Plant Antioxidants and Health (Reference Series in Phytochemistry) 3030781593, 9783030781590

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

Halina Maria Ekiert Kishan Gopal Ramawat Jaya Arora  Editors

Plant Antioxidants and Health

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, Mohanlal Sukhadia University, Udaipur, 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. More information about this series at http://www.springer.com/series/13872

Halina Maria Ekiert • Kishan Gopal Ramawat • Jaya Arora Editors

Plant Antioxidants and Health With 144 Figures and 63 Tables

Editors Halina Maria Ekiert Department of Pharmaceutical Botany Jagiellonian University, Medical College Kraków, Poland

Kishan Gopal Ramawat Department of Botany Mohanlal Sukhadia University Udaipur, India

Jaya Arora Department of Botany Mohanlal Sukhadia University Udaipur, India

ISSN 2511-834X ISSN 2511-8358 (electronic) ISBN 978-3-030-78159-0 ISBN 978-3-030-78160-6 (eBook) ISBN 978-3-030-78161-3 (print and electronic bundle) https://doi.org/10.1007/978-3-030-78160-6 © 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

Antioxidants are small molecules, such as tocopherol, ascorbate, selenite, and many more, which occur naturally in fruits, vegetables, and beverages and possess a unique chemical activity that quenches the reactive oxygen species (ROS). ROS can be very harmful for human system as it damages macromolecules and cell components by oxidation reaction. Daily intake of natural antioxidants prevents the occurrence of many cardiovascular, heart, and neurological diseases and extends the life span. Polyphenols and carotenoids are some major bioactive molecule groups which are obtained from plants and play significant role as antioxidants. Currently, various research groups are actively working on various cellular models to evaluate the antioxidant capacity of bioactive molecules and their role in prevention of various ailments. Examples of such compounds are epigallocatechin gallate, a catechin-based flavonoid in green tea leaves, curcuminoids from turmeric, cinnamon extract, and resveratrol from red grapes. In the present COVID-19 pandemic, natural dietary sources rich in antioxidants, such as polyphenols and carotenoids, have been clinically proven to reduce oxidative stress and inflammation, which play important role in progression of COVID-19 severity. Therefore, this is a timely compilation of information as one book. This book aims to provide a comprehensive account of sources of antioxidants, their beneficial activity, mechanism of action of these antioxidants, and their involvement in prevention of various diseases and improvement of general health (anti-aging effect). The chapters are written by wellrecognized group leaders working in this field. The book is divided into four parts: I “Antioxidant Resources,” II “Utilization of Antioxidants,” III “Antioxidants and Health,” and IV “Screening, Preservation, and Determination Methods for Antioxidants,” spread over 29 chapters. The additional attraction of book is the detailed part which gives insights of many analytical methodologies involving diverse instrumental techniques that are being developed for the separation, identification, and quantification of antioxidant compounds with detailed description of certain advanced methods of extraction, such as microwave-, ultrasound-, enzyme-assisted, and supercritical fluid extraction. Microencapsulation methods for food antioxidants and various methods to measure antioxidant activities can be beneficial literature for budding researchers in this field. Besides dietary supplements, the antioxidants play key role in industrial chemicals added during synthesis of synthetic rubber, plastics, and fuels to prevent oxidation, or as preservatives in food and cosmetics. v

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Preface

This aspect is covered in the book by emphasizing role of antioxidants in edible and non-edible active packaging films. The book will be useful for academicians, biotechnologists, researcher, and medical practitioners as well as industries involved in manufacturing of antioxidants-rich dietary supplements. The editors are thankful to all the contributors for their cooperation and patience during the process of publication. The editors are also grateful to the editorial team at Springer, Sylvia Blago, and Johanna Klute for their continued professional expertise and support during book production. Kraków, Poland Udaipur, India Udaipur, India

Professor H. M. Ekiert Professor K. G. Ramawat Dr. Jaya Arora

Contents

Part I

Antioxidant Resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

1

1

Natural Food Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Aniket P. Sarkate, Vaishnavi S. Jambhorkar, and Bhagwan K. Sakhale

3

2

Polyphenols in Herbal Extracts . . . . . . . . . . . . . . . . . . . . . . . . . . . Aleksandra Sentkowska and Krystyna Pyrzyńska

19

3

Grape Polyphenolics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . R. F. Chavan and Bhagwan K. Sakhale

35

4

Betalains as Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Erick L. Bastos and Willibald Schliemann

51

5

Selected Species of Medicinal/Arboreal Mushrooms as a Source of Substances with Antioxidant Properties . . . . . . . . . . . . . . . . . . . Katarzyna Sułkowska-Ziaja, Agata Fijałkowska, and Bożena Muszyńska

6

Antioxidant and Pro-oxidant Activities of Carotenoids . . . . . . . . . Mariana Lucas, Marisa Freitas, Félix Carvalho, Eduarda Fernandes, and Daniela Ribeiro

7

Selenium: Prospects of Functional Food Production with High Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Nadezhda Golubkina, Viktor Kharchenko, and Gianluca Caruso

8

Antioxidant Activity and Fresh Goat Cheese . . . . . . . . . . . . . . . . . Leticia Hernández Galán, Rosa Vazquez-Garcia, and Sandra T. Martín del Campo

9

Extraction of Natural Plant Polysaccharides and Their In Vitro Antioxidant Activities . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Boris Nemzer and Diganta Kalita

10

Poisonous Mushroom (Nonedible) as an Antioxidant Source . . . . . Mustafa Sevindik

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123

149 177

189 205 vii

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11

12

Contents

Antioxidant and Photoprotective Properties of Neotropical Bamboo Species . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Maria Tereza Grombone-Guaratini, Cláudia Maria Furlan, Patricia Santos Lopes, Karine Pires Barsalobra, Vânia R. Leite e Silva, and Paulo Roberto H. Moreno Cultures of Medicinal Plants In Vitro as a Potential Rich Source of Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Halina Maria Ekiert, Paweł Kubica, Inga Kwiecień, Karolina Jafernik, Marta Klimek-Szczykutowicz, and Agnieszka Szopa

Part II

Utilization of Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . .

13

Applications of Antioxidants: A Review . . . . . . . . . . . . . . . . . . . . . Neeti Mehla, Aditi Kothari Chhajer, Kanishka Kumar, Shefali Dahiya, and Vanshika Mohindroo

14

Plant Antioxidants from Agricultural Waste: Synergistic Potential with Other Biological Properties and Possible Applications . . . . . M. Carpena, P. Garcia-Oliveira, A. G. Pereira, A. Soria-Lopez, F. Chamorro, N. Collazo, A. Jarboui, J. Simal-Gandara, and M. A. Prieto

15

Natural Antioxidants Used in Meat Products . . . . . . . . . . . . . . . . . Jéssica Souza Ribeiro, Larissa Kauly Rosa Silva, and Marcondes Viana da Silva

16

Antioxidants in Health and Disease with Their Capability to Defend Pathogens that Attack Apple Species of Kashmir . . . . . . . Ashfaq Ahmad Shah and Amit Gupta

Part III 17

18

Antioxidants and Health

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

The Role of Natural Antioxidants in Reducing Oxidative Stress in Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Najmeh Kaffash Farkhad, Majid Asadi-Samani, Fatemeh Asadi-Samani, and Hossein Asadi-Samani The Cytoprotective Activity of Nrf2 Is Regulated by Phytochemicals (Sulforaphane, Curcumin, and Silymarin) . . . . . . Nancy Vargas-Mendoza, Eli Mireya Sandoval-Gallegos, Eduardo O. Madrigal-Santillán, Mauricio Morales-Martínez, Marvin Antonio Soriano-Ursúa, Marcelo Angeles-Valencia, Ángel Morales-González, Jacqueline Portillo-Reyes, and José Antonio Morales-González

231

267

311 313

343

381

411

437

439

455

Contents

19

20

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Current Evidence for Disease Prevention and Treatment by Protocatechuic Acid (PCA) and Its Precursor Protocatechuic Aldehyde (PCAL) in Animals and Humans . . . . . . . . . . . . . . . . . . Ewa Widy-Tyszkiewicz Reduction of Oxidative Stress in Human Body via Inhibitory Effect of Plant Phenolics on Circulating Neutrophils: Results of In Vitro and In Vivo Studies . . . . . . . . . . . . . . . . . . . . . . . . . . . . Piotr Nowak, Michał Nowak, and Dariusz Nowak

21

Anti-inflammatory Effects of Different Dietary Antioxidants . . . . Anirban Roy, Sourav Das, Indranil Chatterjee, Sukanta Roy, and Runu Chakraborty

22

The Beneficial Role of Natural Antioxidants in Alleviating Neuroinflammatory Disorders Including Neurodegeneration Mamali Das and Kasi Pandima Devi

23

24

545 573

....

599

Beneficial and Detrimental Effects of Antioxidants in Allergic Contact Dermatitis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Radoslaw Spiewak and Danuta Plichta

619

Vitamin E: The Wonderful “One-for-All” Gift of Health . . . . . . . . Siti Syairah Mohd Mutalip

661

Part IV Screening, Preservation, and Determination Methods for Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 25

507

Extraction and Assessment Methods as Well as Resources of Natural Antioxidants in Foods and Herbs . . . . . . . . . . . . . . . . . . . Ao Shang, Min Luo, Ren-You Gan, Bang-Yan Li, Hang-Yu Li, and Hua-Bin Li

26

Antioxidant Activity and Capacity Measurement . . . . . . . . . . . . . Esra Capanoglu, Senem Kamiloglu, Sema Demirci Cekic, Kevser Sozgen Baskan, Asli Neslihan Avan, Seda Uzunboy, and Resat Apak

27

Recovery and Purification of Antioxidant Compounds from Plant Origin Agro-Industrial By-products . . . . . . . . . . . . . . . . . . . Fatih Mehmet Yılmaz, Ahmet Görgüç, and Esra Gençdağ

677

679

709

775

28

Microencapsulation Methods for Food Antioxidants . . . . . . . . . . . Büşra Gültekin Subaşı, Beyza Vahapoglu, and Esra Capanoglu

799

29

Plant Antioxidants and Antimicrobials in Edible and Non-edible Active Packaging Films . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Vassiliki Oreopoulou and Theofania Tsironi

837

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

861

About the Editors

Professor Halina Maria Ekiert is Head of Chair and Department of Pharmaceutical Botany in the Pharmaceutical Faculty, Medical College, Jagiellonian University, Kraków (Poland), since 2015. Her scientific career was associated first with the Pharmaceutical Faculty at Medical Academy in Kraków (Poland) and after reorganization (since 1993) with the Pharmaceutical Faculty at Medical College of Jagiellonian University. In the years 1999–2014, she was acting Head of Chair and Department of Pharmaceutical Botany. The areas of her scientific interests are associated mainly with pharmaceutical sciences with strong background in plant biotechnology, phytochemistry, analysis of natural products, and biological activity of plant secondary metabolites. Her biotechnological interests include medicinal and/or cosmetic plant in vitro cultures, endogenic production of bioactive plant secondary metabolites, and biotransformations of exogenic substrates in in vitro cultures. Coumarins, phenolic acids, flavonoids, schisandra lignans, phenylpropanoid glycosides, iridoids, catechins, glucosinolates, and arbutin are the special objects of her interest. Throughout her career, Prof. Ekiert received postdoctoral internships at German universities (Bonn – 1993, Würzburg – 1998, and Marburg am Lahn – 2000, two trainings). The trainings in Bonn and in Marburg were supported by DAAD – German Academic Exchange Service. Her scientific achievements include more than 130 published articles with total number of citation of approximately 1480 and H-index of 24 (according to Web of Science), a few book chapters (published by Springer, Science Publisher, and Studium Press), and the role of co-editor and/or editor at Springer

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About the Editors

Nature and also guest-editor with the MDPI journal – Molecules. Prof. Ekiert has collaborated with Würzburg University, and she currently collaborates with Technical University of Braunschweig (Germany), the University of Messina (Sicily, Italy), and the University of Split (Croatia). She is academic teacher with extensive and broad experience in pharmaceutical botany, plant biotechnology, and phytochemistry. She has guided PhD students and candidates for habilitation in the field of plant biotechnology. Prof. Dr. Kishan Gopal Ramawat is a former professor and head of the Botany Department, M.L. Sukhadia University, Udaipur, India, and has longstanding research experience. He received his PhD in plant biotechnology in 1978 from the University of Jodhpur, India, and afterwards joined the university as a faculty member. In 1991 he moved to the M.L. Sukhadia University in Udaipur as associate professor and became professor in 2001. He served as the head of the Department of Botany (2001–2004, 2010–2012); was in charge of the Department of Biotechnology (2003–2004); was a member of the task force on medicinal and aromatic plants in the Department of Biotechnology, Government of India, New Delhi (2002–2005); and coordinated UGC-DRS and DST-FIST program (2002–2012). Prof. Ramawat completed his postdoctoral studies at the University of Tours, France, from 1983 to 1985, and later returned to Tours as visiting professor (1991). He also visited the University of Bordeaux 2, France, several times as visiting professor (1995, 1999, 2003, 2006, 2010), and in 2005, he went to Poland in an academic exchange program (2005). Through these visits in France, Prof. Ramawat and Prof. Mérillon established a strong connection, which has resulted in productive collaborations and several book and reference work publications. Prof. Ramawat has published more than 170 wellcited peer reviewed papers and articles, and edited several books and reference works on topics such as the biotechnology of medicinal plants, secondary metabolites, bioactive molecules, herbal drugs, and other

About the Editors

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topics. His research was funded by several funding agencies. In his research group, Prof. Ramawat has supervised doctoral thesis of 25 students. He is an active member of several academic bodies, associations, and editorial boards of journals. Dr. Jaya Arora, assistant professor, Department of Botany, Mohanlal Sukhadia University, Udaipur, has been teaching botany since 2012. She obtained her MSc and PhD in botany, with specialization in plant tissue culture and secondary metabolite production, from Mohanlal Sukhadia University. She was awarded the Maharana Fateh Singh Award in 2000 for meritorious performance during her matriculation and the Gargi Award and Scholarship for matriculation by the Government of Rajasthan, India, 2000. Dr. Arora joined the Council of Scientific & Industrial Research (CSIR) NET–JRF in 2008. She has been working the past 14 years on production of useful metabolites from medicinal plants using biotechnological methods and published 25 papers in journals of repute. This work is funded by various funding agencies such as UGC, CSIR, and RUSA, MHRD. Currently, she is supervising five PhD students. Dr. Arora has co-authored one comprehensive textbook for UG students entitled Molecular Biology and Plant Biotechnology and co-edited one international reference book entitled Medicinal Plants: Domestication, Biotechnology and Regional Importance, published by Springer International Publishing.

Contributors

Marcelo Angeles-Valencia Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico Resat Apak Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Avcilar, Istanbul, Turkey Turkish Academy of Sciences (TUBA), Cankaya, Ankara, Turkey Fatemeh Asadi-Samani Student Research Committee, Shahrekord University of Medical Sciences, Shahrekord, Iran Hossein Asadi-Samani Student Research Committee, Shahid Beheshti University of Medical Sciences, Tehran, Iran Majid Asadi-Samani Cellular and Molecular Research Center, Basic Health Sciences Institute, Shahrekord University of Medical Sciences, Shahrekord, Iran Cancer Research Center, Shahrekord University of Medical Sciences, Shahrekord, Iran Asli Neslihan Avan Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Avcilar, Istanbul, Turkey Karine Pires Barsalobra Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo, Diadema, São Paulo, Brazil Erick L. Bastos Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil Esra Capanoglu Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Maslak, Istanbul, Turkey M. Carpena Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain Gianluca Caruso Department of Agricultural Sciences, University of Naples Federico II, Naples, Italy Félix Carvalho UCIBIO, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal xv

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Contributors

Runu Chakraborty Department of Food Technology and Biochemical Engineering, Jadavpur University, Kolkata, West Bengal, India F. Chamorro Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain Indranil Chatterjee Department of Surgical Oncology, Saroj Gupta Cancer Centre and Research Institute, Thakurpukur, Kolkata, West Bengal, India R. F. Chavan Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India N. Collazo Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain Shefali Dahiya Sri Venkateswara College, University of Delhi, New Delhi, India Mamali Das Department of Biotechnology, Alagappa University [Science Campus], Karaikudi, India Sourav Das School of Pharmacy, The Neotia University, Sarisha, West Bengal, India Marcondes Viana da Silva Department of Exact and Natural Sciences (DCEN), State University of Southwest Bahia (UESB), Itapetinga, Brazil Sema Demirci Cekic Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Avcilar, Istanbul, Turkey Halina Maria Ekiert Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland Eduarda Fernandes LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal Agata Fijałkowska Faculty of Pharmacy, Department of Pharmaceutical Botany, Jagiellonian University Medical College, Kraków, Poland Marisa Freitas LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal Cláudia Maria Furlan Departamento de Botânica, Instituto de Biociências, Universidade de São Paulo, São Paulo, Brazil Leticia Hernández Galán Zentrela Inc., Hamilton, ON, Canada Ren-You Gan Research Center for Plants and Human Health, Institute of Urban Agriculture, Chinese Academy of Agricultural Sciences, Chengdu, China

Contributors

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P. Garcia-Oliveira Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolonia, Bragança, Portugal Esra Gençdağ Department of Food Engineering, Faculty of Engineering, Aydın Adnan Menderes University, Aydın, Turkey Nadezhda Golubkina Laboratory Analytical Department, Federal Scientific Center of Vegetable Production, Moscow, Russia Ahmet Görgüç Department of Food Engineering, Faculty of Engineering, Aydın Adnan Menderes University, Aydın, Turkey Maria Tereza Grombone-Guaratini Núcleo de Pesquisa em Ecologia, Instituto de Botânica -SMA/SP, São Paulo, Brazil Büşra Gültekin Subaşı Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Istanbul, Turkey Cumhuriyet University, Hafik Kamer Ornek MYO, Sivas, Turkey Amit Gupta Department of Biotechnology, Graphic Era (Deemed to be) University, Dehradun, India Karolina Jafernik Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland Vaishnavi S. Jambhorkar Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India A. Jarboui Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain Najmeh Kaffash Farkhad Immunology Research Center, Mashhad University of Medical Science, Mashhad, Iran Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran Diganta Kalita Department of Research and Development, VDF FutureCeuticals, Inc., Momence, IL, USA Senem Kamiloglu Science and Technology Application and Research Center (BITUAM), Bursa Uludag University, Gorukle, Bursa, Turkey Viktor Kharchenko Laboratory of Selection and Seed Production of Green, Spice and Flower Crops, Federal Scientific Center of Vegetable Production, Moscow, Russia Marta Klimek-Szczykutowicz Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland

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Contributors

Aditi Kothari Chhajer Department of Botany, Sri Venkateswara College, University of Delhi, New Delhi, India Paweł Kubica Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland Kanishka Kumar Sri Venkateswara College, University of Delhi, New Delhi, India Inga Kwiecień Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland Vânia R. Leite e Silva Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo, Diadema, São Paulo, Brazil Bang-Yan Li Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China Hang-Yu Li Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China Hua-Bin Li Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China Patricia Santos Lopes Departamento de Ciências Farmacêuticas, Universidade Federal de São Paulo, Diadema, São Paulo, Brazil Mariana Lucas LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal Min Luo Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China Eduardo O. Madrigal-Santillán Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico Sandra T. Martín del Campo School of Science and Engineering, Tecnologico de Monterrey, Querétaro, Qro, Mexico Neeti Mehla Department of Botany, Sri Venkateswara College, University of Delhi, New Delhi, India Siti Syairah Mohd Mutalip Faculty of Pharmacy, Universiti Teknologi MARA (UiTM) Selangor Branch, Puncak Alam Campus, Selangor, Malaysia Vanshika Mohindroo Sri Venkateswara College, University of Delhi, New Delhi, India

Contributors

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Ángel Morales-González Escuela Superior de Cómputo, Instituto Politécnico Nacional, Mexico City, Mexico José Antonio Morales-González Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico Mauricio Morales-Martínez Licenciatura en Nutrición, Universidad Intercontinental, Mexico City, Mexico Paulo Roberto H. Moreno Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, Brazil Bożena Muszyńska Faculty of Pharmacy, Department of Pharmaceutical Botany, Jagiellonian University Medical College, Kraków, Poland Boris Nemzer Department of Research and Development, VDF FutureCeuticals, Inc., Momence, IL, USA Department of Food Science and Human Nutrition, University of Illinois at UrbanaChampaign, Urbana, IL, USA Dariusz Nowak Department of Clinical Physiology, Medical University of Lodz, Lodz, Poland Michał Nowak Radiation Protection, University Hospital No 2, Medical University of Lodz, Lodz, Poland Piotr Nowak Department of Nephrology, Hypertension, and Kidney Transplantation, Medical University of Lodz, Lodz, Poland Vassiliki Oreopoulou School of Chemical Engineering, Laboratory of Food Chemistry and Technology, National Technical University of Athens, Athens, Greece Kasi Pandima Devi Department of Biotechnology, Alagappa University [Science Campus], Karaikudi, India A. G. Pereira Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolonia, Bragança, Portugal Danuta Plichta Department of Experimental Dermatology and Cosmetology, Jagiellonian University Medical College, Krakow, Poland Jacqueline Portillo-Reyes Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico M. A. Prieto Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain

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Contributors

Centro de Investigação de Montanha (CIMO), Instituto Politécnico de Bragança, Campus de Santa Apolonia, Bragança, Portugal Krystyna Pyrzyńska Department of Chemistry, University of Warsaw, Warsaw, Poland Daniela Ribeiro LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal Jéssica Souza Ribeiro Center for Science and Technology in Energy and Sustainability (CETENS), Federal University of Recôncavo of Bahia (UFRB), Feira de Santana, Brazil Anirban Roy Department of Food Technology and Biochemical Engineering, Jadavpur University, Kolkata, West Bengal, India Sukanta Roy School of Pharmacy, The Neotia University, Sarisha, West Bengal, India Bhagwan K. Sakhale Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India Food Technology Division University Department of Chemical Technology (UDCT), Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India Eli Mireya Sandoval-Gallegos Centro de Investigación Interdisciplinario, Área Académica de Nutrición, Instituto de Ciencias de la Salud, Universidad Autónoma del Estado de Hidalgo, Pachuca, Mexico Aniket P. Sarkate Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India Willibald Schliemann Leibniz Institute of Plant Biochemistry, Department of Secondary Metabolism, Halle (Saale), Germany Aleksandra Sentkowska Heavy Ion Laboratory, University of Warsaw, Warsaw, Poland Mustafa Sevindik Bahçe Vocational School, Department of Food Processing, Osmaniye Korkut Ata University, Osmaniye, Turkey Ashfaq Ahmad Shah Department of Life Sciences (Microbiology), Graphic Era (Deemed to be) University, Dehradun, India Ao Shang Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, China Larissa Kauly Rosa Silva Federal University of Western Bahia (UFOB), Barreiras, Brazil

Contributors

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J. Simal-Gandara Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain A. Soria-Lopez Nutrition and Bromatology Group, Analytical and Food Chemistry Department, Faculty of Food Science and Technology, University of Vigo, Ourense, Spain Marvin Antonio Soriano-Ursúa Academia de Fisiología Humana, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico Kevser Sozgen Baskan Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Avcilar, Istanbul, Turkey Radoslaw Spiewak Department of Experimental Dermatology and Cosmetology, Jagiellonian University, Medical College, Krakow, Poland Katarzyna Sułkowska-Ziaja Faculty of Pharmacy, Department of Pharmaceutical Botany, Jagiellonian University Medical College, Kraków, Poland Agnieszka Szopa Department of Pharmaceutical Botany, Jagiellonian University, Medical College, Kraków, Poland Theofania Tsironi Department of Food Science and Human Nutrition, Laboratory of Food Process Engineering, Agricultural University of Athens, Athens, Greece Seda Uzunboy Department of Chemistry, Faculty of Engineering, Istanbul University-Cerrahpasa, Avcilar, Istanbul, Turkey Beyza Vahapoglu Department of Food Engineering, Faculty of Chemical and Metallurgical Engineering, Istanbul Technical University, Maslak, Istanbul, Turkey Nancy Vargas-Mendoza Laboratorio de Medicina de Conservación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico Rosa Vazquez-Garcia School of Science and Engineering, Tecnologico de Monterrey, Querétaro, Qro, Mexico Ewa Widy-Tyszkiewicz Department of Experimental and Clinical Pharmacology, Centre for Preclinical Research and Technology CePT, Medical University of Warsaw, Warsaw, Poland Fatih Mehmet Yılmaz Department of Food Engineering, Faculty of Engineering, Aydın Adnan Menderes University, Aydın, Turkey

Part I Antioxidant Resources

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Natural Food Antioxidants Aniket P. Sarkate, Vaishnavi S. Jambhorkar, and Bhagwan K. Sakhale

Contents 1 2 3 4

Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Free Radicals and Oxidative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Oxidative Stress . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Antioxidants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Vitamin C (Fig. 2) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Vitamin E (Fig. 3) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.3 Lycopene (Fig. 4) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.4 β- Carotene (Fig. 5) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.5 Gallic Acid (Fig. 6) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.6 Catechin (Fig. 7) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.7 Resveratrol (Fig. 8) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.8 Glutathione (Fig. 9) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.9 Coumarin (Fig. 10) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.10 Selenium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Antioxidants in Human Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

4 5 6 7 7 8 8 9 10 10 11 11 12 12 12 15 15

Abstract

Due to increasing awareness about various effects of antioxidants, it has become an essential part to understand and thoroughly study the various antioxidants and their biological effect on day to day lifestyle. Oxidative stress being major A. P. Sarkate · V. S. Jambhorkar Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India B. K. Sakhale (*) Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India Food Technology Division University Department of Chemical Technology (UDCT), Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India © Springer Nature Switzerland AG 2022 H. M. Ekiert et al. (eds.), Plant Antioxidants and Health, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-78160-6_32

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problem these days leading to chronic diseases. The lean towards natural products is tremendously increased due to the revolution around us. Hence, “non chemical” or plant-derived aspect of living is accepted. In this chapter, basics of study starts with definition of antioxidants, knowledge of free radical, combating mechanism of antioxidants, generation of oxidative stress due to disproportion of free radical and antioxidants have been explained. Various antioxidants along with their sources are also included. Importance of antioxidants in living, a wellbeing state is studied which may prove to be useful in the future as well. Research and development in this particular field has led its roots deep down. Most attention is paid towards oral administration, such as fruits, vegetables, etc., in order to achieve the desired benefits. Therefore, it is vital to include food rich in antioxidant in our diet. Keywords

Antioxidants · Free radicals · Oxidative stress · Carotenoids · Flavonoids · etc.

1

Introduction

Due to the increasing awareness about the foodstuff consumption, the culinary skills have more bent towards the health promoting aspect of life. Today’s world demand for chemical free products, even in food and other aspects as cosmetics, pharmaceuticals, etc. Hence, wave of natural products is emerging the new trends. Natural products have a rich history in terms of nontoxic, non-harming but potent effect. Contemporary research on antioxidants has been significantly seen in food. Customer has become more interested by “NON-CHEMICAL” antioxidants in food [1]. Antioxidant is defined as, “Any substance that, when present at low concentrations compared to those of an oxidisable substrate, significantly delays or prevents oxidation of that substrate” [2]. Antioxidants obtained from herbs and spices such as turmeric [3], parsley piert [4], bushes which used as additives in jellies [5]; day to day used common vegetables such as potatoes [6], white cabbage [7], dried tomatoes [8], ginger [9]; and fruits such as grapes [10], blueberries, and strawberries [11]. There are many other sorts of things rich in antioxidants. It is observed that in processing such as drying, freeze drying of fruits and vegetables, the antioxidant property will be affected. Hence, maximum optimization is practiced in industries like dietary fiber [12, 13]. Main mechanism of antioxidants is to balance the free radical that causes oxidation of protein, carbohydrates, lipid, and nucleic acid. Mechanism malfunctioning causes many dangerous diseases like cancer, atherosclerosis, diabetes, etc. which are worst age-prone diseases [14]. Generation of free radical is due to the uncoupled flow of electrons or unpaired valence electron in an atom, molecule, or ion. Considering oxygen as a main reactive element, many subspecies such as reactive oxygen species (ROS), include superoxide (O2
), peroxyl (ROO), hydroxyl (HO), nitric oxide (NO), alkoxyl (RO), etc. are most dreadful free radicals which affects the cell directly [15]. Similarly, nitrogen-

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Fig. 1 Classification of antioxidants [17]

centered free radicals also exist. Further, these free radicals become nonreactive free radical such as hydrogen peroxide, peroxy nitrate, etc. though free radicals played significant role in biological evolution, but still works as scavengers today. The toxic effect of these radicals is highly remarkable [16]. In this chapter, details about free radicals, oxidative stress, information about antioxidants and their mechanism are discussed. Increasing awareness about antioxidants made people more inquisitive of how to implement in lifestyle in order to see the provoking health benefit effects (Fig. 1).

