis species: a short review. Rec Nat Prod 11:334–344 80. Sharma S, Kumari A, Sharma M (2016) Comparative GC-MS analysis of bioactive compounds in methanolic extract of Calotropis gigantea (L) WT Aiton leaf and latex. Int J Pharmacogn Phytochem Res 8:1823–1827 81. Arulmozhi S, Mazumder PM, Ashok P, Narayanan LS (2007) Pharmacological activities of Alstonia scholaris Linn. (Apocynaceae)-a review. Pharmacogn Rev 1:163–170 82. Vikneshwaran D, Viji M, Lakshmi KR (2008) A survey of the ethnomedicinal flora of the Sirumalai Hills, Dindugul District, India. Ethnobot Leafl 12:948–953 83. Pandey K, Shevkar C, Bairwa K, Kate AS (2020) Pharmaceutical perspective on bioactives from Alstonia scholaris ethnomedicinal knowledge, phytochemistry, clinical status, patent space, and future directions. Phytochem Rev 19:191–233 84. Keawpradub N, Kirby GC, Steele JCP, Houghton PJ (1999) Antiplasmodial activity of extracts and alkaloids of three Alstonia pecies from Thailand. Planta Med 65:690–694 85. Mishra M (2020) Pharmacognostic and pharmacological activity of Alstonia scholaris a review. JETIR 9:986–996 86. Ganjewala D, Gupta AK (2013) Study on phytochemical composition, antibacterial and antioxidant properties of different parts of Alstonia scholaris Linn. Adv Pharm Bull 3:379–384 87. Kawiwong J, Injard A, Riankrasin A, Kamonlakorn K, Srisoithongsug P, Pekthong D, Parhira S (2020) Chemical constituents and antioxidant activity of the Alstonia scholaris latex extract. In: The 12th NPRU National Academic Conference, Nakhon Pathom Rajabhat University, July 9–10, Thailand 88. Da Silva TF, Coelho MRR, Vollú RE, Gourlat FRV, Alviano DS, Alviano CS, Seldin L (2011) Bacterial community associate with the trunk latex of Hancornia speciosa Gomes (Apocynaceae) grow in the northeast of Brazil. Anton Van Leeuw 9:523–532 89. Silva GC, Braga FC, Lima MP, Pesquero JL, Lemos VS, Cortes SF (2011) Hancornia speciosa Gomes induces hypotensive effect through inhibition of ACE and increase on NO. J Ethnopharmacol 137:709–713 90. Da Silva AV, Soares AN, Ledo AS, Costa TS, Almeida CS, Amorim JA, Santos PS, Vitoria MF (2017) Uses and technological prospects for the Mangaba, a native fruit of Brazil. Afr J Biotechnol 16:307–311 91. Neto G, Guarim-Morais RG (2003) Medicinal plants resources in the Cerrado of Mato Grosso state, Brazil: a review. Acta Bot Bras 17:561–584 92. Santos PO, Barbosa Junior AM, Mélo DLFM, Trindade RC (2007) Study on the anti-microbial activity of the latex of Mangaba’s tree (Hancornia speciosa GOMES). Rev Bras Pl Med 9: 108–111 93. Sampaio TS (2008) Phytochemical study of Hancornia speciosa Gomes: isolation, structural determination, and biological activity. Master Thesis – Federal University of Sergipe, São Cristóvão, pp 148

32

Chemistry, Biological Activities, and Uses of Latex from Selected Species. . .

865

94. Floriano JF, Mota LSL, Furtado EL, Rossetto VJV, Graeff CFO (2013) Biocompatibility studies of natural rubber latex from different tree clones and collection methods. J Mater Sci Mater Med 25:461–470 95. Frade MA, Assis RV, Coutinho-Netto J, Andrade TA, Foss NT (2012) The vegetal biomembrane in the healing of chronic venous ulcers. An Bras Dermatol 87:45–51 96. Almeida LM, Floriano JF, Ribeiro TP, Magno LN, da Mota LS, Peixoto N, Mrué F, MeloReis P, Junior RD, de Oliveira Graeff CF, Gonçalves PJ (2014) Hancornia speciosa latex for biomedical applications: physical and chemical properties, biocompatibility assessment and angiogenic activity. J Mater Sci Mater Med 25:2153–2162 97. Almeida LM, Magno LN, Pereira AC, Guidelli ÉJ, Baffa Filho O, Kinoshita A, Goncalves PJ (2019) Toxicity of silver nanoparticles released by Hancornia speciosa (Mangabeira) biomembrane. Spectrochim Acta A Mol Biomol Spectrosc 210:329–334 98. D’Abadia PL, Bailao EF, Lino RS, Oliveira MG, Silva VB, Oliveira LA, Conceicao EC, MeloReis PR, Borges LL, GonÇalves PJ, Almeida LM (2020) Hancornia speciosa serum fraction latex stimulates the angiogenesis and extracellular matrix remodeling processes. An Acad Bras Ciênc 92:2 99. Marinho DG, Alviano DS, Matheus ME, Alviano CS, Fernandes PD (2011) The latex obtained from Hancornia speciosa Gomes possesses anti-inflammatory activity. J Ethnopharmacol 135: 530–537 100. Santos Neves J (2019) Evaluation of the osteogenic potential of Hancornia speciosa latex in rat calvaria and its phytochemical profile. J Ethnopharmacol 183:151–158 101. Pegorin GS, Leite MN, Antoniassi M, Chagas AL, Santana LA, Garms BC, Marcelino MY, Herculano RD, Cipriani Frade MA (2021) Physico-chemical characterization and tissue healing changes by Hancornia speciosa Gomes latex biomembrane. J Biomed Mater Res Part B: Appl Biomater 109:938–948 102. Coombs G, Peter CI, Johnson SD (2009) A test for Allee effects in the self-incompatible wasppollinated milkweed Gomphocarpus physocarpus. Austral Ecol 34(6):688–697 103. Pina S, Pedrosa C, Santos C, Feijóo B, Pego P, Vendrell C, Santos MJ, Prieto I (2014) Ocular toxicity secondary to Asclepias physocarpa: the balloon plant. Case Rep Ophthalmol Med 2014:1–5 104. Marzouk A (2009) Hepatoprotective triterpenes from hairy root cultures of Ocimum basilicum L. z Naturforsch 64:201–220 105. Marzouk AM, Osman SM, Gohar AA (2016) A new pregnane glycoside from Gomphocarpus fruticosus growing in Egypt. Nat Prod Res 30:1060–1067 106. El Gamal M, Hanna A, Morsy N, Duddeck H, Simon A, Gáti T, Tóth G (1999) Complete 1H and 13c signal assignments of 5α-cardenolides isolated from Calotropis procera R. BR J Mol Struct 477:201–208 107. Prachi S, Pradeep T (2014) 13α-methyl-27-norolean-14-en-3β-ol, a triterpene isolated from the stem of Euphorbia hirta (Linn.) possess anti-asthmatic properties. Res J Chem Sci 4:21–26 108. Kiranmayee P, Prabhudas N, Nandini HS, Kutty AVM (2020) Comparative analysis of transition and post-transition metal mediated Allamanda cathartica L latex nanoparticles on human peripheral blood mononuclear cells. Adv Nat Sci Nanosci Nanotechnol 11:015016 109. Das Nelaturi P, Sriramaia NH, Nagaraj S, Kotakadi VS, Moideen Kutty AVV, Pamidimukkala K (2017) An in-vitro cytotoxic and genotoxic properties of Allamanda cathartica L. latex green NPs on human peripheral blood mononuclear cells. Nano Biomed Eng 9:34–323 110. Di Santo MP, Fait ME, Foresti ML, Morcelle SR (2014) Biocatalytic characterization of a naturally immobilized lipase found in Araujia sericifera Brot. (Apocynaceae) latex. Cat Sci Technol 4:1386–1394 111. Shivaprasad HV, Rajesh R, Nanda BL, Dharmappa KK, Vishwanath BS (2009) Thrombin like activity of Asclepias curassavica L. latex: action of cysteine proteases. J Ethnopharmacol 123: 106–109 112. Parhira S, Yang ZF, Zhu GY, Chen QL, Zhou BX, Wang YT, Liu L, Bai LP, Jiang ZH (2014) In vitro anti-influenza virus activities of a new lignan glycoside from the latex of Calotropis gigantea. PLoS One 9:1–13

866

C. M. Naidoo et al.

113. Parhira S, Zhu GY, Jiang RW, Liu L, Bai LP, Jiang ZH (2014) 20 -Epi-uscharin from the latex of Calotropis gigantea with HIF-1 inhibitory activity. Sci Rep 4:1–7 114. Parhira S, Zhu GY, Chen M, Bai LP, Jiang ZH (2016) Cardenolides from Calotropis gigantea as potent inhibitors of hypoxia-inducible factor-1 transcriptional activity. J Ethnopharmacol 194:930–936 115. Freitas CD, Freitas DC, Cruz WT, Porfírio CT, Silva MZ, Oliveira JS, Carvalho CP, Ramos MV (2017) Identification and characterization of two germin-like proteins with oxalate oxidase activity from Calotropis procera latex. Int J Biol Macromol 105:1051–1061 116. Ramos MV, Freitas AP, Leitão RF, Costa DV, Cerqueira GS, Martins DS, Martins CS, Alencar NM, Freitas LB, Brito GA (2020) Anti-inflammatory latex proteins of the medicinal plant Calotropis procera: a promising alternative for oral mucositis treatment. Inflamm Res 69:951–966 117. Rabelo AC, Borghesi J, Carreira AC, Hayashi RG, Bessa F, Barreto RD, da Costa RP, Cantanhede Filho AJ, Carneiro FJ, Miglino MA (2021) Calotropis procera (Aiton) Dryand (Apocynaceae) as an anti-cancer agent against canine mammary tumor and osteosarcoma cells. Res Vet Sci 138:79–89 118. Fujita K, Inui H (2021) Review: biological functions of major latex-like proteins in plants. Plant Sci 306:1–6 119. Albuquerque TM, Alencar NM, Figueiredo JG, Figueiredo IS, Teixeira CM, Bitencourt FS, Secco DD, Araújo ES, Leão CAM, Ramos MV (2009) Vascular permeability, neutrophil migration and edematogenic effects induced by the latex of Cryptostegia grandiflora. Toxicon 53:5–23 120. Viana CA, Oliveira JS, Freitas CD, Alencar NM, Carvalho CP, Nishi BC, Ramos MV (2013) Thrombin and plasmin-like activities in the latices of Cryptostegia grandiflora and Plumeria rubra. Blood Coagul Fibrin 24:386–392 121. Ramos MV, Souza DP, Gomes MTR, Freitas CDT, Carvalho CPS, Júnior PAVR, Salas CE (2014) A phytopathogenic cysteine peptidase from latex of wild rubber vine Cryptostegia grandiflora. Protein J 33:199–209 122. Santos GJ, Oliveira ES, Pinheiro AD, da Costa PM, de Freitas JC, de Araújo Santos FG, Maia FM, de Morais SM, Nunes-Pinheiro DC (2018) Himatanthus drasticus (Apocynaceae) latex reduces oxidative stress and modulates CD4+, CD8+, FoxP3+ and HSP-60+ expressions in Sarcoma 180-bearing mice. J Ethnopharmacol 220:159–168 123. de Miranda ALP, Silva JR, Rezende CM, Neves JS, Parrini SC, Pinheiro ML, Cordeiro MC, Tamborini E, Pinto AC (2000) Anti-inflammatory and analgesic activities of the latex containing triterpenes from Himatanthus sucuuba. Planta Med 66:284–286 124. Silva JRA, Rezende CM, Pinto AC, Amaral ACF (2010) Cytotoxicity and antibacterial studies of iridoids and phenolic compounds isolated from the latex of Himatanthus sucuuba. Afr J Biotechnol 9:7357–7360 125. Soares DC, Andrade AL, Delorenzi JC, Silva JR, Freire-de-Lima L, Falcão CA, Pinto AC, Rossi-Bergmann B, Saraiva EM (2010) Leishmanicidal activity of Himatanthus sucuuba latex against Leishmania amazonensis. Parasitol Int 59:173–177 126. Da Silva MB, da Silva MP, dos Reis Júnior JDD, Lima CAC, de Oliveira SA (2021) Therapeutics activities of Amazonian plant Himatanthus sucuuba (Spruce ex Müll. Arg.) Woodson (Apocynaceae): a review. J Adv Biol Biotechnol 24:1–14 127. Calero-Armijos LL, Herrera-Calderon O, Arroyo-Acevedo JL, Rojas-Armas JP, HañariQuispe RD, Figueroa-Salvador L (2020) Histopathological evaluation of latex of BellacoCaspi, Himatanthus sucuuba (Spruce) Woodson on wound healing effect in BALB/C mice. Vet World 13:1045–1049 128. Rao YV, Raju M (2016) Antioxidant and protease activities of seven native plant sources. IJBSM 7:1346–1350 129. Mendonça PM, Lima MG, Albuquerque LR, Carvalho MG, Queiroz MM (2011) Effects of latex from “Amapazeiro” Parahancornia amapa (Apocynaceae) on blowfly Chrysomya megacephala (Diptera: Calliphoridae) post-embryonic development. Vet Parasitol 178:379–382

32

Chemistry, Biological Activities, and Uses of Latex from Selected Species. . .

867

130. Lopes MB, Mendonça PM, Mallet JR, Carvalho MG, Queiroz M (2014) Bioactivity of the latex from Parahancornia amapa (Apocynaceae) on the development of Rhodnius nasutus (Hemiptera, Reduviidae, Triatominae) under laboratory conditions. RBE 58:379–383 131. Miladi M, Abdellaoui K, Hamouda AB, Boughattas I (2018) Toxicity of the active fraction of Pergularia tomentosa and the aggregation pheromone phenylacetonitrile on Schistocerca gregaria fourth-instar nymph: effects on behavior and acetylcholinesterase activity. J Plant Prot 13:201–216 132. Sequeiros C, Torres MJ, Trejo SA, Esteves JL, Natalucci CL, López LMI (2005) Philibertain g I, the most basic cysteine endopeptidase purified from the latex of Philibertia gilliesii hook. et Arn. (Apocynaceae). Protein J 24:445–453 133. Sequeiros C, Torres MJ, Nievas ML, Caffini NO, Natalucci CL, López LM, Trejo SA (2016) The proteolytic activity of Philibertia gilliesii latex. Purification of Philibertain g II. Appl Biochem Biotechnol 179:332–346 134. Rengaswami S, Venkatarao E (1960) Chemical components of Plumeria alba. Proc Indian Acad Sci 52:173–181 135. Imrana M, Asif M (2020) Morphological, ethnobotanical, Pharmacognostical and pharmacological studies on the medicinal plant Plumeria alba Linn. (apocynaceae). AJMAP 6: 54–84 136. Kusuma CG, Gubbiveeranna V, Sumachirayu CK, Bhavana S, Ravikumar H, Nagaraju S (2021) Thrombin-and plasmin-like and platelet-aggregation-inducing activities of Plumeria alba L. latex: action of cysteine protease. J Ethnopharmacol 273:114000–114009 137. Fernandes HB, Machado DL, Dias JM, Brito TV, Batista JA, Silva RO, Pereira AC, Ferreira GP, Ramos MV, Medeiros JVR, Aragão KS (2015) Laticifer proteins from Plumeria pudica inhibit the inflammatory and nociceptive responses by decreasing the action of inflammatory mediators and pro-inflammatory cytokines. Rev Bras Farmacogn 25:269–277 138. Santana LDAB, Aragão DP, Araújo TDSL, de Sousa NA, de Souza LKM, Oliveira LES, da Cunha Pereira ACT, Ferreira GP, de Moraes Oliveira NV, da Silva SB, Sousa FBM (2018) Antidiarrheal effects of water-soluble proteins from Plumeria pudica latex in mice. Biomed 97:1147–1154 139. de Moraes Oliveira NV, da Silva Souza B, Moita LA, Oliveira LES, Brito FC, Magalhães DA, Batista JA, Sousa SG, de Brito TV, de Melo Sousa FB, Alves EHP (2019) Proteins from Plumeria pudica latex exhibit protective effect in acetic acid-induced colitis in mice by inhibition of pro-inflammatory mechanisms and oxidative stress. Life Sci 231:116535–116542 140. Chamakuri SR, Suttee A, Mondal P (2020) An eye-catching and comprehensive review on Plumeria pudica Jacq. (Bridal Bouquet). Plant Arch 20:2076–2079 141. Oliveira LE, Moita LA, Souza BS, Oliveira NM, Sales AC, Barbosa MS, Silva FD, Farias AL, Lopes VL, França LF, Alves EH (2021) Latex proteins from Plumeria pudica reduce ligatureinduced periodontitis in rats. Oral Dis 00:1–10 142. Rastogi RP, Mehrotra BN (1990) Compendium of Indian medicinal plants, vol 1. CSIR, New Delhi, pp 118–122 143. Chanda I, Basu SK, Dutta SK, Das SRC (2011) A protease isolated from the latex of Plumeria rubra Linn (Apocynaceae) 1: purification and characterization. Trop J Pharm Res 10:705–711 144. Patil CD, Patil SV, Borase HP, Salunke BK, Salunkhe RB (2012) Larvicidal activity of silver nanoparticles synthesized using Plumeria rubra plant latex against Aedes aegypti and Anopheles stephensi. Parasitol Res 110:1815–1822 145. Alencar NMND, Pinheiro RSP, Figueiredo ISTD, Luz PB, Freitas LBN, Souza TDFGD, Carmo LDD, Marques LM, Ramos MV (2015) The preventive effect on ethanol-induced gastric lesions of the medicinal plant Plumeria rubra: involvement of the latex proteins in the NO/cGMP/KATP signaling pathway. J Evid-Based Complement Altern Med 2015:1–10 146. Rajasekhar KK, Shankarananth V, Venkateswarlu M, Nirosha M, Bindhu DT, Reddy KN (2009) Local anaesthetic activity of Tabernaemontana coronaria latex in frog and guinea pig. J Pharm Res 2:1691–1693