2

Free Radicals and Oxidative Stress

Free radicals can be generated by natural or man-made radiation when humans are exposed. For example, intensification of hydroxyl radical is observed when gamma rays split water inside the body leading to horrifyingly reaction with whatever next which is difficult to get rid of. Similarly, oxygen free radical can also be generated by body when they react with the normal oxygen molecule (O2), for example, adrenaline, etc. or when there is an excess action of phagocytes against foreign material. This leads to diseases such as rheumatoid arthritis etc. [18]. When two radicals react, a covalent bond is formed as seen in O2- react with nitric oxide radical (NO) which form nonradical peroxynitrite. As observed, most of the radicals are nonradicals; hence, they react and form a new radical which leads to chain reaction. For example, peroxidation of lipids, which is a major manufacturing concern as a result in

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Table 1 Natural defensive mechanism by human body [19] Damage area DNA(OH
, etc.) PROTEINS(ROS, OH
) Lipids(ROS)

Repair system Removal by enzymes with processes like excision, resynthesis, and rejoining of DNA strands. Removal by enzymes like methionine reductase and cellular proteases. Chain breaking antioxidants like tocopherols, etc.

rancidity [19]. Some antioxidants have also proven to be helpful. Breakage of DNA strand is also observed with base pair. The damage rate is more than the recovery rate and hence, one of the lethal effect of oxygen radicals [20]. Naturally occurring free radicals are the random reaction in various organelles in the cell. Mitochondria, power house of cell is one of the contributors. In the electron transport chain, namely, complex I (NADH dehydrogenase) and complex III (ubiquinone cytochrome c reductase) are the foremost site for the production of superoxide radicals. Formation of reduced form of coenzyme Q (QH2) is consequence of the transfer of electrons from complex I or II to coenzyme Q or ubiquinone (Q). The reduced form QH2 redevelops coenzyme Q via an unstable intermediate semi Quinone anion (*Q
) in the Q-cycle. Formed *Q
immediately transfers electrons to oxygen molecule results in the formation of superoxide radical. Superoxide increases the production of reactive oxygen species (ROS). H2O2, O2
*, OH*, and NO are some of the radicals generated by peroxisomes. ROS is also generated by endoplasmic reticulum in body [21]. Human body has natural defensive mechanism against these free radicals as listed below (Table 1):

3

Oxidative Stress

In oxidative stress, disproportion among free radicals and antioxidants causes damage. It is mostly observed in mitochondria due to the vigorous reaction going in organelles. Some symptoms include spontaneous mutations, aging, etc. [22]. Various harmful diseases includes inflammatory diseases (vasculitis glomerulonephritis, lupus erythematous, adult respiratory distress syndrome), ischemic diseases (heart disease, stroke, intestinal ischemia), hemochromatosis, acquired immunodeficiency syndrome (AIDS), emphysema, organ transplantation, gastric ulcers, hypertension and preeclampsia, neurologic diseases (multiple sclerosis, Alzheimer’s disease, Parkinson disease, amyotrophic lateral sclerosis, muscular dystrophy), alcoholism, smoking-related diseases, and many others [23]. Main reason is depletion of antioxidants in the body or a buildup of ROS. The natural mechanism to control oxidative stress is by redox balance, transcription factors, and structural proteins. But still several damages are observed in DNA, protein, and lipids. • Damage occurring in DNA:- Accumulation of ROS can affect DNA in numerous ways, such as degradation of bases; ss or ds DNA breakage; purine, pyrimidine,

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or sugar-bound modifications; mutations, deletions, or translocations; and crosslinking with proteins. This change leads to carcinogens, aging, cardiovascular diseases, etc. For example, at transcription factor binding site, there is development of 8-OH-G DNA which changes the expression of the particular genes. • Damage occurring in proteins:- ROS can lead to shattering of peptide chain, modification of electrical charge of proteins, cross-linking of proteins, and oxidation of specific amino acids and consequently leads to amplified exposure to proteolysis by degradation by specific proteases. More prone to oxidation are cysteine and methionine residues in proteins. Metal catalyzed oxidation is more prone in enzymes with metals close to active sites which showed alteration in activities. • Damage occurring in lipids:- Interruption in lipid bilayer membrane by ROS which induces lipid peroxidation outcomes in inactivation of membrane-bound receptors, enzymes, and rise tissue permeability. Inactivating cellular protein by forming cross linkage is ability of MDA and unsaturated aldehydes. 4-Hydroxy2-nonenal has proven to activate epidermal growth factor receptor [EGFR] and induces fibronectin production. Isoprostanes and thiobarbituric acid are some of the products of lipid peroxidation, which act as an indirect biomarker of oxidative stress [24]. Moreover, the part of antioxidants is very essential in order to combat free radical and oxidative stress. Several kinds of antioxidants are existing within body. There are various enzymatic and nonenzymatic antioxidants. Former are endogenous antioxidants, which are produced by body while later exist as food supplement to the body. Example include enzymatic- Superoxide Dismutase (SOD), Catalase (CAT), etc. and nonenzymatic-Vitamins, flavonoids, etc. [25]. Enzymatic antioxidants contribute to first-line defense whereas the nonenzymatic antioxidant contributes to second-line defense [26].

4

Antioxidants

4.1

Vitamin C (Fig. 2)

NAME:-Vitamin C or Ascorbic acid CLASS: - Vitamins Fig. 2 Structure of Vitamin C [27]

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CHEMICAL NAME:
2-oxo-L-threo-hexono-1,4-lactone2,3-enedio STRUCTURAL CHEMISTRY:- The chief dietary forms of vitamin C are Lascorbic and dehydroascorbic acid. Stability of ascorbic acid is impacted by pH. It is highly stable between pH 4 and 6. Affected by degree of heating, surface area exposed to water, oxygen, pH, and presence of transition metals. Exist in L and D forms [28]. MODE OF ACTION:- Chain termination reaction or by reaction with other radicals [29] APPLICATION:- Prevents scurvy, vasodilation in bronchial and coronary arteries, etc. [30] SOURCES: - Broccoli, white cabbage, cauliflower [31].

4.2

Vitamin E (Fig. 3)

NAME: - Vitamin E or Tocopherols CLASS:- Vitamins CHEMICAL NAME:- 2-methyl-2-(40 ,80 ,120 -trimethyltridecyl)-chroman-6-ol(parent compound) [33] STRUCTURAL CHEMISTRY:- Exist in four forms α, β, γ, δ in which α- tocopherol is mostly effective as antioxidants [34]. Chromone group is responsible for the antioxidant activity of molecule, while the kinetics of transport and retention within membranes is regulated by the phytyl group largely [35]. MODE OF ACTION:- Peroxyl radical scavenger [34] APPLICATION:- Inhibits the oxidation of low-density lipoprotein cholesterol [36]. SOURCES: - Soybean, Oats, Corns, Evening primrose oils, etc. [37]

4.3

Lycopene (Fig. 4)

NAME:- Lycopene CLASS:- Carotenoids

Fig. 3 Structure of Vitamin E [32]

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CHEMICAL NAME:- Ψ,Ψ-Carotene [39] STRUCTURAL CHEMISTRY:- It is an aliphatic hydrocarbon with 13 double bond in the structure. It doesn’t have vitamin A activity as expressed by other carotenoid. It is the longest carotenoids due to eleven conjugated carbon-carbon double bond [40]. MODE OF ACTION:- –Singlet oxygen quenching, peroxyl radical scavenging [41] APPLICATION:- In atherosclerosis, cardio-vascular diseases [42], as anti-cancer, etc. [43] SOURCES:-Watermelon, tomatoes, etc. [44]

4.4

β- Carotene (Fig. 5)

NAME:- β-carotene CLASS:- Carotenoid CHEMICAL NAME:- β, β-carotene [38] STRUCTURAL CHEMISTRY:- Contributes to form vitamin A in body [46] MODE OF ACTION:- Singlet oxygen quenching [47] APPLICATION:- Reduces risk in lung cancer [48] SOURCES:-Mango, etc. [49]

Fig. 4 Structure of Lycopene [38]

Fig. 5 Structure of β-carotene [45]

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Gallic Acid (Fig. 6)

NAME:- Gallic Acid CLASS:- Polyphenols [51] CHEMICAL NAME: - 3, 4, 5-trihydroxybenzoic acid [52] STRUCTURAL CHEMISTRY:- It is a planar molecule, with four stable conformers. The presence of hydroxyl group and any other functional group determines the antioxidant activity [50]. MODE OF ACTION: - Acting as an electron donor or hydrogen atom donor [50] APPLICATION:- Anti-inflammatory, Anti mutagenic, Anticancer [53, 54] SOURCES:-Longan seed, mango kernel [54]

4.6

Catechin (Fig. 7)

NAME:- Catechin CLASS:-Flavonoids [56] CHEMICAL NAME:- 2-(3,4-dihydroxyphenyl)-3,4-dihydro-2Hchromene-3,5,7triol [57] STRUCTURAL CHEMISTRY:- Position and number of hydroxyl group in the moiety determines antioxidant activity. Presence of catechol moiety and unsaturation increases activity in catechins. (+) catechin is more effective [58]. MODE OF ACTION:- Inhibits lipid peroxidation [59] Fig. 6 Structure of Gallic acid [50]

Fig. 7 Structure of Catechin [55]

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APPLICATION:- Anti-allergic, Anti-inflammatory, Antiviral, Anti-proliferative, and Anti-carcinogenic activities [60] SOURCES:- Apples, hops, tea, beer, etc. [60]

4.7

Resveratrol (Fig. 8)

NAME:- Resveratrol CLASS:- Stilbenes [61] CHEMICAL NAME:- 3, 40 , 5 trihydroxystilbene [62] STRUCTURAL CHEMISTRY:- Resveratrol exist in cis as well as trans form isomers [62]. It has three pKa values as 6.4, 9.4, and 10.5. pH affects activity of the molecule [63]. MODE OF ACTION:- Increases plasma antioxidant activity and decreases lipid peroxidation [64] APPLICATION:- Anti-inflammatory, Neuroprotective, and Antiviral properties [65] SOURCES: - Peanuts, Mulberries, Grapes [65]

4.8

Glutathione (Fig. 9)

NAME:- Glutathione CLASS:- Thiols [67] CHEMICAL NAME:- (GSH)γ-glutamylcysteinylglycine [68] Fig. 8 Structure of Resveratrol [61]

Fig. 9 Structure of Glutathione [66]

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Fig. 10 Structure of Coumarin [70]

STRUCTURAL CHEMISTRY:- It is low molecular weight thiol. There are variations as per the species [69]. Due to presence of peptide bond, it doesn’t undergo hydrolysis [68] MODE OF ACTION:- Glutathione peroxidase mechanism [69] SOURCES:- Mushroom etc. [66]

4.9

Coumarin (Fig. 10)

NAME:- Coumarin CLASS:- Coumarins CHEMICAL NAME:- 1,2-benzopyrone [70] STRUCTURAL CHEMISTRY:- They show chemical similarities with flavonoids and classified depending on the benzene and lactone ring present. Promising antioxidant activity is due to the benzopyrone ring [71]. MODE OF ACTION:- Free radical scavenger [72] APPLICATION:- Anti- Inflammatory [73], Anti-cancer, Anti-coagulant, Antiviral etc. [72]. SOURCES:- Bilberry, cloudberry, green tea, etc. [71].

4.10

Selenium

NAME:- Selenium. CLASS:- Minerals [74] STRUCTURAL CHEMISTRY:- Contributes mainly as selenoprotein or selenoenzyme [75] Selenium possess high reactivity and essential for the protein in the plasma [76]. MODE OF ACTION:- Combines with several enzymes and protein and show variable activity [74]. APPLICATION:- Useful in heart diseases, cancer [74] SOURCES:- Fish, egg, meat, legumes, etc. [77]

5

Antioxidants in Human Health

Due to the benefits of natural product over any other, various fruits, vegetables, herbs, spices, condiments, etc. have been taken into consideration knowing their curative properties. Many chronic diseases can be cured with the use of naturally derived antioxidants. Ecstasy of disease-free life is more by using nature as a basis of

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treatment. Nature-derived antioxidants have shown promising effects in many illnesses such as diabetes, cancer, neurological disorder, obesity, etc. There are various objective that should be considered during antioxidant therapy which are listed below:1. Has oxidative impairment been involved within the disease pathophysiology? (Amplified lipid peroxidation or oxidation of protein or DNA should be associated with the disease). 2. Is the oxidative activity act as an essential pathophysiological feature of the disease? (As sometimes it is the offshoot generated by common tissue damage and cell loss, hence, if not the major cause, the resulting impairment may cause avoidable morbidity). 3. Are there known defects in antioxidant status? 4. Where is the place at which oxidative damage occurs? (May be intracellular, extracellular or in membranes or else lipoproteins) 5. Will the antioxidant reach that area? (The amount of antioxidants should be sufficient to reach protected areas such as CSF, etc.) 6. Will the chosen antioxidant hit the target? (For example, preventive antioxidants are more potent in iron-dependent lipid peroxidation but fails for iron-independent reactions.) 7. Can the antioxidant be given and tolerated in the necessary doses? 8. Is antioxidant therapy “safe”? [78]. After understanding question one can predict the use of antioxidants in diseases. Many such are reported such as use of tomato extract in hypertension. Hypertension is most widely spread diseases which affect billions of people over the globe. Types are grade I–II. Any one medication merely controls the patients’ blood pressure (BP), weather the disease is considered mild to moderate. Hence, two or more drugs along with the alteration of lifestyle are done. The termination is associated with adverse effects in patients. Hence, focus over natural products provokes much faster these days. Antioxidant vitamin has shown to improve vascular function, as a result, daily supply may reduce the threat of BP values. Tomato (Lycopersicon esculentum Mill.) is a source of vitamins and carotenoids. Tomato juice (rich in lycopene) also showed greater than before resistance against low-density lipoprotein (LDL) to oxidation in type 2 diabetic individual [79]. Natural antioxidants are suitable drug for the deteriorating bugs such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) as there are complex targets as well as pathways associated and pathogenesis is complex. Natural antioxidants had protecting effects on neuron in neurodegenerative diseases. Oxidative stress causes nerve cell death which leads to stroke, trauma, and diseases such as AD and PD. Flavonoids, polyphenols and nicotine were effect natural antioxidants against these diseases. As per reports, Ginkgo-Biloba extract (EGb) provide defense against hypoxic damage and inhibit ROS formation in cerebellar neurons. The flavonoid such as ginkgolides and biolobalids were useful. The powerful action against several diseases such as atherosclerosis, the diseases

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associated with postmenopausal estrogen deficiency, the cancer associated with breast and prostate which depends on hormones is shown by the soy isoflavones. It was reported that genistein showed protection against neurons [80]. The major causes of deaths are due to cancer. Around 13% of mortality is due to cancer and if continue will reach in the year 2030 to 1.1 crores. It becomes a very vital consideration reducing cancer affected patients. Studies showed that the sufficient consumption of fruits and vegetables, specifically carotenoid-rich diet decreased the risk of more than a few types of cancers. Antioxidants like α-carotene, lutein, lycopene, β-cryptoxanthin, β-carotene, and α-Tocopherol has shown an inverse relationship to lung cancer. The oral, pharynx, and larynx cancer were prevented by the use of β-carotene. More than half of the oral and throat cancers were reduced by ingestion of natural substances. A study also showed that 40–50% risk of cancer was lowered due to high intake of fruits and vegetables. Colon cancer risk was reduced due to the consumption of vegan diet (Active plus high sources of natural antioxidants) [81]. Oxidative stress plays a major part in both Type 1 as well as Type 2 diabetes pathogenesis. Oxidation of LDL has increased the risk of atherosclerosis with people with diabetes. Higher markers of oxidation and lipid peroxides are more common in diabetic patients. Oxidation stress leads to more breakage of DNA strands and oxidized pyrimidines in Type 1 patients as compared with normal subjects. Elevation of blood glucose level is observed in altered purines. A major source of free radicals is linked with diabetic complication, i.e., is glycation finish products. As a result, many alterations are seen, such as the release of superoxide, reduction in the glutathione levels [82]. After cancer, cardiovascular diseases (CVDs) are prominent reason of death. Flavonoids prove to be boon in CVDs as a reduction in the mortality rate was observed in Western country such as Europe and the United States. Oxidation makes the etiology of CVDs difficult. Endothelial cell injuries and deleterious vasodilator effects are primarily caused by oxidative stress. Antioxidant polyphenol lead to improvement in endothelial functions, hence, play a very important role. In vitro studies show that flavonoids extracted from Euterpeoleracea pulp showed atheroprotective effect. Various other diseases such as obesity, aging, inflammatory bowel diseases, cataract [83], renal disorders, infertility, pregnancy, etc. [84] also showed promising results when natural antioxidants came into the picture. Change in the standard of living, food habits, pollution, and stress, we are further intended towards ROS-induced oxidative stress even though the presence of endogenous antioxidants mechanism. Diseases more than 100 are reported not less due to ROS. This leads us to explore more about the antioxidants present naturally. Proper understanding the development of antioxidants leads to enormous research and treatment in various disorders associated. Food which is prime asset of bioactive compounds and antioxidants should be added to our body nourishment which is the best advice provoking to the better life. Ongoing research and development about antioxidants may pave a path in therapeutic analysis of antioxidants for better treatment of tomorrow. Role of antioxidants in human health can become additional apparent [84].

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Conclusion

The various aspects of antioxidants with examples are explained in the above discussion. There is increasing proof that consumption of a variety of antioxidant present in natural foods might lower the danger of significant health illnesses owing to their antioxidant activity, among different mechanisms. Variation in the mechanism gives every antioxidant a unique way to combat the oxidative stress and manage free radicals within body. The main cause of oxidative stress in the body and various diseases are discussed as well. The classification of antioxidants gives us a brief idea about the structural summary and proper information on the individual. Due to the increasing need of natural products and “NON–CHEMICAL” approach, industries are more optimized in the process as well as consumption from daily food intake. Natural antioxidants have a huge way to pave and more development will lead to a healthy life and save lives.

References 1. Peschel W, Sánchez-Rabaneda F, Diekmann W, Plescher A, Gartzía I, Jiménez D, LamuelaRaventós R, Buxaderas S, Codina C (2006) An industrial approach in the search of natural antioxidants from vegetable and fruit wastes. Food Chem 97:137–150 2. Halliwell B, Gutteridge JM (1995) The definition and measurement of antioxidants in biological systems. Free Radic Biol Med 18:125–126 3. Tangkanakul P, Auttaviboonkul P, Niyomwit B, Lowvitoon N, Charoenthamawat P, Trakoontivakorn G (2009) Antioxidant capacity, total phenolic content and nutritional composition of Asian foods after thermal processing. Int Food Res J 16:571–580 4. Hamad I, Erol-Dayi Ö, Pekmez M, Önay-Uçar E, Arda N (2010) Antioxidant and cytotoxic activities of Aphanes arvensis extracts. Plant Foods Hum Nutr 65:44–49 5. Périno-Issartier S, Zill-E-Huma A-VM, Chemat F (2010) Solvent free microwave-assisted extraction of antioxidants from sea buckthorn (Hippophae rhamnoides) food by-products. Food Bioprocess Techno 4:1020–1028 6. Brown CR (2005) Antioxidants in potato. Am J Potato Res 82:163–172 7. Kusznierewicz B, Śmiechowska A, Bartoszek A, Namieśnik J (2008) The effect of heating and fermenting on antioxidant properties of white cabbage. Food Chem 108:853–861 8. Giovanelli G, Zanoni B, Lavelli V, Nani R (2002) Water sorption, drying and antioxidant properties of dried tomato products. J Food Eng 52:135–141 9. Chan E, Lim Y, Wong S, Lim K, Tan S, Lianto F, Yong M (2009) Effects of different drying methods on the antioxidant properties of leaves and tea of ginger species. Food Chem 113:166–172 10. Kanner J, Frankel E, Granit R, German B, Kinsella JE (1994) Natural antioxidants in grapes and wines. J Agric Food Chem 42:64–69 11. Shebis Y, Iluz D, Kinel-Tahan Y, Dubinsky Z, Yehoshua Y (2013) Natural antioxidants: function and sources. Food Nutr Sci 04:643–649 12. Chang C, Lin H, Liu Y (2006) Comparisons on the antioxidant properties of fresh, freeze-dried and hot-air-dried tomatoes. J Food Eng 77:478–485 13. Borchani C, Besbes S, Masmoudi M, Blecker C, Paquot M, Attia H (2011) Effect of drying methods on physico-chemical and antioxidant properties of date fibre concentrates. Food Chem 125:1194–1201 14. Dryáková A, Pihlanto A, Marnila P, Čurda L, Korhonen HJT (2010) Antioxidant properties of whey protein hydrolysates as measured by three methods. Eur Food Res Technol 230:865–874

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15. Gülçin I (2011) Antioxidant activity of food constituents: an overview. Arch Toxicol 86:345–391 16. Fang Y, Yang S, Wu G (2002) Free radicals, antioxidants, and nutrition. Nutrition 18:872–879 17. Shahidi F, Ambigaipalan P (2015) Phenolics and polyphenolics in foods, beverages and spices: antioxidant activity and health effects – a review. J Funct Foods 18:820–897 18. Halliwell B (1996) Antioxidants in human health and disease. Annu Rev Nutr 16:33–50 19. Halliwell B, Murcia MA, Chirico S, Aruoma OI (1995) Free radicals and antioxidants in food andin vivo: what they do and how they work. Crit Rev Food Sci 35:7–20 20. Jenkins RR (1988) Free radical chemistry. Sports Med 5:156–170 21. Phaniendra A, Jestadi DB, Periyasamy L (2014) Free radicals: properties, sources, targets, and their implication in various diseases. Ind J Clin Biochem 30:11–26 22. Sies H (2000) What is oxidative stress? Developments in cardiovascular medicine oxidative stress and vascular disease. Springer, Boston, MA, pp 1–8 23. Mccord JM (2000) The evolution of free radicals and oxidative stress. Am J Med 108:652–659 24. Birben E, Sahiner UM, Sackesen C, Erzurum S, Kalayci O (2012) Oxidative stress and antioxidant defense. WAO J 5:9–19 25. Finaud J, Lac G, Filaire E (2006) Oxidative stress. Sports Med 36:327–358 26. Sindhi V, Gupta V, Sharma K, Bhatnagar S, Kumari R, Dhaka N (2013) Potential applications of antioxidants – a review. J Pharm Res 7:828–835 27. Schuler P (1990) Natural antioxidants exploited commercially. In: Hudson BJF (ed) Food antioxidants. Elsevier applied food science series. Springer, Dordrecht 28. Naidu KA (2003) Vitamin C in human health and disease is still a mystery? An overview. Nutr J 2(1):7 29. Bendich A, Machlin L, Scandurra O, Burton G, Wayner D (1986) The antioxidant role of vitamin C. Adv Free Radical Biol Med 2:419–444 30. Padayatty SJ, Katz A, Wang Y, Eck P, Kwon O, Lee J, Chen S, Corpe C, Dutta A, Dutta SK, Levine M (2003) Vitamin C as an antioxidant: evaluation of its role in disease prevention. J Am Coll Nutr 22:18–35 31. Podsędek A (2007) Natural antioxidants and antioxidant capacity of Brassica vegetables: a review. LWT 40:1–11 32. Azzi A, Stocker A (2000) Vitamin E: non-antioxidant roles. Prog Lipid Res 39:231–255 33. Eitenmiller R, Lee J (2004) Vitamin E: food chemistry, composition, and analysis. Marcel Dekker, New York 34. Traber MG, Atkinson J (2007) Vitamin E, antioxidant and nothing more. Free Radic Biol Med 43:4–15 35. Burton GW, Traber MG (1990) Vitamin E: antioxidant activity, biokinetics, and bioavailability. Annu Rev Nutr 10:357–382 36. Thiel R (2000) Natural vitamins may be superior to synthetic ones. Med Hypotheses 55:461– 469 37. Shahidi F (2000) Antioxidants in food and food antioxidants. Nahrung 44:158–163 38. Britton G (1996) Carotenoids. In: Hendry GAF, Houghton JD (eds) Natural food colorants. Springer, Boston 39. Müller L, Caris-Veyrat C, Lowe G, Böhm V (2015) Lycopene and its antioxidant role in the prevention of cardiovascular diseases—a critical review. Crit Rev Food Sci 56:1868–1879 40. Srivastava S, Srivastava AK (2013) Lycopene; chemistry, biosynthesis, metabolism and degradation under various abiotic parameters. J Food Sci Technol 52:41–53 41. Stahl W, Sies H (2003) Antioxidant activity of carotenoids. Mol Aspect Med 24:345–351 42. Riccioni G, Scotti L, Di Ilio E, Bucciarelli V, Ballone E, De Girolamo M, Bucciarelli T (2011) Lycopene and preclinical carotid atherosclerosis. J Biol Regul Homeost Agents 25:435–441 43. Hamid AA, Aiyelaagbe OO, Usman LA, Ameen OM, Lawal A (2010) Antioxidants: its medicinal and pharmacological applications. Afr J Pure Appl Chem 4:142–151 44. Collins J, Arjmandi B, Claypool P, Perkins-Veazie P, Baker R, Clevidence B (2004) Lycopene from two food sources does not affect antioxidant or cholesterol status of middle-aged adults. Nutr J 3:15

1

Natural Food Antioxidants

17

45. Jergensen K, Skibsted LH (1993) Carotenoid scavenging of radicals. Z Lebensm Unters Forsch 196:423–429 46. Bugianesi R, Salucci M, Leonardi C, Ferracane R, Catasta G, Azzini E, Maiani G (2004) Effect of domestic cooking on human bioavailability of naringenin, chlorogenic acid, lycopene and ?carotene in cherry tomatoes. Eur J Nutr 43:360–366 47. Pokorný J (2007) Are natural antioxidants better – and safer – than synthetic antioxidants? Eur J Lipid Sci Technol 109:629–642 48. Rietjens IM, Boersma MG, Haan LD, Spenkelink B, Awad HM, Cnubben NH, Zanden JJV, Woude HVD, Alink GM, Koeman JH (2002) The pro-oxidant chemistry of the natural antioxidants vitamin C, vitamin E, carotenoids and flavonoids. Environ Toxicol Pharmacol 11:321–333 49. Ribeiro SM, Queiroz JH, De Queiroz MELR, Campos FM, Sant’Ana HM (2007) Antioxidant in mango (Mangifera indica L.) pulp. Plant Food Hum Nutr 62:13–17 50. Badhani B, Sharma N, Kakkar R (2015) Gallic acid: a versatile antioxidant with promising therapeutic and industrial applications. RSC Adv 5:27540–27557 51. Yen G, Duh P, Tsai H (2002) Antioxidant and pro-oxidant properties of ascorbic acid and gallic acid. Food Chem 79:307–313 52. Lu Z, Nie G, Belton PS, Tang H, Zhao B (2006) Structure–activity relationship analysis of antioxidant ability and neuroprotective effect of gallic acid derivatives. Neurochem Int 48:263– 274 53. Soong Y, Barlow P (2006) Quantification of gallic acid and ellagic acid from longan (Dimocarpuslongan Lour.) seed and mango (Mangifera indica L.) kernel and their effects on antioxidant activity. Food Chem 97:524–530 54. Locatelli C, Filippin-Monteiro FB, Creczynski-Pasa TB (2013) Alkyl esters of gallic acid as anticancer agents: a review. Eur J Med Chem 60:233–239 55. Zanwar AA, Badole SL, Shende PS, Hegde MV, Bodhankar SL (2014) Antioxidant role of catechin in health and disease. Polyphenols Hum Health Dis:267–271 56. Chander V (2003) Catechin, a natural antioxidant protects against rhabdomyolysis-induced myoglobinuric acute renal failure. Pharmacol Res 48:503–509 57. Yeni G, Syamsu K, Suparno O, Mardliyati E, Muchtar H (2014) Repeated extraction process of raw gambiers (Uncaria gambier Robx.) for the catechin production as an antioxidant. Int J Appl Eng Res 9:24565–24578 58. Senanayake SN (2013) Green tea extract: chemistry, antioxidant properties and food applications – a review. J Funct Foods 5:1529–1541 59. Someya S, Yoshiki Y, Okubo K (2002) Antioxidant compounds from bananas (Musa Cavendish). Food Chem 79:351–354 60. Yao LH, Jiang YM, Shi J, Datta N, Singanusong R, Chen SS, TomÁS-BarberÁN FA (2004) Flavonoids in food and their health benefits. Plant Foods Hum Nutr 59:113–122 61. Lima DP, Rotta R, Beatriz A, Marques MR, Montenegro RC, Vasconcellos MC, Pessoa C, Moraes MOD, Costa-Lotufo LV, Sawaya ACHF, Eberlin MN (2009) Synthesis and biological evaluation of cytotoxic properties of stilbene-based resveratrol analogs. Eur J Med Chem 44:701–707 62. Frémont L (2000) Biological effects of resveratrol. Life Sci 66:663–673 63. Mahal HS, Mukherjee T (2006) Scavenging of reactive oxygen radicals by resveratrol: antioxidant effect. Res ChemIntermed 32:59–71 64. Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506 65. Gülçin I (2010) Antioxidant properties of resveratrol: a structure–activity insight. Innov Food Sci Emerg Technol 11:210–218 66. Kalaras MD, Richie JP, Calcagnotto A, Beelman RB (2017) Mushrooms: a rich source of the antioxidants ergothioneine and glutathione. Food Chem 233:429–433 67. Flora SJS (2009) Structural, chemical and biological aspects of antioxidants for strategies against metal and metalloid exposure. Oxidative Med Cell Longev 2:191–206

18

A. P. Sarkate et al.

68. Anderson ME (1998) Glutathione: an overview of biosynthesis and modulation. Chem Biol Interact 111-112:1–14 69. Noctor G, Mhamdi A, Chaouch S, Han Y, Neukermans J, Marquez-Garcia B, Queval G, Foyer CH (2011) Glutathione in plants: an integrated overview. Plant Cell Environ 35:454–484 70. Kostova I (2006) Synthetic and natural coumarins as antioxidants. Mini-Rev Med Chem 6:365– 374 71. Bubols GB, Vianna DD, Medina-Remon A, Poser GV, Lamuela-Raventos RM, Eifler-Lima VL, Garcia SC (2013) The antioxidant activity of coumarins and flavonoids. Mini-Rev Med Chem 13:318–334 72. Kostova I, Bhatia S, Grigorov P, Balkansky S, Parmar VS, Prasad AK, Saso L (2011) Coumarins as antioxidants. Curr Med Chem 18:3929–3951 73. Bansal Y, Sethi P, Bansal G (2012) Coumarin: a potential nucleus for anti-inflammatory molecules. Med Chem Res 22:3049–3060 74. Lorgeril MD, Salen P (2006) Selenium and antioxidant defences as major mediators in the development of chronic heart failure. Heart Fail Rev 11:13–17 75. Tinggi U (2008) Selenium: its role as antioxidant in human health. Environ Health Prev Med 13:102–108 76. Burk RF (2002) Selenium, an antioxidant nutrient. Nutr Clin Care 5:75–79 77. Berdanier CD, Dwyer JT, Heber D (2014) Handbook of nutrition and food. CRC Press, Taylor & Francis Group, Boca Raton 78. Maxwell SR (1995) Prospects for the use of antioxidant therapies. Drugs 49:345–361 79. Paran E, Novack V, Engelhard YN, Hazan-Halevy I (2008) The effects of natural antioxidants from tomato extract in treated but uncontrolled hypertensive patients. Cardiovasc Drugs Ther 23:145–151 80. Zhao B (2009) Natural antioxidants protect neurons in Alzheimer’s disease and Parkinson’s disease. Neurochem Res 34:630–638 81. Fiedor J, Burda K (2014) Potential role of carotenoids as antioxidants in human health and disease. Nutrients 6:466–488 82. Willcox JK, Ash SL, Catignani GL (2004) Antioxidants and prevention of chronic disease. Crit Rev Food Sci 44:275–295 83. Zhang Y, Gan R, Li S, Zhou Y, Li A, Xu D, Li H (2015) Antioxidant phytochemicals for the prevention and treatment of chronic diseases. Molecules 20:21138–21156 84. Sen S, Chakraborty R (2011) The role of antioxidants in human health. Oxidative stress: diagnostics, prevention, and therapy. American Chemical Society, Washington, DC, pp 1–37

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Polyphenols in Herbal Extracts Aleksandra Sentkowska and Krystyna Pyrzyńska

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Commonly Consumed Herbal Beverages . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Extraction of Polyphenols from Herbs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Fortification of Beverages with Herbs . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abstract

Herbs are well known and often used in everyday life. This work is a review of commonly used herbs. The focus was on their short characteristics, therapeutic effects, and polyphenolic profile. The most popular methods of extracting polyphenolic compounds from herbs were compared. The main attention was paid to water and alcoholic extraction as they are used in domestic conditions. A separate section is devoted to fortification of beverages with herbs. Keywords

Polyphenols · Herbs · Herbal beverages · Extraction · Infusions · Mint · Chamomile · Sage · Thyme

A. Sentkowska (*) Heavy Ion Laboratory, University of Warsaw, Warsaw, Poland e-mail: [email protected] K. Pyrzyńska Department of Chemistry, University of Warsaw, Warsaw, Poland e-mail: [email protected] © Springer Nature Switzerland AG 2022 H. M. Ekiert et al. (eds.), Plant Antioxidants and Health, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-78160-6_5

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Introduction

Herbs have been used since ancient times for medicinal purposes due to their beneficial health effects. Today we know that various health-related compounds with a broad spectrum of activity are responsible for their properties, which is why herbs are increasingly used in today’s medicine. There is also a wide variety of herbs which are used for culinary purposes worldwide. Herbs are natural products and their chemical composition varies depending on several factors ranging from the kind of plant to the method of preparing a final product. Despite these differences, herbs are an excellent source of flavonoids, polyphenolic acids, tannins, vitamins, and terpenoids. Within these bioactive components, polyphenolic compounds are one of the major groups contributing to herbal plants. They are an essential part of human diet and are a considerable interest due to their antioxidant, antimutagenic, anticancer, and anti-inflammatory properties [1–3]. Rich in polyphenolic compounds, herbal extracts can act as free-radicals scavengers and quenchers of singlet oxygen present in the environment, thus, protect against the destruction of lipids, proteins and DNA [4]. Phenolic antioxidants have been shown to play important roles in delaying the development of chronic diseases such as cardiovascular diseases, cancer, inflammatory bowel syndrome, and Alzheimer’s disease [2, 4]. Due to safety concerns and limitation on the use of synthetic antioxidants, natural compounds obtained from edible materials have been of increasing interest. For such reason, herbal medicine has become a popular form of healthcare, even though several differences between the herbal and conventional medicine. From the point of view of pharmacological treatment, herbal medicine needs to be tested for efficacy using conventional trial methodology [5]. The differences in the scientific and traditional view on the medicinal use of herbs are summarized in Table 1. In this work, traditional ways of herb preparation (infusion, decoction, tincture, and maceration) will be presented from the scientific point of view. The effect of the extraction procedure on the content of polyphenolic compounds in selected, most

Table 1 The comparison of scientific and traditional aspect of herbal therapy Traditional use of herbs Use of any part of the plant (flowers, stems), freedom in the preparation of the infusion (different preparation time, extraction with water or a mixture of water-ethanol) The use of a mixture of several herbs increases the health-promoting properties of the infusion

The use of herbal infusions without restrictions is healthy and does not affect the parallel pharmacological treatment

Scientific aspect It is necessary to optimize the entire extraction process from selecting a specific part of the plant to the type of extractant and time of extraction [6–8] Antioxidant interactions between bioactive compounds take place in such mixture. In this case, more ingredients do not mean that the health-promoting properties of the final product also increase [9–11] When herbs are used in large quantities, side effects are possible, and drug interactions have been confirmed [12–16]

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popular herbal beverages will be discussed. The greatest emphasis will be paid on the home herb extraction methods. Additionally, the fortification of beverages with herbs will be shown allowing to obtain new healthy drinks.

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Commonly Consumed Herbal Beverages

There are many common herbs that have documented uses in folk medicine for treating various physical conditions. While some of them have a global footprint, such a well-known chamomile or mint, others are used only regionally or locally [17, 18]. Commonly used parts of herbs in beverages and their bioactive phenolic compounds are given in Table 2 and their short characteristics are given below.

Table 2 Properties of some herbs commonly used for beverages Name of herb Chamomile (Matricaria chamomilla) Echinacea (Echinacea purpurea)

Used part Aerial parts

Main phenolic compounds Apigenin, quercetin, luteolin Caffeic, chlorogenic, and ferulic acids

Fresh or dried roots and rhizomes, aerial parts

Rutin, kaempferol, nicotiflorin Caffeic acid derivatives Kaempferol, quercetin, apigenin, luteolin Caffeic and protocatechuic acids Quercetin, rutin, myricetin Rosmarinic, chlorogenic, p-coumaric, and p-hydroxybenzoic acids Catechin, eriodictyol, luteolin, apigenin Rosmarinic, sinapic, and caffeic acids Rutin and quercetin Ferulic, gallic, and chlorogenic acids Quercetin Chlorogenic acid Quercetin, rutin, isoquercitrin, orientin, luteolin, vitexin Caffeic, protocatechuic, syringic, ferulic, vanillic, p-hydroxybenzoic acids Quercetin, quercitrin, catechin, hyperoside, taxifolin Gallic, p-benzoic, chlorogenic, p-coumaric, and ferulic acids Luteolin, apigenin Rosmarinic, caffeic, and syringic acid Quercetin, kaempferol, rutin, catechin Chlorogenic acid

Horsetail (Equisetum arvense)

Stems and leaves

Lemon balm (Melissa officinalis)

Dried aerial parts

Mint (Mentha piperita)

Dried leaves

Mulberry (Morus)

Fruits and leaves

Nettle (Urtica dioica)

Fresh or dried aerial parts, roots

Rooibos (Aspalathus linearis)

Dried leaves and steams

Rosehip (Rosa canina)

Fruits, petals

Sage (Salvia officinalis)

Dried leaves

St. John’s wort (Hypericum perforatum)

Aerial parts

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Chamomile: Is commonly regarded as a mild tranquilizer or sleep inducer. Its calming effects may be attributed to an antioxidant apigenin, belonging to the flavone class. Chamomile will also help with stomach pain. Gargle with the infusion to relieve mouth sores. Recent studies proved that chamomile extract can be used against obesity, hyperglycemia, and hyperlipidemia [19]. Echinacea: It is well-known herbal remedy for the common cold or flu. In addition, the fresh flower buds are used also to make an infusion to treat pain, inflammation, migraines, and other health issues. Echinacea contains several antioxidants, such as flavonoids, cichoric and rosmarinic acids, which may help defend a body against oxidative stress [20]. Lavender: Used in an infusion, lavender has antiseptic and antibacterial properties that can be used to wash skin. It is said to help clear up acne and will speed the healing of skin wounds. Lavender essential oil is one of the most popular in aromatherapy. Lemon balm: This herb is cultivated in many countries for its carminative and antispasmodic properties. It is used for treatment of headache, rheumatism, indigestion, and hypersensitivities as well as to help relieve anxiety and insomnia. Natural essential oils obtained from various parts of plant due to its citrus fragrance are used in the cosmetic industry and perfumery. All of these properties of lemon balm have been related to the high levels of polyphenolic compounds such as rosmarinic, chlorogenic, p-coumaric, and p-hydroxybenzoic acids as well as quercetin, rutin, and myricetin [6, 8]. Mint: The mint family, including peppermint, when steeped in an infusion or tea can soothe an upset stomach, relieve gas pains, and prevent nausea and vomiting. This herb exhibits antioxidant, antimicrobial, and insecticidal effects which are attributed to the high content of polyphenolic compounds [21]. Mint leaves due to presence of the monoterpene menthol perfectly neutralize the unpleasant smell from the mouth, and hence they are used in chewing gums and mouthwash. Nettle: Used in an infusion or tea, stinging nettle is said to strengthen adrenal function, and help with eczema, arthritis, gout, and joint pain. Recent studies confirmed nettle extract to have natriuretic, diuretic, and hypotensive effects [22]. Red clover: Like peas and beans, red clover belongs to the family of plants called legumes. The infusion of its blossoms, leaves, and stems are very high in protein and vitamins, and it is an excellent source of phytosterols. It contains also isoflavones, compounds similar to the female hormone estrogen, and thus, it may have benefits for menopausal symptoms. Preliminary research suggests that it may have some cancer-prevention properties [23]. Rosehip: The fruits of this plant have been discovered to be rich in polyphenols (triterpene acids, flavonoids, proanthocyanidins, catechin), essential fatty acids, galactolipid, folate, vitamins A, C, and E, and minerals (Ca, Mg, K, S, Si, Se, Mn, and Fe), among other bioactive components. The extracts have been proven to possess antioxidant, anti-inflammatory, cardioprotective, antidiabetic, neuroprotective, and antimicrobial properties [24]. Consumption of rosehips is popular in some European countries in the form of desserts, cookies, cakes, jelly, marmalade, ice cream, syrup, and herbal tea.

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Sage: This member of the salvia family is not only good for cooking. For a long time, sage (Salvia) species have been used in traditional medicine for the relief of pain, protecting the body against oxidative stress, angiogenesis, inflammation, and bacterial and viral infections. Using an infusion of sage in a vaporizer can relieve asthma and other respiratory problems. Sage rinses are recommended for the treatment of mouth and throat conditions [25]. St. John’s wort: It is one of the oldest used and most extensively investigated medicinal herbs. The primary ingredients of interest are naphthodianthrones, xanthones, and flavonoids (quercetin, kaempferol, rutin, hyperforin, hypericin). It is mainly used as an antidepressant drug in the treatment of mild/moderate depression. Recent research suggests the effectiveness of this herb in treating other ailments, including cancer, inflammation-related disorders, and bacterial and viral diseases. St. John’s wort extracts have relatively few adverse effects when taken alone at the recommended dosages; however, numerous interactions with other drugs have been reported [15]. Thyme: It is commonly used as a culinary herb and also for medicinal purposes. This perennial herb contains an oil containing thymol, which has a notable antiseptic property. Use an infusion of thyme as a gargle to combat bad breath and mouth sores, and to help with tonsillitis and laryngitis. Pure extracts of thyme can relieve bronchitis and asthma. Recently this herb is used as a food additive to prevent bacterial growth and contamination [26]. Although some herbs are used alone as a beverage, they are often blended in mixtures in order to enhance their pharmacological effects [27]. Moreover, some herbal extracts are added to improve the taste or flavor. Hence, the possible synergistic or antagonistic interactions between antioxidants may significantly change their final antioxidant activity [28–30]. For example, Guimarães et al. [28] studied the interaction in the antioxidant activity of infusions and decoctions from mixtures of herbs (lemon-verbena, fennel, and spearmint). It was found that the composition of lemon-verbena-fennel exhibited synergistic effect in DPPH scavenging activity method, while the infusion prepared with lemon, verbena, and spearmint revealed antagonistic effect.

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Extraction of Polyphenols from Herbs

Household herb brewing usually is done in the form of an infusion, where dried plant materials are steeped in boiling water or as a decoction, where herbs are boiled in water. Decoction is preferred method for brewing herbal tea from the tougher, denser herb materials such as roots, bark, and berries. Using water with a high degree of total hardness results in lower content of phenolic compounds, which is also associated with significant decreased antioxidant capacities [31]. Other conventional domestic extraction methods include maceration, where powdered crude herb material is mixed with solvent (usually water-ethanol mixture) and digestion – macerated herb with solvent is gently heated. The advances of extraction techniques for the production of herbal drugs, nutraceuticals, and ingredients for cosmetics applied

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supercritical fluids, pressurized liquids, and enzymes or typical liquid extraction are very often accelerated with the use of microwave energy and ultrasound waves with the aim to reducing volume of organic solvents and extraction time as well as maximizing the active ingredients [32–38]. Different factors can affect the extraction efficiency of polyphenolic compounds such as the properties of extraction solvent, its ratio to the solid material, as well as the particle size of raw material and the temperature of this process [32–35]. The selection of extraction solvent is crucial; however, from the point of view of herbal infusions, this chapter will be mainly focus on water, alcohols, and their mixtures. It needs to be highlighted that alcohols such as ethanol and methanol are universal solvents in the phytochemical analysis. Increasing the extraction time usually increase the extraction efficiency until the equilibrium between the analyte in the plant material and in the solvent is achieved. Dróżdż et al. [39] studied the total phenolic content in heather flowers using water and water ethanol (40/60, v/v) mixture. For both solvents the extraction efficiency of total phenolics (evaluated by Folin-Ciocalteu assay) increased to about 10 min, then equilibrium was achieved (Fig. 1). The same observation was done for the water infusions of chamomile and peppermint [40]. Albuquerque et al. [41] compared three extraction techniques (maceration, microwave, and ultrasound) for recovery of catechin from Arbutus unedo fruits using ethanol-water mixture. Maceration and microwave extraction (MAE) were found to be the most effective method, while ultrasound assisted extraction (UAE) was the least effective solution. Jovanović et al. [42] found that maceration with 50% (v/v)

Fig. 1 Content of total phenolics extracted from wild heater flowers using water and water-ethanol (40/60, v/v) mixture [39]. (Reprinted with permission from Academia Publishing)

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ethanol showed comparable efficiency to heat-assisted extraction for polyphenolic compounds from Thymus serpyllum herb; however, the obtained results were significantly lower in comparison to those using UAE method. According to total flavonoid yields, the efficiency of extraction was the highest in UAE. Sentkowska et al. [43] studied the effect of extraction time on the content of rutin and chlorogenic acid in water extracts of St. John’s wort prepared as infusion and decoction. Rutin was extracted very quickly in infusion mode, but the prolonged time of extraction caused its degradation (Fig. 2). The extraction yield in decoction for 20 min was similar to that obtained for 10 min in infusion. The efficiency of chlorogenic extraction did not depend on time. Several studies reported that chemical profiles of infusion and decoction extracts are very similar, differing from each other in terms of quantities of particular compounds [44–46]. In general, an increase in the extraction temperature can promote higher polyphenol solubility and mass transfer rate during extraction process [47, 48]. However, the degradation of thermolabile compounds can be also observed as a result of polyphenol oxidase activity [49, 50]. Organic solvents such as methanol, ethanol, acetone, ethyl acetate, or their mixture with water are widely used in the extraction of polyphenolic compounds from plant material for the analysis of their content [51–57]. Extraction of Psidium guajava L. leaves with pure ethanol or ethanol-water mixture (8:2, v/v) resulted in

Fig. 2 The effect of extraction time on the content of rutin and chlorogenic acid in the aqueous extracts of St. John’s wort in infusion (solid points) and decoction (empty points) [43]. (Reprinted with permission from Springer)

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highest extraction yield and maximum content of flavonoids, tannins, and alkaloids in comparison to other used extraction solvents such as water, chloroform, or petroleum ether [51]. In water extracts There are no indications for the presence of alkaloids. Methanolic extracts of Garnica atriviridis showed higher antioxidant activity in comparison to water samples; however, aqueous extracts showed higher anti-hyperlipidemic activity [52]. The free radical scavenging activity of the extracts of leaves from Kedrostis foetidissima decreased depending on the used solvent in the order: methanol > chloroform > water > acetone > petroleum ether [53]. The results showed that binary solvent systems (ethanol/water) were more efficient than mono-solvent systems (water or pure alcohol) in the extraction of polyphenolic compounds in regard to their relative polarity [54–57]. To reduce the extraction time and solvent volume as well as to increase the extraction efficiency, other extraction techniques such as MAE and UAE are used. However, this kind of extraction procedure is not appropriate for the extraction of temperature-sensitive compounds [58]. The effect of MAE on phytochemical degradation was observed during the analysis of Dioscorea hispida as well as Andrographis paniculata [59, 60]. The benefits of using UAE is mainly the reduction of extraction time; however, the use of ultrasound energy more than 20 kHz may have an effect on the polyphenolic compounds through the free radicals formulation, which are immediately scavenged by polyphenols [61]. However, the values of polyphenols extracted from sage using 30% ethanol and USA (11 min) were 20% higher in comparison to conventional extraction (60 °C, 30 min) using the same solvent [62]. This chapter mainly focuses on water and alcohol as these two extrahents are usually used for domestic purposes. However, a few sentences should be devoted to the description of ionic liquids (ILs), which are increasingly popular as so-called green solvents, also in the extraction of polyphenolic compounds. ILs are a group of organic salts, in general, composed of organic cation (such as imidazolium, pyrrolidinium, pyridinium tetraalkyl ammonium, tetraalkyl phosphonium) and inorganic or organic anion (e.g., tetrafluoroborate, hexafluorophosphate, and bromide) and presented in the form of liquid when below 100 °C [63]. They show many unique properties such as good thermal stability, miscibility with water and organic solvents, tunable viscosity, or negligible vapor pressure. Their polarity and hydrophobicity as well as other chemical physical properties can be selected by choosing the cationic and anionic constituents. Lou et al. reported that ILs can absorb microwave energy so their combination with MAE or USA can be a potential tool in the extraction [64]. Yang et al. [65] compared extraction efficiency of chlorogenic acid from ramie, a flowering plant in the nettle family Urticaceae, with water, alcohols, and ionic liquid (1-butyl-3methyl-midazolium hydrogen sulfate) as the extraction media. The extraction procedures were also assisted with MAE, UAE, and heat reflux extraction (HRE). The results presented in Fig. 3 clearly show that extraction techniques involved ILs gave much higher extraction yield in comparison to other techniques. However, it has been confirmed that commonly used ionic liquids are not easily biodegradable [66]. When ultimately disposed of or accidentally released, they would accumulate in the environment. Moreover, some of the ILs appear to be highly toxic [67, 68].

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Fig. 3 Comparison of different method for extraction of chlorogenic acid from ramie (Boehmeria nivea L.) leaves [65]. The experiments were carried out at the conditions of 40% IL, 100:1 liquidsolid ratio, and pH 3. The extraction time for HRE was 6 h for MAE and 45 min for USE. (Reprinted with the permission from Elsevier)

Natural deep eutectic solvents (NADES) present a new generation of liquid salts and green alternative to conventional solvents [69]. NADES are based on mixtures of naturally derived uncharged hydrogen-bond donors (e.g., amines, sugars, alcohols, and carboxylic acids) and nontoxic quaternary ammonium salts (e.g., cholinium chloride) as the cationic moiety. They offer low costs, simple preparation, a low toxicity profile, and sustainability. For example, the NADES composed of choline chloride and maltose possessed excellent extractability for extraction of phenolic compounds in Cajanus cajan leaves [70] and that composed of choline chloride and lactic acid was proposed for extraction of baicalin, wogonoside, baicalein, and wogonin in Radix Scutellariae, the dried root of the Chinese traditional medicinal plant [71].

4

Fortification of Beverages with Herbs

Beverages are a convenient way for many essential nutrients that can enhance overall well-being. Consumers now look for health benefits from their beverages, not just good flavors. Thus, in order to meet these demands, the fortification of beverages plays an important role [72, 73]. The most common approach is to fortify them with plant extract or isolated vitamin. Traditionally used medicinal plants and herbal teas contain a wide range of polyphenolic compounds that act as a powerful antioxidant. Combination of different herbs with various bioactive compounds has been shown to result in synergistic effects to enhance the antioxidant, antidiabetic, and antimicrobial activity of the individual substance [74–76]. The herbal extracts, particularly the

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infusion type, may be incorporated with fruit juices, mineral water-based drinks, and energy drinks to obtain beverages with fresh-tasting, high nutritional value, and satisfactory organoleptic properties [77–81]. Tamer et al. [77] studied the blended beverages containing lemonade and water extracts of linden, heather, green tea, lemon verbena, clove, peppermint, ginger, and mate. The lemonades with linden, ginger, and peppermint, which had been found to be rich in total phenolic compounds and ascorbic acid, showed higher antioxidant activity than the control sample. Generally, the most preferred lemonades based on the sensory evaluation were heather- and ginger-added beverages and the control sample, while lemonade with mate was the least preferred. The lyophilized wild edible plants such as rosehip (Rosa canina) fruits, acorns from oak trees (Quercus ballota), and young leaves of burnet (Sanguisorba minor) were added to orange and kiwifruit juices for increasing their nutritional properties [79]. The content of phenolic compounds and antioxidant capacity in the obtained beverages from both juices increased more than 30%. Moreover, the addition of R. canina and Q. ballota significantly reduced darkening of kiwi cremogenate. This is a big advantage as one of the main limitations for obtaining kiwifruit minimally processed is the difficulty for maintaining the original green color which, due to oxidation, changes to brown. Ivanišová et al. [80] examined the biological activity of apple juice enriched by several herbal extracts such as mint, lemon balm, oregano, wild thymus, and sage. The addition of water extracts of these herbs (infusion was prepared using 1 g of each herb and 100 mL of water) increased antioxidant activities and also total polyphenol and flavonoid contents in comparison to pure apple juice. Total polyphenol content of prepared mixtures containing 60% (v/v) of apple juice and 40% of a given herbal extracts decreased in the following order: oregano > lemon balm > sage > wild thyme > mint > 100% apple juice, while total flavonoid content in the order: sage > oregano > lemon balm > wild thyme > mint > 100% apple juice. Sensorial analysis of samples showed that enriched juices had better properties for evaluators in comparison with pure juice. The most intense, pleasurable herbal smell and taste was found for apple juice with mint and with sage. The in vitro antioxidant effects, the cellular antioxidant activities, and the antiadipogenic effects of the extracts prepared from 20 fruits and medicinal herbs cultivated in the Gyeongnam area of Korea were studied for the development of functional foods and nutraceuticals [81].

5

Conclusions

This chapter showed that herbal beverages are great source of antioxidants like flavonoids and polyphenolic acids. High content of these compounds was found in extract obtained as well in infusion as in decoction processes. This seems that domestic way of preparing herbal beverages is quite good extraction procedure of herbs.

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References 1. Barreira JCM, Morais AI, Ferreira ICFR, Oliviera MB (2013) Insights on the formulation of herbal beverages with medicinal claims according to their antioxidant properties. Molecules 18:2851–2863 2. Carvalho-Costa D, Costa HS, Goncalves Albequerque T, Ramos F, Castilho MC, Sanches-Silva A (2015) Advances in phenolic compounds analysis of aromatic plants and their potential application. Trends Food Sci Technol 45:336–354 3. Chan EWC, Lim YY, Chong KI, Tan JBI, Wong SK (2012) Antioxidant properties of tropical and temperate herbal teas. J Food Compos Anal 23:185–189 4. Galleano M, Verstraeten SV, Oleiza PI, Fraga G (2010) Antioxidant actions of flavonoids: thermodynamic and kinetic analysis. Arch Biochem Biophys 401:23–30 5. Firenzuoli F, Gori L (2007) Herbal medicine today: clinical and research issues. Evid Based Complement Alternat Med 4(Suppl 1):37–40 6. Sentkowska A, Biesaga M, Pyrzyńska K (2015) Polyphenolic composition and antioxidative properties of lemon balm (Melissa officinalis L.) extract affected by different brewing processes. Int J Food Prop 18:2009–2014 7. Zhang QW, Lin LG, Ye WC (2018) Techniques for extraction and isolation of natural products: a comprehensive review. Chin Med 13:20–46 8. Barros L, Duenas M, Dias MI, Sousa MJ, Santos-Buelga C, Ferreira ICFR (2013) Phenolic profiles of cultivated, in vitro cultured and commercial samples of Melissa officinalis L. infusions. Food Chem 136:1–8 9. Enko J, Gliszczyńska-Świgło A (2015) Influence of the interactions between tea (Camellia sinensis) extracts and ascorbic acid on their antioxidant activity: analysis with interaction indexes and isobolograms. Food Addit Contam Part A Chem Anal Control Expo Risk Assess 32:1234–1242 10. Sentkowska A, Pyrzyńska K (2018) Zwitterionic hydrophilic interaction liquid chromatography coupled to mass spectrometry for analysis of beetroot juice and antioxidant interaction between its active compounds. LWT Food Sci Technol 93:641–648 11. Palafox-Carlos H, Gil-Chaves J, Sotelo-Mundo SS, Namieśnik J, Gorinstein S, GonzalesAguilar GA (2012) Antioxidant interaction between major polyphenolic compounds found in “Atafulo” mango pulp: chlorogenic, gallic, protocatechuic and vanillic acids. Molecules 17:12657–12664 12. Sentkowska A, Pyrzyńska K (2019) Evaluation of the antioxidant interactions between green tea polyphenols and nonsteroidal anti-inflammatory drugs. Open Chem J 6:47–51 13. Sentkowska A, Pyrzyńska K (2018) Investigation of antioxidant interaction between green tea polyphenols and acetaminophen using isobolographic analysis. J Pharm Biomed Anal 159:393–397 14. Sentkowska A, Pyrzyńska K (2020) Simultaneous determination of vitamin B6 and catechins in dietary supplements by ZIC-HILIC chromatography and their antioxidant interactions. Eur Food Res Technol. https://doi.org/10.1007/s00217-020-03516-w 15. Mouly S, Lioret-Linares C, Sellier PO, Sene D, Bergmann JF (2017) Is the clinical relevance of drug–food and drug–herb interactions limited to grapefruit juice and Saint-John’s wort? Pharmacol Res 118:82–92 16. Izzo AA, Hoon-Kim S, Radhakrishnan R, Williamson EM (2016) A critical approach to evaluating clinical efficacy, adverse events and drug interactions of herbal remedies. Phytother Res 30:691–700 17. Zhao J, Deng JW, Chen YW, Li SP (2013) Advanced phytochemical analysis of herbal tea in China. J Chromatogr A 1313:2–23 18. Carabajal MPA, Isla MI, Zampini IC (2017) Evaluation of antioxidant and antimutagenic activity of herbal teas from native plants used in traditional medicine in Argentina. S Afr J Bot 110:258–265

30

A. Sentkowska and K. Pyrzyńska

19. Jabria MA, Saklya M, Marzoukib L, Hichem Sebala H (2017) Chamomile (Matricaria recutita L.) decoction extract inhibits in vitro intestinal glucose absorption and attenuates high fat dietinduced lipotoxicity and oxidative stress. Biomed Pharmacother 87:153–159 20. Manayi A, Vazirian M, Saeidnia S (2015) Echinacea purpurea: pharmacology, phytochemistry and analysis methods. Pharmacogn Rev 9:63–72 21. Castada HZ, Mirondo R, Sigurdson GT, Giusti MM, Barringer S (2017) Deodorization of garlic odor by spearmint, peppermint and chocolate mint leaves and rosmarinic acid. LWT Food Sci Technol 84:160–167 22. Jan NN, Zarafshan K, Singh S (2017) Stinging nettle (Urtica dioica L.): a reservoir of nutrition and bioactive components with great functional potential. J Food Meas Charact 11:423–433 23. Fritz H, Seely D, Flower G, Skidmore B, Fernandes R, Vadeboncoeur S, Kennedy D, Cooley K, Wong R, Sagar S, Sabri E, Fergusson D (2013) Soy, red clover, and isoflavones and breast cancer: a systematic review. PLoS One 8:e81968 24. Patel S (2017) Rose hip as an underutilized functional food: evidence-based review. Trends Food Sci Technol 63:29–38 25. Hamidpour M, Hamidpour R, Hamidpour S, Shahlari M (2014) Chemistry, pharmacology and medicinal property of sage (Salvia) to prevent and cure illnesses such as obesity, diabetes, depression, dementia, lupus, autism, heart disease and cancer. J Tradit Complement Med 4:82–88 26. Salehi B, Abu-Darwishb MS, Tarawnehc AH, Cabrald C, Gadetskayag AV, Salgueiroh L, Hosseinabadii T, Rajabij S, Chandak W, Sharifi-Radl M, Mulaudzim RB, Ayatollahin SA, Farzad Kobarfardn F, Arserim-Ucarr DK, Sharifi-Rads J, Atap A, Baghalpourn N, Contrerast MM (2019) Thymus spp. plants – food applications and phytopharmacy properties. Trends Food Sci Technol 85:287–306 27. Finimundy TC, Pereira C, Dias MI, Caleja C, Calhelha RC, Sokovic M, Stojković D, Carvalho AM, Rosa E, Barros L, Ferreira ICFR (2020) Infusions of herbal blends as promising sources of phenolic compounds and bioactive properties. Molecules 25:2151 28. Guimarães R, Barros L, Dueňas M, Calhelka RC, Carvalho AM, Santos-Buelga C, Queiroz MJ, Ferreira ICF (2013) Infusion and decoction of wild German chamomile: bioactivity and characterization of organic acids and phenolic compounds. Food Chem 136:947–954 29. Vinholes J, Vizzotto M (2017) Synergisms in alpha-glucosidase inhibition and antioxidant activity of Camellia sinensis L. Kuntze and Eugenia uniflora L. ethanolic extracts. Pharmacogn Res 9:101–107 30. Che CT, Wang ZJ, Chow MS, Lam CWK (2013) Herb–herb combination for therapeutic enhancement and advancement: theory, practice and future perspectives. Molecules 18:5125–5141 31. Riehle P, Vollmer M, Rohn S (2012) Phenolic compounds in Cistus incanus herbal infusions – antioxidant capacity and thermal stability during brewing process. Food Res Int 53:891–899 32. Zhang QW, Lin LG, Ye WC (2018) Techniques for extraction and isolation of natural products: a comprehensive review. Chin Med 13:20–46 33. Azmin SNHM, Manan ZA, Alwi SB, Chua LS, Mustaffa AA, Yunus NA (2016) Herbal processing and extraction technologies. Sep Purif Rev 45:305–320 34. Yahya N. A., N. Attan, and R. A. Wahab. 2018. An Overview of Cosmeceutically Relevant Plant Extracts and Strategies for Extraction of Plant-based Bioactive Compounds. Food and Bioproducts Processing. 112: 69–85. https://doi.org/10.1016/j.fbp.2018.09.002. 35. Belwal T, Ezzat SM, Rastrelli L, Bhatt ID, Daglia M, Baldi A, Devkota HP, Orhan IE, Patra JK, Das G, Anandharamakrishnan C, Gomez LG, Nabavi SF, Nabavi SM, Atanasov AG (2018) A critical analysis of extraction techniques used for botanicals: trends, priorities, industrial uses and optimization strategies. TrAC Trends Anal Chem 100:82–102 36. Vinatoru M, Mason TJ, Calinescu I (2017) Ultrasonically assisted extraction (UAE) and microwave assisted extraction (MAE) of functional compounds from plant materials. TrAC Trends Anal Chem 97:159–178