868

C. M. Naidoo et al.

147. Singh MK, Usha R, Hithayshree K, Bindhu OS (2015) Hemostatic potential of latex proteases from Tabernaemontana divaricata (L.) R. Br. ex. Roem. and Schult. and Artocarpus altilis (Parkinson ex. FA Zorn) Forsberg. J Thromb Thromboly 39:43–49 148. Banu SH, Nagashree S, Latha B, Chethankumar M (2017) Biochemical characterization of proteases isolated from the latex of Tabernaemontana divaricata L. and Carissa carandas L.: their role in hemostasis. J Pharmacogn Phytochem 6:06–09 149. Raju M, Rao YV (2020) Identification and characterization of proteases from Tabernaemontana divaricata. Agric Nat Res 54:279–286 150. da Silva Menecucci C, Mucellini KL, de Oliveira MM, Higashi B, de Almeida RTR, Porto C, Pilau EJ, Gonçalves JE, Gonçalves RAC, de Oliveira AJB (2019) Latex from Tabernaemontana catharinensis (A. DC)—Apocynaceae: an alternative for the sustainable production of biologically active compounds. Ind Crop Prod 129:74–84 151. Arambewela LS, Ranatunge T (1991) Indole alkaloids from Tabernaemontana divaricata. Phytochemistry 30:1740–1758 152. Kam TS, Pang HS, Choo YM, Komiyama K (2004) Biologically active ibogan and vallesamine derivatives from Tabernaemontana divaricata. Chem Biodivers 25:491–498 153. Low YY, Lim KH, Choo YM, Pang HS, Etoh T, Hayashi M, Kam TS (2010) Structure, biological activity, and a biomimetric partial synthesis of lirofolines, nocel pentacyclic indole alkaloids from Tabernaemontana. Tetrahedron Lett 51:269–272 154. Sibi G, Wadhavan R, Singh S, Shukla A, Dhananjaya K, Ravikumar KR, Mallesha H (2013) Plant latex: a promising antifungal agent for post-harvest disease control. PJBS 16:1737–1743 155. de Freitas CD, da Cruz WT, Silva MZ, Vasconcelos IM, Moreno FB, Moreira kRA, MonteiroMoreira AC, Alencar LM, Sousa JS, Rocha BA, Ramos MV (2016) Proteomic analysis and purification of an unusual germin-like protein with proteolytic activity in the latex of Thevetia peruviana. Planta 243:1115–1128 156. Udo S, Ekpiken E (2016) The use of plant latex as a biocontrol agent for the inhibition of Moroccan watermelon mosaic virus (Mwmv) sourced from three latex producing plants. J Biopest 3:41–51 157. Cruz WT, Bezerra EH, Ramos MV, Rocha BA, Medina MC, Demarco D, Carvalho CPS, Oliveira JS, Sousa JS, Souza PF, Freire VN (2020) Crystal structure and specific location of a germin-like protein with proteolytic activity from Thevetia peruviana. Plant Sci 298:110590 158. Bastos ML, Sarmento RM, de Oliveira BM, da Silva RJ, Vale VV, Percário S, Dolabela MF (2020) Antitumor activity of Apocynaceae species used in Amazon traditional medicine. Res Soc Develop 9:19–57

Part V Plant Waxes

Chemistry, Biological Activities, and Uses of Carnauba Wax

33

Eli Jose´ Miranda Ribeiro Junior, Joy Ruby Violet Stephen, Murugan Muthuvel, Amitava Roy, Patrícia de Arau´jo Rodrigues, Maraja´ Joa˜o Alves de Mendonc¸a Filho, Renato Arau´jo Teixeira, Antony de Paula Barbosa, and Stephen Rathinaraj Benjamin

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Ethnobotanical Investigation of Carnauba Wax . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Food Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Food Packaging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

873 875 876 876 877

E. J. M. R. Junior Faculty of Inhumas (FacMais), Inhumas, Goiás, Brazil J. R. V. Stephen Department of Geography, Queen Mary’s College (A), Chennai, India M. Muthuvel Department of Pharmaceutical Chemistry, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research, Porur, Chennai, India e-mail: [email protected] A. Roy Department of Pharmaceutical Technology, University of North Bengal, Siliguri, India e-mail: [email protected] P. d. A. Rodrigues · S. R. Benjamin (*) Post-Graduate Programme in Medical Sciences, Department of Medicine, Faculty of Medicine, Drug Research and Development Center (NPDM), Federal University of Ceará, Fortaleza, Ceará, Brazil M. J. A. d. Mendonça Filho Network Teaching and Learning Center, Department of Geography, State University of Goiás, Anapolis, Goiás, Brazil e-mail: [email protected]; [email protected] R. Araújo Teixeira Department of Geography, Federal Institute of Goiás, Inhumas, Goiás, Brazil A. d. P. Barbosa Department of Pharmaceutical Products, Faculty of Pharmacy, Federal University of Minas Gerais, Belo Horizonte, Minas Gerais, Brazil © Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6_37

871

872

E. J. M. R. Junior et al.

2.4 Fruit Coating . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Post-Harvest Storage . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6 Carnauba Wax-Based Solid Lipid Nanoparticles . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.7 Microencapsulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.8 Pharmaceutical Processing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.9 Pharmacological Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Environmental Application . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Conclusion and Future Directions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

879 880 881 882 885 886 887 887 889

Abstract

The major vegetable wax in the economy, carnauba wax (Copernicia prunifera (Miller) H. E. Moore) is used widely in food owing to the physiochemical properties of the food, with a majority of esters. Many recent studies have focused on the use of this wax in food preservation and processing, highlighting its function in taste microencapsulation, edible films, and superhydrophobic and biodegradable packaging. This book chapter explores the requirements for coating and discusses the various types of coating materials, biological effects, and physical and chemical properties of carnauba wax powder. Keywords

Biotechnological applications · Carnauba wax · Cinnamic acid · Copernicia prunifera · Ethnopharmacology · Phytochemistry Abbreviation

AA ABTS ANVISA BW CAR/CW CNCs CP CSW CWN CWNs DPPH DSC ECF-125 EO FAO FDA FRAP GML GMP

Atomic absorption spectroscopy 2,20 -Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) Agência Nacional de Vigilância Sanitária Bees wax Carnauba Wax Cellulose nanocrystals Cold plasma Carnauba-shellac wax Carnauba wax nano-emulsion Carnauba wax nanoparticles Compound 2,2-diphenyl-1-picrylhydrazyl Differential scanning calorimetry Extracellular fluid Ethylene oxide Food and Agriculture Organization Food and Drug Administration Ferric-reducing action potential Glycerol monolaurate Good manufacturing practice

33

Chemistry, Biological Activities, and Uses of Carnauba Wax

GRAS GSEs HBO-HOSO HIV-gp KGM KSO-NLC LBL LO ME MPa NE NLC NLSs NSAID OEO PG pH PUT ROS SDS SEM SiO2 SLM SLNPs SPF SS TA UV WVP X-ray ZnO

1

873

Generally recognized as safe Grapefruit seed extracts High oleic soyabean oil hydroboration-oxidation Human immunodeficiency virus – glycoprotein Konjac glucomannan Kenaf seed oil-nanostructured lipid carrier Layer by layer Lemongrass oil Microemulsion Megapascal pressure unit Nanoemulsion Nanostructured lipid carriers Solid lipid nanoparticles Nonsteroidal anti-inflammatory drug Oregano essential oil Peptidoglycan Potential of hydrogen Putrescine Reactive oxygen species Sodium dodecyl sulfate Scanning electron microscope Silicon dioxide Solid lipid microparticles Solid lipid nanoparticles Sun protection factor Soluble solids Titratable acidity Ultraviolet Water vapor permeability X-radiation Zinc oxide

Introduction

Plant wax is the generic term for describing the lipid constituents of the cuticle, a material that coats the surface of aerial plant tissues. These waxes protect plants from many stresses, including sweat loss, exposure to dry atmospheric conditions, high solar radiation, and ultraviolet radiation, and protect plants against diseases and herbicides [1]. Carnauba wax is a natural “vegetable” wax derived from the leaves of the carnauba palm (Copernicia prunifera (Miller) H. E. Moore) family – Arecaceae (Fig. 1), a Brazilian plant found exclusively in the arid climate of the northeast caatingas under economic circumstances (scrublands) [2]. Carnauba wax is extensively utilized in the chemical, pharmaceutical, food, cosmetic, computer, and automotive sectors because of its antioxidant, photoprotective, and stable

874

E. J. M. R. Junior et al.

Fig. 1 Typical image of a carnauba tree (Copernicia prunífera)

characteristics due to its lipophilic and nonpolar nature. This palm, also called “The Tree of Life” during the dry season in Brazil, defends itself from loss of moisture by secreting the coating on both sides of the leaf. “Brazil Wax,” “Ceará Wax,” “Palm Wax,” and “Queen of wax,” and the local names are “carandauba,” “carnauba,” “carnaubeira,” “carnaba,” “carnaúva,” and “caranaiba,” among others [3]. The primary economic application of carnauba is wax manufacturing, and its fruits are utilized for animal feed in vast systems throughout the plant’s range. Furthermore, its extraction is a significant economic activity in the Brazilian Northeast, where Ceará is among the most prominent exporters [4]. Waxes are water-repellent solids and are part of the protective coating of many living things, including plant leaves, animal skin, and bird feathers. In general, they are mixtures of esters formed by carboxylic acids and long-chain alcohols [5]. Carnauba wax is a natural wax and is a Brazilian plant exudate of Copernica cerifera, mainly composed of C24 and C28 carboxylic acid esters and C32 and C34 linear chain primary alcohols [6]. Carnauba wax is mainly composed of fatty acid esters (80–85%), fatty alcohols (10–16%), acids (3–6%), and hydrocarbons (1–3%). It consists of about 20% esterified fatty diols, 10% cinnamic acid, methoxylated or hydroxylated, and 6% hydroxylated fatty acids that are composed by the chemistry of carnauba wax [7–9]. Some of the inorganic components present in wax include aluminum, calcium, iron, manganese, copper, magnesium, sodium, and zinc [10]. Carnauba wax is the strongest, with melting point (84  C) of any commercialized natural wax, has a limited solubility (insoluble in water but is soluble in alcohols and

33

Chemistry, Biological Activities, and Uses of Carnauba Wax

875

Fig. 2 Carnauba wax’s uses

oils), and is mostly composed of aliphatic esters and cinnamic acid diesters [11]. It has generally inert and stable components [12]. Carnauba wax has been extensively utilized in food because of these and other properties. Moreover, it is traditionally used to treat, notably rheumatism and syphilis. ANVISA [13], the FDA (Food and Drugs Administration) [14], the FAO (Food and Agriculture Organization), and the European Union [15] are presently authorizing it. Carnauba wax is classified as generally recognized as safe (GRAS) in the United States and is used in a range of foods in the amounts necessary to comply with good manufacturing practice (GMP). Furthermore, a considerable investigation has been performed to introduce potential uses for this raw material. The wax has tremendous potential for application in the food supply chain. To maximize the benefits of this raw resource, food industry experts must first comprehend it. Thus, this chapter covers the use of carnauba wax in food, including the extraction method, classifications, chemical, and physical properties, and authorized applications (Fig. 2).

2

Ethnobotanical Investigation of Carnauba Wax

In spite of various applications for carnauba wax in food products, many researchers across the globe are continuously attempting to develop new uses, potential goods, and new technology. In recent years, numerous research has been carried out on carnauba wax, including its manufacturing, storage, and food processing uses, and various studies are addressed in depth below.

876

2.1

E. J. M. R. Junior et al.

Antioxidant Activity

Phytoconstituents and extracts from particular species of Copernicia prunifera plants have been shown to possess the strong antioxidant potential and have been found valuable in diseases of oxidative stress respectively. da Silva Andrade et al. [1] studied that ethanolic (EtA, EtB) and aqueous (AqA, AqB) extracts of Copernicia prunifera (type A and B) exhibited high free radical scavenging activity by 2,2diphenyl-1-picrylhydrazyl (DPPH) and ABTS assays. In this study, type A wax powder with extracts of EtB and AqB gave better results than type A wax extracts and presented the higher antioxidant activity of wax secreted by mature leaves, indicated that the bioactive compounds of carnauba wax. The highest activity was found in the type B ethanolic wax powder (EtB) extract, with an EC50 of 365  7 mg/mL (by the PPH test) and 317  6 mg/mL (via a DPPH assay) values. All the extracts exhibited antioxidant activity (by ABTS). Phenolic, flavonoid content and flavonol total content vary from 280.73  4.85 to 114.06  4.45 gallic acid (GAE), 24.59  0.45 to 5.34  0.12, and 32.36  0.93 to 9.41  0.37 catechin equivalents (CTE). Rufino et al. [16] showed that substantial antioxidants activity of rich tropical fruit and dry fruit extracts was conducted, in particular carnauba, DPPH, ABTS, FRAP, β-carotene oxidation techniques, and total phenolic content. The antioxidants of the methanolic and ethanol extract from carnauba fresh fruits were observed to lower the DPPH values of 3549  184 g of fruits/g of DPPH and increased ABTS values to 10.7 + 0.2 μmoL of Trolox/g and FRAP values to 15.5  0.4 μmoL Fe2SO4/g, and high blanching values for β-carotene have been found to be 87.7  2.7 (percent O.I) and extractable polyphenols 830  28.3 mg of GAE/100 g, respectively. Furthermore, bioactive components values such as vitamin C (78.1  2.6), total anthocyanins (4.1  0.1), Yellow flavonoids, and total carotenoids (0.6  0.2), chlorophyll (4.2  0.2), respectively are included in the bioactive compound values (mg/100 g fresh matter).

2.2

Food Processing

The natural wax coatings are utilized for the development of superhydrophobic coatings. Bashari et al. [17] employed carnauba wax/ZnO nanoparticles to create anti-weathering textiles. In this study, water repellent and antibacterial characteristics of CWNs and ZnO nanoparticles were assessed using layer-by-layer selfassembly on cotton, cotton/nylon6, and nylon6 textiles. ZnO was utilized to make positive charge carnauba/ZnO bilayers on textiles. The findings demonstrate that plasma treatment enhances textile performance and that it is an appropriate substrate for CWN/ZnO bilayer absorption. Four bilayers were deposited in fabrics to make them water-resistant. ZnO on textiles has antibacterial properties toward grampositive and gram-negative microorganisms. Gupta et al. [18] demonstrated that composite coatings based on carnauba wax offer an efficient and prominent option to achieve environmentally friendly

33

Chemistry, Biological Activities, and Uses of Carnauba Wax

877

superhydrophobic coating. Furthermore, owing to its high hardness and mechanical properties, the composite covering outperformed its non-enforced equivalent in terms of resistance to degradation during simulated rain, erosion, and weathering (14 MPa). The authors revealed that composite carnauba wax coatings are an effective and environmentally acceptable option for the development of superhydrophobic self-cleaning surfaces that are resistant to water. Lozhechnikova et al. [6] performed a novel and easy technique for the production of stable aqueous micro- and nanoparticles of carnauba wax. In combination with positively charged ZnO nanoparticles for a protecting wood surface coating, these negative wax colloids were formed via a layer-by-layer easy and ecologically acceptable procedure. In addition to superior hydrophobicity, the developed coating exhibits excellent humidity buffering and UV protection, despite preserving the wood’s natural appearance and improving indoor air quality and comfort.