2

Polyphenols in Herbal Extracts

31

37. Belwal T, Chemat F, Venskutonis PR, Cravotto G, Jaiswal DK, Bhatt ID, Devkota HP, Luo Z (2020) Recent advances in scaling-up of non-conventional extraction techniques: learning from successes to failures. TrAC Trends Anal Chem 127:15895 38. Plaza M, Marina ML (2019) Pressurized hot water extraction of bioactives. TrAC Trends Anal Chem 116:236–247 39. Dróżdż P, Sentkowska A, Pyrzyńska K (2016) Calluna vulgaris (L.) hull as a source of chlorogenic acid. Acad J Med Plants 12:75–80 40. McAlpine MD, Ward WE (2016) Influence on sleeping time on polyphenols content and antioxidant capacity of black, green, rooibos and herbal teas. Beverages 2:17–29 41. Albuquerque BR, Pieto MA, Barreiro MF, Rodrigues A, Curran TP, Barros L, Fereira ICFR (2017) Catechin-based extract optimization obtained from Arbutus unedo L. fruits using maceration/microwave/ultrasound extraction techniques. Ind Crop Prod 95:404–415 42. Jovanović AA, Đorđević VB, Zdunić GM, Pljevljakušić DS, Šavikin KP, Gođevac DM, Bugarski BM (2017) Optimization of the extraction process of polyphenols from Thymus serpyllum L. herb using maceration, heat and ultrasound assisted techniques. Sep Purif Technol 179:369–390. https://scholar.google.com/citations?user=g_1Y8qMAAAAJ&hl=en 43. Sentkowska A, Biesaga M, Pyrzyńska K (2016) Effects of brewing process on phenolic compounds and antioxidant activity of herbs. Food Sci Biotechnol 25:965–970 44. Kratachanova M, Denev P, Ciz M, Lojek A, Atanas Mihailov A (2010) Evaluation of antioxidant activity of medicinal plants containing polyphenol compounds. Comparison of two extraction systems. Acta Biochim Pol 57:229–234 45. Dias MI, Barros L, Sousa MJ, Ferreira ICF (2012) Systematic comparison of nutraceuticals and antioxidant potential of cultivated, in vitro cultured and commercial Melissa officinalis samples. Food Chem Toxicol 50:1866–1873 46. Fotakis C, Tsigrimani D, Tsiaka T, Lantzouraki DZ, Strati IF, Makris C, Tagkouli D, Proestos C, Sinanoglou VJ, Zoumpoulakis P (2016) Metabolic and antioxidant profiles of herbal infusions and decoctions. Food Chem 211:963–971 47. Ajila CM, Brar SK, Verma M, Tyagi RD, Godbout S, Valero JR (2011) Extraction and analysis of polyphenols: recent trends. Crit Rev Anal Chem 31:227–249 48. Acosta-Estrada BA, Gutierrez-Uribe JA, Serna-Saldivar SO (2014) Bound phenolics in foods, a review. Food Chem 152:46–55 49. Marete EN, Jacquier JC, O’Riordan D (2009) Effects of extraction temperature on the phenolic and parthenolide contents, and colour of aqueous feverfew (Tanacetum parthenium) extracts. Food Chem 117:226–231 50. Dawidowicz AL, Typek R (2010) Thermal stability of 5-O-caffeoylquinic acid in aqueous solutions at different heating conditions. J Agric Food Chem 58:12578–12584 51. Arya V, Thakur NM, Kashyap C (2012) Preliminary phytochemical analysis of the extracts of Psidium leaves. J Pharmacogn Phytochem 1:1–5 52. Al-Mansoub MA, Asmawi MZ, Murugaiyah V (2014) Effects of extraction solvents and plant parts used on the antihyperlipidemic and antioxidant effects of Garcinia atroviridis: a comparative study. J Sci Food Agric 94:1552–1558 53. Pavithra K, Vadivukkarasi S (2015) Evaluation of free radical scavenging activity of various extracts of leaves from Kedrostis foetidissima (Jacq.) Cogn. Food Sci Human Wellness 4:42–46 54. Dróżdż P, Sentkowska A, Pyrzyńska K (2017) Flavonoid content and antioxidant properties in different extracts of Calluna vulgaris (L.) flowers. J Agric Sci Technol A 7:39–44 55. Dent M, Dragović-Uzelac V, Penić M, Brnčić, M, Bosiljkov T, Levaj B (2013) The effect of extraction solvents, temperature and time on the composition and mass fraction of polyphenols in Dalmatin wild sage (Salvia officinalis L.) extracts. Food Technol Biotechnol 51:84–91. https://www.bib.irb.hr/625347?rad=625347 56. Waszkowiak K, Gliszczyńska-Świgło A (2016) Binary ethanol–water solvents affects phenolic profile and antioxidant capacity of flaxseed extracts. Eur Food Res Technol 242:777–786 57. Marques V, Farah A (2009) Chlorogenic acids and related compounds in medicinal plants and infusions. Food Chem 113:1370–1376

32

A. Sentkowska and K. Pyrzyńska

58. Kala HK, Mehta R, Sen KK, Tandey R, Mandal V (2016) Critical analysis of research trends and issues in microwave assisted extraction of polyphenolics: have we really done enough. Trends Anal Chem 85:140–152 59. Kumoro C, Hartari I (2015) Microwave assisted extraction of dioscorin from Gadung (Dioscorea hispida Dennst) Tuber Flour. Procedia Chem 14:47–55 60. Hartari I, Kurniasari L, Anas Y (2015) Mathematical model of the hydrotropic microwave assisted extraction of antimalarial agent from Andrographis paniculata. Procedia Chem 14:186–192 61. Kufmann B, Christen P (2002) Recent extraction techniques for natural products: microwaveassisted extraction and pressurized solvent extraction. Phytochem Anal 13:105–113 62. Dent M, Dragović-Uzelac V, Garofulić IE, Bosiljkov T, Ježek D, Brnčić M (2015) Comparison of conventional and ultrasound assisted techniques on mass fraction of phenolic compounds from sage (Salivia officinalis L.). Chem Biochem Eng 29:475–484. https://scholar.google.com/ citations?user=4CuR0akAAAAJ&hl=en#d=gs_md_cita-d&u=%2Fcitations%3Fview_op% 3Dview_citation%26hl%3Den%26user%3D4CuR0akAAAAJ%26citation_for_view% 3D4CuR0akAAAAJ%3A_FxGoFyzp5QC%26tzom%3D-120 63. Xiao J, Chen G, Li N (2018) Ionic liquid solutions as a green tool for the extraction and isolation of natural products. Molecules 23:1765 64. Lou Z, Wang H, Zhu S, Chen S, Zhang M, Wang Z (2012) Ionic liquids based simultaneous ultrasonic and microwave assisted extraction of phenolic compounds from burdock leaves. Anal Chim Acta 715:28–33 65. Yang Z, Tan Z, Li F, Li X (2016) An effective method for the extraction and purification of chlorogenic acid from ramie (Boehmeria nivea L.) leaves using acidic ionic liquids. Ind Corps Prod 89:78–86 66. Jordan A, Gathergood N (2015) Biodegradation of ionic liquids – a critical review. Chem Soc Rev 44:8200–8237 67. Li XY, Jing CQ, Lei WL, Li J, Wang JJ (2012) Apoptosis caused by imidazolium-based ionic liquids in PC12 cells. Ecotoxicol Environ Saf 83:102–107 68. Kudłak B, Owczarek K, Namieśnik J (2015) Selected issues related to the toxicity of ionic liquids and deep eutectic solvents – a review. Environ Sci Pollut Res 22:11975–11992 69. Skarpalezos D, Detsi A (2019) Deep eutectic solvents as extraction media for valuable flavonoids from natural sources. Appl Sci 9:4169 70. Wei Z, Qi X, Li T, Luo M, Wang W, Zu Y, Fu Y (2015) Application of natural deep eutectic solvents for extraction and determination of phenolics in Cajanus cajan leaves by ultra performance liquid chromatography. Sep Purif Technol 149:237–244 71. Wei ZF, Wang XQ, Peng X, Wang W, Zhao CJ, Gang Zu Y, Fu YJ (2015) Fast and green extraction and separation of main bioactive flavonoids from Radix Scutellariae. Ind Crop Prod 63:175–181 72. Ansari MM, Kumar DS (2012) Fortification of food and beverages with phytonutrients. Food Pub Health 2:241–253 73. Jaeger SR, Axten LG, Wohlers MW, Sun-Waterhouse D (2009) Polyphenol-rich beverages: insights from sensory and consumer science. J Sci Food Agric 89:2356–2362 74. Malongane F, McGaw LJ, Mudau FN (2017) The synergistic potential of various teas, herbs and therapeutic drugs in health improvement: a review. J Sci Food Agric 97:4679–4689 75. Sentkowska A, Pyrzyńska K (2019) Investigation of antioxidant activity of selenium compounds and their mixtures with tea polyphenols. Mol Biol Rep 46:3019–3024 76. Freeman BL, Eggett DL, Parker TL (2010) Synergistic and antagonistic interactions of phenolic compounds found in navel oranges. J Food Sci 75:C570–C576 77. Tamer CE, Yekeler FZ, Çopur ÖU, İncedayi B, Suna S (2017) A study of fortification of lemonade with herbal extracts. Food Sci Technol 37:45–51 78. Sharma SK, Yadav VK, Rao VK, Dixit AK (2014) Enhancement of health-promoting properties while substituting exogenous citric acid by seabuckthorn (Hippophae salicifolia) pulp in

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preparation of sweet orange (Citrus sinensis) ready-to-serve beverage. J Food Process Preserv 38:1427–143.8 79. Sanchez-Bel P, Romojaro A, Egea I, Pretel MT (2015) Wild edible plants as potential antioxidant or nutritional supplements for beverages minimally processed. LWT Food Sci Technol 62:830–837 80. Ivanišová E, Frančáková H, Ritschlová P, Dráb Š, Solgajová M, Tokár M (2015) Biological activity of apple juice enriched by herbal extracts. J Microbiol Biotechnol Food Sci 4:69–73 81. Shon MS, Lee Y, Song JH, Park T, Lee JK, Kim M, Park E, Kim GN (2014) Anti-aging potential of extracts prepared from fruits and medicinal herbs cultivated in the Gyeongnam area of Korea. Prev Nutr Food Sci 19:178–186

3

Grape Polyphenolics R. F. Chavan and Bhagwan K. Sakhale

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Chemical Composition and Medicinal Benefits of Grapes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Grape Polyphenols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Forms and Structure of Grape Polyphenols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Antioxidant Activities of Some Polyphenolic Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Analysis of Antioxidant Activity of Grapes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Measurement of Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Application of Grape Polyphenols . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 6 Examples of Some Important Polyphenolic Compounds of Grapes . . . . . . . . . . . . . . . . . . . . . . . . 7 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abstract

Grapes are largely produced popular berry fruits potentially rich in some of the vital bioactive components which have several functional properties in general and specifically health-promoting medicinal properties. Grape contains a wide range of polyphenols along with wine as a popular grape product and is potentially rich in many phenolic compounds. Phenolic compounds are structurally different; linear and branched forms of the phenolic molecules perform many active biological functions. The grape polyphenols are traditionally classified into flavonoids and nonflavonoids, but it is subdivided into many subgroups according to the nature of R. F. Chavan Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India B. K. Sakhale (*) Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India Food Technology Division University Department of Chemical Technology (UDCT), Dr. Babasaheb Ambedkar Marathwada University, Aurangabad, Maharashtra, India © Springer Nature Switzerland AG 2022 H. M. Ekiert et al. (eds.), Plant Antioxidants and Health, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-78160-6_30

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chemical arrangement of the polyphenol molecule within its chemical structure. These subdivided groups have their different target-specific biological actions which increase the demand of characterization of these molecules since they have several important medicinal functions in human health. Many extraction and analytical techniques are used for the estimation, characterization, and isolation of these active polyphenolic components. Moreover, various analytical techniques are developed for the determination of total phenolic contents as well as for subcategorization of these extracted polyphenols. Some traditional processes and spectrophotometric analysis are ceaselessly improved so as to attain adequate separation of phenolic molecules, their further identification, and quantification. Keywords

Grapes · Polyphenols · Flavonoids · Antioxidants · Anthocyanin · Chemical structure · Extraction · Wine

1

Introduction

Fruits and vegetables are rich with innumerable chemical compounds including vitamins, minerals, and other potentially helpful phytochemicals. The consumption of fruits and vegetables has since long been associated with lesser incidences of certain diseases like cataract, scurvy, cancer, and cardiovascular diseases (CVD) in populations consuming them. The disease prevention ability of fruits and vegetables is mainly attributed to the phytochemicals present in minor quantities. Plants synthesize several classes of antioxidants, including vitamin C, as well as phenolic compounds, e.g., flavonoid pigments, carotenoids, and tocopherols (principally vitamin E). There are innumerous compounds in fruits and vegetables that could individually or synergistically contribute to improvements in human health. The number of identified physiologically active phytochemical has increased considerably in the last decades. The grape (Vitis vinifera) is one of the important fruits consumed across the globe. It is having potential health benefits and economic importance, and therefore it is widely cultivated around the globe. Over 72 million tons of grapes are grown each year worldwide, mostly to produce wine. Grapes are also a popular finger food since the nutrients in grapes offer a number of possible health benefits. They have been associated with prevention of cancer, heart disease, high blood pressure, and constipation. Vitis vinifera L. is a perennial woody vine cultivated throughout the world and its fruits are consumed as fresh fruits, juice, dried fruits (raisins) as well as in wine making [1]. Polyphenolics are important constituents of grapes in determining the color, taste, and organoleptic properties of wine. Wines prepared from grapes are an abundant source of various polyphenolics, particularly flavonoids and stilbenes. Resveratrol monomers, a stilbene, form different oligomers (dimers, trimers, tetramers) by oxidative condensation during wine maturation [2, 3].

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Production Scenario of Grapes As per the latest estimations of Food and Agriculture Organization, grape cultivation is carried out over 75,866 km2 area across the globe. Out of total grape production, 71% of the grapes are utilized for manufacturing of wines, 2% of the grapes are utilized in the dried form, and around 27% are consumed in fresh form. However, comparatively lesser portion of its production is utilized for preparation of the grape juice [4]. There are no confirmed statistics for indicating variety wise production of the grapes. However, a very popular variety of grapes which is used for cultivation around the world is Sultana that is also known as Thompson Seedless. Other common grape varieties include Airen, Cabernet Sauvignon, Sauvignon blanc, Cabernet Franc, Merlot, Grenache, Tempranillo, Riesling, and Chardonnay [5, 6]. Grapes Production in India Grape is grown from temperate to warm regions; however, hot and dry climate is ideal. Indian grapes come in varied characteristics namely, colored, white, seeded, seedless, large, and small berries. Indian grapes are successfully grown at and above 250 mean sea levels [7]. Modern packhouse facility with automatic forced air system for precooling is available in all the commercial production areas. Traceability system is maintained for the product tracking. Extensive Residue Monitoring plan for monitoring the pesticide residues in grapes is implemented for consumer safety. The major varieties commercially cultivated in India is shown in Table 1. They can be grouped under following four categories based on color and seeds [8, 9]. Grape is one of the important fruit crops covering an area of 123 thousand hectares occupying 2.01% of the total area. Currently, Thompson Seedless is the ruling grape Indian variety occupying major area with its clones followed by Bangalore Blue varieties. Major grape-growing states are Maharashtra, Karnataka, Telangana, Andhra Pradesh, Tamil Nadu, and the north-western region covering Punjab, Haryana, western Uttar Pradesh, Rajasthan, and Madhya Pradesh [10]. Maharashtra ranks first in terms of production accounting for more than 81.22% of total production and highest productivity in the country [11]. India is also a major exporter of fresh grapes to the world. The country has exported 1, 93,690.55 MT of grapes to the world for the worth of Rs. 2176.88 crores (298.05 USD millions) during the year 2019–2020. Major export destinations (2019–2020) are the Netherland, Russia, the UK, Bangladesh, and Germany [10, 11]. Table 1 Grape varieties cultivated in India Colored seeded Colored seedless White seeded White seedless

Bangalore Blue, Gulabi (Muscat) Beauty Seedless and Sharad Seedless Anab-e-Shahi, Dilkhush (clone of Anab-e-Shahi) Perlette, Pusa Seedless, Thompson Seedless and its clones, Tas-A-Ganesh, Sonaka, and Manik Chaman

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Chemical Composition and Medicinal Benefits of Grapes

Grapes (Vitis vinifera) are berries that grow in clusters are very delicious, and enticing with variable tastes, and colors. Grapes are consumed largely as whole fruits; but they are additionally utilized in preparation of diverse food merchandise and therefore the seeds of seeded varieties are utilized in medication, preponderantly antimicrobial medication and nematicides [12, 13]. Grapes cultivation dates back to 5000 BC; but, the wide unfold propagation of grapes was started in Europe, so unfold to Australia, America, and alternative countries through invaders and sailors. Egyptians used the grapes for wine, and later the technology was developed in varied western countries, notably Spain, France, and Federal Republic of Germany [13]. The history of grapes is protracted and ample. Wine making from grapes are recorded in the historic Greek and Roman civilization. European grapes (Vitis vinifera), North American Grapes (Vitis labrusca and Vitis rotundifolia), and French hybrid are mainly predominant species these days. Grapes are classified as table grapes, wine grapes (utilized in viniculture), raisin grapes, and whether to be eaten with seeds or seedless. The diverse varieties of the grapes are experienced by the peoples across the globe. Grapes consist principally of two varieties; one contains seeds whereas the others are seedless. The seedlessness may be an extremely fascinating quality of the grape. Among these seedless grape varieties are natural and a few are genetically obtained from basic seedless varieties that all belong to basic styles of genus Vitis [14, 15]. The grapes which are rich in polyphenols help in pressure regulation and protection of epithelial cells. They conjointly facilitate to fight cancer and minimize the chance of cardiopathy. The essential oil extracted from grape seeds are used in several health care products like cosmetics. These oils conjointly contain vitamin E, an unsaturated carboxylic acid of n-3, n-6, and n-9 series that protects the body from atom attacks. The grape juice helps to fight cancer, reduces the risk of coronary failure, improves brain health, and permits the body to withstand aging issues with the passage of time [15–17]. Grape juice is also supposed to be normalizing the cardiovascular disorders. It is crucial to understand the composition of grape with its biological process and health properties very well [18, 19].

3

Grape Polyphenols

Grape includes diverse nutrient elements, inclusive of vitamins, minerals, carbohydrates, fit to be eaten fibers, and phytochemicals. The phytochemicals are effective antioxidants that prevent free radical-mediated degenerative diseases like cancer, coronary heart diseases (CHD), etc. Polyphenols are the maximum vital phytochemicals in grape due to the fact that they own many organic compounds and providing benifits for better health [20]. Phenolic compounds are the important and most plentiful secondary metabolites present in the plant kingdom. Chemical structural similarity is observed of these compounds containing aromatic benzene ring with one and more hydroxyl substituents. In plants, they not only play an essential role in growth, fertility,

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reproduction, and defense mechanism but also act as a shield against abiotic and biotic stresses [21, 22]. The basic components of pigments, essences, and flavors are contributed by the phenolics. The properties like anticarcinogenic, cardioprotective, anti-inflammatory, antibacterial, and antiviral along with major antioxidant and antiradical activity are active biological functions reported in polyphenols such as catechin, resveratrol, quercetin, and rutin [23–26]. Polyphenolic compounds are very fundamental for the biological excellence of naturally derived food products through their contribution to oxidative stability and organoleptic characteristics. Indeed, the organoleptic properties of grapes and wines are largely related to phenolic compounds extracted from the grapes. The major compounds responsible for wine quality are flavonoids, including anthocyanins and flavan-3-ols. Moreover, the red color of wine is due to anthocyanins pigment which is present in grape skin. Flavan-3-ols exist not only as monomers but also as oligomers and polymers, called condensed tannins or proanthocyanidins. Condensed tannins are important quality parameter of wine due to their astringent, bitter taste [27, 28], and their role in the long-term color stability [29–33].

3.1

Forms and Structure of Grape Polyphenols

Some common structures of phenolic compounds have been already identified and quantified in grapes but others such as high molecular mass phenolics or novel compounds formed during aging process of wines still remain to study. The different methods have been improved through the years. General approach allows the determination of total polyphenols by spectrophotometric detection. It is conflicting to more specific analyses based on the separation of the individual polyphenolic species typically by high-performance liquid chromatography or capillary electrophoresis, and their subsequent detection by different detectors, UV-vis, mass spectrometry [34, 35]. The polyphenols may be broadly categorized into two main group viz., flavonoids and nonflavonoids. The common structures of some important grape polyphenols are shown in the Fig. 1.

3.1.1 Flavonoids Flavonoids are a various cluster of phytochemicals found in the grapes in conjunction with carotenoids, and they impart vivid colors and also have potential antioxidant activities. Flavonoids are the most important cluster of phytonutrients, with quite more than half a dozen of types such as catechin, anthocyanin, proanthocyanin, flavonol, quercetin, etc. The phenolic compounds obtained from grapes primarily encompass anthocyanins, flavanols, flavonols, stilbenes (resveratrol), and phenolic acids [36, 37]. The anthocyanins pigment are found in grape skin. Flavonoids have broad categorization in grapes such as seeds and stems which majorly contain catechins, epicatechin, and procyanidin polymers. Anthocyanins are the primary polyphenolics in Thompson Seedless grapes, whereas flavan-3-ols are also present in ample quantity among various grape varieties [37–39]. The researcher’s attention leans toward chemical compositions and health benefits of polyphenols from grapes and crimson wines [40].

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Anthocyanin

Proanthocyanidin

Flavanol

Fig. 1 Structure of polyphenols

The suggested scientific evidences have proved that polyphenols have potential of inhibiting few degenerative disorders, inclusive of cardiovascular diseases [41–44], and some other varieties of grapes are effective in decreasing plasma oxidation strain and decreasing the momentum of aging of the fruits [31, 45]. Phenolic compounds also are appeared as preservatives in opposition to microbes and oxidation for food [46–49] and in vivo assays confirmed that phenolic compounds are bioavailable [50, 51]. Moreover, a few scientific evidences have been additionally proven that at better concentrations, the effect of phenolic compounds on health becomes bad, and a few systems particularly showed the bad consequences [52, 53]. However, some high molecular weight phenolics showed poor absorption [54, 55]. Grapefruit, grape seed, and grape skin extracts along with fruit juice are all supposed to contain a various array of potent antioxidants within the sort of polyphenols, which include phenolic acids (e.g., gallic acid), anthocyanins, and flavonoids (e.g., proanthocyanidins). Counting on their localization within the grape tissues, the grape proanthocyanidins showed difference in the number, structure, and degree of polymerization [56]. Moreover, grape contains higher concentrations of monomeric, oligomeric, and polymeric flavan-3-ols in seeds as compared to grape skins [56, 57]. Grape seeds contain approximately 2.3 to 8.2 mg/g of monomeric, oligomeric, and polymeric flavan-3-ols like catechin, epicatechin, and their gallates [58]. Grape skin contains approximately 20-fold less (on a milligram per gram basis) monomeric, oligomeric, and polymeric flavan-3-ols as compared to grape seeds [59]. It’s also documented that the polyphenol composition and content of grapes varies

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between different cultivars, and is influenced by geographic location and the climate [60]. Although the skin and seeds of grapes are reported to contain “cardioprotective” polyphenolic antioxidants, a recent animal study demonstrated that extracts from the flesh of grapes possessed cardioprotective actions [61]. The entire polyphenolic index was lower within the grape flesh as compared with the grape skin; however, the anthocyanins were exclusively within the grape skin, whereas the reactive oxygen scavenging activities were similar within the two groups. The results indicated that the flesh of grapes could also be equally cardioprotecive despite the very fact that the grape flesh doesn’t contain anthocyanin activity.

3.1.2 Nonflavonoids Among nonflavonoids, principal compounds are hydroxybenzoic acids also called as synthetic resin acids, hydroxycinnamic acids, and stilbens. Hydroxybenzoic acids support C6-C1 structure, a benzene ring with one carbon acyclic chain substituent. Subclasses are vanillic, syringic, and gallic acids. Many hydroxycinnamic acids (C6C3) are observed in grapes and wines (Fig. 2). Within the free morpheme they are known in tiny quantities which are majorly esterified with salt acid [60, 61]. They might be direct glycosides of aldohexose. A lot of complex polyphenols from another family is also found in grapes, wine, and oak wood. Among the trans-isomer compounds, resveratrol, or 3,5,4-trihydroxy stilben, is known to be created in wines in response to a mycosis [61]. Flavonoids, the foremost plethoric stilbene synthetic resin compounds in grapes and wines, own a typical C15skeleton, composed of 3 rings (A, B, C). The family of this molecules is set up by totally different subcategories, flavones, flavonols, flavanones, flavanols and anthocyanins differs by the ring C in saturation degree and substituents. Flavylium ion, includes two benzene rings associated with unsaturated cationic ventilated

Hydroxybenzoic acids

Stilbene

Hydroxycinnamic acids Fig. 2 Structure of some nonflavonoid polyphenols

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heterocycle, derived from the 2-phenyl-benzopyrylium nucleus. These are glycosylated derivatives of 5 aglycones or anthocyanidins family such as cyanidin, peonidin, petunidin, delphinidin, and malvidin [61, 62]. The diversity in structure results from spontaneous chemical process of the aldohexose by carboxylic acid, pcoumaric, and caffeic acids. These compounds consist linear chain monomers however, additionally oligomers or polymers known as proanthocyanidins. Proanthocyanin structures shows variation within the nature of their organic subunits, mean degree of polymerization (mDP), and linkage position. The grape skin contains relatively lower amounts of proanthocyanidins than seeds and their structural characteristics showed difference significantly. Grape seed proanthocyanidins are composed mainly of procyanidins, whereas grape skin proanthocyanidins contains both procyanidins and prodelphinidins. A better mDP and a lower proportion of galloylated subunits are observed in skin proanthocyanidins than in seeds. Condensed tannins derived from grapes have great importance in the quality of wines [62].

4

Antioxidant Activities of Some Polyphenolic Compounds

The antioxidant activity of the grapes has been studied in terms of inhibition of lipid oxidation, scavenging of free radicals, reduction of hydroperoxide formation [63, 64]. Various analytical methods are generally used to estimate the antioxidant capabilities of the various phenolic compounds extracted from various grape varieties or several parts of grapes. These generally includes crocin bleaching assay (CBA) [64], 1,1-diphenyl-2-picryhidrazyl (DPPH) method [65], oxygen radical absorbance capacity (ORAC) assay [63], the thiobarbituric acid reactant substances (TBARS), 2, 20 -azino-bis-(3- ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay [66], ferric reducing antioxidant power (FRAP) assay, and Trolox equivalent antioxidant capacity (TEAC) assay [67, 68].

4.1

Analysis of Antioxidant Activity of Grapes

Many sophisticated techniques have been developed for estimation and evaluation of the antioxidant activities of the grapes. The available analytical techniques have helped in thorough analysis of these antioxidant activities of many grape polyphenols. The simplified techniques have the classification of these activities based on different analytical parameters. Certain general steps which are usually followed as standard processes for evaluating antioxidant activities. Selection of the Grape Varieties Almost all the varieties of the grapes yield nearly similar sort of polyphenols. Moreover, some popular grape varieties are generally selected for evaluation of the antioxidant activities of the polyphenols extracted from these varieties. Every region of the world has different popular varieties according to their regional climatic conditions [69]. Although there are different grape varieties, but the chemical content of the grapefruit

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has much constant similarity compositional index as compared with chemical compositions of other fruits. Therefore, selection of grape varieties for the evaluation of antioxidant activities has significant regional impact [69, 70].

4.2

Measurement of Antioxidant Activity

The grapes of selected varieties are pretreated to make it ready for separation of the grape pomace. The obtained grape pomace is then freeze-dried followed by fine grinding, and then stored at 20 °C until its further use. The fine ground material is then utilized for extraction by using methanol as a solvent along with 1% HCL solution. The obtained extract is then concentrated by using hexanal followed by removal of methanol and hexanal residues. The percent yield is expressed in gram extract per 100 g of dry grape pomace [71]. The obtained extracts are further subjected to HPLC analysis by using suitable combination of the eluents, and then ESI-MS used exclusively for the detection and characterization of the metabolites [72]. Moreover, positive mode is applied for detection and characterization of anthocyanin whereas flavanols are characterized using negative mode followed by DAD analysis between 200 and 700 nm. The antioxidant activity of the grape extracts is measured by using DPPH method in terms of radical scavenging activity. The extracted sample is prepared in appropriate dilution for analysis by using UV-spectrophotometer. Initially, standard curve is obtained at 515 nm by using standard solution of the DPPH at different concentrations. The freshly prepared DPPH solution and methanolic extract solutions are mixed at varied proportions, incubated at 25 °C for 5 hrs, and then kept in dark to bring the prepared solution concentration at steady state [73, 74]. Moreover, the Trolox Equivalent Antioxidant Capacity (TEAC) assay is used for evaluation of free radical scavenging activity. The ability of polyphenolic contents in grape extract to scavenge the free radicals of ABTS Azino-bis (3-ethylbenzothiazoline-6-sulfonate) is recorded in terms of the value of TEAC assay. The samples are initially diluted with methanol at different concentrations followed by addition of diluted ABTS solution, and then absorbance is measured at 734 nm wavelength [74].

5

Application of Grape Polyphenols

The polyphenols extracted from the grapes are having tremendous potential of preventing the lipid peroxidation and therefore it protects free radicals from undergoing damages caused by the oxygen scavenging, in this way these polyphenols helps to extend the shelf life of the foods which are vulnerable to oxidative damages during their storage [66]. Modern research findings suggest that application of the polyphenols extracted from the grapes is more suitable to food industry than pharmaceutical applications. Many polyphenols have proved their potency in extending the shelf life of foods which are prone to free radical oxygen scavenging damages that compromises their

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storage qualities. These polyphenols also shows antimicrobial activities which have proved effective particularly against Salmonella typhimurium which is responsible for staling of the some frozen food products [67, 68]. Many research studies have been undertaken by using grape polyphenols along with different combinations of nisin, EDTA, and other agents in which polyphenols are found influencing the antioxidant and antimicrobial potential. These functional properties of grape polyphenols help to improve the storage stability of the fried and frozen foods. These grape polyphenols found effective against Salmonella typhimurium, Listeria monocytogenes, and Escherichia coli. The research findings also proved the potential use of these polyphenolic compounds in extending the storage life of the different food products. Moreover, the increasing trend of application of grape polyphenols is observed as a modern food preservation technique in food processing industries [68].

6

Examples of Some Important Polyphenolic Compounds of Grapes

I. Catechin: (Fig. 3) Name: Catechin Class: Flavonoids [76]. Chemical name: 2-(3,4-dihydroxyphenyl)-3,4-dihydro-2Hchromene-3,5,7-triol [77]. Structural chemistry: The position and number of hydroxyl group in the moiety determines antioxidant activity. The presence of catechol moiety and unsaturation increases activity in catechins. (+) Catechin is more effective [78] . Mode of action: Inhibits liquid peroxidation [79]. Application: Anti allergic, Anti-inflammatory, Antiviral, Antiproliferative, and Anticarcinogenic activities [80]. Sources: Apples, hops, tea, beer, etc. [80]. II. Resveratrol: (Fig. 4) Name: Resveratrol Class: Stilbenes [81] Chemical name: 3,4’, 5 trihydroxystilbene [82] . Fig. 3 Structure of catechin [75]

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Fig. 4 Structure of resveratrol [81]

Fig. 5 Structure of Vanillic acid

Structural chemistry: Resveratrol exist in cis as well as trans form isomers [82]. It has three pKa values, 6.4, 9.4, and 10.5. The pH affects the activity of the molecule [83]. Mode of action: Increases plasma antioxidant activity and decreases lipid peroxidation [84]. Application: Anti-inflammatory, Neuroprotective, and Antiviral properties [85]. Sources: Peanuts, Mulberries, Grapes [85]. III. Vanillic Acid: (Fig. 5) Name: Vanillic acid Class: Polyphenols Chemical name: 4-Hydroxy-3-methoxybenzoic acid [86]. Structural chemistry: The ester and hydroxyl groups present and their position affects the antioxidant capacity in the body [87]. Mode of action: Radical-scavenging activity [88]. Application: Showed chemopreventive against experimentally-induced carcinogenesis, Antibacterial, Antimicrobial properties, etc. [89]. Sources: Potato tuber, cereals like oats, wheat, barley, wine, etc. [90].

7

Conclusion

Grape is one of the major fruit crops cultivated across the globe with specific growing conditions, and its production is ever increasing. Grapes and its various value added processed products particularly wines are rich in many bioactive polyphenols, which are having potential health benefits to humans. The polyphenols from the grapes poses significant and versatile structural arrangement, some are flavonoids while others being nonflavonoids, and also includes many subcategories. Various novel techniques are developed for categorization and analysis of the

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versatile polyphenol composition within the various varieties of the grapes. This chapter reviews many modern techniques for the analysis and characterization of these active polyphenols from the grapes and its wines. These modern techniques are under continual improvement which includes spectrophotometric techniques, solvent extraction, supercritical extractions, and many more. Moreover, modern polyphenols manufacturing industries are in need of appropriate solutions to their industrial problems as far as the isolation of these polyphenolic compounds are concerned. Considering the tremendous versatility in the types of polyphenols in the different varieties of the grapes, many traditional spectrophotometric techniques are upgraded for identification, analysis, extraction, and characterization of the various polyphenolic compounds. Some advanced techniques are also developed by using HPLC, GC, and Mass Spectroscopy (MS) for target-specific phenolic components.

References 1. Vitrac X, Krisa S, Decendit A, Deffieux G, Merillon JM (2007) Grapevine polyphenols and their biological effects. In: Ramawat KG (ed) Biotechnology of medicinal plants: vitalizer and therapeutic. CRC press, Boca Raton, pp 33–75 2. Vidal S, Francis L, Guyot S, Marnet N, Kwiatkowski M, Gawel R, Cheynier V, Waters EJ (2003) The mouth-feel properties of grape and apple proanthocyanidins in a wine-like medium. J Sci Food Agric 83:564–573 3. Waffo-Teguo P, Krisa S, Richard T, Mérillon JM (2008) Grapevine stilbenes and their biological effects. In: Ramawat KG, Merillon JM (eds) Bioactive molecules and medicinal plants. Springer, Berlin/Heidelberg.https://doi.org/10.1007/978-3-540-74603-4_2 4. Urpi-Sarda M, Monagas M, Khan N, Lamuela-Raventos RM, Santos-Buelga C, Sacanella E, Castell M, Permanyer J, Andres-Lacueva C (2009) Epicatechin, procyanidins, and phenolic microbial metabolites after cocoa intake in humans and rats. Anal Bioanal Chem 394:1545–1556 5. Ugartondo V, Mitjans M, Lozano C, Torres JL, Vinardell MP (2006) Comparative study of the cytotoxicity induced by antioxidant epicatechin conjugates obtained from grape. J Agric Food Chem 54:6945–6950 6. Tsanga C, Higginsa S, Duthiea GG, Duthiea SJ, Howiea M, Mullena W, Leana ME, Crozier A (2005) The influence of moderate red wine consumption on antioxidant status and indices of oxidative stress associated with CHD in healthy volunteers. Br J Nutr 93:233–240 7. Wang CC, Chu CY, Chu KO, Choy KW, Khaw KS, Rogers MS, Pang CP (2004) Trolox equivalent antioxidant capacity assay versus oxygen radical absorbance capacity assay in plasma. Clin Chem 50:952–954 8. Spranger I, Sun B, Mateus AM, de Freitas V, Ricardo-da-Silva JM (2008) Chemical characterization and antioxidant activities of oligomeric and polymeric procyanidin fractions from grape seeds. Food Chem 108:519–532 9. Wroblewski K, Muhandiram R, Chakrabartty A, Bennick A (2001) The molecular interaction of human salivary histatins with polyphenolic compounds. Eur J Biochem 268:4384–4397 10. Spacil Z, Novakova L, Solich P (2008) Analysis of phenolic compounds by high performance liquid chromatography and ultra-performance liquid chromatography. Talanta 76:189–199 11. Shanmuganayagam D, Warner TF, Krueger CG, Reed JD, Folts JD (2007) Concord grape juice attenuates platelet aggregation, serum cholesterol and development of atheroma in hypercholesterolemic rabbits. Atherosclerosis 190:135–142 12. Serra AT, Matias AA, Nunes AVM, Leitao MC, Brito D, Bronze R, Silva S, Pires A, Crespo MT, Romao MVS, Duarte CM (2008) In vitro evaluation of olive- and grape-based natural extracts as potential preservatives for food. Innov Food Sci Emerg Technol 9:311–319

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13. Vatai T, Skerget M, Knez Z (2009) Extraction of phenolic compounds from elder berry and different grape marc varieties using organic solvents and/or supercritical carbon dioxide. J Food Eng 90:246–254 14. Serra A, Macia A, Romero MP, Salvado MJ, Bustos M, Fernandez-Larrea J, Motilva MJ (2009) Determination of procyanidins and their metabolites in plasma samples by improved liquid chromatography-tandem mass spectrometry. J Chromatogr 877:1169–1176 15. Meyer AS, Yi OS, Pearson DA, Waterhouse AL, Frankel EN (1997) Inhibition of human low density lipoprotein oxidation in relation to composition of phenolic antioxidants in grapes (Vitis vinifera). J Agric Food Chem 45:1638–1643 16. Sato M, Ramarathnam N, Suzuki Y, Ohkubo T, Takeuchi M, Ochi H (1996) Varietal differences in the phenolic content and superoxide radical scavenging potential of wines from different sources. J Agric Food Chem 44:37–41 17. Rubilar M, Pinelo M, Shene C, Sineiro J, Nunez MJ (2007) Separation and HPLC-MS identification of phenolic antioxidants from agricultural residues: almond hulls and grape pomace. J Agric Food Chem 55:10101–10109 18. Sano A, Uchida R, Saito M, Shioya N, Komori Y, Tho Y, Hashizume N (2007) Beneficial effects of grape seed extract on malondialdehyde-Modified LDL. J Nutr Sci Vitaminol 53:174–182 19. Rodriguez-Vaquero MJ, Alberto MR, Manca-de-Nadra MC (2007) Antibacterial effect of phenolic compounds from different wines. Food Control 18:93–101 20. Singletary KW, Stansbury MJ, Giusti M, Breemen RBV, Wallig M, Rimando A (2003) Inhibition of rat mammary tumorigenesis by concord grape juice constituents. J Agric Food Chem 51:7280–7286 21. Silva RC, Rigaud J, Cheynier V, Chemina A (1991) Procyanidin dimers and trimers from grape seeds. Phytochemistry 30:1259–1264 22. Shrikhande AJ (2000) Wine by-products with health benefits. Food Res Int 33:469–474 23. Radovanovic A, Radovanovic B, Jovancicevic B (2009) Free radical scavenging and antibacterial activities of southern Serbian red wines. Food Chem 11:326–331 24. Prior RL, Hoang H, Gu LW, Wu XL, Bacchiocca M, Huang DJ, Ou BX, Jacob R (2003) Assays for hydrophilic and lipophilic antioxidant capacity (oxygen radical absorbance capacity) of plasma and other biological and food samples. J Agric Food Chem 51:3273–3279 25. Poudel PR, Tamura H, Kataoka I, Mochioka R (2008) Phenolic compounds and antioxidant activities of skins and seeds of five wild grapes and two hybrids native to Japan. J Food Compos Anal 21:622–625 26. Pinelo M, Rubilar M, Sineiro J, Nunez MJ (2005) A thermal treatment to increase the antioxidant capacity of natural phenols: catechin, resveratrol and grape extract cases. Eur Food Res Technol 221:284–290 27. Rivero-Perez MD, Muniz P, Gonzalez-Sanjose ML (2008) Contribution of anthocyanin fraction to the antioxidant properties of wine. Food Chem Toxicol 46:2815–2822 28. Rhodes PL, Mitchell JW, Wilson MW, Melton LD (2006) Antilisterial activity of grape juice and grape extracts derived from Vitis vinifera variety Ribier. Int J Food Microbiol 107:281–286 29. Pastrana-Bonilla E, Akoh CC, Sellappan S, Krewer G (2003) Phenolic content and antioxidant capacity of muscadine grapes. J Agric Food Chem 51:5497–4503 30. Panico AM, Cardile V, Avondo S, Garufi F, Gentile B, Puglia C, Bonina F, Santagati NA, Ronsisvalle G (2006) The in vitro effect of a lyophilized extract of wine obtained from Jacquez grapes on human chondrocytes. Phytomedicine 13:522–526 31. Olas B, Wachowicz B, Tomczak A, Erler J, Stochmal A, Oleszek W (2008) Comparative antiplatelet and antioxidant properties of polyphenol-rich extracts from: berries of Aronia melanocarpa, seeds of grape and bark of Yucca schidigera in vitro. Platelets 19:70–77 32. Mazza GJ (2007) Anthocyanins and heart health. Ann Ist Super Sanita 43:369–374 33. Majo DD, Guardia ML, Giammanco S, Neve LL (2008) Giammanco, M. The antioxidant capacity of red wine in relationship with its polyphenolic constituents. Food Chem 111:45–49 34. Maier T, Schieber A, Kammerer DR, Carle R (2009) Residues of grape (Vitis vinifera) seed oil production as a valuable source of phenolic antioxidants. Food Chem 112:551–559

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35. Luther M, Parry J, Moore J, Meng JH, Zhang YF, Cheng ZH, Yu L (2007) Inhibitory effect of chardonnay and black raspberry seed extracts on lipid oxidation in fish oil and their radical scavenging and antimicrobial properties. Food Chem 104:1065–1073 36. Makris DP, Boskou G, Andrikopoulos NK, Kefalas P (2008) Characterization of certain major polyphenolic antioxidants in grape (Vitis vinifera) stems by liquid chromatography-mass spectrometry. Eur Food Res Technol 226:1075–1079 37. Lu Y, Bennick A (1998) Interaction of tannin with human salivary proline-rich proteins. Arch Oral Biochem 43:717–728 38. Karadeniz F, Durst RW, Wrolstad RE (2000) Polyphenolic composition of raisins. J Agric Food Chem 48:5343–5350 39. Laurent C, Besancon P, Caporiccio B (2007) Flavonoids from a grape seed extract interact with digestive secretions and intestinal cells as assessed in an in vitro digestion/Caco-2 cell culture model. Food Chem 100:1704–1712 40. Jung K, Wallig M, Singletary K (2006) Purple grape juice inhibits 7, 12-dimethylbenz- [a] anthracene (DMBA)-induced rat mammary tumorigenesis and in vivo DMBA-DNA adduct formation. Cancer Lett 233:279–288 41. Hurrell RF, Reddy M, Cook JD (1999) Inhibition of non-haem iron absorption in man by polyphenolic-containing beverages. Br J Nutr 81:289–295 42. Jeffery DW, Mercurio MD, Herderich MJ, Hayasaka Y, Smith PA (2008) Rapid isolation of red wine polymeric polyphenols by solid-phase extraction. J Agric Food Chem 56:2571–2580 43. Hogan S, Zhang L, Li J, Zoecklein B, Zhou K (2009) Antioxidant properties and bioactive components of Norton (Vitis aestivalis) and Cabernet Franc (Vitis vinifera) wine grapes. LWTFood Sci Technol 42:37–55 44. Ju ZY, Howard LR (2005) Subcritical water and sulfured water extraction of anthocyanins and other phenolics from dried red grape skin. J Food Sci 70:270–276 45. Hernandez-Jimenez A, Gomez-Plaza E, Martinez-Cutillas A, Kennedy JA (2009) Grape skin and seed proanthocyanidins from Monastrell  Syrah grapes. J Agric Food Chem 57:10798–10803 46. Guerrero RF, Liazid A, Palma M, Puertas B, Gonzalez-Barrio R, Gil-Izquierdo A, GarciaBarroso C, Cantos-Villar E (2009) Phenolic characterization of red grapes autochthonous to Andalusia. Food Chem 112:949–955 47. God JM, Tate P, Larcom LL (2007) Anticancer effects of four varieties of muscadine grape. J Med Food 10:54–59 48. Garcia-Alonso J, Ros G, Vidal-Guevara ML, Periago MJ (2006) Acute intake of phenolic-rich juice improves antioxidant status in healthy subjects. Nutr Res 26:330–339 49. Fiori L, De-Faveri D, Casazza AA, Perego P (2009) Grape by-products: extraction of polyphenolic compounds using supercritical CO2 and liquid organic solvent—a preliminary investigation. CYTA-J Food 7:163–171 50. Falchi M, Bertelli A, Scalzo RL, Morassut M, Morelli R, Das S, Cui JH, Das DK (2006) Comparison of cardioprotective abilities between the flesh and skin of grapes. J Agric Food Chem 54:6613–6622 51. Dopico-Garcia MS, Fique A, Guerra L, Afonso JM, Pereira O, Valentao P, Andrade PB, Seabra RM (2008) Principal components of phenolics to characterize red Vinho Verde grapes: anthocyanins or non-coloured compounds. Talanta 75:1190–1202 52. De Ruiter N, Ottenwalder O, Muliawan H, Kappus H (1982) Lipid peroxidation in isolated rat hepatocytes measured by ethane and n-pentane formation. Arch Toxicol 49:265–273 53. Hong N, Yaylayan VA, Raghavan GSV, Pare JRJ, Belanger JMR (2001) Microwave-assisted extraction of phenolic compounds from grape seed. Nat Prod Lett 15:197–204 54. Dani C, Oliboni LS, Vanderlinde R, Pra D, Dias JF, Yoneama ML, Bonatto D, Salvador M, Henriques JAP (2009) Antioxidant activity and phenolic and mineral content of rose grape juice. J Med Food 12:188–192 55. Chatterjee S, Poduval TB, Tilak JC, Devasagayam TP (2005) A modified, economic, sensitive method for measuring total antioxidant capacities of human plasma and natural compounds using Indian saffron (Crocus sativus). Clin Chim Acta 352:155–165

3

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49

56. Feliciano RP, Bravo MN, Pires MM, Serra AT, Duarte CM, Boas LV, Bronze MR (2009) Phenolic content and antioxidant activity of moscatel dessert wines from the Setúbal region in Portugal. Food Anal Methods 2:149–161 57. Chafer A, Pascual-Marti MC, Salvador A, Berna A (2005) Supercritical fluid extraction and HPLC determination of relevant polyphenolic compounds in grape skin. J Sep Sci 28:2050–2056 58. Bagchi D, Bagchi M, Stohs SJ, Das DK, Ray CA, Kuszynski SS, Joshi HG (2000) Free radicals and grape seed proanthocyanidin extract: importance in human health and disease prevention. Toxicology 148:187–197 59. Auger C, Teissedre PL, Gerain P, Lequeux N, Bornet A, Serisier S, Besançon P, Caporiccio B, Cristol JP, Rouanet JM (2005) Dietary wine phenolics catechin, quercetin, and resveratrol efficiently protect hypercholesterolemic hamsters against aortic fatty streak accumulation. J Agric Food Chem 53:2015–2021 60. Chacona MR, Ceperuelo-Mallafrea V, Maymo-Masipa E, Mateo-Sanzb JM, Arolac L, Guitierreza C, Fernandez-Reald JM, Ardevolc A, Simona I, Vendrella J (2009) Grape-seed procyanidins modulate inflammation on human differentiated adipocytes in vitro. Cytokine 47:137–142 61. Bruno G, Sparapano L (2007) Effects of three esca-associated fungi on Vitis vinifera L: V. Changes in the chemical and biological profile of xylem sap from diseased cv. Sangiovese vines. Physiol Mol Plant Pathol 71:210–229 62. Brand-williams W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT- Food Sci Technol 28:25–30 63. Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of antioxidant power: the FRAP assay. Anal Biochem 239:70–76 64. Bell JRC, Donovan JL, Wong R, Waterhouse AL, German JB, Walzem RL, Kasim-Karakas SE (2000) Catechin in human plasma after ingestion of a single serving of reconstituted red wine. Am J Clin Nutr 71:103–108 65. Arnous A, Makris DP, Kefalas P (2002) Correlation of pigment and flavanol content with antioxidant properties in selected aged regional wines from Greece. J Food Compos Anal 15:655–665 66. Amico V, Chillemi R, Mangiafico S, Spatafora C, Tringali C (2008) Polyphenol-enriched fractions from Sicilian grape pomace: HPLC–DAD analysis and antioxidant activity. Bioresources 99:5960–5966 67. Cantos E, Espin JC, Tomas-Barberan FA (2002) Varietal differences among the polyphenol profiles of seven table grape cultivars studied by LC-DAD-MS-MS. J Agric Food Chem 50:5691–5696 68. Esposito E, Rotilio D, Di Matteo V, Di Giulio C, Cacchio M, Algeri S (2002) A review of specific dietary antioxidants and the effects on biochemical mechanisms related to neurodegenerative processes. Neurobiol Aging 23:719–735 69. Halpern MJ, Dahlgren AL, Laakso I, Seppanen-Laakso T, Dahlgren J, McAnulty PA (1998) Red-wine polyphenols and inhibition of platelet aggregation: Possible mechanisms, and potential use in health promotion and disease prevention. J Int Med Res 26:171–180 70. Ruiz-Larrea MB, Martin C, Martinez R, Navarro R, Lacort M, Miller NJ (2000) Antioxidant activities of estrogens against aqueous and lipophilic radicals, differences between phenol and catechol estrogens. Chem Phys Lipids 105:179–188 71. Cano A, Hernandez-Ruiz J, Garcia-Canovas F, Acosta M, Arnao MB (1998) An end-point method for estimation of the total antioxidant activity in plant material. Phytochem Anal 9:196–202 72. Thomas JH, Drake JM, Paddock JR, Conklin S, Johnson J, Seliskar CJ (2004) Characterization of ABTS at a polymermodified electrode. Electroanalysis 16:547–555 73. Mazza G (1995) Anthocyanins in grapes and grape products. Crit Rev Food Sci Nutr 35:341–371 74. Schlesier K, Harwat M, Bohm V, Itsch R (2002) Assessment of antioxidant activity by using different in vitro methods. Free Radic Res 36:177–187

50

R. F. Chavan and B. K. Sakhale

75. Zanwar AA, Badole SL, Shende PS, Hegde MV, Bodhankar SL (2014) Antioxidant role of catechin in health and disease. Polyphenol Human Health & Dis 32:267–271 76. Chander V (2003) Catechin, a natural antioxidant protects against rhabdomyolysis-induced myoglobinuric acute renal failure. Pharmacol Res 48:503–509 77. Yeni G, Syamsu K, Suparno O, Mardliyati E, Muchtar H (2014) Repeated extraction process of raw gambiers (Uncaria gambier Robx.) for the catechin production as an antioxidant. Int J Appl Eng Res 9:24565–24578 78. Senanayake SN (2013) Green tea extract: chemistry, antioxidant properties and food applications – a review. J Funct Foods 5:1529–1541 79. Someya S, Yoshiki Y, Okubo K (2002) Antioxidant compounds from bananas (Musa cavendish). Food Chem 79:351–354 80. Yao LH, Jiang YM, Shi J, Datta N, Singanusong R, Chen SS, Tomas-Barber ANFA (2004) Flavonoids in food and their health benefits. Plant Foods Hum Nutr 59:113–122 81. Lima DP, Rotta R, Beatriz A, Marques MR, Montenegro RC, Vasconcellos MC, Pessoa C, Moraes MOD, Costa-Lotufo LV, Sawaya ACHF, Eberlin MN (2009) Synthesis and biological evaluation of cytotoxic properties of stilbene-based resveratrol analogs. Eur J Med Chem 44:701–707 82. Frémont L (2000) Biological effects of resveratrol. Life Sci 66:663–673 83. Mahal HS, Mukherjee T (2006) Scavenging of reactive oxygen radicals by resveratrol: antioxidant effect. Res Chem Intermed 32:59–71 84. Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5:493–506 85. Gülçin I (2010) Antioxidant properties of resveratrol: a structure–activity insight. Innov Food Sci Emerg Technol 11:210–218 86. Maksimuk Y, Antonava Z, Ponomarev D, Sushkova A (2018) Standard molar enthalpies of formation for crystalline vanillic acid, methyl vanillate and acetovanillone by bomb calorimetry method. J Therm Anal Calorim 134(3):2127–2136 87. Palafox-Carlos H, Gil-Chávez J, Sotelo-Mundo R, Namiesnik J, Gorinstein S, GonzálezAguilar G (2012) Antioxidant interactions between major phenolic compounds found in ‘Ataulfo’ mango pulp: chlorogenic, gallic, protocatechuic and vanillic acids. Molecules 17(11):12657–12664 88. Tai A, Sawano T, Ito H (2012) Antioxidative Properties of vanillic acid esters in multiple antioxidant assays. Biosci Biotechnol Biochem 76(2):314–318 89. Prince PS, Rajakumar S, Dhanasekar K (2011) Protective effects of vanillic acid on electrocardiogram, lipid peroxidation, antioxidants, proinflammatory markers and histopathology in isoproterenol induced cardiotoxic rats. Eur J Pharmacol 668(1–2):233–240 90. Tomas-Barberan FA, Clifford MN (2000) Dietary hydroxybenzoic acid derivatives – nature, occurrence and dietary burden. J Sci Food Agric 80:1024–1032

4

Betalains as Antioxidants Erick L. Bastos and Willibald Schliemann

Contents 1 Introduction and Scope . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 A General Survey of Betalains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Antioxidant Properties of Betalains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Betalain-Rich Plant Extracts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Isolated Betalains . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Chemical Mechanisms of Antioxidant Action . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 Model Pseudo-natural Betaxanthins . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Conclusions and Perspectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

52 53 56 57 60 71 75 76 77

Abstract

An overview is provided of the status of research on the antioxidant and radicalscavenging properties of betalains, water-soluble pigments found in plants, fungi, and bacteria. Together with anthocyanins, betalains are responsible for most of the red, purple, and blue colors of fruits and flowers, although both classes of secondary metabolites are mutually exclusive in nature. The 1,7-diazaheptamethinium scaffold of betalains promotes their radical-scavenging properties, which involve the occurrence of proton-coupled electron transfer. Betalains derived from cyclo-DOPA, namely betacyanins, are antioxidants as potent as epicatechin gallate from green tea. The other betalains, classified as betaxanthins, also show high antioxidant potential whether they are phenolic or not. Since much of the current understanding E. L. Bastos (*) Departamento de Química Fundamental, Instituto de Química, Universidade de São Paulo, São Paulo, SP, Brazil e-mail: [email protected] W. Schliemann (*) Leibniz Institute of Plant Biochemistry, Department of Secondary Metabolism, Halle (Saale), Germany e-mail: [email protected] © Springer Nature Switzerland AG 2022 H. M. Ekiert et al. (eds.), Plant Antioxidants and Health, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-78160-6_9

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of the antioxidant properties of betalains has been derived from studies of model compounds that mimic the reactivity patterns of natural pigments, comprehensive data on the antioxidant action of both natural and pseudo-natural betalains are presented. Keywords

Betalains · Betacyanins · Betaxanthins · Antioxidants · Radical scavenging · Proton-coupled electron transfer · Caryophyllales · Basidiomycete

1

Introduction and Scope

Natural products, or secondary metabolites, from bacteria, fungi, and plants are involved in their reproduction, interspecies communication, and defense mechanisms against biotic and abiotic stresses [1]. Due to their chemical diversity, properties, and availability, natural products are part of our daily life, being found in foodstuff, cosmetics, and health care products. Antioxidant secondary metabolites have high added value due to their antiaging and health-promoting effects as well as to the general consumer preference for products containing natural ingredients rather than their synthetic counterparts. Projections indicate that the global natural antioxidant market size should reach approximately 1.3 bi USD/year by 2024 [2]. Anthocyanins, betalains, and carotenoids are classes of natural pigments with marked antioxidant properties [3–5]. Although betalains and anthocyanins share similar functions in vivo, they have differing biosynthetic origins, show striking structural and physicochemical differences, and were never found together in the same organism [6–10]. Betalains are hydrophilic alkaloids restricted to plants of most families of the order Caryophyllales, some fungi in the Basidiomycota phylum [11–13], and the bacterium Gluconacetobacter diazotrophicus [14]. Anthocyanins, however, are flavonoids widespread within angiosperms but are absent in fungi and bacteria [15]. The historical connection between anthocyanins and betalains is presented in Box 1. Box 1 Historical aspects of the discovery of betalains

Early reports on betalains describe the use of juice of beetroot (Beta vulgaris L.) and pokeweed (Phytolacca americana L.) to adulterate wine [16]. In 1918, the red-magenta pigments from beetroots were found to contain nitrogen and named as betacyanins by Willstätter and Schudel, who also named the most abundant derivative as betanin (betanidin 5-O-β-D-glucoside) [16–20]. Although the etymology of the word betacyanin is the Latin word beta for beet and the Greek kyanós for blue, the suffix seems to originate from the connection between betacyanins and anthocyanins during the early days of their discovery [16]. Since betacyanins, such as betanin, are difficult to isolate (continued)

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53

Box 1 (continued)

and purify, Robinson assumed them to be “nitrogenous anthocyanins” based on the properties of synthetic aminoflavylium salts [21, 22]. The distinction between betacyanins and anthocyanins was only possible when betanin was crystallized and fully characterized by Wyler and Dreiding [23–25]. The betacyanins from beetroots were accompanied by yellow betalains, which Wyler and Dreiding classified as betaxanthins (from Ancient Greek, xanthós: yellow) [26]. The isolation and characterization of the first betaxanthin, indicaxanthin (L-Pro-betaxanthin) from prickly pear fruits [Opuntia ficusindica (L.) Mill.] [27, 28], and studies on the interconversion of betanin and indixanthin in vitro revealed that betacyanins and betaxanthins had the same chemical precursor, which was named betalamic acid [29]. Ultimately, the variability of the relative proportions of betacyanins and betaxanthins is responsible for the enormous range of colors of several species of plants and fungi [20].