2.3

Food Packaging

Food packaging is mainly constructed of petrochemical polymers like propylene, ethylene, and styrene owing to its low cost and widespread production. Furthermore, its non-biodegradability has raised significant environmental impacts. In order to develop biodegradable films for food packaging, researchers are increasingly turning to biopolymers derived from food sources [19]. de Oliveira Filho et al. [20] investigated the inclusion of carnauba wax (0–15 wt%) in the properties of arrowroot starch films utilizing emulsion technology micro- (ME) and nanoemulsions (NE). The inclusion of carnauba wax in the films enhanced the hydrophobic qualities of the films and reduced water solubility, humidity, vapor permeability, and thermal stability. Films with NE have a lower permeability of the water vapor and luminous barrier, higher tensile strength, and smoother microstructure than films with ME. In addition, nanoemulsification appeared to be an appropriate method for hydrophilic compound incorporation into starch films. Recently, Filho and his colleagues developed a new functional food packaging material, which contains carnauba wax nanoemulsion (CWN) (to increase the water vapor barrier), CNCs (to improve the tensile characteristics), and EO from the green mint plant and palmarosa grass (for supplying antifungal qualities). The features of AA/CWN/CNC/EO have demonstrated that films are promising the main packaging or cover various food products, including fresh fruit, vegetables, bread, and cheese [21]. Commercial eggs were coated with carnauba wax, both at 12% and 15% concentrations, to preserve their interior quality throughout storage both at 10  C and 25  C. Eggs held at 25  C showed poorer quality characteristics when stored than those kept undercooling. Wax coating eggs did not reduce the oxidation processes of egg yolk [22]. Fei et al. [23] developed a new single pendant hydroxy-functional soy wax that was synthesized using high oleic soyabean oil hydroboration-oxidation (HBO-HOSO). Furthermore, the low viscosity emulsions are an alternative to the high-cost carnauba

878

E. J. M. R. Junior et al.

wax (CAR) and resin-based emulsions, which are employed in citric fruit coatings, primarily to allow strength and avoid loss of moisture. In addition, low viscosity and a reasonably transparent emulsion from soy wax that is appropriate for citrus fruit coating have been produced effectively. The emulsion with a solid content of 20% of the soybean component (HBO-HOSO) has given citrus fruit a similar surface gloss, firmness, and superior humidification characteristics compared to commercial emulsions. At present, the integration of CP (cold plasma) is a low-cost approach that may serve as an alternative to heat-based technologies utilized in food product processing. Cold plasma has been studied in recent years in food industries, including the inactivation of microorganisms and packaging characteristics. The use of cold plasma can reduce both microbiological and chemical risks at various food supply chain stages as a threat to food standards, food safety, and sustainability. Romani et al. [24] made significant contributions to the development of better bilayer films for use in two-layer sustainable food packaging. Bilayer films are made using protein casting, plasma treatment (glow discharge), and carnauba wax coating. The combination of cold plasma and carnauba wax is an option for improving the packaging characteristics of fish-protein films while also reducing the development of synthetic plastics in nature utilizing resources and methods that respect the environment. In contrast, to control films, the use of glow discharge plasma coupled with carnauba wax coating led to an increase in a 175% increase in tensile strength and a 65% decrease in water vapor permeability in fish protein films until the optimum circumstances were found, as compared to control films. Lufu et al. [25] have systematically evaluated variables that influence the water loss of economically significant fresh fruit in pre-harvest, harvest, and postharvest. According to most experts, the fresh fruit business is more aware of post-harvest variables; however, this literature analysis shows that there are many pre-harvest and harvest parameters that may be adjusted to substantially decrease water loss during extended storage and marketing, for example, cultivars less moistures-prone may be chosen, and orchard operations, such as watering schedules and daytime harvests, can be readily changed. By adopting the required control measures during pre-harvest and harvest phases, the burden of using loss control methods after harvest may be reduced, thus increasing the industry’s profitability. Carnauba wax nanoparticles exhibited excellent adherence in cellulose chains and fully covered the surface, which improved the hydrophobicity of fiber. The association between the nanoparticles and the cellulose fibers resulted in improvements in the physical, hydrophobicity, and water vapor barrier characteristics of the material. The prospect of employing carnauba wax emulsions to improve the physical and mechanical properties of cellulose sheets, allowing materials to be utilized in low-cost food packaging [26]. The use of mineral and vegetable wax particles to maintain emulsions was investigated (without surfactants). The waxes utilized were paraffin, ceresin, and carnauba. The wax particle concentration and water to oil ratio (50%) were shown to be critical for emulsion stability. Some emulsions included liquid wax (i.e., jojoba oil). However, two vegetable emulsions showed phase separation (jojoba oil and

33

Chemistry, Biological Activities, and Uses of Carnauba Wax

879

carnauba wax). It may be connected to the high moisture resistance of the wax surface using jojoba oil, which could have rendered wax particles inappropriate for pickering emulsion stability [27]. Due to the commercial availability of carnauba wax and beeswax (BW), their use in the production of superhydrophobic coatings was promoted. Recently, Celik et al. [28] reported the fabrication of superhydrophobic covering for carnauba wax/silica that shows strong endurance alongside other nanomaterials (SiO2, ZnO) for the manufacture of structured surfaces with an abrasion and mechanical durability that approaches or surpasses those found in the environment [28, 29]. Analyzing carnauba wax/soybean oil systems may benefit the development of a variety of organogels with various characteristics for food applications. The diversity of unsaturated fatty acid-rich carnauba organogels can decrease saturated fatty acid consumption. Recently, Buitimea-Cantúa et al. [30] developed a concentration of wax type (5.5% w/w). Soybean oil with carnauba waxes structure produced solid, thermally stable organogels.

2.4

Fruit Coating

The edible coating is regarded to be future packages and may contribute to reducing the losses due to withering (i.e., loss of water). These layers are thin layers of edible biopolymers produced from proteins, polysaccharides, or lipids, directly placed on a product surface and adhered to as part of the finished product. Such materials provide an obstacle to physical injury, microbial contamination, moisture loss or gain, and nutritional oxidation. As a result, they assist in preventing product degradation, thus prolonging storage life, sensory quality, and product safety. The distinction between these coatings and plastic packaging is that the former is edible and biodegradable and can also be used in place of the latter partly or entirely [31]. Won et al. [32] described the development of biopolymer coating for the preservation of fruit as well as the antifungal effects of biopolymer coatings with essential oils or grapefruit seed extracts (GSEs). The authors demonstrated that GSE–CW coating offers effective post-harvest protection technology against mandarins without altering physicochemical characteristics. During storage, CW coating prevented oxygen input in the flesh, preventing ascorbic acid oxidation, which is more effective than CW coating when decreased fungal disease was caused by P. italicumon on the mandarin fruit surface. Due to significant water losses and redness seen in postharvest sweet potato (Ipomoea batatas) roots, a high energy emulsification method to carnauba wax (CW)–based nanoemulsion without or with glycerol monolaurate (CW-GML) has been developed. Both coatings have investigated the effects on cardiovascular disease, respiration, surface color, loss of weight, starch content, total soluble sugar, and sensory characteristics of sweet potato roots at 20  C during storage over 50 days [33]. Md Nor et al. [34] improved the evaluation of trends and developments in foodstuff covering biopolymer for tropical fruits. The combination of carnauba wax coating and extend packaging allowed “Tommy Atkins” mangoes to be stored

880

E. J. M. R. Junior et al.

in the storage at 12  C for 21 days and thus to maintain the desired properties, including firmness, decreased mass loss, and fruit acidity [35]. Lipid coating provides the greatest moisture barrier for its hydrophobic properties, and many natural lipid sources are employed as edible coating materials [36] (carnauba wax, candelilla wax, and beeswax). Carnauba wax treatment may reduce water loss in the presence of wax and sorbitol, fatty acid delayed pineapple coating [37], that maintain the quality of the mango at the cooling temperatures [38]. The galactomannan-carnauba wax cover improves quality and storage by retaining the firmness of color for over 15 days (25  C) of storage in the atmosphere. The coating also enhanced the cooling quality of guava (11  C), while the untreated fruit showed signs of chilling. The suggested mechanism of action is to delay the respiration of galactomannancarnauba wax to reduce the ROS generation and activate the enzyme antioxidant defense that further averted the oxidative imbalance [39]. This study demonstrates that edible coating is a potential way to prolong the life of tropical fruits after harvest. The carnauba wax and oregano essential oil (OEO) carnauba wax coating were the most efficient in decreasing weight loss, while microbial load reduction in treated fresh cucumber was best achieved with chitosan and chitosan wax [40]. A significant amount of studies have concentrated on the topic of post-harvest storage, including investigations on the usage of carnauba wax in food, as shown below.

2.5

Post-Harvest Storage

Applying edible coatings to fruit surfaces had the dual purpose of protecting the fruit from decay and improving its appearance. So it’s feasible to extend shelf life and reduce post-harvest losses. The persimmon is a popular fruit with great export potential but demanding handling and storage. According to the findings applying lower concentrations (25%) of carnauba wax had slower discharge rates in persimmon cv [41]. The authors highlighted the use of carnauba wax in persimmon as a post-harvest preservation method that may be coupled with other approaches to preserve fruit quality for export. Machado et al. [42] studied the performance of Murcott “Ortanique” following coating with Aruá Tropical ® or “Star Light ®” carnauba wax. The authors claimed that storage conditions were similar to marketing settings (22  C, 60% relative humidity). The Aruá Tropical ® carnauba wax coating preserved visual quality by retaining green color and prevent weight loss and dehydration. The covered fruit’s water content, chlorophyll content, and reduced juiciness, soluble solids (SS), and titratable acidity (TA, pH, and SS/TA) did not alter during storage. Sensory research revealed that Aruá Tropical ® extended the shelf life of the fruit by 6 days. Wan-Shin Jo et al. [43] tested the efficacy and microbial stability of Fuji apple nanoemulsions with lemongrass oil. The authors claimed that uncoated apples lost 3.3 N hardness and 7.7% weight after storage (5 months). However, the coated apples retained their firmness and lost less weight (5.2%). Compared to uncoated apples, covered apples had lower populations of total aerobic bacteria, molds, and yeasts during storage. The coating also enhanced sensory ratings and reduced quality

33

Chemistry, Biological Activities, and Uses of Carnauba Wax

881

loss during storage. In conclusion, a coating of carnauba wax and shellac with lemongrass oil (lemongrass) may be utilized to prolong the shelf life of Fuji apples. The functional quality (anthocyanins, antioxidant activity, ascorbic acid, tannins) and sensory characteristics of pomegranate (Punica granatum L.) were examined by Barman et al. [44]. The results indicate that the combination of putrescine + carnauba wax maintained functional characteristics higher than the fruit treated or not with putrescine (PUT). Notwithstanding the storage conditions, putrescine + carnauba wax had 25% greater antioxidant activity after 60 days. According to the authors, exogenous putrescine and carnauba wax treatment maintain increasing levels of anthocyanins, antioxidants, ascorbic acid, tannins, and sensory quality of pomegranate throughout storage at 3  C and 5  C. They also highlighted the use of PUT + carnauba wax as a simple method to preserve the pomegranate’s functional qualities at low temperatures and extended storage. Barman et al. [45] examined pomegranate (Punica granatum cv. Mridula) fruits treated before to 2  C frozen storage with putrescine, carnauba wax, and putrescine + carnauba wax combination. Before the analysis, fruits were exposed to physical, physiological, and biochemical characteristics for 3 days at 20  C after cold storage. However, under storage circumstances, pomegranate fruits may last for 60 days, at a lower temperature. Germano et al. [39] have investigated how to enhance the post-harvest quality and conservation of the guava fruit’s color-galactomannan wax over 15 days (25  C) environmental conditions. After the coating, guava respiration revealed significant circumstances for ROS generation, and enzyme-mediated antioxidant activity was generated to decrease the oxidative imbalances and the cold sensations during cooling (11  C). In addition, cell membrane permeability and PG cell wall inhibition are also significantly related to firmness, with hydrolytic activity. Motamedi et al. [46] first assessed the effectiveness, simulating storage, and marketing of the carnauba wax-nanoclay emulsions to preserve the quality of “Valencia.” In addition to reducing weight loss, wax coats preserve fruit antioxidant activity throughout storage and distribution. Weight loss after 8 weeks of cold storage at 4  C and 8 weeks cold storage plus 1 week at 20  C was typically lower in untreated control fruit than coated fruit (0.05). The impact of nanoclay on weight loss reduction was more substantial after storage for 1 week at 20  C for all three produced emulsion waxes. To explain this, a greater dose of nanoclay in the present coating formulation may enhance water vapor barrier characteristics, reducing water loss via the coatings. As a consequence, high relative humidity surrounding the fruit reduced the gradient to the exterior and reduced wax covering weight loss.

2.6

Carnauba Wax-Based Solid Lipid Nanoparticles

Solid lipid microparticles (SLM) is the most advanced lipid carrier technology. They originate from the emulsions of oil-in-water, change the liquid by lipid and solid lipids at ambient temperature, and are stabilized by surfactants. Triglycerides, glycerides, and waxes are all types of lipids that may be utilized. Carnauba wax,

882

E. J. M. R. Junior et al.

as a gelling, releasing, and glazing agent, is already utilized by many sectors for diverse reasons. It has a high melting point (between 82.0  C and 85.5  C), making it an excellent option in food systems, for example, in SLNPs manufacturing. As a result, SLMs were suggested as colloidal carriers for low solubility drugs. The model drug ketoprofen was integrated into NLSs made of beeswax and carnauba wax with Tween 80 and egg lecithin as emulsifiers. A high drug encapsulation effectiveness (97%) showed NLS’ capacity to integrate a water-insoluble drug-like ketoprofen. The analyses carried out indicated stability of the nanoparticles concerning the amount of bioactive, as the “release” of the action was insignificant after 45 days of storage [47]. Madureira et al. [48] developed stable solid lipid nanoparticles (NLSs) utilizing carnauba wax as a solid lipid matrix for rosmarinic acid administration and subsequent incorporation in food matrices. A high association efficiency was also obtained (approximately 99%). The physicochemical characteristics were preserved after 28 days of cold storage, and no rosmarinic acid migrated to the water medium from nanoparticles, which indicates that the rosmarinic acid has excellent compatibility with the core of carnauba wax NLSs. In a work developed by Arias et al. [49] carnauba wax nanoparticles were used to transport the HIV-gp 140 protein antigen. The results showed that they are capable of inducing strong humoral/noninflammation cellular immune responses in the mucosa and have the potential to be used as anti-HIV vaccines. Carnauba wax NLSs are also being used to develop more effective sunscreens. Carnauba wax is a novel vehicle for chemotherapy medicines such as traditional doxorubicin and the new Quinazolinone derivative. The use of the lipid and surfactant cell membrane has a major effect on particle size, efficiency of imposition, and release percentage. The potential application for cancer medications of SLNPs and substantial effects on conventional and resistant strains of different cell lines [50]. Villalobos-Hernández and Goymann [51] studied the transport of inorganic sunscreens in a carnauba wax and decyl oleate matrix. The encapsulated species had particle sizes between 239 and 750 nm, and the formulations made with them had excellent viscosity and stability, rendering formulations suitable for dermal application of inorganic sunscreens. However, soil nanoparticles (NP) enhance scattering, and the inorganic UV filter (encapsulated in a complicated combination of carnauba wax) absorbs more UV than free TiO2, increasing SPF by up to 50. A sunscreen formulation with carnauba wax and caprylic/capric triglycerides including NLC incorporating an organic UV filter, bemotrizinol (BEMT), was developed using ultrasound technique. The authors [52] indicate a favorable synergism between BEMT and carnauba wax-based nanostructured lipid carrier, supporting an overall enhancement of photoprotective activity which may result in a cost-effective economic benefit.