The antioxidant performance of most betalains and betalamic acid is superior to that of many flavonoids, ascorbic acid, and tocopherols [30–32], and hence, their use as substitutes for artificial dyes is appealing [18]. In particular, betacyanins are antioxidants (AOx) as potent as epicatechin gallate from green tea due in part to the presence of a phenolic moiety derived from the precursor cyclo-3-(3,4dihydroxyphenyl)-L-alanine (cyclo-L-DOPA) [30, 31, 33, 34]. The mechanism of their antioxidant action, however, still needs to be fully clarified [30, 35–38]. In the following sections, we provide a survey of the status of research at the frontiers of the investigation of the antioxidant properties of betalains, compiling the available data on their antioxidant action. An in-depth description of other aspects of betalain research can be found elsewhere [12, 13, 30, 39–49]. The text is subdivided into four sections that include a brief introduction to betalains, the description of the antioxidant properties of betalain-containing plant extracts and isolated compounds, considerations on the mechanisms of antioxidant action of betalains, and some perspectives and remaining challenges in the field. In view of the large amount of data on this subject, there are certainly important studies that we do not discuss here, for which we apologize.

2

A General Survey of Betalains

Betalains impart yellow, orange, and/or bright red-violet colors, and occasionally green fluorescence, to living organisms [50]. More than 200 examples of natural betacyanins and betaxanthins have been identified [30, 42], mostly in plants, where they are located in the cell sap of vacuoles [51]. The antioxidant properties of betalains in red and yellow beetroots [52–61], prickly pear [59, 62–69], and pitaya (Hylocereus spp.) [70–72] have been investigated due to their use as food [73]. However, extracts of

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other betalain-pigmented plants have also been reported to show high antioxidant potential. Examples include amaranth (Amaranthus ssp.) [74–77], quinoa (Chenopodium quinoa Willd.) [78], swiss chard (Beta vulgaris var. cicla L.) [79], ayrampo [O. soehrensii (Britton & Rose)] [80], cactus berry [Myrtillocactus geometrizans (Mart. ex Pfeiff.) Console] [81, 82], djulis (Chenopodium formosanum Koidz.) [83], ullucus (Ullucus tuberosus Caldas), pigeonberry (Rivina humilis L.), bougainvillea (Bougainvillea spp.) [84], and gray ghost organ pipe [Stenocereus pruinosus (Otto ex Pfeiff.) Buxb.] [85]. Therefore, several methods for the extraction of betalains from crude plant extracts and their stabilization have been developed [86]. Chemically, betalains are Schiff base adducts of nitrogen nucleophiles and betalamic acid, which is an aldehyde biosynthesized from L-tyrosine (Fig. 1) [20, 42, 87]. The reaction is spontaneous, nonstereoselective and allegedly occurs in the cytoplasm and/or the cell nucleus [88]. The resulting chiral polymethine compounds contain the 1,7-diazaheptamethinium chromophore [39, 89, 90], a structural scaffold that is also key for their high radical-scavenging action [35, 36]. Betacyanins derive from two epimeric aglycones, betanidin and isobetanidin, which differ by the configuration of C2 of the 1,2,3,4-tetrahydropyridine ring (Fig. 1). Betanin, gomphrenin, amaranthin, and bougainvillein, the four structural groups of betacyanins, have different glucosylation patterns and are more stable toward thermal degradation than their aglycones [91–94]. The biosynthesis of betacyanins in the leaves of red beet is induced by the oxidative burst caused by wounding and bacterial infiltration [95], suggesting that the antioxidant properties of betalains play a role in plant physiological homeostasis. Some fungi of the genera Amanita, Hygrocybe, and Hygrophorus also produce betalains. Among them, fly agaric (Amanita muscaria (L.) Lam.) was extensively studied due to its broad global distribution and the psychoactive (and toxic) properties of some of its components [96–102]. In this fungus, the dioxygenase-catalyzed oxidative splitting of L-DOPA produces both 4,5- and 2,3-seco-DOPA, which cyclizes into betalamic acid and muscaflavin, respectively (Fig. 1) [97, 98, 101, 103, 104]. The coupling between muscaflavin and amino acids or amines leads to the rare and scarcely investigated hygroaurins [105], whose potential application as antioxidants is yet to be verified, regardless of the reported antioxidant potential of A. muscaria extracts [106–108]. Despite its economic relevance, the chemical synthesis of betalains still does not seem feasible for their commercial production due to the numerous steps required to synthesize betalamic acid [115–119] and the low yield of the final products [119, 120]. However, betaxanthins can be conveniently semisynthesized in vitro using betalamic acid extracted from base-hydrolyzed red beetroot juice [90]. In addition, several methods for the biotechnological production of betalains based either on transgenic organisms able to express DODs [120–125] or callus cultivation [126–131] have emerged. Both natural and pseudo-natural [132] betalains have been prepared and used to establish structure-property relationships and to explore the potential application of betalains [37, 133–135]. The solubility in water, chirality, redox properties, and chemical versatility of these safe natural pigments have extended their technological application far beyond antioxidants. Examples of use of betalains include metal-free

O

NH2

L-DOPA

5

2

E

L-Tyrosine

NH2

OH

OH

O2

E

E NH2

O

L-4,5-seco-DOPA

O

NH2

O

L-2,3-seco-DOPA

HOOC

HO

HO

HOOC

O

OH

OH

2O

2O

O

O

O

H

N H

(S)

O

O

Muscaflavin

N H

(S)

OH

OH

Betalamic acid

HO

HO

O

2O

amino acid or amine

2O

amino acid or amine

N

HO

N H

(S)

H

O

N H

(S)

N

R2

O

Betaxanthins

O

H

R1

R3

R 5O R 4O

HO

Betalains

OH

OH

Hygroaurins

O

R3

R1 HO

R2

N H

(S)

O

CO2H

Betacyanins

O

H

N

OH

Fig. 1 Biosynthesis of betalains and hygroaurins from L-tyrosine. E indicates an enzymatic step. The enzymatic 3-hydroxylation of L-tyrosine produces 3,4dihydroxy-L-phenylalanine (L-DOPA), which is oxidatively cleaved in the presence of extradiol DOPA dioxygenases (DODs). The resulting 2,3- and 4,5-secoDOPAs undergo spontaneous cyclization affording muscaflavin and betalamic acid, respectively [48, 87, 90, 109–112]. Betacyanins are produced by convergent biosynthesis, as both cyclo-DOPA and betalamic acid originate from L-DOPA [88, 113, 114]

HO 4

HO 3

HO

(S)

O

H

4 Betalains as Antioxidants 55

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blue dyes [135], food colorants [136], redox mediators [137–139], fluorescent dyes and probes [140–142], colorimetric sensors [143], and reducing agents for the synthesis of metal nanoparticles [144]. Last, apart from their antioxidant potential in vivo [12, 30, 41, 42, 44, 145], other aspects of the biological activity and therapeutic application of betalains, especially betanin and indicaxanthin, have also been extensively investigated [146–149].

3

Antioxidant Properties of Betalains

The endogenous overproduction of radical and closed-shell (nonradical) reactive oxidant species, hereafter called ROS, induces oxidative stress and related conditions, such as cancer, atherosclerosis, Alzheimer’s disease, and Parkinson’s disease [150–158]. Antioxidant small molecules and enzymes contribute to the maintenance of the physiological redox balance [41, 159]. Although it is too simplistic to consider antioxidants as the ultimate panacea, several foods rich in antioxidants, either naturally occurring or supplemented, were shown to promote beneficial health effects [160, 161]. In a broad sense, antioxidants act by scavenging ROS and interrupting the oxidative chain reaction, preventing its initiation, and/or promoting the action of other antioxidant species [162–165]. Potent chain-breaking antioxidants are expected to have high antioxidant activity (kinetics, reactivity toward radicals) and/or antioxidant capacity (thermodynamics, number of radicals scavenged), although these terms are often used indiscriminately [158, 166]. The large variety of methods for measuring the antioxidant activity and capacity have been classified as single electron transfer (SET) and hydrogen atom transfer (HAT) assays [167– 169]. SET-based assays, such as the ferric-reducing antioxidant power (FRAP) assay, involve the monitoring of the endpoint of one-electron redox processes. HAT-based methods, such as the oxygen radical absorbance capacity (ORAC) assay, generally involve the competition between an antioxidant of interest and an oxidizable probe to reduce a radical species. The antioxidant capacity is often reported in equivalents of standard antioxidants, such as Trolox, a water-soluble analog of vitamin E, or ascorbic acid [166, 170–172]. The Trolox equivalent antioxidant capacity (TEAC) assay [173], which has several experimental variations, is very popular for the study of antioxidant capacity of natural products [167, 174, 175]. Since the value of TEAC for pure compounds is the number of radicals scavenged by each molecule of the analyte divided by two (the number of radicals quenched per molecule of Trolox [173, 176–178]), the physical significance of very high TEAC values must be carefully evaluated. However, there is a lack of standardization in experimental procedures for the analyses of antioxidants and form of expressing the results making the comparison of data challenging [168]. In this section, we provide an overview of the antioxidant potential of betalainrich plant extracts and compare the antioxidant capacity of isolated compounds. Although the methods for the study of antioxidant potential have been widely reviewed [167, 179, 180], and are the focus of another chapter in this series [181],

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57

for completeness some details of the most common assays used for the study of betalain-containing plant extracts and isolated compounds are presented in Box 2. Box 2 Some methods used for the evaluation of the antioxidant properties of betalains

SET-based assays FRAP, ferric-reducing antioxidant power assay, FeIII/tripyridyltriazine (TPTZ) complex is submitted to reduction to produce FeII–TPTZ, colorimetric, monitored at 593 nm, 37 °C, 15 min in the dark [182]. HAT-based assays. ORAC, oxygen radical absorbance capacity assay, thermolysis of 2,20 azobis-(2-amidinopropane) dihydrochloride (AAPH), produces peroxyl radicals that bleach fluorescein. The antioxidant capacity is accessed by calculating the area under the fluorescence decay curve (AUC) relative to that of a blank in which no antioxidant was present [183]. AAPH-β-carotene assay, the peroxyl radicals produced by thermolysis of AAPH bleach β-carotene in the presence of linoleic acid and Tween 20 in PBS solution. The percentage of bleaching is measured by measuring changes in absorbance at 452 nm and 50 °C [184]. Mixed SET/HAT-based assays Total antioxidant capacity (TAC) assays; results often reported as TEAC. ABTS 2,20 -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid (ABTS•+) (variation I) generated by using myoglobin type III/H2O2, various solvents, pH variation allowed, colorimetric, usually measured at 734 nm [185, 186]; (variation II), ABTS•+ generated with S2O82 [173]; (variation III), ABTS•+ generated with HRP/H2O2 [187]. DPPH 2,2-diphenyl-1-picrylhydrazyl radical in ethanol or hydroalcoholic solution, colorimetric, usually measured at 515 or 517 nm [188–190]. Other assays GAR, global antioxidant response, [191, 192]. In vitro digestion of the sample before measuring the TAC. The GAR value is the sum of the TAC of soluble (bioaccessible) and insoluble (nonbioaccessible) fractions obtained by centrifugation of the digested sample. QUENCHER (QUick, Easy, New, CHEap, and Reproducible), [193]. Based on mixing grinded solid samples with the desired radical species and perform spectrophotometric measurement. ABTS•+ and DPPH• are commonly used as radical probes.

3.1

Betalain-Rich Plant Extracts

Betalains have been consumed in foods for millennia and are regarded as nontoxic [20]. Therefore, it is logical that plants pigmented by them be included in studies seeking biocompatible antioxidants [77, 152, 153, 194–198]. There is extensive evidence that

58

E. L. Bastos and W. Schliemann

betalains act as dietary antioxidants [199], having a positive effect on the overall redox state in vivo [30, 41–43, 200]. The in vitro radical-scavenging properties of betalain-rich plant extracts have been used as evidence of high antioxidant potential. However, as stated by Prior and coauthors [167], claims about the bioactivity of a sample based solely on radicalscavenging assays must be considered with care since other parameters, such as bioavailability, compartmentalization, stability and retention by tissues, and in situ reactivity, are expected to influence the antioxidant properties in vivo [201]. Furthermore, results obtained using antioxidant capacity assays in general and tests measuring oxidative damage, such as the production of thiobarbituric acid-reactive substances (TBARS), are frequently poorly correlated [168]. In this sense, there are several factors that must be considered for the critical evaluation of the data available on the radical-scavenging properties of betalains-rich plant extracts, which are summarized as follows. (i) The antioxidant capacity is influenced by the compositional pattern of the sample. The cultivar, the geographical origin, and the harvest time of the plant material under investigation are expected to affect the results [196]. B. vulgaris subsp. vulgaris, for example, has five main cultivar groups, altissima (sugar beet), cicla (chard), flavescens (swiss chard), conditiva (beetroot), and crassa, which encompass several species of plants that are not expected to have the same metabolites and antioxidant response [202–207]. (ii) The discrimination between antioxidants in complex matrices, such as plant extracts, can be very difficult and, although the identification of the most active components benefits from the use of antioxidant capacity/activity assays [170], the rationalization of the results is not always straightforward. For example, beetroots and other plants contain, in addition to betalains, a variety of antioxidant phenolic compounds such as gallic acid, ferulic acid, chlorogenic acid, caffeic acid, vanillic acid, syringic acid, ellagic acid, myricetin, quercetin, rutin, and kaempferol [208, 209]. (iii) Because the total antioxidant capacity of samples containing betalains depends on the characteristics of the assay used, data comparison is often inconclusive [196]. Consequently, the judicious choice of the method used to characterize both the antioxidant activity and capacity of antioxidant dietary supplements is required to obtain meaningful results. For example, the correlation between the FRAP and ORAC of beet extract has a coefficient of determination (R2) of 0.96, which may be fortuitous or have no physical meaning since it is much higher than that of several other common vegetables [196]. More importantly, antioxidant and radical-scavenging properties are not synonymous. Most assays reporting antioxidant capacity are based on the reaction between a putative antioxidant and radical species that are not necessarily ROS. These aspects are of major importance for the analysis of the antioxidant profile of natural products and will be elaborated further in the following section. (iv) Variations in the oxidative status of a medium containing ROS and the redox potential of the active components are expected to correlate with the total

4

Betalains as Antioxidants

59

antioxidant capacity of the extract under investigation [168]. However, data analysis requires proper distinction between kinetic and thermodynamic effects in order to provide a proper molecular perspective on the properties of a sample containing several components [167]. Some assays used for the quantification of the antioxidant capacity also provide a measure of antioxidant activity. Despite the difficulties in interpreting the results of in vitro assays, there is solid evidence for the in vivo antioxidant potential of plant extracts containing betalains. For example, the beneficial nutraceutical properties of beetroots in functional foods are well documented [55, 195, 210–213]. The introduction of table beets (B. vulgaris var. rubra) in the diet of rats submitted to hepatic ischemia-reperfusion reduced the concentration of enzymes involved in antioxidant protection in vivo, such as glutathione peroxidase (GPx) and superoxide dismutase (SOD), and increased the concentration of zinc and copper, suggesting that the diet had positive effects on redox homeostasis [214]. Red beetroot juice reduced the DNA damage in leukocytes by 20% and reduced the amount of carbonyl compounds in plasma proteins by up to 30% [215]. Other examples of biological and therapeutical activities can be found elsewhere [148, 149]. Interestingly, the bioavailability of betalains is low, [30] and beeturia, the peculiar passage of red or pink urine upon consumption of betalain-rich food, or [216], has greatly stimulated the study of the biodistribution and metabolism of betalains [217]. Other betalain-containing crude plant extracts [197, 198, 218, 219] demonstrate the substantial antioxidant potential of betalains [13–20]. For example, the presence of betalains increases the added value of prickly pear cactus fruits, whose antioxidant properties have been extensively studied [67]. The study of the effect of digestion of the pulp and peels of prickly pear varieties from the Canary Islands revealed that antioxidant betalains, such as betanin and indicaxanthin, were stable enough to survive the gastric phase and reach the intestinal phase. Indicaxanthin presented a higher bioaccessibility, and its decomposition depended on the variety of prickly pear studied, reaching a maximum value of 42% after both gastric and intestinal digestion [220]. Red-purple pitaya [Hylocereus polyrhizus (Weber) Britton & Rose] is also a source of antioxidant betalains, including betanin, phyllocactin (6-Omalonylbetanin), and hylocerenin [6’-O-(300 -hydroxy-300 -methyl-glutaryl)-betanin] [70, 221–223]. The assessment of antioxidant properties and the biodistribution of betaxanthins in vivo was carried out by using a simple yet ingenious approach based on their fluorescence. Gandía-Herrero and coauthors used the fluorescence of betaxanthins of Opuntia fruit extracts to monitor their passage through the translucid digestive tube of the nematode Caenorhabditis elegans and to investigate the antioxidant effect of pure betalains on its life span [224]. It is of note that the biological relevance of fluorescence in flowers pigmented by betaxanthins, e.g., Mirabilis jalapa L. and Portulaca grandiflora Hook [50]. is still not entirely clear [225, 226]. Plants containing antioxidant betalains are, however, not necessarily colored or fluorescent, though. The “Śnieżna kula” variety of beetroot, also known as snowball beetroot, is a betanin-free non-GMO (genetic-modified organism) beetroot cultivar

60

E. L. Bastos and W. Schliemann

[227, 228]. The leaves of Śnieżna kula contain lower amounts of betalains than red beetroot, red rhubarb swiss chard, and white swiss chard. However, it shows expressive antioxidant capacity in vitro, as inferred by the FRAP and TEAC/ ABTS•+ (var. II) assays [228].

3.2

Isolated Betalains

The seminal report on the use of beetroot juice to scavenge hydroxyl and peroxyl radicals was published in 1996 [194], and in the same year, a patent on the use of betacyanins and betaxanthins as antioxidants to prevent lipid peroxidation was issued [229]. The radical scavenging capacity of the catechol group of the cycloDOPA moiety of betacyanins was evoked to explain the antioxidant properties of betacyanins [31]. However, although betacyanins can scavenge a higher number of ABTS•+ than betaxanthins [230], the opposite is true for lipoperoxyl radicals [231]. Phenolic betaxanthins, e.g., miraxanthin V, the dopamine-betaxanthin, show marked antioxidant properties, but not all antioxidant betaxanthins are phenolic, as demonstrated by the high antioxidant capacity and biological effect of indicaxanthin, the Lproline-betaxanthin [64]. Sekiguchi and coauthors synthetized 24 betaxanthins from amino acids using recombinant Mirabilis jalapa DOPA 4,5-dioxygenase and determined their antioxidant properties using the DPPH• method. They found that the antioxidant capacity of dopamine-betaxanthin is comparable to that of betanin and the anthocyanin cyanidin 3-glucoside [232]. The structures of some antioxidant betalains and betalamic acid are presented in Table 1. Among all known betalains, betanin is the most widely used and studied. This betacyanin is partially responsible for the high antioxidant potential of beetroots extracts and other magenta varieties of Caryophyllales plants such as the red pitaya [194, 197, 244]. It is also the main color component of the food additive approved by both the EFSA/E162 and FDA/73.40 [3, 44, 136, 245–251]. The autoxidation of betanin was investigated long before its antioxidant properties were discovered [252–256]. Nowadays, it is quite well established that betanin activates several mechanisms of antioxidant defense in vivo, interacts with oxidant and prooxidant species, and scavenges reactive radicals [235]. The structural features and redox properties of betanin promoted its application as a mediator in dye-sensitized solar cells [137, 257–259] and hydrogen production systems [138, 139], and as a reductant and stabilizing agent in the synthesis of metal nanoparticles [144]. Most studies of the antioxidant capacity of betalains and betalamic acid are based on the scavenging of ABTS•+ or DPPH• [167, 174, 190, 260], which rely on both PCET/HAT and SET processes [190] (Table 1). The concentration of the betalains of Amaranthaceae plants required to halve the concentration of DPPH• in hydroalcoholic solution, or EC50, was, on average, 2.5 times lower than that of ascorbic acid [74]. The mean EC50 of gomphrenin-type betacyanins (6-O-glucosyl betanidin) is 3.73 μmol L1, which is lower than that of betaxanthins (4.15 μmol L1), and indicates higher antioxidant capacity. The values of EC50 of gomphrenin, acylated gomphrenin, miraxanthin V, and L-tryptophan-betaxanthin are lower than that of

[38, 44, 64, 230, 235]

[74, 119, 236]

7659-95-2 209056-04-2

209056-03-1 58012-26-3 (C15R/S) 98742-35-9 (Zwitterionic form, C15R/S) 1633353-64-6 (A ¼ F3CCO2–)

Betanin Betanidin 5-O-β-D-glucopyranoside; Glc ¼ glucose

Betanidin cyclo-L-DOPA betacyanins; 15S ¼ betanidin and 15R ¼ isobetanidin

Betalains as Antioxidants (continued)

Ref. [90, 233, 234]

CAN RN(s)c 18766-66-0 80939-16-8 (disodium salt)

Name Betalamic acid

Structureb

Table 1 Structures of betalamic acid and natural betaxanthins and betacyanins and references that describe their antioxidant propertiesa

4 61

1047-87-6

Vulgaxanthin II L-Glutamic acid-betaxanthin

CAN RN(s)c 1870912-57-4 94983-34-3 (C15R/S)

904-62-1

Structureb

Vulgaxanthin I L-Glutamine-betaxanthin

Name Indicaxanthin L-Proline-betaxanthin

Table 1 (continued)

[208, 232, 240]

[208, 232, 240]

Ref. [64, 237–239]

62 E. L. Bastos and W. Schliemann

[232]

135545-99-2

135545-98-1

Portulacaxanthin III Glycine-betaxanthin

Portulacaxanthin II L-Tyrosine-betaxanthin

(continued)

[232, 241]

[232, 241, 242]

5375-64-4

Miraxanthin V Dopamine-betaxanthin

4 Betalains as Antioxidants 63

[232, 243]

1007894-70-3

L-Phenylalanine-betaxanthin

Ref. [232]

[232]

CAN RN(s)c 5589-85-5

71199-31-0 1259557-04-4

Structureb

Dopaxanthin L-DOPA-betaxanthin

Name Miraxanthin III Tyramine-betaxanthin

Table 1 (continued)

64 E. L. Bastos and W. Schliemann

81943-08-0

Muscaaurin VII L-Histidine-betaxanthin

(continued)

[232, 242, 243]

1007894-71-4

L-Tryptophan-betaxanthin

[232]

[232, 243]

81943-10-4

Vulgaxanthin IV L-Leucine-betaxanthin

4 Betalains as Antioxidants 65

L-Valine-betaxanthin

Name 3-Methoxytyramine-betaxanthin

Table 1 (continued) Structureb

Ref. [242]

[232, 243]

CAN RN(s)c 371157-07-2

81943-11-5

66 E. L. Bastos and W. Schliemann

[232, 243]

1007894-69-0

L-Isoleucine-betaxanthin

(continued)

[232]

81943-09-1

Vulgaxanthin III L-Asparagine-betaxanthin

4 Betalains as Antioxidants 67

L-Methionine-betaxanthin

Name GABA-betaxanthin γ-Aminobutyric acid-betaxanthin

Table 1 (continued) Structureb

839705-50-9

CAN RN(s)c 1007894-68-9

[232]

Ref. [232, 243]

68 E. L. Bastos and W. Schliemann

1007894-67-8

[232]

Although other stereoisomers, in particular the iso analogues, are expected to be found in solution during analysis, we only show the structure of the derivatives of betalamic acid, which contains the 2-(S)-1,2,3,4-tetrahydropyridine-2,6-dicarboxylic acid moiety b The species are presented in the neutral nonzwitterionic form, and in certain cases, the generic anion (A) is added to reach neutrality. When available, the identity of the A counterion is provided c Chemical Abstract Services Registry Number

a

L-Threonine-betaxanthin

4 Betalains as Antioxidants 69

70

E. L. Bastos and W. Schliemann

betanin and are inversely correlated with the number of hydroxyl and imine/iminium functional groups [74]. However, it is worth mentioning that antioxidant assays based on the bleaching of DPPH• are performed by monitoring the disappearing of its absorption band centered at approximately 515 nm, which overlaps with the absorption of betacyanins (λmax ~ 535 nm). Hence, experimental planning and data analysis must take measures to avoid the misestimation of the TEAC of betacyanins and magenta-colored betaxanthins when using the TEAC/DPPH• method. The TEAC/ABTS•+ of betanidin was reported to be identical to that of betanin in the pH 5–9 range, but higher in acidic medium (pH 2–4) [236]. These are important results since the stability of betalains is enhanced by glucosylation and acylation [223]. Glucosylation of the 5-OH of the cyclo-DOPA moiety reduces the antioxidant capacity of betacyanins, as evidenced, for example, by the superior radical scavenging capacity of betanidin against peroxyl radicals and nitric oxide compared to glucosylated betacyanins, such as betanin, and phyllocactin [261]. Acylation of the glucosyl moiety, however, has no apparent effect on the antioxidant capacity of these betacyanins. Betaxanthins and betacyanins from red pitaya scavenge more DPPH• and ABTS•+ than ascorbic acid and gallic acid and the betacyanin fraction was shown to be a better radical scavenger than the flavonoid fractions of red pitaya flesh and peel [71]. The strong electronic coupling between the betalamic portion and the cyclo-DOPA moiety of the betacyanins was used to explain their higher antioxidant capacity against ABTS•+ compared to betaxanthins [64]. Betanin also has slightly lower anodic potentials, i.e., 404, 616, and 998 mV vs. 611 and 895 mV vs. Ag|AgCl for indicaxanthin, which is expected to enhance its antioxidant properties [64]. Studies on the reaction between betanin and DPPH•, as well as other radicals, were performed by using electron paramagnetic resonance (EPR) spectroscopy, which circumvents possible spectrophotometric artifacts [235]. The EPR signal of DPPH• decreased as the concentration of betanin was increased from 1.0– 10 μmol L1, and the same dose-dependent profile was observed for galvinoxyl radical. Betanin had the same effect on the signals corresponding to the adducts of 5,5-dimethyl-l-pyrroline-N-oxide (DMPO) spin trap and O2•– or HO•. These results, together with the positive effects of betanin on the H2O2-induced DNA damage in the human colon cancer cell line HT-29 and its transactivation of NRF2 and induction of heme oxygenase 1 (HO-1), indicate that betanin acts both as a radical scavenger and an activator of endogenous cellular enzymatic antioxidant defense mechanisms [235]. The results with NRF2 transcription factor are particularly relevant in the context of skin photoprotection [262]. Although several studies of the radical-scavenging capacity, cytotoxicity, and absorption of betalains have been performed [237, 239], clinical studies of the efficacy of betalains against diseases related to oxidative stress and of the bioavailability of betalains are still scarce [30]. It is known, however, that the antioxidant capacity of indicaxanthin in vitro was higher than that of betanin and both pigments may be absorbed from the gastrointestinal tract via different pathways. Betanin can be absorbed from both the stomach and small intestine whereas the absorption of indicaxanthin occurs only from the small intestine [61]. Extensive work has been

4

Betalains as Antioxidants

71

done by the group of Livrea in Palermo investigating the biological activity of betaxanthins, in particular indicaxanthin [63–65, 217, 237–239, 263–265]. Betalains are emerging as therapeutical agents obtainable from renewable sources, and further details of their biological activity are reviewed elsewhere [41, 148, 149]. Miraxanthin V and betanidin are expected to have the highest antioxidant capacities among betaxanthins and betacyanins, respectively, although these betalains are probably not stable enough to perform properly as antioxidants in product formulations [30]. The reactivity of betalains, which is the origin of their promising applied properties, may thus also be a major drawback. The study of the thermal stability and metabolic transformations of betalains in vivo is needed to unravel the mechanisms behind their bioactivity. Thermal effects on the antioxidant properties of betalains have been well characterized, including the pigments of djulis (C. formosanum) [83], S. pruinosus [85], beetroots submitted to processing [73, 266–268] and prickly pears [68]. Several betalains, including betanin, betanidin, and miraxanthin V have been encapsulated to prevent their decomposition [269] and to facilitate their application as antioxidants since this process has negligible effect on their radical-scavenging properties and color [269–273].