2.7

Microencapsulation

The microencapsulation system design influenced the physical and oxidative stability, textural properties, and iron entrapment efficiency. Naktinienė and colleagues [53] developed a food-grade microencapsulation system for iron, consisting of

33

Chemistry, Biological Activities, and Uses of Carnauba Wax

883

double emulsions and water-in-oleogel dispersions, which were used as carriers for iron. Iron-containing double emulsions with iron dissolved in the inner water phase demonstrated encapsulation effectiveness greater than 95%. In contrast to systems structured with carnauba wax, water-in-oleogel dispersions solidified with beeswax showed greater firmness (0.6–29.6 N) and encapsulation efficiency (19–100%) values than systems built with carnauba wax. Water-in-oleogel dispersions exhibited a slow rate of lipid oxidation, reaching 20–30 meq/kg peroxide after 60 days. On the other hand, Aliasl Khiabani et al. [54] investigated the possible use of reinforced carnauba wax (CW)-based oleogel with AA in cake and beef burgers. Adding AA to CW-based oleogels created additional intramolecular or intermolecular hydrogen bonds, improving thermal behavior and crystallinity. AA concentrations greater than 3% in oleogel formulations also improved oleogel strength. The optimized sample (cake and beef burger) had appropriate texture, color, and organoleptic qualities. Furthermore, using reinforced oleogel with carnauba wax/adipic acid in bread and meat products may help reduce saturated and trans fats. Nanocarriers have been a global trend, particularly nanostructured lipid carriers (NLC). NLC has significant advantages in their use such as improved therapeutic impact, higher hydration of skin [55], excellent speed of the encapsulated active components, shelf life, and consumer acceptance among others. Several oils, including kenaf seed oil [55, 56], pumpkin oils [57], clove oil [58], previously have been utilized in the manufacture of NLC as cosmetic formulation. Also, various lipid excipients may be utilized in the synthesis of NLCs which include most commonly used vegetable oils and wax (e.g., carnauba wax, beeswax, acetyl palmitate) [59]. The research by Lee et al. [55] and Chu et al. [56] used kenaf seed oil-nanostructured lipid carrier (KSO-NLC) formulations in the production of a novel sunscreen composition as a renewable source. It has shown significant promise to be used in the cosmetic industry due to the functional characteristics of KSO. However, KSO was used to create a novel sunscreen formulation since it is a renewable resource and a possible active component. The use of kenaf seed oil for UV filter encapsulation in the lipid phase of the nanostructured lipid carrier has shown a synergetic effect to improve the photoprotective characteristics of the formulation. Due to their high biodegradability and biocompatibility, films and edible coatings of natural polymers were implied as a promising alternative to traditional plastic packaging. dos Santos et al. [60] found that the optical and barrier characteristics of chitosan films enhanced when carnauba wax (50%) is integrated into the matrix without affecting its optical properties, which are promising in the use as packaging. Carnauba wax was incorporated into chitosan and cashew tree gum films to enhance opacity but decreased WVP and water solubility. However, enhanced gelatin films and natural waxes like beeswax and carnauba wax help prevent food oxidation and deterioration by blocking light and moisture [61]. Bio-based waxes are already gaining popularity among customers due to their many benefits over mineral-based waxes in the food sector. Candelilla wax-CLW, carnauba wax-CRW, rice bran wax (RBW), and beeswax (BW) are typical bio-based waxes used as oleogelators and are widely available. These waxes are easily accessible and may transform liquid oil into an edible oleogel [54, 62–65]. Öğütcü

884

E. J. M. R. Junior et al.

et al. [62] have found that cod liver oil oleogel oxidation has prompted the development of oxidation in carnauba wax, but not beeswax. In addition, they stated that the existence of textural stabilities in 90 days and the stickiness value of Carnauba wax (CW) organogels were greater than that of beeswax (BW) organogels which were shown by the presence of textural stabilities in 90 days. In another research on grapes oleogels produced with carnauba wax and beeswax; on the other hand, the opposite behavior has been observed [65]. As a result, compared to oleogels mainly based on beeswax, carnauba wax has higher melting and crystallization temperatures, as well as higher enthalpies of crystallization and melting, resulting in increased stability against oxidation. Canola oil was incorporated into oleogels with varying amounts of carnauba wax and their performance as a substitute for solid fat was examined for saturated fat-free cheese imitation were analyzed largely for rheological and proton mobility characteristics. In addition, oleogels containing cheese demonstrated nutritional efficiency by substantially reducing the proportion of saturated fat from 0.84 to 0.06 [66]. Recent research has identified carnauba and candelilla waxes as effective organogelators at low concentrations [67]. Despite the outstanding properties of carnauba wax (CW), in particular, its hydrophobicity, the complementing impact of carnauba wax on the improvement of konjac glucomannan (KGM) films has received limited attention to date. KGM is a potential material for the food bio-packaging with outstanding filmforming capabilities, which may further be enhanced by changing its hydrophilic nature with CW. According to Haruna et al. [68], CW-based emulsified composite films (KW) were developed, and the inclusion of CW resulted in both an increase in hydrophobicity (moisture barrier, solubility, and contact angle) and a decrease in opacity characteristics. The hydrophobicity, barrier characteristics, and mechanical properties of KW films were substantially enhanced by increasing the CW content. Carnauba wax is a natural wax with a firm texture and the greatest melting point among wax-based oleogelators used in foods [69]. Various investigations have confirmed the pharmacological activities of carnauba leaves, which include carnauba wax. Oliveira et al. [70] have designed a modified emulsion congealing method to develop new ketoprofen containing a multiparticulate system integrated into the carnauba wax microsphere. Due to their features, carnauba wax microphone products produced by this research are ideal for preparing pharmaceutical forms of permanent release such as ketoprofen tablets and capsules or other medicinal products with identical physicochemical qualities. In this study, carnauba wax microparticles indicate a novel multiparticularly sustained release method for NSAID ketoprofen with a strong potential to be used in other pharmaceutical procedures. Recently, quinine microcrystals with carnauba wax (1:1) were regulated to release under 50 μm by the dry coating technique of the ball mill. The chosen technique may prevent the reduction of coating size in pharmaceutical production. Furthermore, the ball milling method ensured the integrity of the confinement when controlled during the dry coating procedure [71].

33

2.8

Chemistry, Biological Activities, and Uses of Carnauba Wax

885

Pharmaceutical Processing

Many waxes are utilized for ointments, creams, and lotions, including for the production of tablet formulations and tablet coatings by the pharmaceutical industry. In addition to carnauba wax, excipients were also investigated for the modification of the release of drugs in tablets made using the technique of direct compression [72] and for the production of gastroretentive tablets [73]. The research aimed at the production of film-coated products [74, 75], granules [76], and nanoparticles [48, 49]. Nart et al. [77] developed mini-tablets for sustained release of soluble drugs employing melt granulation targeting method to show carnauba wax as a viable excipient. In this study, sustained drug release dosage forms of two completely soluble drugs (captopril and metformin hydrochloride) used mini-tablet formulations. It shows that carnauba wax is a great alternative to promote the prolonged release of mini-tablets and that it reduces the interaction of drug particles with dissolving medium and delays the disintegration medium with drug release rate. A new lycopene-loaded nanostructured lipid carrier (NLC) was constructed by combining carboxymethyl oil palm empty fruit bunch cellulose (CM-OPEFBC), carnauba wax, and palm oil. NLCs improve the drug release profile of an active agent, allowing it to enter more effectively through the skin after it has been administered externally. Lycopene entrapment effectiveness was determined to be 98% for all of the formulations tested. It was discovered that the size distribution, zeta potential, and particle size of the lycopene-loaded NLC had not changed much after being kept at room temperature for 8 weeks. This demonstrated that the formulations had good colloidal stability. The lycopene-loaded NLCs are more effective and sophisticated for the stability and distribution of lycopene in the pharmaceutical sector than their non-loaded counterparts [78]. The superamphiphobic coating is produced by immersing the titanium carboxylate hybrid gel in a fluorosilane-modified titanium carboxylate hybrid gel and carnauba wax solution. Using ammonia vapor, Liu et al. [79] prepared a new superamphiphobic coating that can be switched between superhydrophilicity and superoleophobicity. The coating is then utilized to clean oil effluent and remove bottom water from oil storage tanks using porous materials like cloth and sponge. A study by Carvalho Neto et al. [80] used carnauba wax to preserve methionine microparticles against degradation. However, this research showed improved microencapsulation yield and efficiency, higher degradation temperatures, and improved methionine retention. Melt coating of solids is a well-known technique in the pharmaceutical, food, and chemical industries. Complex solidification is one of the most difficult techniques to employ compared to solvent-based coatings. Furthermore, carnauba wax, beeswax, and palm oil are mixed to alter the agglomeration behavior of the coated product [81].

886

2.9

E. J. M. R. Junior et al.

Pharmacological Activities

2.9.1 Anti-Inflammatory Activity da Rocha et al. [82] developed curcumin-loaded solid lipid microparticles from carnauba wax and tested their anti-inflammatory effects. SEM, DSC, infrared spectroscopy, and X-ray diffraction were used to analyze the microparticles produced by heat homogenization. The anti-inflammatory effect of free curcumin and curcumin encapsulated by carrageenan was tested in rat paw edema. Aside from that, rat plantar tissue was tested for myeloperoxidase activity and nitric oxide concentration. To test for anti-inflammatory effectiveness, researchers used encapsulated curcumin at dosages of 25 and 50 mg kg1, which outperformed free curcumin at the same doses, and free curcumin at 400 mg kg1. They had 16-fold anti-inflammatory effectiveness over free curcumin and excellent encapsulation efficiency.

2.9.2 Antiprotozoal Activity De Almeida et al. [7] demonstrated antiprotozoal activity of “carnauba” wax (type 1 and 4) extracts in hexane and ethanol. The antiprotozoal activity against intracellular amastigotes of Leishmania infantum and trypomastigote forms of Trypanosoma cruzi and Leishmania infantum amastigotes compared with standard drug benznidazole.

2.9.3 Antifungal Activity Copernicia cerifera wax includes proteins such as chitinase and β-1,3-glucanase (26,000 and 24,000 Da) that appear to inhibit the early development of all fungus and induce hyphal morphologic changes to fungi in the presence of these proteins in comparison to control medium development [83]. The automated N-terminal amino acid sequencing was conducted, and the sequences obtained revealed a significant degree of similarity of proteins to class III chitinases and β-1,3 glucanase. The presence of separated proteins inhibited the early development of all fungi (Fusarium oxysporum and Colletotrichum lindemuthianum) on agar plates using the SDSTricine-gel electrophoresis method. Fungal cell walls and β-1,3-glucans strongly indicate a protective function for these hydrolases. Gonçalves et al. [84] reported substantially lowering the incidence of Monilinia fructicola and Rhizopus stolonifer in nectarines and plums with the protective treatment of 4.5% and 9% carnauba wax. However, no mycelial development of M. fructicola was detected at any wax concentration, including both M. fructicola and R. stolonifer no in vitro germination was found at a concentration (above 1%) of carnauba wax. In addition, this wax has tremendous potential for usage in fruits and vegetables without damaging the health or the environment of consumers. da Silva Andrade et al. [1] investigated an antifungal activity against M. canis in aqueous carnauba extract which exhibited moderate antifungal activity against M. canis and T. rubrum inactivity. Due to the bioactive potential of phenolic chemicals and flavonoids, the antifungal effects of the extracts may be responsible.

33

Chemistry, Biological Activities, and Uses of Carnauba Wax

887

2.9.4 Anti-Microbial Activity Wan-Shin Jo et al. [43] investigated CSW/LO nanoemulsion in the storage of microbiological safety in relation to the quality of “Fuji” apples and assessed the coating as a method of extending the shelf-life of apples. By using high-pressure homogenization carnauba-shellac wax (CSW)-based nanoemulsion containing lemongrass oil (LO) was prepared by monitoring the results; it was clearly shown that the CSW-LO coating reduces total aerobic bacteria and yeast and molds on the apple surface for 5 months with regard to quality and microbiological safety. Additionally, CSW-LO showed antibacterial activity against E. coli O157:H7: H7 and L. monocytogenes, two of the most common pathogens.

3

Environmental Application

In recent years the use of electrostatically charged powders has been shown for the formulation of additional crop protection chemicals, such as insecticides and acaricides. The “Entostat” technique is based on micronized wax particles, particularly carnauba wax. Carnauba wax has been demonstrated to be a potentially effective carrier for the development of powder-based entomopathogenic fungus delivery systems [79, 85]. The authors investigated the use of powdered carnauba wax as an electrically charged dust carrier to increase the pathogenicity of fungal spores as a new formulation approach for combating this pest. The authors showed the results to summarize the B. bassiana virulence against adults in L. sericata and to demonstrate the capacity of dust carnauba wax as an electrostatic carrier to improve the insecticide activity of conidium generated by the entomopathogenic fungus. These findings may serve as a basis in the development of field methods for L. sericata management by promoting the dispersion of entomopathogens formed by carnauba wax powder [79]. Carnauba wax has been shown to be useful in the integrated control of blowflies as an ecologically sustainable strategy for reducing over-reliance on chemical pesticides and the danger of resistance to such insecticides (Table 1).

4

Conclusion and Future Directions

Although Copernicia prunifera is now recognized as a typical Brazilian plant with a rising interest in research and increasing the commercial and industrial use of therapeutic products, it could reasonably be claimed that its therapeutic potential was not completely explored. Research and commercial interest in carnauba wax is now directed toward its cosmeceutical, food, and medicinal uses that have undermined research interests as a cure for other diseases. Further investigations into its pharmacological action are thus suggested to elucidate pharmacodynamics, pharmacokinetics, and clinical implications. In addition, greater emphasis must be paid to research on toxicity risk assessments for bioactive extracts and separated components. In addition, because of its apolar nature and UV retention capability, it

Source: Ref. [86]

Physical characteristics Melting point ( C min) Refinement process Samples of carnauba wax in its industrialized form

Origin

Carnauba wax Types

Pó do “Olho” Folha (eye-powder sheet) Light yellow 83  C Filtration

Prime 1 or filtered yellow

Table 1 Brazilian categorization of refined carnauba wax Medium 2 or filtered extra fatty Pó de “Palha” (“straw” powder) Orange-yellow 82.5  C Filtration

Clear 3 or filtered fatty Pó de “Palha” (“straw” powder) Dark orange 82.5  C Filtration

Brown 4 or filtered grey Pó de “Palha” (“straw” powder) Dark brown 82.5  C Filtration

Black 5 or centrifuged grey Pó de “Palha” (“straw” powder) Black 82.5  C Centrifugation

888 E. J. M. R. Junior et al.

33

Chemistry, Biological Activities, and Uses of Carnauba Wax

889

holds promise for the development of dynamic active food packaging applications. Consequently, further studies on its pharmacological actions are needed to understand its pharmacodynamics, pharmacokinetics, and clinical significance. Also, research on toxicity risk assessment of bioactive extracts and isolated components should be emphasized. Nonetheless, further research and long-term human trials are needed to elucidate the connection between cinnamic acid diesters and their beneficial effects on the human body. Acknowledgments The authors are thankful to Coordination for the Improvement of Higher Education Personnel (CAPES)-Brazil and Drug Research and Development Center (NPDM), Federal University of Ceará (UFC), Fortaleza, Brazil.

References 1. da Silva Andrade LB, da Silva Julião MS, Carneiro Vera Cruz R et al (2018) Antioxidant and antifungal activity of carnauba wax powder extracts. Ind Crops Prod 125:220–227 2. de Carvalho FPA, Gomes JMA (2008) Eco-efficiency in the production of Carnaúba wax in the municipality of Campo Maior, Piauí, 2004. Rev Econ Sociol Rural 46:421–453 3. da Ponte IA, Muthuvel M, Saravanabhavan S, Benjamin SR (2020) The phytochemical composition of medicinal plants: Brazilian semi-arid region (Caatinga). In: Rao V, Mans D, Rao L (eds) Phytochemicals in human health. IntechOpen, Rijeka 4. Taube E (1952) Carnauba wax-product of a Brazilian palm. Econ Bot 6:1952 5. Anzenberger C, Li S, Bouzidi L, Narine SS (2016) Synthesis of waxes from vegetable oil derived self-metathesized aliphatic esters. Ind Crops Prod 89:368–375 6. Lozhechnikova A, Bellanger H, Michen B et al (2017) Surfactant-free carnauba wax dispersion and its use for layer-by-layer assembled protective surface coatings on wood. Appl Surf Sci 396: 1273–1281 7. de Almeida BC, Araújo BQ, Carvalho AA, Freitas SD, Maciel DD, Ferreira AJ, Tempone AG, Martins LF, Alexandre TR, Chaves MH, Lago JH (2016) Antiprotozoal activity of extracts and isolated triterpenoids of ‘carnauba’ (Copernicia prunifera) wax from Brazil. Pharm Biol 54 (12):3280–3284. https://doi.org/10.1080/13880209.2016.1224257. Epub 2016 Aug 28. PMID: 27569846 8. Harron AF, Powell MJ, Nunez A, Moreau RA (2017) Analysis of sorghum wax and carnauba wax by reversed phase liquid chromatography mass spectrometry. Ind Crops Prod 98:116–129 9. de Brito CJ, Braz-Filho R, Assunção MV et al (2006) 1H and 13C NMR spectral assignments of four dammarane triterpenoids from carnauba wax. Magn Reson Chem 44:641–643 10. de S Dantas AN, Magalhães TA, Matos WO et al (2013) Characterization of carnauba wax inorganic content. J Am Oil Chem Soc 90:1475–1483 11. Zlokarnik M (2012) Ullmann’s encyclopedia of industrial chemistry, vol 25. Wiley, Weinheim, pp 1–40 12. European Food Safety Authority (2012) Scientific opinion on the re-evaluation of carnauba wax (E 903) as a food additive. EFSA J 10:10 13. Anvisa (2011)Agência Nacional de Vigilância Sanitária Agenda Nacional de Prioridades de Pesquisa em Vigilância Sanitária. Brasília: Núcleo de Educação, Pesquisa e Conhecimento – NEPEC/ANVISA. 1–15 14. FDA (1983) Food and drugs. Chapter 9 – federal food, drug, and cosmetic act. Subchapter II – definitions. Sect. 321 – definitions; generally 15. Triebold HO (1946) Quantitative analysis: with applications to agricultural and food products. D. van Nostrand, New York