4

Chemical Mechanisms of Antioxidant Action

Despite the beneficial health effects related to the consumption of betalains, the knowledge of their multifaceted mechanisms of antioxidant protection is still modest compared to other natural antioxidants, such as anthocyanins [30, 41–43, 47, 111, 200, 274]. In this section, we briefly introduce key concepts for the study of the chemical mechanisms of antioxidant action mainly in the context of chain-breaking betalains and discuss the available experimental and computational results for antioxidant betalains. The study of the antioxidant properties of flavonoids, betacyanins, and phenolic betaxanthins has benefited from the use of phenols as models of chain-breaking antioxidants [30, 31, 275]. Phenols react with radical ROS, yielding less reactive, resonance-stabilized phenoxyl radicals that can be converted into stable substances, terminating the radical chain [275–277]. The stabilization of phenoxyl radicals via mesomeric, inductive, and captodative effects, as well as by intramolecular hydrogen bonding, has been reported to enhance the antioxidant performance of phenolic compounds [278, 279]. Ideally, the transient phenoxyl radical must be able to react as fast as possible, namely at the diffusion-controlled limit, with at least one other radical. The scavenging of more than two radicals per antioxidant molecule is often related to the regeneration of the antioxidant and/or the presence of multiple oxidation sites [275]. Because both phenolic and nonphenolic betalains show marked antioxidant properties [42], the mechanisms used to describe the reaction of phenols with radical ROS are not sufficient to explain the available experimental data. Compounds with relatively weak O–H, N–H, and S–H bonds are able to slow oxidative chain reactions by inactivating reactive radicals [280]. In particular, aromatic amines and

72

E. L. Bastos and W. Schliemann

other compounds with weak N–H bonds are efficient chain-breaking antioxidants, and their study is of interest to rationalize the antioxidant properties of betalains. Nevertheless, the overall process of radical chain inhibition by nitrogen-based antioxidants is frequently more complex than that of phenols [281]. For example, the aminyl radical may give rise to chain-transfer reactions besides reacting with a peroxyl radical to give a stable closed-shell product [281]. According to Mayer and coauthors, chain-breaking antioxidants interact with radicals preferentially via proton-coupled electron transfer (PCET) or single electron transfer (SET) [169, 280]. PCET processes can occur in a concerted or stepwise manner. HAT and concerted proton-electron transfer (CPET) are both concerted PCET pathways that have different stereoelectronic requirements [169]. The sequential proton loss electron transfer (SPLET) and the electron transfer followed by proton transfer (ET-PT) mechanisms involve stepwise electron-proton transfer [276, 282]. A general scheme for the processes involved in antioxidant action, as well as the parameters most used to investigate the mechanisms, is presented in Fig. 2. The ionization potential (IP) of antioxidants and the AOx–H bond dissociation energy (BDE) have been used to discriminate between the PCET and SET pathways [278]. BDEs lower than 370 kJ mol1 (the highest BDE reported for ROO–H bonds [283]) can indicate the occurrence of PCET/HAT [278, 284]. Phenols containing electron-donating substituents able to stabilize the resulting phenoxyl radicals show low O–H BDE and increased antioxidant potential. However, as the number and type of strong electron-donating groups increases, the IP of the antioxidant may decrease to a point where SET becomes feasible, enabling, among other reactions, the detrimental reduction of oxygen to produce superoxide ions, i.e., prooxidant behavior may arise [285]. Nitrogen-containing antioxidants may react by PCET or SET depending on their structure, the solvent, and the reacting radical. For example, the reaction of biliverdin esters with peroxyl radicals occurs via PCET/HAT due to the stabilization of the transient pyrrolic radical by intramolecular hydrogen bonding [286]. The study of the mechanism of antioxidant action of betalains is particularly challenging, partly because these pigments are subject to hydrolysis and other forms of thermal and photochemical decomposition [47, 136, 223, 287]. Betanin, for example, is reasonably stable at room temperature and at pH 4 to 7 [136]. However, although its alkaline hydrolysis leads to betalamic acid and 5-O-β-glucosyl cyclo-DOPA, which are well-known antioxidants, the radical-scavenging capacity of betanin is reduced upon thermal treatment [288, 289]. Hence, proper assessment of the antioxidant capacity of betalains requires careful evaluation of the species in solution. Pioneer mechanistic work by Gliszczyńska-Świglo and coworkers rationalized the effect of pH on the capacity of betanin to scavenge ABTS•+ [31, 236]. DFT calculations show that the deprotonation of the carboxylic acid groups reduces the BDE of the cycloDOPA 5-O–H group and the IP of betanin, explaining its pH-dependent TEAC [31]. Attempts to interpret the effect of pH on the 1H NMR and MS data of betanin using DFT calculations suggested that, under highly acidic conditions, betanin can assume a dicationic form and betalamic acid may exist as a cation [136]. Although the positive effect of pH on the antioxidant capacity of most betalains is well documented [47], reports on the pKa of betalains are scarce since the titration of betalains is difficult since

4

Betalains as Antioxidants

Fig. 2 More O’Ferrall– Jencks diagrams showing concurrent PCET processes of a generic antioxidant AOx–H. (a) Concerted (HAT and CPET) and stepwise (SPLET and ET-PT) pathways. (b) Parameters often used in mechanistic studies, i.e., pKas, redox potentials (E), proton affinity (PA), proton dissociation energy (PDE), ionization potential (IP), electron transfer enthalpy (ETE), homolytic bond dissociation enthalpy (BDE), and bond dissociation free energy (BDFE) [169, 278, 280]

73

a

ET-PT

CPET or HAT +

SPLET

+

AOx

AOx

IP

b

E

)

BDE or BDFE

PA(AOx ) pKa

+

+

AOx

PDE pKa

) )

AOx

ETE(AOx ) E(AOx |AOx )

many derivatives have rather limited solubility in water ( 10 mmol L1) and fast hydrolysis and/or decomposition under acidic or alkaline conditions [16, 50, 51, 62, 63]. A brief discussion on the pKa of betalains is presented in Box 3. Box 3 Considerations on the pKa of betalains

The literature often refers to the values of pKa reported by Nilsson for betanin (pKa of two of the carboxylic groups ≈ 3.4 and pKa of the 5-OH group ¼ 8.5) [18] and by Piattelli and Minale for indicaxanthin, pKaCOOH ≈ 3.3 [28]. The pKa of betanidin, the aglycon of betanin, was determined by means of DFT calculations, and although the results were dependent on the number of explicit water molecules included in the calculation, the C(sp2)–COO–H (continued)

74

E. L. Bastos and W. Schliemann

Box 3 (continued)

group was found to be the most acidic group and inferred to have a pKa < 2 [290]. The group of Gandía-Herrero from Murcia measured the apparent rate constant for the reaction between betalamic acid and 4-methylcatecholquinone at several pH values [133, 291] and inferred the pKa of betalamic acid to be 6.8. This method is based on the nucleophilicity of betalamic acid and the pKa may refer to the deprotonation of the nitrogen atom of the 5-aminopenta-2,4dienal system of betalamic acid [133]. An attempt to estimate the pKas of betalamic acid using methods implemented in commercial software packages is reasonably consistent with the experimental results [292]

Some compounds inhibit multiple stages of the oxidative pathway, making their classification as preventive or chain-breaking antioxidants difficult [281]. Preventive antioxidants may chelate prooxidant metal ions, act as optical filters of UV-Vis light to preclude the photochemical generation of radical ROS, and/or quench electronically excited species [281]. Phenols, which are well-known chain-breaking antioxidants, are not particularly good ligands for metal cations [293]. Nevertheless, σbonding between phenols and metal cations favors proton transfer to produce stable complexes, even under slightly acidic conditions [294–296], e.g., the pKas of phenol and of the CuII-phenol complex are 9.9 and 5.9, respectively [297, 298]. The phenolate group, on the other hand, is a hard ligand that interacts with cations of high charge density, such as FeIII, FeII, CuII, and ZnII, influencing their tendency of undergoing redox reactions. Flavonoids such as quercetin and kaempferol have been widely reported to chelate metals [293, 299–301]. Betanin shows chelating properties and their complexes with CuII and NiII have been reported [302, 303]. However, betalains can also chelate metal cations via their 2,6-dicarboxy-1,2,3,4-tetrahydropyridine moiety, as shown for EuIII-betanin complexes by using RAMAN spectroscopy combined with density-functional theory (DFT) calculations [143]. The capacity to chelate prooxidant metal cations ultimately jeopardizes the stability of betalains [47, 252, 254, 302]. Gandía-Herrero and coauthors showed by using the FRAP assay that betalamic acid can reduce two equivalents of FeIII to FeII. The complexation of betanin and CuII results in a labile (betanin)2CuII complex and the oxidation of betanin mediated by CuII leads to the same neobetanin and xanneobetanin derivatives produced by oxidation of betanin by ABTS•+, suggesting that decarboxylation and/or aromatization are the main pathways for betanin oxidation [302, 303]. Although betanin was found to form a CuII-complex, no spectrophotometric evidence for complexation was found for indicaxanthin [64], suggesting that complexation involves the catechol moiety. The mechanisms of oxidation of betacyanins have been extensively studied by the group of Wybraniec in Cracow [287, 304–307]. Betanidin and betanin have low oxidation potentials, supporting the role of betacyanins as strong reductants [304]. Oxidative decarboxylation of betanidin leads to 2-decarboxy-2,3-dehydrobetanidin and 2,17-didecarboxy-2,3-dehydrobetanidin, suggesting that the reaction can occur

4

Betalains as Antioxidants

75

through dopachrome and quinone methide intermediates. Subsequent oxidation and rearrangement of the conjugated chromophoric system results in the formation of 14,15-dehydrogenated derivatives [304]. Finally, the direct or sensitized excitation of biomolecules can promote photoredox processes that generate ROS, such as superoxide ion (O2•–), the hydroxyl radical (HO•), and singlet oxygen (1O2), in vivo. Therefore, species able to absorb ultraviolet and/or blue light may offer protection against oxidative damage [308– 310]. Betanin was found to quench 1O2, creating new opportunities to investigate the connection between excited state formation and antioxidant protection [311, 312]. In addition, betaxanthins show intense absorption in the blue region of the spectrum (λmax ~ 470 nm), and the ultrafast nonradiative decay of their singlet excited state to the ground state prevents them from acting as triplet photosensitizers, which might otherwise be involved in photochemical ROS production [134, 313, 314].

4.1

Model Pseudo-natural Betaxanthins

Through the systematic study of structure-property relationships, Gandía-Herrero and coauthors have made important contributions to the understanding of how the structural features of betalains contribute to their antioxidant properties. They found that phenolic betalains have higher antioxidant capacities and lower fluorescence compared to their nonphenolic counterparts [37, 43, 133, 315]. The study of structural effects on the absorption and fluorescence properties of betalains pointed to a major importance of the 1,7-diazaheptamethinium chromophore of betalains, which also plays a role in their radical scavenging properties for the rationalization of electronic effects. The capacity to scavenge ABTS•+ radicals of betaxanthin analogs of dopaxanthin is enhanced by the presence of phenolic hydroxy groups but does not rely on them completely, i.e., the TEAC drops from approximately 6.0 for dopaxanthin, which is catecholic [315], to 4.0 for the nonphenolic analogue, (S)-indoline-2-carboxylic acid [37, 315]. The conjugation of the 1,7-diazaheptamethinium system with an aromatic ring produces an enhancement of the antiradical activity, increasing the TEAC value by around 0.4 compared to a nonconjugated counterpart. If indoline-like substructures are formed, the enhancement is higher, up to 1.6 units. Monoglucosylation of the catechol group reduced the TEAC, and no effect of the presence of carboxylic groups near the imine/iminium bond was observed [37]. The same group used the worm C. elegans as an in vivo model to characterize the antioxidant and antiaging properties of a betaxanthin derived from the biopolymer chitosan [316]. Galactosamine-betaxanthin and glucosamine-betaxanthin were used as model compounds and were found to decrease the oxidative stress of the worms. Although the glucosamine-betaxanthin did not produce any significant effect on the lifespan of C. elegans, the galactosamine-betaxanthin (0.1 mmol L1) increased the mean lifespan by up to 8.5%. The study of model betaxanthins has provided further insight into the effect of the cyclo-DOPA moiety on the antioxidant properties of betacyanins [35, 36]. The comparison of the antioxidant capacity of aniline-betaxanthin (pBeet), 3-hydroxyaniline-betaxanthin (m-OH-pBeet), and 4-hydroxyaniline-betaxanthin

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( p-OH-pBeet) using the TEAC/ABTS•+ (II) assay at pH 7.4 revealed that, although m-OH-pBeet has a single phenolic hydroxyl group, its antiradical capacity (5.1  0.3) is similar to that of betanin (4.7  0.3), quercetin (4.9  0.4) [185], and epicatechin gallate (4.8 [317, 318]; 4.9 [319]). The TEACs of pBeet and p-OHpBeet are at least twice as high as that of ascorbic acid (AscH, TEAC ¼ 1.2  0.1) [36]. Quantum-chemical results suggest that SPLET is the favored thermodynamic pathway for the chain reaction inhibition in water. The effect of the 1,7diazaheptamethinium system on the antioxidant capacity and redox properties of betalains was investigated by comparing these results with those for the N-methyl analogues of pBeet and m-OH-pBeet, in which PCET involving the imine nitrogen atom is precluded. N-methyl pBeet and N-methyl m-OH-pBeet show the same TEAC value as ascorbic acid, and their preferred oxidation pathways involve the 1,2,3,4-tetrahydropyridine N–H and the phenolic O–H group, respectively. For all compounds studied, the occurrence of single electron transfer followed by proton transfer (ET-PT) is energetically less probable than either the SPLET or HAT mechanisms [175, 320]. Taken together, these results show that the 1,7diazaheptamethinium moiety can be involved in efficient concerted PCET and, hence, contribute to the high radical scavenging capacity of betalains.

5

Conclusions and Perspectives

As pointed out by Schwinn [145, 321], we are indeed in the golden age of betalain research and the study of the antioxidant properties of betalains is just beginning to flourish. Food containing meaningful amounts of betalains is not merely visually appealing but also can exert beneficial health effects upon consumption. Nevertheless, the biological activity of betalains remains to be fully scrutinized. Also, metabolites can exert completely different specific bioactivities compared to their parent antioxidants [201], and the study of the properties of betalain metabolites is still incipient. Natural betalains have emerged as multifaceted dietary antioxidant phytochemicals, with multiple sites of oxidation and a propensity to produce stable oxidized radical intermediates and products. Betanin is the main betalain component of E162 [35, 53], whose application as a food color additive has been reevaluated by the European Food Safety Authority [250, 251]. The remarkable biological properties of indicaxanthin from Opuntia fruits are shedding light on the potential application of betaxanthins. Advances in biotechnological methods for the production of betalains make possible to scale up betalain production, which no longer solely depends on the availability of plant source materials and efficient extraction protocols. The pivotal enzyme for betalain biosynthesis, 4,5-DOPA dioxygenase [322], has been found in several organism with no obvious phylogenetic relation to each other such as the P. grandiflora plant [323, 324] and the aquatic cyanobacterium Anabaena cylindrica [325]. The insertion of the DOD gene into plants naturally pigmented by anthocyanins results in concomitant betalain production, apparently without affecting plant development [88, 122, 326, 327].

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The establishment of structure-property relationships points to derivatives having high applicability, in particular as antioxidants and for therapeutic agents under conditions related to oxidative stress [149]. Betalains are efficient preventive antioxidants, acting as metal chelators and quenchers of electronically excited species, or can interrupt oxidative radical chain reactions via PCET and activate the mechanisms of antioxidant defense in vivo. Betanin also undergoes PCET-mediated hole stabilization in nanohybrid plasmonic systems for hydrogen production [139], indicating that studies of the mechanism of oxidation and reduction of betalains are relevant beyond the context of their antioxidant properties. Betalain analogues can be tailored to enhance their radical scavenging/antioxidant properties leading to new derivatives that mimic the reactivity patterns of the natural pigments [328]. In particular, a focus on the mechanisms of antioxidant action, as well as on methods to improve their bioavailability and hydrolytic stability, is of paramount importance for the rational design of novel betalaininspired antioxidants. It must be pointed out, however, that several natural antioxidants, such as vitamin C and green tea epicatechin gallate [285, 329], can act as prooxidants, depending on the dose, pointing to a need for in-depth investigation of the prooxidant properties of betalains. Acknowledgments E.L.B thanks the São Paulo Research Foundation – FAPESP (ELB, 2014/ 14866-2 and 2019/06391-8), the Brazilian National Council for Scientific and Technological Development – CNPq (ELB, 304094/2013-7), and the Coordination for the Improvement of Higher Education Personnel (CAPES, Finance code 001) for financial support.

References 1. Wink M (2010) Introduction: biochemistry, physiology and ecological functions of secondary metabolites. In: Wink M (ed) Annual plant reviews volume 40: Biochemistry of plant secondary metabolism, vol 40. Wiley-Blackwell, Chichester, pp 1–19. https://doi.org/10. 1002/9781444320503.ch1 2. Market Research Future (2020) Global natural antioxidants market research report, MRFR/FB & N/3693-HCR. https://www.marketresearchfuture.com/reports/natural-antioxidants-mar ket-5129. Accessed 10/30/2020 3. Delgado-Vargas F, Paredes-López O (2002) Chemicals and colorants as nutraceuticals. In: Delgado-Vargas F, Paredes-López O (eds) Natural colorants for food and nutraceutical uses. CRC Press, Boca Raton. https://doi.org/10.1201/9781420031713.ch10 4. Lila MA (2004) Plant pigments and human health. In: Davies K (ed) Plant pigments and their manipulation. Blackwell Publishing Ltd, Oxford, pp 248–274 5. Tanaka Y, Sasaki N, Ohmiya A (2008) Biosynthesis of plant pigments: anthocyanins, betalains and carotenoids. Plant J 54:733–749 6. Stafford HA (1994) Anthocyanins and betalains: evolution of the mutually exclusive pathways. Plant Sci 101:91–98. https://doi.org/10.1016/0168-9452(94)90244-5 7. Brockington SF, Walker RH, Glover BJ et al (2011) Complex pigment evolution in the Caryophyllales. New Phytol 190:854–864. https://doi.org/10.1111/j.1469-8137.2011.03687.x 8. Kimler L, Mears J, Mabry TJ et al (1970) On the question of the mutual exclusiveness of betalains and anthocyanins. Taxon 19:875–878. https://doi.org/10.2307/1218301 9. Mabry TJ, Taylor A, Turner BL (1963) The betacyanins and their distribution. Phytochemistry 2:61–64

78

E. L. Bastos and W. Schliemann

10. Davies KM (2015) Swapping one red pigment for another. Nat Genet 47:5–6. https://doi.org/ 10.1038/ng.3174 11. Lodge DJ, Padamsee M, Matheny PB et al (2013) Molecular phylogeny, morphology, pigment chemistry and ecology in Hygrophoraceae (Agaricales). Fungal Divers 64:1–99. https://doi. org/10.1007/s13225-013-0259-0 12. Polturak G, Aharoni A (2018) La vie en rose'': biosynthesis, sources, and applications of betalain pigments. Mol Plant 11:7–22. https://doi.org/10.1016/j.molp.2017.10.008 13. Khan MI, Giridhar P (2015) Plant betalains: chemistry and biochemistry. Phytochemistry 117: 267–295. https://doi.org/10.1016/j.phytochem.2015.06.008 14. Contreras-Llano LE, Guerrero-Rubio MA, Lozada-Ramirez JD et al (2019) First betalainproducing bacteria break the exclusive presence of the pigments in the plant kingdom. mBio 10:e00345-00319. https://doi.org/10.1128/mBio.00345-19 15. Gil-Ramírez A, Pavo-Caballero C, Baeza E et al (2016) Mushrooms do not contain flavonoids. J Funct Foods 25:1–13. https://doi.org/10.1016/j.jff.2016.05.005 16. Dreiding AS (1961) The betacyanins, a class of red pigments in the centrospermae. In: Ollis WD (ed) Recent developments in the chemistry of natural phenolic compounds. Pergamon Press Ltd, London, pp 194–211 17. Mabry TJ, Dreiding AS (1968) The betalains. In: Mabry TJ, Alston RE, Runeckles VC (eds) Recent advances in phytochemistry, vol 1. Appleton-Century Crofts, New York, pp 145–160 18. Nilsson T (1970) Studies into the pigments in beetroot (Beta vulgaris L. ssp. vulgaris var. rubra L.). Lantbr högsk Annlr 36:179–219 19. Lawrence WJC, Price JR, Robinson GM et al (1997) The distribution of anthocyanins in flowers, fruits and leaves. Philos Trans R Soc B 230:149–178. https://doi.org/10.1098/rstb. 1939.0006 20. Quina FH, Bastos EL (2018) Chemistry inspired by the colors of fruits, flowers and wine. An Acad Bras Cienc 90:681–695. https://doi.org/10.1590/0001-3765201820170492 21. Robinson AM, Robinson R (1932) Synthetical experiments on the nature of betanin and related nitrogenous anthocyanins. Part I. J Chem Soc:1439–1445 22. Ainley AD, Robinson R (1937) Nitrogenous anthocyanins. Part V. Synthesis of substituted aminoflavylium salts. J Chem Soc: 453–456. https://doi.org/10.1039/JR9370000453 23. Wyler H, Dreiding AS (1957) Kristallisiertes betanin. Helv Chim Acta 40:191–192 24. Wyler H, Vincenti G, Mercier M et al (1959) Zur Konstitution des Randenfarbstoffes Betanin. 2. Vorläufige Mitteilung. Helv Chim Acta 42:1696–1698 25. Wyler H, Dreiding AS (1959) Darstellung und Abbauprodukte des Betanidins. 3. Vorläufige Mitteilung. Über die Konstitution des Randenfarbstoffes Betanin. Helv Chim Acta 42:1699– 1702 26. Wyler H, Dreiding AS (1961) Über Betacyane, die stickstoffhaltigen Farbstoffe der Centrospermen. Vorläufige Mitteilung Experientia 17:23–25 27. Piattelli M, Minale L (1964) Pigments of Centrospermae. I Betacyanins from Phyllocactus hybridus Hort and Opuntia ficus-indica Mill. Phytochemistry 3:307–311 28. Piattelli M, Minale L, Prota G (1964) Isolation, structure and absolute configuration of indicaxanthin. Tetrahedron 20:2325–2329 29. Wyler H, Wilcox ME, Dreiding AS (1965) Umwandlung eines Betacyans in ein Betaxanthin. Synthese von Indicaxanthin aus Betanin. Helv Chim Acta 48:361–366 30. Khan MI (2016) Plant betalains: safety, antioxidant activity, clinical efficacy, and bioavailability. Compr Rev Food Sci Food Saf 15:316–330. https://doi.org/10.1111/1541-4337.12185 31. Gliszczyńska-Świgło A, Szymusiak H, Malinowska P (2006) Betanin, the main pigment of red beet: molecular origin of its exceptionally high free radical-scavenging activity. Food Addit Contam A 23:1079–1087 32. Gliszczyńska-Świgło A, Oszmianski J (2013) Antioxidant and prooxidant activity of food components. In: Bartosz G (ed) Food oxidants and antioxidants: chemical, biological, and functional properties. CRC Press, Boca Raton, pp 375–431

4

Betalains as Antioxidants

79

33. Parikh I, Hilpert H, Hermann K et al (1986) Synthese von Betenamin und von BetalainModellsubstanzen. Helv Chim Acta 69:1588–1596. https://doi.org/10.1002/hlca. 19860690712 34. Albano C, Negro C, Tommasi N et al (2015) Betalains, phenols and antioxidant capacity in cactus pear [Opuntia ficus-indica (L.) Mill.] fruits from Apulia (South Italy) genotypes. Antioxidants 4:269–280. https://doi.org/10.3390/antiox4020269 35. Nakashima KK, Bastos EL (2019) Rationale on the high radical scavenging capacity of betalains. Antioxidants 8:222. https://doi.org/10.3390/antiox8070222 36. Gonçalves LCP, Lopes NB, Augusto FA et al (2020) Phenolic betalain as antioxidants: meta means more. Pure Appl Chem 92:243–253. https://doi.org/10.1515/pac-2019-0108 37. Gandia-Herrero F, Escribano J, Garcia-Carmona F (2010) Structural implications on color, fluorescence, and antiradical activity in betalains. Planta 232:449–460. https://doi.org/10. 1007/s00425-010-1191-0 38. da Silva DVT, Baiao DD, Silva FD et al (2019) Betanin, a natural food additive: stability, bioavailability, antioxidant and preservative ability assessments. Molecules 24:458. https:// doi.org/10.3390/molecules24030458 39. Steglich W, Strack D (1990) Betalains. In: Brossi A (ed) The alkaloids, vol 39. Academic Press, London, pp 1–62 40. Guerrero-Rubio MA, Escribano J, Garcia-Carmona F et al (2020) Light emission in betalains: from fluorescent flowers to biotechnological applications. Trends Plant Sci 25:159–175. https://doi.org/10.1016/j.tplants.2019.11.001 41. Rahimi P, Abedimanesh S, Mesbah-Namin SA et al (2019) Betalains, the nature-inspired pigments, in health and diseases. Crit Rev Food Sci Nutr 59:2949–2978. https://doi.org/10. 1080/10408398.2018.1479830 42. Slimen IB, Najar T, Abderrabba M (2017) Chemical and antioxidant properties of betalains. J Agric Food Chem 65:675–689. https://doi.org/10.1021/acs.jafc.6b04208 43. Gandia-Herrero F, Escribano J, Garcia-Carmona F (2016) Biological activities of plant pigments betalains. Crit Rev Food Sci Nutr 56:937–945. https://doi.org/10.1080/10408398. 2012.740103 44. Esatbeyoglu T, Wagner AE, Schini-Kerth VB et al (2015) Betanin – a food colorant with biological activity. Mol Nutr Food Res 59:36–47. https://doi.org/10.1002/mnfr.201400484 45. Zrÿd J-P, Christinet L (2004) Betalains. In: Davies K (ed) Annual plant reviews: plant pigments and their manipulation, vol 14. Wiley-Blackwell, Chichester, pp 185–213 46. von Elbe JH (2005) Betalains. In: Wrolstad RE (ed) Handbook of food analytical chemistry. John Wiley & Sons, New York, pp 123–129 47. Herbach KM, Stintzing FC, Carle R (2006) Betalain stability and degradation - structural and chromatic aspects. J Food Sci 71:R41–R50 48. Strack D, Vogt T, Schliemann W (2003) Recent advances in betalain research. Phytochemistry 62:247–269 49. Azeredo HMC (2009) Betalains: properties, sources, applications, and stability - a review. Int J Food Sci Technol 44:2365–2376 50. Gandía-Herrero F, García-Carmona F, Escribano J (2005) Floral fluorescence effect. Nature 437:334–334. https://doi.org/10.1038/437334a 51. Mabry TJ, Kimler L, Chang C (1972) The betalains: structure, function, and biogenesis, and the plant order Centrospermae. In: Runeckles VC, Tso TC (eds) Recent advances in phytochemistry, vol 5. Elsevier, pp 105–134. https://doi.org/10.1016/B978-0-12-612405-7.50010-2 52. Carrillo C, Rey R, Hendrickx M et al (2017) Antioxidant capacity of beetroot: traditional vs novel approaches. Plant Food Hum Nutr 72:266–273. https://doi.org/10.1007/s11130-017-0617-2 53. Georgiev VG, Weber J, Kneschke E-M et al (2010) Antioxidant activity and phenolic content of betalain extracts from intact plants and hairy root cultures of the red beetroot Beta vulgaris cv. Detroit dark red. Plant Food Hum Nutr 65:105–111. https://doi.org/10.1007/s11130-0100156-6

80

E. L. Bastos and W. Schliemann

54. Czapski J, Mikołajczyk K, Kaczmarek M (2009) Relationship between antioxidant capacity of red beet juice and contents of its betalain pigments. Pol J Food Nutr Sci 59:119–122 55. Wootton-Beard PC, Ryan L (2011) A beetroot juice shot is a significant and convenient source of bioaccessible antioxidants. J Funct Foods 3:329–334. https://doi.org/10.1016/j.jff.2011.05.007 56. Vulic J, Canadanovic-Brunet J, Cetkovic G et al (2012) Antioxidant and cell growth activities of beet root pomace extracts. J Funct Foods 4:670–678. https://doi.org/10.1016/J.Jff.2012.04.008 57. Vulic JJ, Cebovic TN, Canadanovic-Brunet JM et al (2014) In vivo and in vitro antioxidant effects of beetroot pomace extracts. J Funct Foods 6:168–175. https://doi.org/10.1016/J.Jff. 2013.10.003 58. Koubaier HB, Snoussi A, Essaidi I et al (2014) Betalain and phenolic compositions, antioxidant activity of tunisian red beet (Beta vulgaris L. conditiva) roots and stems extracts. Int J Food Prop 17:1934–1945. https://doi.org/10.1080/10942912.2013.772196 59. Stintzing FC, Schieber A, Carle R (2002) Identification of betalains from yellow beet (Beta vulgaris L.) and cactus pear [Opuntia ficus-indica (L.) Mill.] by high-performance liquid chromatography-electrospray ionization mass spectrometry. J Agric Food Chem 50:2302– 2307 60. Wettasinghe M, Bolling B, Plhak L et al (2002) Phase II enzyme-inducing and antioxidant activities of beetroot (Beta vulgaris L.) extracts from phenotypes of different pigmentation. J Agric Food Chem 50:6704–6709 61. Takahashi A, Okumura J, Morita Y et al (2017) Intestinal absorption and antioxidant activity of betalain: a nitrogen-containing pigment from table beets and cactus pear fruit juice. J Jpn Soc Food Sci 64:51–58. https://doi.org/10.3136/nskkk.64.51 62. Stintzing FC, Herbach KM, Mosshammer MR et al (2005) Color, betalain pattern, and antioxidant properties of cactus pear (Opuntia spp.) clones. J Agric Food Chem 53:442– 451. https://doi.org/10.1021/jf048751y 63. Gentile C, Tesoriere L, Allegra M et al (2004) Antioxidant betalains from cactus pear (Opuntia ficus-indica) inhibit endothelial ICAM-1 expression. Ann N Y Acad Sci 1028:481–486. https://doi.org/10.1196/annals.1322.057 64. Butera D, Tesoriere L, Di Gaudio F et al (2002) Antioxidant activities of sicilian prickly pear (Opuntia ficus-indica) fruit extracts and reducing properties of its betalains: betanin and indicaxanthin. J Agric Food Chem 50:6895–6901 65. Tesoriere L, Butera D, Pintaudi AM et al (2004) Supplementation with cactus pear (Opuntia ficus-indica) fruit decreases oxidative stress in healthy humans: a comparative study with vitamin C. Am J Clin Nutr 80:391–395 66. Abdel-Hameed ESS, Nagaty MA, Salman MS et al (2014) Phytochemicals, nutritionals and antioxidant properties of two prickly pear cactus cultivars (Opuntia ficus-indica Mill.) growing in Taif, KSA. Food Chem 160:31–38. https://doi.org/10.1016/J.Foodchem.2014.03.060 67. Patel S (2013) Reviewing the prospects of Opuntia pears as low cost functional foods. Rev Environ Sci Biotechnol 12:223–234. https://doi.org/10.1007/s11157-012-9295-6 68. Gouws CA, D'Cunha NM, Georgousopoulou EN et al (2019) The effect of different drying techniques on phytochemical content and in vitro antioxidant properties of Australian-grown prickly pears (Opuntia ficus-indica). J Food Process Pres 43. https://doi.org/10.1111/jfpp. 13900 69. Smeriglio A, Bonasera S, Germano MP et al (2019) Opuntia ficus-indica (L.) Mill. Fruit as source of betalains with antioxidant, cytoprotective, and anti-angiogenic properties. Phytother Res 33:1526–1537. https://doi.org/10.1002/ptr.6345 70. Stintzing FC, Schieber A, Carle R (2002) Betacyanins in fruits from red-purple pitaya, Hylocereus polyrhizus (Weber) Britton & Rose. Food Chem 77:101–106 71. Wu LC, Hsu HW, Chen YC et al (2006) Antioxidant and antiproliferative activities of red pitaya. Food Chem 95:319–327 72. Suh DH, Lee S, Heo DY et al (2014) Metabolite profiling of red and white pitayas (Hylocereus polyrhizus and Hylocereus undatus) for comparing betalain biosynthesis and antioxidant activity. J Agric Food Chem 62:8764–8771. https://doi.org/10.1021/Jf5020704