890

E. J. M. R. Junior et al.

16. Rufino MSM, Alves RE, de Brito ES et al (2010) Bioactive compounds and antioxidant capacities of 18 non-traditional tropical fruits from Brazil. Food Chem 121:996–1002 17. Bashari A, Koohestani AHS, Salamatipour N (2020) Eco-friendly dual-functional textiles: green water-repellent & anti-bacterial. Fibers Polym 21:317–323 18. Gupta S, Ivvala J, Grewal HS (2021) Development of natural wax based durable superhydrophobic coatings. Ind Crops Prod 171:113871 19. Mahcene Z, Khelil A, Hasni S et al (2020) Development and characterization of sodium alginate based active edible films incorporated with essential oils of some medicinal plants. Int J Biol Macromol 145:124–132 20. de Oliveira Filho JG, de Oliveira Nobre Bezerra CC, Albiero BR et al (2020) New approach in the development of edible films: the use of carnauba wax micro- or nanoemulsions in arrowroot starch-based films. Food Packag Shelf Life 26:100589 21. de Oliveira Filho JG, Albiero BR, Cipriano L et al (2021) Arrowroot starch-based films incorporated with a carnauba wax nanoemulsion, cellulose nanocrystals, and essential oils: a new functional material for food packaging applications. Cellulose 28:6499–6511 22. Eyng C, Nunes KC, Matumoto-Pintro PT et al (2021) Carnauba wax coating preserves the internal quality of commercial eggs during storage. Semin Cienc Agrar 42:1229–1244 23. Fei T, Leyva-Gutierrez FMA, Wan Z, Wang T (2021) Development of a novel soy-wax containing emulsion with enhanced antifungal properties for the postharvest treatment of fresh citrus fruit. LWT Food Sci Technol 141:110878 24. Romani VP, Olsen B, Pinto Collares M et al (2020) Cold plasma and carnauba wax as strategies to produce improved bi-layer films for sustainable food packaging. Food Hydrocoll 108:106087 25. Lufu R, Ambaw A, Opara UL (2020) Water loss of fresh fruit: influencing pre-harvest, harvest and postharvest factors. Sci Hortic 272:109519. https://doi.org/10.1016/j.scienta.2020.109519 26. de Campos A, Claro PC, Luchesi BR et al (2019) Curaua cellulose sheets dip coated with micro and nano carnauba wax emulsions. Cellulose 26:7983–7993 27. Szumała P, Luty N (2016) Effect of different crystalline structures on W/O and O/W/O wax emulsion stability. Colloids Surf A Physicochem Eng Asp 499:131–140 28. Celik N, Torun I, Ruzi M et al (2020) Fabrication of robust superhydrophobic surfaces by one-step spray coating: evaporation driven self-assembly of wax and nanoparticles into hierarchical structures. Chem Eng J 396:125230 29. Celik N, Kiremitler NB, Ruzi M, Onses MS (2021) Waxing the soot: practical fabrication of all-organic superhydrophobic coatings from candle soot and carnauba wax. Prog Org Coat 153: 106169 30. Buitimea-Cantúa GV, Serna-Saldívar SO, Pérez-Carrillo E et al (2021) Effect of quality of carnauba wax (Copernicia cerífera) on microstructure, textural, and rheological properties of soybean oil-based organogels. LWT Food Sci Technol 136:110267 31. Lacroix M, Le Tien C (2005) Edible films and coatings from non-starch polysaccharides. In: Han JH (ed) Innovations in food packaging. Elsevier Academic Press, San Diego 32. Won MY, Min SC (2018) Coating Satsuma mandarin using grapefruit seed extract–incorporated carnauba wax for its preservation. Food Sci Biotechnol 27:1649–1658 33. Yang H, Li X, Lu G (2018) Effect of carnauba wax-based coating containing glycerol monolaurate on decay and quality of sweet potato roots during storage. J Food Prot 81:1643–1650 34. Md Nor S, Ding P (2020) Trends and advances in edible biopolymer coating for tropical fruit: a review. Food Res Int 134:109208 35. Costa JDDS, Neto AF, Almeida FDAC, Costa MDS (2018) Conservation of “Tommy atkins” mangoes stored under passive modified atmosphere. Rev Caatinga 31:117–125 36. Wang D, Huang J, Guo Z, Liu W (2021) Durable mixed edible wax coating with stretching superhydrophobicity. J Mater Chem A 9:1495–1499 37. da Mota WF, Salomão LCC, Cecon PR, Finger FL (2003) Waxes and plastic film in relation to the shelf life of yellow passion fruit. Sci Agric 60:51–57

33

Chemistry, Biological Activities, and Uses of Carnauba Wax

891

38. Rastegar S, Hassanzadeh Khankahdani H, Rahimzadeh M (2019) Effectiveness of alginate coating on antioxidant enzymes and biochemical changes during storage of mango fruit. J Food Biochem 43:e12990 39. Germano TA, Aguiar RP, Bastos MSR et al (2019) Galactomannan-carnauba wax coating improves the antioxidant status and reduces chilling injury of “Paluma” guava. Postharvest Biol Technol 149:9–17 40. Gutiérrez-Pacheco MM, Ortega-Ramírez LA, Silva-Espinoza BA et al (2020) Individual and combined coatings of chitosan and carnauba wax with oregano essential oil to avoid water loss and microbial decay of fresh cucumber. Coatings 10:614 41. da Silva MC, Atarassi ME, Ferreira MD, Mosca MA (2011) Post-harvest quality of “fuyu” persimmon with use of different edible coverage concentrations. Sci Agrotechnol 35:144–151 42. Machado FLC, Costa JMC, Batista EN (2012) Application of carnauba-based wax maintains postharvest quality of “Ortanique” tangor. Food Sci Technol 32:261–268 43. Jo W-S, Song H-Y, Song N-B et al (2014) Quality and microbial safety of “Fuji” apples coated with carnauba-shellac wax containing lemongrass oil. LWT Food Sci Technol 55:490–497 44. Barman K, Asrey R, Pal RK et al (2014) Influence of putrescine and carnauba wax on functional and sensory quality of pomegranate (Punica granatum L.) fruits during storage. J Food Sci Technol 51:111–117 45. Barman K, Asrey R, Pal RK (2011) Putrescine and carnauba wax pretreatments alleviate chilling injury, enhance shelf life and preserve pomegranate fruit quality during cold storage. Sci Hortic 130:795–800 46. Motamedi E, Nasiri J, Malidarreh TR et al (2018) Performance of carnauba wax-nanoclay emulsion coatings on postharvest quality of “Valencia” orange fruit. Sci Hortic 240:170–178 47. Kheradmandnia S, Vasheghani-Farahani E, Nosrati M, Atyabi F (2010) Preparation and characterization of ketoprofen-loaded solid lipid nanoparticles made from beeswax and carnauba wax. Nanomedicine 6:753–759 48. Madureira AR, Campos DA, Fonte P et al (2015) Characterization of solid lipid nanoparticles produced with carnauba wax for rosmarinic acid oral delivery. RSC Adv 5:22665–22673 49. Arias MA, Loxley A, Eatmon C et al (2011) Carnauba wax nanoparticles enhance strong systemic and mucosal cellular and humoral immune responses to HIV-gp140 antigen. Vaccine 29:1258–1269 50. El-Menshawe SF, Sayed OM, Abou Taleb HA et al (2020) The use of new quinazolinone derivative and doxorubicin loaded solid lipid nanoparticles in reversing drug resistance in experimental cancer cell lines: a systematic study. J Drug Deliv Sci Technol 56:101569 51. Villalobos-Hernández JR, Müller-Goymann CC (2005) Novel nanoparticulate carrier system based on carnauba wax and decyl oleate for the dispersion of inorganic sunscreens in aqueous media. Eur J Pharm Biopharm 60:113–122 52. Medeiros TS, Moreira LMCC, Oliveira TMT et al (2020) Bemotrizinol-loaded carnauba wax-based nanostructured lipid carriers for sunscreen: optimization, characterization, and in vitro evaluation. AAPS PharmSciTech 21:288 53. Naktinienė M, Eisinaitė V, Keršienė M et al (2021) Emulsification and gelation as a tool for iron encapsulation in food-grade systems. LWT Food Sci Technol 149:111895 54. Aliasl Khiabani A, Tabibiazar M, Roufegarinejad L et al (2020) Preparation and characterization of carnauba wax/adipic acid oleogel: a new reinforced oleogel for application in cake and beef burger. Food Chem 333:127446 55. Lee XY, Chu CC, Hasan ZABA et al (2019) Novel nanostructured lipid carriers with photoprotective properties made from carnauba wax, beeswax, and Kenaf seed oil. J Am Oil Chem Soc 96:201–211 56. Chu CC, Tan CP, Nyam KL (2019) Development of nanostructured lipid carriers (NLCs) using pumpkin and Kenaf seed oils with potential photoprotective and antioxidative properties. Eur J Lipid Sci Technol 121:1900082

892

E. J. M. R. Junior et al.

57. Chu CC, Hasan ZABA, Chua SK, Nyam KL (2020) Formulation and characterization of novel nanostructured lipid carriers with photoprotective properties made from carnauba wax, beeswax, pumpkin seed oil, and UV filters. J Am Oil Chem Soc 97:531–542 58. de Meneses AC, Marques EBP, Leimann FV et al (2019) Encapsulation of clove oil in nanostructured lipid carriers from natural waxes: preparation, characterization and in vitro evaluation of the cholinesterase enzymes. Colloids Surf A Physicochem Eng Asp 583:123879 59. Galvão JG, Santos RL, Lira AAM et al (2020) Stearic acid, beeswax and carnauba wax as green raw materials for the loading of carvacrol into nanostructured lipid carriers. Appl Sci 10:6267 60. dos Santos FKG, Silva KNO, Xavier TDN et al (2017) Effect of the addition of carnauba wax on physicochemical properties of chitosan films. Mater Res 20:479–484 61. Zhang Y, Simpson BK, Dumont M-J (2018) Effect of beeswax and carnauba wax addition on properties of gelatin films: a comparative study. Food Biosci 26:88–95 62. Öğütcü M, Arifoğlu N, Yılmaz E (2015) Storage stability of cod liver oil organogels formed with beeswax and carnauba wax. Int J Food Sci Technol 50:404–412 63. Lim J, Jeong S, Oh IK, Lee S (2017) Evaluation of soybean oil-carnauba wax oleogels as an alternative to high saturated fat frying media for instant fried noodles. LWT Food Sci Technol 84:788–794 64. Yang S, Yang G, Chen X et al (2020) Interaction of monopalmitate and carnauba wax on the properties and crystallization behavior of soybean oleogel. Grain Oil Sci Technol 3:49–56 65. Yi B, Kim M-J, Lee SY, Lee J (2017) Physicochemical properties and oxidative stability of oleogels made of carnauba wax with canola oil or beeswax with grapeseed oil. Food Sci Biotechnol 26:79–87 66. Moon K, Choi K-O, Jeong S et al (2021) Solid fat replacement with canola oil-carnauba wax oleogels for dairy-free imitation cheese low in saturated fat. Foods 10:1351 67. Mert B, Demirkesen I (2016) Evaluation of highly unsaturated oleogels as shortening replacer in a short dough product. LWT Food Sci Technol 68:477–484 68. Haruna MH, Wang Y, Pang J (2019) Konjac glucomannan-based composite films fabricated in the presence of carnauba wax emulsion: hydrophobicity, mechanical and microstructural properties evaluation. J Food Sci Technol 56:5138–5145 69. Galus S, Gaouditz M, Kowalska H, Debeaufort F (2020) Effects of candelilla and carnauba wax incorporation on the functional properties of edible sodium caseinate films. Int J Mol Sci 21: 9349 70. Oliveira RB, Nascimento TL, Lima EM (2012) Design and characterization of sustained release ketoprofen entrapped carnauba wax microparticles. Drug Dev Ind Pharm 38:1–11 71. Matsumoto A, Ono A, Murao S, Murakami M (2018) Microparticles for sustained release of water-soluble drug based on a containment, dry coating technology. Drug Discov Ther 12: 347–354 72. El-Bagory I, Barakat N, Ibrahim MA, El-Enazi F (2012) Formulation and in vitro evaluation of theophylline matrix tablets prepared by direct compression: effect of polymer blends. Saudi Pharm J 20:229–238 73. Pawar HA, Dhavale R (2014) Development and evaluation of gastroretentive floating tablets of an antidepressant drug by thermoplastic granulation technique. Beni-Suef Univ J Basic Appl Sci 3:122–132 74. Chiumarelli M, Hubinger MD (2014) Evaluation of edible films and coatings formulated with cassava starch, glycerol, carnauba wax and stearic acid. Food Hydrocoll 38:20–27 75. Rodrigues DC, Caceres CA, Ribeiro HL et al (2014) Influence of cassava starch and carnauba wax on physical properties of cashew tree gum-based films. Food Hydrocoll 38:147–151 76. Miyagawa Y (1996) Controlled-release of diclofenac sodium from wax matrix granule. Int J Pharm 138:215–224 77. Nart V, Beringhs AO, França MT et al (2017) Carnauba wax as a promising excipient in melt granulation targeting the preparation of mini-tablets for sustained release of highly soluble drugs. Mater Sci Eng C 70:250–257

33

Chemistry, Biological Activities, and Uses of Carnauba Wax

893

78. Sharma S, Sathasivam T, Rawat P, Pushpamalar J (2021) Lycopene-loaded nanostructured lipid carrier from carboxymethyl oil palm empty fruit bunch cellulose for topical administration. Carbohydr Polym Technol Appl 2:100049 79. Liu W, He Y, Zhang Y, Liu Y, Long L, Shen F, Yang G, Zhang X, Zhang S, Deng S (2020) A novel smart coating with ammonia-induced switchable superwettability for oily wastewater treatment. J Environ Chem Eng 8(5):104164. ISSN 2213-3437. https://doi.org/10.1016/j.jece. 2020.104164 80. Neto JPC, Bezerra LR, da Silva AL et al (2019) Methionine microencapsulated with a carnauba (Copernicia prunifera) wax matrix for protection from degradation in the rumen. Livest Sci 228:53–60 81. Müller MG, Lindner JA, Briesen H et al (2018) On the properties and application of beeswax, carnauba wax and palm fat mixtures for hot melt coating in fluidized beds. Adv Powder Technol 29:781–788 82. da Rocha BA, Francisco CRL, de Almeida M et al (2020) Antiinflammatory activity of carnauba wax microparticles containing curcumin. J Drug Deliv Sci Technol 59:101918 83. Cruz MAL, Gomes VM, Fernandes KVS et al (2002) Identification and partial characterization of a chitinase and a β-1,3-glucanase from Copernicia cerifera wax. Plant Physiol Biochem 40: 11–16 84. Gonçalves FP, Martins MC, Junior GJS et al (2010) Postharvest control of brown rot and Rhizopus rot in plums and nectarines using carnauba wax. Postharvest Biol Technol 58:211–217 85. Meikle WG, Mercadier G, Holst N, Girod V (2008) Impact of two treatments of a formulation of Beauveria bassiana (Deuteromycota: Hyphomycetes) conidia on Varroa mites (Acari: Varroidae) and on honeybee (Hymenoptera: Apidae) colony health. Exp Appl Acarol 46: 105–117 86. Carnaúba R (2004) Técnico de identidade e de qualidade para a classificação da cera de Brasil. Ministério da Agricultura, Pecuária e Abastecimento Gabinete do Ministro Instrução Normativa no. 34, de 30 de novembro de 2004

Index

A Acacia-Commiphora woodlands, 584 Acacia gum, 32, 38, 135–136 Acacia tortuosa gum, 150 Acetone, 27 28-Acetoxy-15α-hydroxymansumbinone, 597 Acid diterpenes, 389 Acid hydrolysis, 251 Acquired immunodeficiency syndrome (AIDS), 508 Acryloylation, 250–251 Activated carbon, 208 Active principles, 294 Adansonia digitata, 39 Adjuvant, 153 Adsorption capacity, 200 Adsorption isotherms, 200, 208 Adsorption kinetics, 201, 208–209 Adsorptive column chromatography, 390 Afro-Brazilian settlements, 707 Agricultural applications, 199, 210–216 Agrohydrogels, 124 Albizia A. chevalieri, 151 A. julibrissin, 151 A. zygia, 152 Albizia gum, 32, 151–153 Alcohol, 27 Alfa amylase inhibitory action, 368 Alismataceae, 706 Alkaloids, 17, 827, 847–849 Almond gum, 162–166 Aloe barbadensis, 152 Aloe vera, 45 gel, 153 gum, 152–154 α-amyrin, 441 α-bisabolol, 600

α-copaene, 441 α-humulene, 731 α-pinene, 440 Alstonia scholaris, 857 Alzheimer’s disease (AD), 511, 539, 540 Alzibia amara, 152 Amazon, 379, 709 Ambroxol hydrochloride, 284 Amino acids, 456 5-Aminosalicylic acid, 164 Amorphous, 206 Amygdalus scoparia, 162 Amylolytic activity of latex, 812 Anacardic acids, 296, 300 Anacardium occidentale, 292, 293 Anaerobic conditions, 209 Analgesic activity, 533 Analgesic effects, 598 Androgen, 464 Anesthetic activity, 598 Angiogenesis, 833 Anionic polysaccharides, 148 Anogeissus latifolia, 139 Anopheles labranchiae, 782 Anti-arthritic effect, 300 Anti-atherosclerotic activity, 462 Antibacterial activity, 366, 673, 887 Anticancer, 463 Anticoagulant, 745 Anti-Dengue virus, 282 Antidepressant activity, 465 Antidiarrheal activity, 537 Antifertility, 465 Antifungal activity, 366, 392, 886 Antihemorrhagic activity, 745 Anti-hemorrhoids, 465 Antihyperglycemic activity, 462 Anti-inflammatory activities, 388, 602, 886

© Springer Nature Switzerland AG 2022 H. N. Murthy (ed.), Gums, Resins and Latexes of Plant Origin, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-91378-6

895

896 Antimicrobial activity, 295, 300, 598, 786 Boswellia serrata, 533–535 carnauba wax, 887 guggul, 463 Antimutagenicity activity, 637 Antineoplastic property, 197 Antineoplastic drug, 443 Antinociceptive effects, 299 Antioxidant, 159, 197 Antioxidant activity asafoetida, 635 Boswellia serrata, 536 carnauba wax, 876 guggul, 462 Antioxidant potential, 365 Antiparasitic activity, 392 Antiplasmodial activity, 546 Antiprotozoal activity, 886 Anti-quorum sensing, 674 Anti-urolithiatic activity, 465 ANVISA, 875 Apis mellifera, 658, 690 Apocynaceae, 846–848, 850–854, 858, 860 Aquaporin-3 (AQP-3), 693 Aqueous-glycolic propolis, 691 Arabinogalactan, 47, 195 Arabinose, 274, 750 Arable soils, 211 Araucaria, 610 A. angustifolia, 612–613 A. araucana, 613–614 A. bernieri, 614 A. bidwillii, 614–615 A. columnaris, 615–616 A. cunninghamii, 616–617 A. heterophylla, 618–619 A. hunsteinii, 619 A. laubenfelsii, 620 A. luxurians, 620 A. montana, 620 A. muelleri, 620 A. nemorosa, 620–621 A. scopulorum, 621 botanical aspects, 611–612 chemistry and biological activities, 612–621 diterpenoids in, 623 lignans in, 624 mono- and sesquiterpenoids in, 622 resins, 611 Arecaceae, 873 Aromatherapy, 583 Arthritis, 449

Index Asafoetida, 630 antimutagenicity activity, 637 antioxidant activity, 635–651 antispasmodic and hypotensive effects, 639–640 anxiolytic and anthelmintic activity, 637 bioactive components, 632–636 blood sugar level property, 636–637 coumarin and derivatives, 632 cytotoxicity and anti-convulsant activity, 638 hepatoprotective activity, 637 hypersensitivity activity, 637 hypochloesteremic effects, 637 neuroprotective effect, 639 relaxant effect, 638–639 secondary metabolites, 636 sulfur containing components, 632–634 traditional uses of, 631–632 Asario, 43 Asthma, 443 Atherosclerosis, 456, 730 Attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR), 70 Avicenna, 690 Azadirachta indica, 155 2,20 -Azino-bis(3-ethylbenzothiazoline-6sulfonic acid (ABTS), 876 Azo dyes, 209

B Bacillus cereus, 599 Bacteria, 301 Badam gum, 32 Balangu, 42 Balsamodendron mukul, 448 Balsams, 13–15 false, 420–427 harvesting methods, 427–428 Liquidambar, 414–417 Styrax, 417–421 Baobab, 45, 46 Barbados, 45 Barbados gooseberry, 46 Barhang, 42 Barks, 27, 28 Basella alba, 41 Basil, 42 Basil seed gum albumin solution, 362 antibacterial effect, 365

Index bile acid-binding, 368 biological properties and uses of, 363–368 cholesterol binding, 368 disintegrating properties, 367 edible coating, 366 foaming stability, 362 gelling, 363 in novel drug delivery system, 368 physical properties, 360–363 prebiotic effect, 365 surface tension, 362 suspending agent for suspension, 367 Bassorin, 137 Batch equilibrium technique, 200 Bengal quince, 45 Benzaldehyde, 563, 567 Benzoic acid, 405, 409 Benzoin resin, 419 anti-allergic activity, 574 anti-asthmatic activity, 565–574 anticonvulsant and sedative activity, 574 anti-inflammatory activity, 574 antimicrobial activity, 573 antioxidant activity, 573 diuretic activity, 572 gastrointestinal activity, 568 hepatoprotective activity, 573 memory enhancer, 573 phytochemistry, 563 in skincare, 566 topical adhesive and antiseptic activity, 574 toxicity profile for, 574 traditional uses of, 574–576 Benzophenones, 747 β-amyrin, 440, 441, 730 β-caryophyllene, 384, 387, 731 Beta cell stimulator, 157 β-bisabolene, 387, 600 β-galactose, 750 β-glycoside bond, 360 β-sitosterol, 197, 726 β-sitosterol-β-D-glucoside, 730 Betulinic acid, 726 Beverages, 277 Bidhi amylase activity, 812 Bile acid, 368 3,800 -Binaringenin-70 -O-beta-glucoside, 737 Binding agent, 159 Biodegradable polysaccharide, 296 Biodegradation, 71, 203 Biodiversity, 702 Bioinformatics analysis, 829

897 Biological activities, 659, 673, 847, 851–854, 860 of latexes, 17 of LBG, 230–232 of propolis, 673–676 Biomaterials, 148 Biomedical applications, plant-based gums bone tissue engineering, 12 drug delivery, 11 wound healing, 11 Biopolymers, 243, 252 Bio-resins, 253 Biowastes, 67 Bissabol, 586 Black benzoin, 573 Body’s oxidative stress, 147 Boswellia, 584 Boswellia serrata analgesic activity, 533 anti-arthritic and anti-inflammatory activities, 540–543 antiasthmatic activity, 536–537 anticancer activity, 537 anticomplementary activity, 537 antidepressant activity, 537 antidiarrheal activity, 537 antihyperlipidemic and antidiabetic activities, 535–536 antimicrobial activity, 533–535 antioxidant activity, 536 antiplasmodial activity, 546 bark, 521 botanical description, 520–521 branded formulations, 548, 549 chemical constituents, 523–531 clastogenic activity, 537 Crohn’s disease and ulcerative colitis, 544–545 diuretic activity, 545–546 flowers, 521 fruits, 521 hepatoprotective activity, 540 immunomodulatory activity, 540, 544 leaves, 521 neuroprotective and anti-Alzheimer’s activities, 539–540 pharmacological activities, 528, 529, 532–547 phytochemistry, 522–534 psoriasis and skin diseases, 544 taxonomy, 521, 522 toxicity studies, 546

898 Boswellia serrata (cont.) traditional uses, 546–548 vernacular names, 521 volatile/essential oil, constituents of, 523–524, 526, 532 Boswellic acids, 523, 535, 538, 542 Boswellin ®, 548 Branched structure, 297 Brazilian green propolis, 663–664 Brazilian red propolis, 664–665 Broom creeper, 46 Brown propolis, 691 BSG-glutathione nanoparticles, 368 Bursera bipinnata, 436 Burseraceae, 434, 448 Bursera copallifera, 436 1,2,3,4-Butanetetracarboxylicdianhydride (BTCA), 124

C Cabraleadiol, 596 Cabreuva balsam, 411–414 Cactus, 47 Cadinene, 450 Caesalpinia pulcherrima gum, 33 Caesalpinia spinosa, 266, 285 Calcium-binding proteins, 152 Calotropis gigantea, 770, 775, 781, 782, 855–857 Calotropis plant latex (CPL) anti-inflammatory, 784 anti-nociceptive properties, 784 anti-tumor activity, 787 antiviral activity, 787 biological activities, 782, 786 chemical constituents, 773, 774 miscellaneous uses, 788 nanoparticles, 788 snake venom antidote, 783 toxicity, 772, 773 wound healing, 785, 786 Calotropis procera, 770–775, 782 Canada balsam, 424–425 Canals, 705 Cancer, 725 Cancer therapy, 812 Candida albicans, 740 Cannabinoid, 387 Canoes, 709 Canola oil, 884 Capsular polysaccharides (CPSs), 89 Carbonyl stretching, 204

Index Carboxymethylation, 248 Carboxymethyl guar gum, 123 Carboxymethyl tara gum (CMTG), 281 Cardenolide, 770, 773, 782, 849–850 Cardioprotective action, 463 Carnauba wax, 873, 874 antifungal activity, 886 anti-inflammatory activity, 886 anti-microbial activity, 886–887 antioxidant activity, 875–876 antiprotozoal activity, 886 environmental application, 887 food packaging, 877–879 food processing, 876–877 fruit coating, 879–880 microencapsulation, 882–884 pharmaceutical processing, 884–885 pharmacological activities, 885–887 post-harvest storage, 880–881 SLM, 881–882 Carnauba wax nano-emulsion (CWN), 877 Carrageenan, 32, 258 Cashew gum, 157–160, 292 botanical description, 292–293 ethnopharmacology, 293–294 phytochemical properties of, 294–298 polysaccharide, 296 preclinical studies, 299–301 Cashew nutshell, 158 Cashew tree, 292 Cassia golden, 42 Cassia gum, 48 Caterpillars, 703 Cationic dyes, 207 Celiac disease, 336 Cellulose gum, 48 Cembrene-A, 450 Cembrenoids, 450 Cerumen, 659 Chamone I, 748 Chamone II, 748 Chañar flour CieLab data, 344 colorimetry, 344 definition, 342 exo-mesocarp, 342 properties, 343 Chañar gum calories, 335 definition, 336, 337 density vs. concentration, 347 diffusion coefficient, 347 fruit, 336, 340

Index FTR, 350 hydrolysis, 345, 352 refractive index, 349 surface tension, 348 thermal extraction, 345, 346 UV-visible spectroscopy, 349 vegetables, 335 viscosity vs. concentration, 347 Cheese, 278 Chemical characterization, 293 Chemical composition, 659, 662, 664, 667, 673, 676, 678 Chemisorption, 202 Cherry juice, 282 Chia, 42 Chitosan (CS), 69, 72 Chlorophyll, 27 Chlorosulfonic acid (CSA)-pyridine, 281 Cholesterol, 601 Chronic bronchitis, 772 Chronic periodontitis, 154 Cinnamic acid, 405, 411, 417, 874, 875, 889 Civet, 582 Clastogenic activity, 537 Clay colloids, 215 Clerodanes, 390 Clusia galactodendron, 718 Clusia latex antihypertensive activity, 745–748 anti-inflammatory and antinociceptive activity, 729–732 antimicrobial and antiparasitic activity, 739–744 anti-obesity and anti-diabetic activity, 734–735 antioxidant activity, 735–738 antitumoral activity, 725–729 anti-venom, antihemorrhagic activity, 744–745 anti-viral activity, 732–734 characterization, 704–708 chemical constituents and biological properties of, 748–755 ethnobotany and traditional uses of, 707–719 in folk medicine, 721–724 ornamental purposes, 720 pharmacological properties of, 724–748 Clusianone, 744 Clusionone A, 729 Clusiparalicoline A, 727 C22 mansumbinanes, 596 13 C NMR, 297, 312

899 Coagulates, 705 Coalescence, 361 Cocculus hirsutus, 41 Codex Mendoza, 437 Cofactor, 211 Coffee, 582 Cold plasma, 878 Collagenase activity, fig latex, 810–812 Colocasia esculenta, 40 Colonial codices, 437 Color, 134, 137, 138, 140, 141 Colorimetric method, 736 Commafric A, 601 Commipherol, 450 Commiphora, 583, 584 C. africana, 601 C. confusa, 602 C. dalzielii, 596, 602 C. habessinica, 587, 601 C. holtziana, 599 C. incisa, 596 maladies of cattle treatment, 587 C. mukul, 448 C. rostrata, 600 safety and efficacy, 602 C. sphaerocarpa, 587, 598 C. tenuis, 601 C. wightii, 448 Complex carbohydrates, 359 Conservation, 602 Constipation, 723 Control release formulation (CRF), 211 Conventional method, 197 Copaiba oils, 378 β-caryophyllene, 387 bioactive diterpenes, 391–393 biosynthesis of terpenes of, 385 chemical composition of, 381–388 diterpenes, 388–393 drilling from tree trunk, 379 humulene, 388 sesquiterpenes, 385–387 uses of, 380 valorization of, 379 Copaifera, 378 C. duckei, 386 C. langsdorffii, 386 C. officinalis, 387 C. paupera, 386 Copal active principles, 436 adhesive, 440 anti-inflammatory, 443

900 Copal (cont.) anti-inflammatory poultice, 439 antimicrobial, 443 antioxidative effect, 442 chemical composition, 440 chemical compounds, 443 chromatography, 442 conservation, copal trees, 435 consistency, 441 cytotoxicity, 443 definition, 434 dioecious, 436 ethnobotany, 436 flavonoids, 440 glyph, 439 interdisciplinary research, 436 livelihoods, 436 Mesoamerican peoples, 437 Nahua people, 439 non-timber forest products, 434 pharmacological properties, 442 phenolic compounds, 443 phytochemistry/biological activity, 436 pneumonia, 439 polygamodioecious, 436 polymerized and oxidized, 440 regional trading networks, 435 resins, 436, 439, 440 scent, 441 traditional management, 436 traditional medicine, 434 volatile liposoluble, 440 Copal blanco, 437 Copal chino, 438 Copalic acid, 393 Copernicia prunifera, 873, 876, 887 Copolymerization, 197 Copper oxide (CuO) nanoparticles, 256 Cordia, 45 Cordia gum, 33 Coronary artery disease, 464 Corrosion inhibitors, 61, 73–74 Cosmetics, 39 Coumarin, 632 Croscarmellose sodium (CCS), 256 Crosslinked guar gum-g-polyacrylate (cl-GG-gPA), 127 Cross-linked Moi gum hydrogel, 203–205 Cross-linker, 199 Cross-linking, 250 Cross-linking density, 215 Crynebacterium diphteriae, 740 Crystalline, 206

Index Culture-specific syndromes, 439 Cumulative release, 214 Curcumagalactomannoside, 162 Cyclooxygenase-2 (COX-2), 511, 784 Cysteine proteases, 785, 788, 809 Cytotoxic activity, 300, 392, 464 Cytotoxicity, 597

D Dammarane triterpenes, 596 Debility, 197 Decoction, 718 Defense proteins, 829 δ-tocotrienilic alcohol, 754 δ-tocotrienolic alcohol, 743 δ-tocotrienol methyl ester, 743 Depolymerization, 150 Derivative thermogravimetry, 150 Dermatitis, 465 Desorption, 202 D-galactose, 195 D-galacturonic acid, 360 Diabetes mellitus, 510 Diarrhea, 600 Diayangambin, 456 Diclofenac sodium, 461 Dietary fiber, 28, 161, 231, 235, 335, 359 Diffusion, 202 Dihydroflavonols, 197 18,19-Dihydroxyclusianone, 733 5,8-Diidroxi-(Z )-γ-tocotrienolic acid, 753 Diluent, 159 Diosgenin, 161 2,2-Diphenyl-1-picrylhydrazyl (DPPH), 876 Distilled water (DW), 244 Diterpenes, 381, 384, 388 copaiba bioactive, 391–393 in copaiba oils, 389 isolation and characterization processes, 390 Diterpenoid chemicals, 827 Diterpenoids A. angustifolia, 612 A. cunninghamii, 617 A. heterophylla, 618 A. laubenfelsii, 620 A. nemorosa, 621 A. scopulorum, 621 Diuretic activity, 545–546 Diverticulitis, 149 Dl-epicatechin, 197 DNA, 211

Index DNA-synthesizing enzymes, 211 Dodecenyl succinic anhydride (DDSA), 70 Dravayas, 449 Drug delivery carrier, 257–259 Drying, 134–136, 140, 142 Dye adsorption, 206 adsorbent amount, 206 adsorption isotherms, 208 adsorption kinetics, 208–209 agitation time, 207 biodegradation study and calculation of half-life, 209–210 initial dye concentration, 206 pH, 206–207 temperature, 207 thermodynamic properties, 209 Dye binding assay, 317 Dye removal, 199, 206 Dye-sensitized solar cells (DSSCs), 252 Dyspepsia, 197

E Edible coating, 142, 234, 235, 879, 880, 883 E-guggulsterone, 450 Ellagitannins (ETs), 272 Electrolytes, 149 Electrospinning, 11 Electrospun fibers, 66 Electrospun nanofibers, 165 Elemental analyzer, 199 Elephantiasis, 197 Ellagic acid, 197 Elovich model, 202 Embalming substance, 690 Emulsification, 362 Emulsifier, 40 Emulsifying agent, 136, 137, 141, 142 Emulsion, 136, 138, 139, 141, 142, 361 Emulsion stability, 136 Endocannabinoid, 387 Endogenous fluid, 772 Endothermic, 209, 217 Enterococcus faecium, 365 Entomopathogens, 887 Entropy, 217 Enzymes, 211 Enzyme test, 29 Epicatechin, 744 3-Epilupeol, 441 Epimeric aryltetralin lignans, 596 7-Epi-nemorosone, 728 Erosion, 214

901 Escherichia coli, 275, 742 Esophageal inflammation, 299 Essential nutrients, 210 Essential oils, 611 A. araucana, 613 A. bidwillii, 615 A. cunninghamii, 617 A. heterophylla, 618 A. luxurians, 620 myrrh, 584 Ethanol-soluble fraction (eSf ), 246 Ethephon, 472 Etherification, 249 Ethnobotanical information, 586 Ethnobotanical usage of Abies balsamea resin, 425 Ethnobotany, 707–719 Ethnopharmacological approach, 747 Ethnopharmacological relevance, 294 Ethnopharmacological uses of fig latex, 814–815 Ethylene glycol di methacrylic acid (EGDMA), 126 Exopolysaccharides (EPSs), 89 Extracellular matrix, 148 Extraction method, 379 Exudate, 293 Exudate gums, 134 Acacia gum, 135–136 dry purification, 135 ghatti gum, 139–141 karaya gum, 138–139 mesquite gum, 141–142 tragacanth gum, 136–138

F False balsams Balsam of Judea, 420–424 Canada balsam, 424–425 Gurjun balsam, 425 Sedum, 426 species of, 422 Farnesoid X receptor (FXR), 460 Fat-free stuff, 363 Febrifuge, 722 Fenugreek glycoside, 162 Fenugreek gum, 34 Fenugreek seed gum, 160–162 Ferula asafoetida, 632, 638, 640 Ferulates, 456, 464 guggulu, 464 fig latex, 810

902 Ficin, 809–810 Fickian diffusion, 214 Ficus carica latex acetylcholinesterase inhibition, 817 amino acids, 808 amylase activity, 812–813 antimicrobial activity of, 816–817 antioxidant capacity, 815 chemical composition, 803–812 collagenase activity, 810–812 cytotoxicity and antiviral activity, 817 economic importance, 818 enzymatic activities isolated and characterized from, 811–812 ethnopharmacological uses of, 814–815 fibrinolytic activity, 810 ficin, 809–810 gum, 808 medications using, 815 organic acids, 807 peroxidase activity, 813 prenyltransferase activity in, 813–814 toxicology, 818 triterpenoids, phytosterols and fatty acids, 805–807 volatile compounds, 803–805 Film/coating qualities, 154 Film formers, 27 Film-forming agent, 156 Films, 61, 68–71, 74 First balsams, 420 Flavonoid content, 363 Flavonoids, 196, 489, 693, 828, 849 Flocculant, 152 Flocculation, 362 Flow properties, 159 Fluro-polymers, 198 Foaming, 141, 142 Folin–Ciocalteu assay, 815 Food, 231 Food additives, 359 Food and Agriculture Organization (FAO), 875 Food and Drugs Administration (FDA), 875 Food industries, 368 Food packaging, 61, 68–70, 74, 877–879 Food preparation, TG breads, 277 cakes, 276 condiment, 278 dairy products, 277 emulsion, 276 frozen desserts, 277 fruit drinks, 276

Index jams, 277 jellies, 277 noodles, 279 pastry, 278 pickles, 278 salad, 278 sauces, 276, 278 seafood, 279 syrups, 276 Food processing, 876–877 Food products, 30 Forced expiratory volume, 166 Fourier transform infrared (FTIR), 68, 199, 204, 350 Frankincense, 582, 598 Free radical initiators, 197, 199, 204 Free radical polymerization, 204 Free radicals, 204 French propolis, 692 Freundlich isotherm, 201 Friedelan-3-one, 746 Fruit coating, 879–880 Fruits/vegetables biomedical properties, 102 color attributes, 100 enzymatic activity, 103 ethylene production, 101 PLW, 92, 97 respiration rate, 101 sensorial properties, 104, 105 shelf life, 92 TA, 98, 99 texture properties, 99, 100 TSS, 98 Fukugetin, 731 Fukugiside, 738 Fungi, 27 Furanogermacranes, 599 Furanosesquiterpenes, 598

G Galactan framework, 296 Galactan units, 296 Galactomannan, 31, 42, 44, 285 Galactomannan polysaccharide, 268, 281 Galactose, 274, 296 Gallic acid, 829 Gamboge, 709 Garcinia resin antibacterial activities, 508 anticancer activities, 509, 510 anti-diabetic activities, 510, 511

Index anti-HIV activities, 508 anti-inflammatory, 511 antimicrobial activities, 490 antioxidants, 490 flavonoids, 489 phytochemicals, 481 terpenoids, 488 xanthones, 481, 486 Gas chromatography, 381 Gas chromatography-mass spectrometry (GC-MS), 661 Gastrointestinal tract (GIT), 281 Gastroprotective effect, 299 Gatifolia, 140 GB1-70 -O-beta-glucoside, 737 Gel, 135, 137, 138, 140, 142 Gelatin, 38 Gelatin-A, 281 Gellan gum, 37, 48 Gel strength, 361 Gene expression, 211 Generally recognized as safe (GRAS), 139, 142, 875 Germacrene D, 440 GG-superabsorbent polymer, 127 Ghatti gum, 33, 139–141 Glass transition temperature, 151 Glazing agent, 164 Global warming ability, 835 Globules, 706 Glucopyranosyl, 195 Glucuronic acids, 204 Glutaraldehyde (GA), 128 Gomphocarpus physocarpus, 858–859 Good manufacturing standards (GMP), 875 Graft copolymer, 147, 198 Grafting, 197–199, 206 MOG, 248–249 reaction, 204 Grandone, 753 Graphene oxide (GO), 66, 67 Green chemistry, 118 Grewia ferruginea, 40, 41 Grewia gum, 33 Grinding, 135, 141 Guar gum, 33, 48, 195 agriculture, 124, 126–128 applications, 119 biodegradable, 126 chemical modifications, 123, 124 chemical structure, 122 definition, 118, 129 dehusking, 121

903 delivery applications, 128 derivatives, 119 drought-tolerant, 120 endosperm, 121 environmental stimuli, 128 extraction, 120 global distribution, 119, 120 hydrogel composites/nanocomposites, 124 in situ grafting polymerization and crosslinking, 129 physical properties, 122 soil amendment, 126, 127 sustained release applications, 124 universal crop, 118 Guggul, 449 antiarthritic activity, 461 anti-atherosclerotic, 462 anticancer, 463 antihyperglycemic, 462 antimicrobial activity, 463 antioxidant, 462 bṛhmaṇa, 461 cardioprotective action, 463 cytotoxic activity, 464 endangered plant, 472 genetic variation, 472 gram-positive, 463 granuloma, 461 guggulosome, 461 Guggulu Shodhana, 449 hyperbole, 473 hypercholesterolemic, 459 hypolipidemic activity, 456 hypotensive, 473 LDL cholesterol, 460 magical, 473 nanoparticle gel, 461 phenylbutazone, 461 prediabetic state, 462 quality of, 449 safety and toxicity, 471–472 scarificant effect, 461 uses of, 466–471 Guggulsterones, 460 Guggultetrols, 456, 457 Gugulipid, 460 Gum arabic (GA), 60, 74, 195 Gum exudates, 194 Gum karaya (GK), 48, 60, 67, 69, 70 Gum kondagogu, 61 Gum mastic, 147 Gummosis, 4 Gummous exudate, 294

904 Gums, 405, 429, 808 applications, 10 biomaterials, 18 chemical compositions, 6 definition, 4 industries, 18 plant based, 9 properties, 7, 8 Gurjun balsam, 425 Guttiferae, 702 Guttiferone E, 729

H Habakhadi, 586 Hematochezia, 196 Haemonchuscontortas, 782 Hakea gum, 34 Hancornia speciosa, 858 Hardwickiic acid, 392 Heartwood, 197 Hepatoprotective activity, 540 asafoetida, 637 benzoin resin, 573 Hepatoprotective effect, 299 Herb, 27 Herbivorous insects, 703 The Herb Queen, 359 Herpesvirus, 733 Heteroderacajani, 782 Heterogeneous, 208 Heterogeneous adsorbent surface, 201 Heteropolysaccharide, 293 Hibiscus mucilage, 40 Hibiscus rosa-sinensis, 46 High energy radiations, 198 High performance liquid chromatography (HPLC) HPLC-DAD, 660 HPLC-MS, 661 HPLC-MSn, 661 High performance thin layer chromatography (HPTLC), 660 Higuchi kinetic model, 257 1 H NMR spectrum of Persian gum, 312 Homoxi region, 719 Honeybees, 658, 659, 666, 667 Human immunodeficiency virus (HIV), 508 Humulene, 388 Hupu gum, 34 Hyaluronic acid, 148 Hydrocolloids, 105, 164, 227, 235 Hydrodistillation, 382

Index Hydrogels, 123, 148, 157, 203 Hydrogen peroxide, 693 Hydrophilicity, 150 Hydrophilic–lipophilic balance (HLB) values, 137 Hydrophobicity, 362 Hymenaea courbaril, 389 Hyperlipidemia, 460 Hyperlipidemic disease, 165 Hypersensitivity activity, 637 Hypertensive rats, 747 Hypochloesteremic effects, 637 Hypocholesterolemic, 161 Hypolipidemic effect, 234 Hypotensive effect, 747

I Immunological modulation, 156 Immunomodulatory potential, 300 Impurities, 135, 138, 141 Incision, 134, 135, 138, 140 Incubator shaker, 200 Industrial applications, 134, 137–139 Inflammation, 449 Inflammatory diseases, 443 Inflammatory signs, 299 Infusion, 718 Injury, 134, 142 Insecticide, 783 Insoluble Dietary Fiber (FDI), 335 International collaboration, 602 Intraparticle diffusion, 202, 209 Intrinsic viscosity, 140, 141 In vitro antioxidant activity of fig latex, 815 Ionic dye groups, 209 Ionic strength, 362 Isomer 2(E)-δ-garcinoic acid, 754 Isoorientin, 732 Isoprene, 705 Isoquercetin, 197, 735 Isotherm, 201 Isovitexin, 736 Isovitexin-20 -O-rhamnoside, 738 Ivy gourd, 43

J Jatropha latex alkaloids, 827, 828 angiogenesis activity of, 833 anti-bacterial screening, 830 anti-fungal activity, 830

Index antioxidant activity, 834 antiviral activities, 831 bioactive compounds isolated from, 827–829 biodiesel feedstock system, 834–836 collagenase activities, 832 cytotoxic activities, 831 defense proteins, 829 flavonoids, 828 hemostatic activity of, 833–834 hunting poison, 834 medicinal uses, 831 mutagenic and antimutagenic activity, 832 phenolic acids, 829 synthesis of green nanoparticles, 836–837 terpenoids, 827–828 wound healing activity, 833 Jatropham, 825, 827 Jatrophine, 825, 827, 830 K Kaempferol, 730 Kaempferol-3-O-alpha-L-rhamnoside, 740 Kaggabba group, 719 Kahli amylase activity, 812 κ-carrageenan, 272, 277 Karaya gum, 34, 138–139 Katira gum, 34 Kaurenoic acid, 392 Kelbsiella pneumoniae, 739 Kenaf seed oil-nanostructured lipid carrier (KSO-NLC), 883 Keratinocyte cell, 692 Khaya gum, 34 Klebsiella pneumonia, 463 Konjac glucomannan (KGM), 271, 884 L Labdane diterpenes, 390, 611, 616, 618 Lacebark, 46 Lactoferrin, 281 Langmuir isotherm, 200–201 Langmuir model, 72 Lanosta-8,24-dien-3-β-ol, 744 L-arabinose, 195 Latex(es), 6, 847–848 alkaloids, 17, 848–849 biological activities, 17 bioactive compounds and biological activities of Apocynaceae species, 850–859 cardenolides, 849–850 chemical composition, 848–850

905 definition, 16 flavonoids, 849 of Jatropha curcas (see Jatropha latex) latex proteins, 850 phenolics, 18 proteins, 18 secondary metabolites, 17 terpenoids, 17 Lathosterol, 601 Laticifers, 705 Leaching, 209 Leaf-cutter ants, 703 Leafless species, 584 Leaves, 27 Leishmaniasis, 755 Lepidium sativum, 40 Leucaena leucocephala gum, 35 Leucaena seed gum, 34 Leucocyanidin, 196, 197 Leucodelphinidin, 196 Light-emitting diode (LED), 67 Light scattering method, 196 Lignanoids, 151 Lignans, 456, 457 Lignocellulosic material, 158 Li-ion batteries, 67, 68 (1!4) Linked xylan backbone, 359 Linseed, 43 Lipid, 456 Lipid metabolic disorders, 449 Liquidambar orientalis, 415 Liquidambar styraciflua, 415 Locust bean gum, 34, 38, 49, 226, 227 acid-based process, 229 applications, 234–236 biological activities of, 230–232 chemistry and composition, 229–230 heat-based process, 229 hydration and solubility, 232 processing of, 227–229 rheological properties, 233 water adsorption isotherm, 234 Lower critical solution temperature (LCST), 128 Low methoxy pectin (LMP), 272 Lupeol, 726, 734 Lyoniresinol, 740

M Maceration, 718 Macronutrients, 210 Macrophages, 833

906 Magnetic nanocarrier systems, 157 Malaria, 741 Male and hermaphrodite flowers, 293 Malic acid, 807 Malva nut gum, 35 Mangifera indica propolis type, 666 Mannose, 274 Mansumbinone, 596 Marin, 197 Mark–Houwink–Sakurada model, 233 Maroons, 709 Matrícula de Tributos, 437 Matrix tablets, 214 Mechanical injury, 293 Mediterranean propolis, 665–666 Medoroga, 461 Meliponini, 659 Meltdown of BSG ice cream, 364 Menthe pulegium oil, 364 Mesquite, 43 Mesquite gum, 141–142 Metallo-collagenases, 810 Methoxyfuranoguaia-9-ene-8-one, 598 Methyl olean-12-en-3-oxo-28-oate, 726 Microbial activities, 209 Microbial attack, 366 Microbial polysaccharides, 89 Microencapsulating agent, 195 Microencapsulation, 136, 363, 882–884 Micro-nucleated polychromatic erythrocytes (MNPCE), 832 Micronutrients loaded hydrogel, 212 kinetic study, 213–214 release study, 213 Microspheres, 195 Microwave-assisted technique, 199, 203, 217 Microwave radiation, 198 Microwave radiation-induced grafting, 198 Microwave reactor, 203 Milky fluid, 703 Mimosa gum, 35 Minimal inhibitory concentration, 300 Minimum fungicidal concentration, 392 Minimum inhibitory concentration, 392 Moi gum, 35, 194 adsorption experiments, 206–209 biodegradation study and determination of half-life, 203 biology habitat and uses of Moi tree, 196–197 chemistry, 195–196 elemental analysis, 204 FTIR, 204

Index nutrient release studies for agricultural applications, 210–216 plant description, 196 polysaccharide gum, modifications of, 197–199 qualitative X-ray diffractometry, 204–205 synthesis of Moi gum hydrogel and experimental plan, 199–202 Moi gum-based hydrogel adsorption isotherms, 200 adsorption kinetics, 201 biodegradation study and determination of half-life, 203 characterization, 199 Elovich model, 202 factors affecting adsorption, 200 Freundlich isotherm, 201 intra-particle diffusion model, 202 Langmuir isotherm, 200–201 pseudo-first-order kinetics, 201 pseudo-second-order kinetics, 202 Temkin isotherm, 201 thermodynamic properties, 202 Moisture barriers, 366 Moisture content, 159 Monolayer adsorption, 208 Monosaccharide composition, 296 Monoterpenes, 384, 804 Monoterpenoids, 587 Morelloflavone, 731, 735 Moringa gum (MOG), 243, 260 acid hydrolysis, 251 acryloylation, 250–251 binding agent, 255–256 biological activities, 251 bio-resins, 253 carboxymethylation, 248 chemistry of, 246–247 cross-linking, 250 drug delivery carrier, 257–259 emulsifying agent, 257 etherification, 249 film-forming agent, 257 gelling agent, 255 grafting, 248–249 physicochemical properties, 247 polymer electrolyte in cells, 252–253 source, collection, isolation, extraction and purification, 244–245 tablet disintegrating agent, 256 thiolation, 249–250 wastewater treatment, adsorbent for, 253–255

Index Moringa oleifera, 243, 244, 246 Moringa oleifera gum, 35 Mucilage content, 367 Mucilages, 4, 361 Mucilaginous fiber, 161 Mucilaginous form, 149 Mucoadhesive, 41 Mucoadhesive polymer, 157 Mucuna gum, 35 Mukulol, 590 Mulder’s chart, 211 Multi-dynamic extraction (MED), 693 Multilayer adsorption, 208 Muscanone, 450 Mutamba, 43 Mutualism, 706 Mycobacterium smegmatis, 740 Myeloperoxidase (MPO) activity, 299 Myiasis, 719 Myrcene, 450 Myroxylon balsams, 406 Myrrh, 582 botanical description, 584 from Commiphora myrrha, 584–585 pharmacological, 583 price of, 583 scented, 583, 586 treating hemorrhoids, 584 Myrrh oleo gum, 35 Myrrhterpenes, 598

N Nano-coating, 364 Nanoemulsions, 877, 887 Nanoparticles, 62–65, 67, 70, 74, 301 Nanostructured lipid carrier (NLC), 883, 885 Natural biodegradable polymers, 154 Natural exudated oil resins, 378 Natural gums (NGs), 26, 243, 248, 255 advantages and disadvantages, 27–30 animal-based, 85 categories, 146 challenges and opportunities, 167–174 definition, 83 edible coating, 91 fruits/vegetables, 92 future research, 41 isolation and purification methods, 90 liquid dosage forms, applications in, 38 marine based, 89 microbial, 89 vs. mucilages, 27–28

907 nutritional contribution of, 149 as pharmaceutical excipients and drug delivery properties, 151–166 pharmaceutical formulations, applications in, 29–32 plant-based, 84, 85 postharvest characteristics, 84, 90 properties and characterization of, 149–151 regulatory status for pharmaceutical formulations, 41–49 semisolid dosage forms, applications in, 38 solid dosage forms, applications in, 38 types, 84, 85 Natural Gums Processing and Marketing Enterprise (NGPME), 583 Natural History of the New Spain, 437 Natural mucilages, 26 advantages and disadvantages, 30 future research, 41 vs. gums, 27–28 liquid dosage forms, applications in, 39–40 in pharmaceutical formulation, 39–47 in semi-solid dosage forms, 41 solid formulations, applications in, 40 Natural polymers, 243 Natural rubber, 808 Neem gum, 29, 35, 155–158 Negative zeta potential, 368 Nemorosone, 728 Nemorosone II, 741 Neotropical region, 703 Neuroprotective effect, 639 Newtonian, 135, 140 Nodules, 134, 140 Nodulocystic acne, 465 Nonadecan-1,2,3,4-tetrol, 456 Non-articulated laticifers (NAL), 772 Non-Fickian diffusion, 214, 257 Non-spontaneous, 217 Nonvolatile long-chain triterpenoids, 440 Nuclear factor kappa beta (NFκB), 784 Nuclear magnetic resonance (NMR), 140, 661–662 Nutraceuticals, 149, 156 Nutrient release, 199, 212, 213, 215, 217 Nutrition management, 210

O O-carboxymethyl-O-hydroxypropyl guar gum (CMHPG), 119 Ocimum basilicum, 162, 360 Ocimum basilicum seed-gum, 359

908 Octanordammarane triterpenes, 597 Oils, 4 Okra, 40, 45 Okra gum, 35 Olean-12-en-3-oxo-28-oic acid, 753 Oleic acid (OA), 283, 807 Oleo-gum resin, 449 Oleoresins, 405, 417, 420, 425 Oligosaccharides, 164 Opopanax, 583, 586 Opoponax anti-settlement activity, 600 human breast cancer cells, 600 larvicidal, 600 Orchis, 47 Orientin, 736 Orthosiphon stamineus, 156

P Pacific propolis type, 664 Parasites, 706 Patamona people, 719 Paya group, 722 Pectin, 29, 38, 49 Pediococcus acidilactisi, 365 Pepper weed, 44 Pereskia aculeata, 40 Periodontal films, 367 Peroxidase activity, fig latex, 813 Peroxidase (POD), 103 Peroxide value, 365 Persian gum, 309 chemical composition, 310 chemical structure, 310–315 coating and packaging, 323–325 emulsification and stabilization, 321–322 encapsulation, 322–323 food applications, 320–326 FTIR analysis, 314 future research, 326 interaction with biomacromolecules, 316–319 in low-fat Iranian white cheese, 325 modification of, 320 molecular weight, 314 monosaccharide composition, 312 NMR spectrum of, 312–314 with polysaccharides, 319 and proteins, 316–319 surface activity, 315–316 texturization, 322 uses, 309

Index Peru, 267, 285 Peru balsam, 407–409 Peruvian carob, 267 Pharmaceutical activity Balsam of Judea, 423 Gurjun balsam, 425 Peru balsam, 409 Sedum, 426 Tolu balsam, 411 Pharmaceutical formulations, 359 advantages and disadvantages of naturally available gums and mucilages for, 30 applications of naturally available gums with sources, 32–37 applications of naturally available mucilages in, 42–47 regularity status of naturally available gums for, 48–49 Pharmaceutical processing, 885 Pharmaceuticals, 136, 138, 139, 275 albizia gum, 151–152 almond gum, 162–166 aloe vera gum, 152–155 cashew gum, 157–160 clinical trials in gum-based products, 167–173 fenugreek seed gum, 160–163 neem gum, 155–157 patents in gum-based products, 166–169 Pharmacological activities Boswellia serrata, 528, 529, 532–547 carnauba wax, 886–887 Phenolic acids, 829 Phenolic compounds, 296 Phenylalanine ammonia-lyase (PAL), 102, 104 Phenylhydrazine, 573 Phlobatannins, 197 Phospholipase A2 (PLA2), 783 Photosensitizer, 198 Phylogenetic groups, 706 Physcion, 197 Physcionanthraxnol B, 197 Physiological loss in weight (PLW), 92 Phytocannabinoid, 387 Phytochemistry benzoin resin, 563 Boswellia serrata, 522–534 Phytomedicines, 358 Phytosterols, 746, 827 Pickering emulsion, 321 Pickle grass, 45 Picropolygamain, 602 Pinocembrin, 692

Index Plant-based gums food industry, 9 nanofibers, 11 pharmaceutical and cosmetic applications, 9 Plant exudate, 208, 326 Plant exudate polysaccharide, 146 Plant resins, 4 Platelet, 462, 464 Poisonous to humans and animals, 597 Pollen, 707 Polyalthic acid, 392 Polyanionic character, 195 Polydispersity index (PDI), 140 Poly(lactic acid) (PLA), 66 Polymer-polymer interaction, 146 Polyphenol oxidase (PPO), 103 Polyphenols, 196, 832 Polypodane, 450 Polyprenylated benzophenones, 727 Polysaccharide-protein complex, 297 Polysaccharides, 4, 146, 750 anionic, 148 gum, 197–199 natural, 147 plant exudate, 146 polymers, 118 swellable, 149 uses, 148 Polyvinyl alcohol (PVA), 124, 283 Pore diffusion, 209 Post-harvest, 878 Post-harvest storage, 880–881 Potassium hydroxide, 390 Prenyltransferase activity, fig latex, 813–814 Preservatives, 30 Proandrogenic activity, 465 Propolis, 658–659, 678, 691 anti-inflammatory, 692 antimicrobial properties, 691 antiviral, 692 applications, 676–677 aspen type, 663–664 biological activities, 673–676 biological properties, 691, 694 Brazilian green, 663–664 Brazilian red, 664–665 chemical composition, 690 composition, 690 GC-MS, 661 HPLC-DAD, 660 HPLC-MS, 661 HPLC-MSn, 661 HPTLC, 660

909 human skin, 692 MED, 693 Mangifera indica, 666 Mediterranean, 665–666 NMR, 661–662 Pacific, 664 plant sources, 667, 668, 678 poplar type, 662–663 production, 690 resins, 666–667 scientific description, 690 standardization, 693 types, 691 uses, 690 Prosopis P. alba, 141 P. juliflora, 141 P. laevigata, 141 P. pubescens, 141 P. velutina, 141 Protease inhibitors, 295 Protein, 750, 775, 779 Prunus P. amygdalus, 164 P. domestica, 151 Pseudo-first-order kinetics, 201 Pseudomonas aeruginosa, 165, 742 Pseudoplastic, 135, 150 Pseudo-second-order kinetics, 202 Psyllium, 44 Puddings, 278 Purification, 135

Q Qodume shirazi seed gum, 35 Qualitative X-ray diffractometry, 204–205 Quechua, 723 Quercetin, 196, 746 Quetiapine fumarate, 284 Quilombo, 720 Quince, 44 Quince seed gum, 36

R Radiation-based modifications, 198 Radiation-induced grafting, 198 Radical chain processes, 165 Radiolysis, 198 RAW 264.7, 597 Red propolis, 691 Relaxant effect, 638–639

910 Release retardants, 27 Remediation, 199, 217 Rennet casein, 364 Resins, 611, 705 A. angustifolia, 612 A. araucana, 613 A. cunninghamii, 617 A. heterophylla, 619 A. scopulorum, 621 applications, 13 balsams, 13–15 definition, 12 oleoresins, 12 varnish and lacquer, 15, 16 Retention index (RI), 441 Rhamnogalacturonoglycan, 138 Rhamnose, 138, 140 Rheological properties, 137 Rheology, 9 Rheumatic-X ®, 548 Rheumatism, 443, 449 RNA, 211 RNA-degrading enzymes, 211 Roots, 28 Rosaceae family, 309 Rubber tree, 802 Ruthenium red, 29 Rutin, 196

S Safed musli, 47 Sage, 44 Sahumar, 723 Salad dressing, 363 Sampsonine N, 729 Saponins, 745, 833 Sea weeds, 27, 29 3,4-Seco-mansumbinoic acid, 596 Sedum, 426 Seed coats, 27, 229 Semi-arid regions, 602 Senna sophera, 42 Sensory parameters, 361 Sesamin, 456 Sesbania gum, 36 Sesquiterpenes, 385–387, 804 Sesquiterpenoids, 587 Shallaki ®, 548 Shatavari, 47 Shear-thinning, 137, 140 Sheep meat, 365

Index Shikimic acid, 807 Shodhanvidhi, 449 Siam benzoin gum, 419 Simulated wound fluid (SWF), 257 Sinomenine hydrochloride (SH-HCl), 128 Skincare products, 583 Skin diseases, 465 Smart drug delivery systems, 147 Smooth muscle relaxing effect, 600 Sodium alginate (SA), 36, 70 Sodium starch glycolate (SSG), 256 Soil moisture, 203 Solid lipid microparticles (SLM), 881–882 Solubility, 215 Soluble Dietary Fiber (FDS), 335 Sonochemical microemulsion, 153 Sorption, 202 Sorting, 134, 137, 141 Spectrophotometry, 442 Spinach, 47 Spinacia oleracea, 40 Sponge, 61, 71–74 Spontaneity, 202 Spray drying, 135, 136, 140 Stabilizers, 27, 29, 38, 359 Stabilizing agent, 136, 141 Staphylococcus aureus, 165, 275, 365 Sterculia foetida gum, 36 Sterculia urens, 138 Steroids, 587 Sterols, 197, 827 Stigmasterol, 827 Stimuli-responsive polymer, 147 Styrax S. benzoin, 560, 563, 565, 573 S. officinalis, 418 S. tonkinensis, 419, 560 Styrax balsams, 417–418 Siam and Sumatra benzoin balsams, 421 Styrax benzoin, 419 Styrax officinalis, 418 Sugars, 28, 456 Sulfated tara gum, 280, 282 Sulfur containing components, 632–634 Sumatra benzoin, 575 Sunscreen, 883 Superoxide dismutase (SOD), 103 Surface activity, 135, 136, 138, 141 Surface morphology, 203 Sustainable extraction, 380 Sustainable utilization, 602 Swellable polysaccharides, 149

Index Syneresis, 361 Synergistic and additive effects, 599 Synergistic effect, 211

T Tabernaemontana ventricosa, 850, 855, 856 Taftoon, 322 Tamarind gum, 36 Tannins, 196, 310 Tapping, 427, 449 Tara T. spinosa, 267 T. tinctoria, 266 Tara galactomannan, 270 Tara gum (TG), 36, 49 acid treatment process, 269 applications, 275, 276 biological activities, 274 carbon NMR, 274 carrageenan, 275 CG/LBG, 270 chemical properties, 274 CMTG, 281 commercial powder, 270 condiments, 275 cosmetic preparation, 284 cosmetics, 282 cream, 275 definition, 267–269 endosperm, 269, 285 food, 283 food-grade, 269 food/pharmaceuticals, 270 food preparation, 276, 282 foundation, 284 frozen foods, 272 hydrolyzed, 282 ice creams, 272 nanoparticles, 282 paper, 283 plant, 267, 274 pods, 269 powder, 269, 270 properties, 269, 271 proton NMR, 274 roasting seeds, 269 seed endosperms, 268 seeds, 267–269 skin, 282 starch, 272 sulfation, 281

911 tablets, 283 toothpaste, 284 tree, 268 uses, 275, 276 water, 283 yogurts, 275 Taro, 47 (+)-T-cadinol, 599 Technical grade, 146 Temkin isotherm, 201 Teniposide, 725 Tensile strength, 366 Terpenoids, 488, 587, 827–828 Tetracycline hydrochloride (TCH), 66, 67 Tetrols, 449 Texture, 138, 139 Thermal stability, 361 Thermal stress, 150 Thermodynamic properties, 209 Thiolation, 249–250 Thromboembolism, 464 Thyroxine, 464 Tincture benzoin, 575 Tissue remodeling, 148 Titratable acidity, 98 Tolu balsam, 410–411 Topical pain relievers, 294 Total flavonoid content (TFC), 103 Total Soluble Solids (TSS), 98 Traditional medicine, 293, 359 Traditional use of cashew gum, 299 Tragacanth, 38, 49 Tragacanth gum (TG), 61, 66, 68, 69, 136–138, 148 Tragacanthin, 137 Transesterification, 835 Transforming growth factor β (TGF-β), 692 Trauma, 709 Tree gums, 60 carbon nanostructures, for energy and environmental applications, 67–68 films, 68–71 greener corrosion inhibitors, 73–74 nanofibers, 65–67 nanoparticles, 62–65 sponges, 71–73 The Tree of Life, 874 Trigonella foenum-graecum, 161 Triiodothyronine, 462 Triterpenes, 746 Triterpenoids, 587 Triton, 460

912 Tropical deciduous forests (TDF), 434 Tropical forest, 718 Tropical regions, 194 True balsams Cabreuva balsam, 411–414 Myroxylon balsams, 406 Peru balsam, 407–409 Tolu balsam, 410–411 Tulsi-seed gum, 364 Tumor necrosis factor-alpha (TNF-α), 511, 539

U Uterine disorders, 439 UV filter, 882 UV radiations, 198 UV-VIS spectrophotometer, 213

V Vaccine adjuvants, 152 Vanillic acid, 829 Vinblastine, 725 Viscosity, 135–142 Viscous emulsion, 233 Vitamin D3, 281, 282 Vitexin-20 -O-rhamnoside, 738 Volatile components, 366 Volatile constituents, 386 Volatile oils, 159, 563 Volatile organic compounds, 295 Volatile organic solvent (VOS), 252 Volkensiflavone, 734

Index W Waimiri-Atroari people, 718, 720 Warts, 812, 814, 815, 817, 819 Water purification, 62 Water retention capacity, 203 Welan gum, 36 Whey protein isolate (WPI), 68 Whipped cream, 364 World Health Organization (WHO), 846 Wound healing, 299, 466, 692, 693, 833 Wounds, 294, 718

X Xanthan gum, 29, 37, 49, 272, 284 Xanthochymol, 729 Xanthones, 481, 709 X-ray diffraction (XRD) analysis, 204 Xylose, 274

Y Yam, 47 Yellow propolis, 691 Yogurt, 363

Z Z-δ-tocotrienoloic acid, 743 Zedo gum, 37 (Z )-γ-tocotrienolic acid, 753 Z-guggulsterone, 450, 464, 590