4

Betalains as Antioxidants

81

73. Montes-Lora S, Hurtado N, Mosquera N et al (2016) Effect of technological practices on individual betalains and antioxidant activity of Columbian betalain-rich raw materials. Int J Food Sci Tech 51:1041–1047. https://doi.org/10.1111/ijfs.13056 74. Cai YZ, Sun M, Corke H (2003) Antioxidant activity of betalains from plants of the Amaranthaceae. J Agric Food Chem 51:2288–2294 75. Li HY, Deng ZY, Liu RH et al (2015) Characterization of phenolics, betacyanins and antioxidant activities of the seed, leaf, sprout, flower and stalk extracts of three Amaranthus species. J Food Compos Anal 37:75–81. https://doi.org/10.1016/j.jfca.2014.09.003 76. Sarker U, Oba S (2019) Antioxidant constituents of three selected red and green color Amaranthus leafy vegetable. Sci Rep 9:18233. https://doi.org/10.1038/s41598-019-52033-8 77. Venskutonis PR, Kraujalis P (2013) Nutritional components of amaranth seeds and vegetables: a review on composition, properties, and uses. Compr Rev Food Sci Food Saf 12:381–412. https://doi.org/10.1111/1541-4337.12021 78. Graf BL, Rojas-Silva P, Rojo LE et al (2015) Innovations in health value and functional food development of quinoa (Chenopodium quinoa Willd.). Compr Rev Food Sci Food Saf 14:431– 445. https://doi.org/10.1111/1541-4337.12135 79. Pyo YH, Lee TC, Logendra L et al (2004) Antioxidant activity and phenolic compounds of Swiss chard (Beta vulgaris subspecies cycla) extracts. Food Chem 85:19–26. https://doi.org/ 10.1016/S0308-8146(03)00294-2 80. Caldas-Cueva JP, Morales P, Ludena F et al (2016) Stability of betacyanin pigments and antioxidants in ayrampo (Opuntia soehrensii Britton & Rose) seed extracts and as a yogurt natural colorant. J Food Process Pres 40:541–549. https://doi.org/10.1111/jfpp.12633 81. Herrera-Hernández MG, Guevara-Lara F, Reynoso-Camacho R et al (2011) Effects of maturity stage and storage on cactus berry (Myrtillocactus geometrizans) phenolics, vitamin C, betalains and their antioxidant properties. Food Chem 129:1744–1750. https://doi.org/10. 1016/j.foodchem.2011.06.042 82. Montiel-Sánchez M, García-Cayuela T, Gómez-Maqueo A et al. (2020) In vitro gastrointestinal stability, bioaccessibility and potential biological activities of betalains and phenolic compounds in cactus berry fruits (Myrtillocactus geometrizans). Food Chem:128087. https:// doi.org/10.1016/j.foodchem.2020.128087 83. Tsai P-J, Sheu C-H, Wu P-H et al (2010) Thermal and pH stability of betacyanin pigment of djulis (Chenopodium formosanum) in Taiwan and their relation to antioxidant activity. J Agric Food Chem 58:1020–1025. https://doi.org/10.1021/jf9032766 84. Lavanya V, Thamaraiselvi SP, Uma D (2019) Studies on extraction of betalain pigments by different solvents and assessing antioxidant activity of Bougainvillea spectabilis and Celosia argentea flowers. Madras Agric J 106:104-108. https://doi.org/10.29321/MAJ 2019.000230 85. Rodriguez-Sanchez JA, Victoria MTCY, Barragan-Huerta BE (2017) Betaxanthins and antioxidant capacity in Stenocereus pruinosus: stability and use in food. Food Res Int 91:63–71. https://doi.org/10.1016/j.foodres.2016.11.023 86. Bastos EL, Gonçalves LCP (2017) Microwave-assisted extraction of betalains. In: González Muñoz MJ (ed) Dominguez González H. Elsevier, Water extraction of bioactive compounds, pp 245–268. https://doi.org/10.1016/B978-0-12-809380-1.00009-7 87. Gandía-Herrero F, García-Carmona F (2013) Biosynthesis of betalains: yellow and violet plant pigments. Trends Plant Sci 18:334–343. https://doi.org/10.1016/j.tplants.2013.01.003 88. Chen N, Yu ZH, Xiao XG (2017) Cytosolic and nuclear co-localization of betalain biosynthetic enzymes in tobacco suggests that betalains are synthesized in the cytoplasm and/or nucleus of betalainic plant cells. Front Plant Sci 8:831. https://doi.org/10.3389/fpls.2017.00831 89. Reichardt C (1995) Chiral polymethine dyes: a remarkable but forgotten conjugated π system. J Phys Org Chem 8:761–773. https://doi.org/10.1002/poc.610081202 90. Schliemann W, Kobayashi N, Strack D (1999) The decisive step in betaxanthin biosynthesis is a spontaneous reaction. Plant Physiol 119:1217–1232 91. Heuer S, Richter S, Metzger JW et al (1994) Betacyanins from bracts of Bougainvillea glabra. Phytochemistry 37:761–767

82

E. L. Bastos and W. Schliemann

92. Heuer S, Wray V, Metzger JW et al (1992) Betacyanins from flowers of Gomphrena globosa. Phytochemistry 31:1801–1807 93. Schliemann W, Strack D (1998) Intramolecular stabilization of acylated betacyanins. Phytochemistry 49:585–588. https://doi.org/10.1016/S0031-9422(98)00047-8 94. Miguel MG (2018) Betalains in some species of the Amaranthaceae family: a review. Antioxidants 7. https://doi.org/10.3390/antiox7040053 95. Sepulveda-Jimenez G, Rueda-Benitez P, Porta H et al (2004) Betacyanin synthesis in red beet (Beta vulgaris) leaves induced by wounding and bacterial infiltration is preceded by an oxidative burst. Physiol Mol Plant Pathol 64:125–133 96. Terradas F, Wyler H (1991) The secodopas, natural pigments in Hygrocybe conica and Amanita muscaria. Phytochemistry 30:3251–3253 97. Michelot D, Melendez-Howell LM (2003) Amanita muscaria: chemistry, biology, toxicology, and ethnomycology. Mycol Res 107:131–146. https://doi.org/10.1017/s0953756203007305 98. Musso H (1979) The pigments of fly agaric, Amanita muscaria. Tetrahedron 35:2843–2853 99. König-Bersin P, Waser PG, Langemann H et al (1970) Monoamines in the brain under the influence of muscimol and ibotenic acid, two psychoactive principles of Amanita muscaria. Psychopharmacologia 18:1–10 100. Bowden K, Drysdale AC, Mogey GA (1965) Constituents of Amanita muscaria. Nature 206: 1359–1360 101. Stintzing F, Schliemann W (2007) Pigments of fly agaric (Amanita muscaria). Z Naturforsch C 62:779–785 102. Döpp H, Musso H (1973) Fliegenpilzfarbstoffe, II. Isolierung und Chromophore der Farbstoffe aus Amanita muscaria. Chem Ber 106:3473–3482. https://doi.org/10.1002/cber. 19731061103 103. Girod PA, Zryd JP (1991) Biogenesis of betalains: purification and partial characterization of DOPA 4,5-dioxygenase from Amanita muscaria. Phytochemistry 30:169–174 104. Hinz UG, Fivaz J, Girod PA et al (1997) The gene coding for the DOPA dioxygenase involved in betalain biosynthesis in Amanita muscaria and its regulation. Mol Gen Genet 256:1–6 105. Barth H, Burger G, Döpp H et al (1981) Fliegenpilzfarbstoffe, VII. Konstitution und Synthese des Muscaflavins. Liebigs Ann Chem 1981:2164–2179 106. Nowacka N, Nowak R, Drozd M et al (2015) Antibacterial, antiradical potential and phenolic compounds of thirty-one polish mushrooms. PLoS One 10:e0140355. https://doi.org/10.1371/ journal.pone.0140355 107. El Babili F, Chatelain C, Souchard JP (2019) Chemical study of some fungi: evaluation of their antioxidant and xanthine oxidase effects. Jpn J Med 2:389–393. https://doi.org/10.31488/jjm. 1000147 108. Reis FS, Heleno SA, Barros L et al (2011) Toward the antioxidant and chemical characterization of mycorrhizal mushrooms from Northeast Portugal. J Food Sci 76:C824–C830. https:// doi.org/10.1111/j.1750-3841.2011.02251.x 109. Harmer RA (1980) Occurrence, chemistry and application of betanin. Food Chem 5:81–90. https://doi.org/10.1016/0308-8146(80)90066-7 110. Stintzing FC, Carle R (2008) Betalains in food: occurrence, stability, and postharvest modifications. In: Socaciu C (ed) Food colorants: chemical and functional properties. CRC Press, Boca Raton, pp 277–299 111. Delgado-Vargas F, Jimenez AR, Paredes-Lopez O (2000) Natural pigments: carotenoids, anthocyanins, and betalains - characteristics, biosynthesis, processing, and stability. Crit Rev Food Sci Nutr 40:173–289 112. Roberts MF, Strack D, Wink M (2010) Biosynthesis of alkaloids and betalains. In: Wink M (ed) Annual plant reviews, volume 40: biochemistry of plant secondary metabolism, 2nd edn, vol 40. Wiley-Blackwell, Chichester, pp 20–91 113. Vogt T, Grimm R, Strack D (1999) Cloning and expression of a cDNA encoding betanidin 5O-glucosyltransferase, a betanidin- and flavonoid-specific enzyme with high homology to inducible glucosyltransferases from the Solanaceae. Plant J 19:509–519

4

Betalains as Antioxidants

83

114. Vogt T (2002) Substrate specificity and sequence analysis define a polyphyletic origin of betanidin 5- and 6-O-glucosyltransferase from Dorotheanthus bellidiformis. Planta 214:492–495 115. Büchi G, Fliri H, Shapiro R (1977) A synthesis of betalamic acid. J Org Chem 42:2192–2194. https://doi.org/10.1021/jo00432a048 116. Hermann K, Dreiding AS (1977) Totalsynthese von Betalainen. Helv Chim Acta 60:673–683 117. Büchi G, Fliri H, Shapiro R (1978) Synthesis of betalains. J Org Chem 43:4765–4769. https:// doi.org/10.1021/jo00419a013 118. Hilpert H, Dreiding AS (1984) Über die Totalsynthese von Betalainen. Helv Chim Acta 67: 1547–1561 119. Guimond N, Mayer P, Trauner D (2014) Development of an iron(II)-catalyzed aerobic catechol cleavage and biomimetic synthesis of betanidin. Chem Eur J 20:9519–9523. https://doi.org/10. 1002/Chem.201403436 120. Pavokovic D, Krsnik-Rasol M (2011) Complex biochemistry and biotechnological production of betalains. Food Technol Biotech 49:145–155 121. Cebi K, Yangilar F (2016) Biotechnological production and application of betalain pigments for food plants. J Biotechnol 231:S42–S43. https://doi.org/10.1016/j.jbiotec.2016.05.165 122. Polturak G, Grossman N, Vela-Corcia D et al (2017) Engineered gray mold resistance, antioxidant capacity, and pigmentation in betalain-producing crops and ornamentals. Proc Natl Acad Sci U S A 114:9062–9067. https://doi.org/10.1073/pnas.1707176114 123. Guerrero-Rubio MA, López-Llorca R, Henarejos-Escudero P et al (2019) Scaled-up biotechnological production of individual betalains in a microbial system. Microb Biotechnol 12:993– 1002. https://doi.org/10.1111/1751-7915.13452 124. Grewal PS, Modavi C, Russ ZN et al (2018) Bioproduction of a betalain color palette in Saccharomyces cerevisiae. Metab Eng 45:180–188. https://doi.org/10.1016/j.ymben.2017.12.008 125. Polturak G, Aharoni A (2019) Advances and future directions in betalain metabolic engineering. New Phytol 224:1472–1478. https://doi.org/10.1111/nph.15973 126. Girod PA, Zryd JP (1987) Clonal variability and light induction of betalain synthesis in red beet cell-cultures. Plant Cell Rep 6:27–30 127. Taya M, Mine K, Kinooka M et al (1992) Production and release of pigments by culture of transformed hairy root of red beet. J Ferment Bioeng 73:31–36 128. Rodriguez-Monroy M, Galindo E (1999) Broth rheology, growth and metabolite production of Beta vulgaris suspension culture: a comparative study between cultures grown in shake flasks and in a stirred tank. Enzym Microb Technol 24:687–693 129. Guadarrama-Flores B, Rodriguez-Monroy M, Cruz-Sosa F et al (2015) Production of dihydroxylated betalains and dopamine in cell suspension cultures of Celosia argentea var. plumosa. J Agric Food Chem 63:2741–2749. https://doi.org/10.1021/acs.jafc.5b00065 130. Bodhipadma K, Noichinda S, Wachirabongkoth P et al (2017) Callus induction and influence of UV-C on betalain content in the callus of an amaranth. Rom Biotech Lett 22:12793–12801 131. Henarejos-Escudero P, Guadarrama-Flores B, Guerrero-Rubio MA et al (2018) Development of betalain producing callus lines from colored quinoa varieties (Chenopodium quinoa Willd). J Agric Food Chem 66:467–474. https://doi.org/10.1021/acs.jafc.7b04642 132. Karageorgis G, Foley DJ, Laraia L et al (2020) Principle and design of pseudo-natural products. Nat Chem 12:227–235. https://doi.org/10.1038/s41557-019-0411-x 133. Gandia-Herrero F, Escribano J, Garcia-Carmona F (2012) Purification and antiradical properties of the structural unit of betalains. J Nat Prod 75:1030–1036. https://doi.org/10.1021/ np200950n 134. Wendel M, Szot D, Starzak K et al (2015) Photophysical properties of betaxanthins: vulgaxanthin I in aqueous and alcoholic solutions. J Lumin 167:289–295. https://doi.org/10. 1016/j.jlumin.2015.06.030 135. Freitas-Dörr BC, Machado CO, Pinheiro AC et al. (2020) A metal-free blue chromophore derived from plant pigments. Sci Adv 6:eaaz0421 136. Esteves LC, Pinheiro AC, Pioli RM et al (2018) Revisiting the mechanism of hydrolysis of betanin. Photochem Photobiol 94:853–864. https://doi.org/10.1111/php.12897

84

E. L. Bastos and W. Schliemann

137. Treat NA, Knorr FJ, McHale JL (2016) Templated assembly of betanin chromophore on TiO2: aggregation-enhanced light-harvesting and efficient electron injection in a natural dye-sensitized solar cell. J Phys Chem C 120:9122–9131. https://doi.org/10.1021/acs.jpcc.6b02532 138. Pavliuk MV, Cieslak AM, Abdellah M et al (2017) Hydrogen evolution with nanoengineered ZnO interfaces decorated using a beetroot extract and a hydrogenase mimic. Sust Energy Fuels 1:69–73. https://doi.org/10.1039/C6SE00066E 139. Pavliuk MV, Fernandes AB, Abdellah M et al (2017) Nano-hybrid plasmonic photocatalyst for hydrogen production at 20% efficiency. Sci Rep 7:8670. https://doi.org/10.1038/s41598-01709261-7 140. Bartoloni FH, Goncalves LCP, Rodrigues ACB et al (2013) Photophysics and hydrolytic stability of betalains in aqueous trifluoroethanol. Monatsh Chem 144:567–571. https://doi.org/ 10.1007/s00706-012-0883-5 141. Rodrigues ACB, Mariz IDA, Macoas EMS et al (2018) Bioinspired water-soluble two-photon fluorophores. Dyes Pigments 150:105–111. https://doi.org/10.1016/j.dyepig.2017.11.020 142. Oliveira E, Bertolo E, Nunez C et al (2018) Green and red fluorescent dyes for translational applications in imaging and sensing analytes: a dual-color flag. ChemistryOpen 7:9–52. https://doi.org/10.1002/open.201700135 143. Gonçalves LCP, Da Silva SM, DeRose P et al (2013) Beetroot-pigment-derived colorimetric sensor for detection of calcium dipicolinate in bacterial spores. PLoS One 8:e73701 144. Fernandes DLA, Paun C, Pavliuk MV et al (2016) Green microfluidic synthesis of monodisperse silver nanoparticles via genetic algorithm optimization. RSC Adv 6:95693–95697. https://doi.org/10.1039/C6RA20877K 145. Gandia-Herrero F, Garcia-Carmona F (2020) The dawn of betalains. New Phytol 227:664– 666. https://doi.org/10.1111/nph.16295 146. Martinez RM, Longhi-Balbinot DT, Zarpelon AC et al (2015) Anti-inflammatory activity of betalain-rich dye of Beta vulgaris: effect on edema, leukocyte recruitment, superoxide anion and cytokine production. Arch Pharm Res 38:494–504. https://doi.org/10.1007/s12272-014-0473-7 147. Klewicka E (2012) Betacyanins - bioavailability and biological activity. Zywn-Nauk Technol Ja 19:5–21 148. Madadi E, Mazloum-Ravasan S, Yu JS et al (2020) Therapeutic application of betalains: a review. Plan Theory 9:1219. https://doi.org/10.3390/plants9091219 149. Silva D, Baiao DDS, Ferreira VF et al (2020) Betanin as a multipath oxidative stress and inflammation modulator: a beetroot pigment with protective effects on cardiovascular disease pathogenesis. Crit Rev Food Sci Nutr:1–16. https://doi.org/10.1080/10408398.2020.1822277 150. Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem 97:55–74. https://doi.org/10.1016/j.ejmech.2015.04.040 151. Liu RH (2004) Potential synergy of phytochemicals in cancer prevention: mechanism of action. J Nutr 134:3479S–3485S 152. Liu RH (2003) Health benefits of fruit and vegetables are from additive and synergistic combinations of phytochemicals. Am J Clin Nutr 78:517S–520S 153. Prior RL, Cao G (2000) Antioxidant phytochemicals in fruits and vegetables: diet and health implications. HortScience 35:588–592 154. Koppenol WH, Hider RH (2019) Iron and redox cycling. Do's and don'ts. Free Radic Biol Med 133:3–10. https://doi.org/10.1016/j.freeradbiomed.2018.09.022 155. Apel K, Hirt H (2004) Reactive oxygen species: metabolism, oxidative stress, and signal transduction. Annu Rev Plant Biol 55:373–399. https://doi.org/10.1146/annurev.arplant.55. 031903.141701 156. Winterbourn CC (2008) Reconciling the chemistry and biology of reactive oxygen species. Nat Chem Biol 4:278–286. https://doi.org/10.1038/nchembio.85 157. Sies H (2015) Oxidative stress: a concept in redox biology and medicine. Redox Biol 4:180– 183. https://doi.org/10.1016/j.redox.2015.01.002 158. Mittler R (2017) ROS are good. Trends Plant Sci 22:11–19. https://doi.org/10.1016/j.tplants. 2016.08.002

4

Betalains as Antioxidants

85

159. Bartosz G (2014) Food oxidants and antioxidants: chemical, biological, and functional properties. CRC Press, Boca Raton 160. Cömert ED, Gökmen V (2017) Antioxidants bound to an insoluble food matrix: their analysis, regeneration behavior, and physiological importance. Compr Rev Food Sci Food Saf 16:382– 399. https://doi.org/10.1111/1541-4337.12263 161. Gutteridge JMC, Halliwell B (2010) Antioxidants: molecules, medicines, and myths. Biochem Biophys Res Commun 393:561–564 162. Herbert V (1994) The antioxidant supplement myth. Am J Clin Nutr 60:157–158. https://doi. org/10.1093/ajcn/60.2.157 163. Prior RL, Cao G (2000) Analysis of botanicals and dietary supplements for antioxidant capacity: a review. J AOAC Int 83:950–956 164. Frei B (1994) Reactive oxygen species and antioxidant vitamins: mechanisms of action. Am J Med 97:5S–13S. https://doi.org/10.1016/0002-9343(94)90292-5 165. Salehi B, Martorell M, Arbiser JL et al (2018) Antioxidants: positive or negative actors? Biomol Ther 8. https://doi.org/10.3390/biom8040124 166. Apak R, Gorinstein S, Böhm V et al (2013) Methods of measurement and evaluation of natural antioxidant capacity/activity (IUPAC technical report). Pure Appl Chem 85:957–998. https:// doi.org/10.1351/pac-rep-12-07-15 167. Huang D, Ou B, Prior RL (2005) The chemistry behind antioxidant capacity assays. J Agric Food Chem 53:1841–1856 168. Apak R, Ozyurek M, Guclu K et al (2016) Antioxidant activity/capacity measurement. 1. Classification, physicochemical principles, mechanisms, and electron transfer (ET)-based assays. J Agric Food Chem 64:997–1027. https://doi.org/10.1021/acs.jafc.5b04739 169. Darcy JW, Koronkiewicz B, Parada GA et al (2018) A continuum of proton-coupled electron transfer reactivity. Acc Chem Res 51:2391–2399. https://doi.org/10.1021/acs.accounts.8b00319 170. Bastos EL, Romoff P, Eckert CR et al (2003) Evaluation of antiradical capacity by H2O2hemin-induced luminol chemiluminescence. J Agric Food Chem 51:7481–7488. https://doi. org/10.1021/Jf0345189 171. Amorati R, Valgimigli L (2018) Methods to measure the antioxidant activity of phytochemicals and plant extracts. J Agric Food Chem 66:3324–3329. https://doi.org/10.1021/acs.jafc. 8b01079 172. Kumar S, Sharma S, Vasudeva N (2017) Review on antioxidants and evaluation procedures. Chin J Integr Med. https://doi.org/10.1007/s11655-017-2414-z 173. Re R, Pellegrini N, Proteggente A et al (1999) Antioxidant activity applying an improved ABTS radical cation decolorization assay. Free Radic Biol Med 26:1231–1237 174. Cano A, Arnao MB (2018) ABTS/TEAC (2,20 -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)/Trolox ®-equivalent antioxidant capacity) radical scavenging mixed-mode assay. In: Apak R, Capanoglu E, Shahidi F (eds) Measurement of antioxidant activity & capacity: recent trends and applications. John Wiley & Sons Ltd, Chichester, pp 117–139 175. Tian X, Schaich KM (2013) Effects of molecular structure on kinetics and dynamics of the Trolox equivalent antioxidant capacity assay with ABTS+•. J Agric Food Chem 61:5511– 5519. https://doi.org/10.1021/jf4010725 176. de Oliveira S, de Souza GA, Eckert CR et al (2014) Evaluation of antiradical assays used in determining the antioxidant capacity of pure compounds and plant extracts. Quim Nova 37:497–503. https://doi.org/10.5935/0100-4042.20140076 177. Alberto ME, Russo N, Grand A et al (2013) A physicochemical examination of the free radical scavenging activity of Trolox: mechanism, kinetics and influence of the environment. Phys Chem Chem Phys 15:4642–4650. https://doi.org/10.1039/c3cp43319f 178. Burton GW, Doba T, Gabe E et al (1985) Autoxidation of biological molecules. 4. Maximizing the antioxidant activity of phenols. J Am Chem Soc 107:7053–7065. https://doi.org/10.1021/ ja00310a049 179. Gulcin I (2020) Antioxidants and antioxidant methods: an updated overview. Arch Toxicol 94: 651–715. https://doi.org/10.1007/s00204-020-02689-3

86

E. L. Bastos and W. Schliemann

180. Xiao F, Xu T, Lu B et al (2020) Guidelines for antioxidant assays for food components. Food Front 1:60–69. https://doi.org/10.1002/fft2.10 181. Apak R, Capanoglu E, Demirci CS et al (in press) Antioxidant acitivity/capacity measurement. In: Arora J (ed) Screening, preservation and determination methods for antioxidants, vol 4. Springer, Plant Antioxidants and Health 182. Benzie IF, Strain JJ (1996) The ferric reducing ability of plasma (FRAP) as a measure of "antioxidant power": the FRAP assay. Anal Biochem 239:70–76. https://doi.org/10.1006/abio. 1996.0292 183. Ou B, Hampsch-Woodill M, Prior RL (2001) Development and validation of an improved oxygen radical absorbance capacity assay using fluorescein as the fluorescent probe. J Agric Food Chem 49:4619–4626. https://doi.org/10.1021/jf010586o 184. Velioglu YS, Mazza G, Gao L et al (1998) Antioxidant activity and total phenolics in selected fruits, vegetables, and grain products. J Agric Food Chem 46:4113–4117. https://doi.org/10. 1021/jf9801973 185. Miller NJ, Rice-Evans CA, Davies MJ et al (1993) A novel method for measuring antioxidant capacity and its application to monitoring antioxidant status in premature neonates. Clin Sci 84:407–412 186. Rice-Evans C, Miller NJ (1994) Total antioxidant status in plasma and body fluids. In: Packer L (ed) Methods in Enzymology, vol 234. Academic Press, pp 279–293. https://doi.org/10. 1016/0076-6879(94)34095-1 187. Cano A, Hernández-Ruíz J, García-Cánovas F et al (1998) An end-point method for estimation of the total antioxidant activity in plant material. Phytochem Anal 9:196–202. https://doi.org/ 10.1002/(SICI)1099-1565(199807/08)9:43.0.CO;2-W 188. Brand-Williams W, Cuvelier ME, Berset C (1995) Use of a free radical method to evaluate antioxidant activity. LWT 28:25–30. https://doi.org/10.1016/S0023-6438(95)80008-5 189. Bondet V, Brand-Williams W, Berset C (1997) Kinetics and mechanisms of antioxidant activity using the DPPH• free radical method. LWT 30:609–615. https://doi.org/10.1006/fstl. 1997.0240 190. Prior RL, Wu X, Schaich K (2005) Standardized methods for the determination of antioxidant capacity and phenolics in foods and dietary supplements. J Agric Food Chem 53:4290–4302 191. Rufián-Henares JA, Delgado-Andrade C (2009) Effect of digestive process on Maillard reaction indexes and antioxidant properties of breakfast cereals. Food Res Int 42:394–400. https://doi.org/10.1016/j.foodres.2009.01.011 192. Pastoriza S, Delgado-Andrade C, Haro A et al (2011) A physiologic approach to test the global antioxidant response of foods. The GAR method. Food Chem 129:1926–1932. https://doi.org/ 10.1016/j.foodchem.2011.06.009 193. Gökmen V, Serpen A, Fogliano V (2009) Direct measurement of the total antioxidant capacity of foods: the ‘QUENCHER’ approach. Trends Food Sci Technol 20:278–288. https://doi.org/ 10.1016/j.tifs.2009.03.010 194. Cao G, Sofic E, Prior RL (1996) Antioxidant capacity of tea and common vegetables. J Agric Food Chem 44:3426–3431. https://doi.org/10.1021/jf9602535 195. Kugler F, Stintzing FC, Carle R (2007) Evaluation of the antioxidant capacity of betalainic fruits and vegetables. J Appl Bot Food Qual 81:69–76 196. Ou B, Huang D, Hampsch-Woodill M et al (2002) Analysis of antioxidant activities of common vegetables employing oxygen radical absorbance capacity (ORAC) and ferric reducing antioxidant power (FRAP) assays: a comparative study. J Agric Food Chem 50:3122– 3128. https://doi.org/10.1021/jf0116606 197. Vinson JA, Hao Y, Su XH et al (1998) Phenol antioxidant quantity and quality in foods: vegetables. J Agric Food Chem 46:3630–3634. https://doi.org/10.1021/jf980295o 198. Žitňanová I, Ranostajová S, Sobotová H et al (2006) Antioxidative activity of selected fruits and vegetables. Biologia 61:279–284. https://doi.org/10.2478/s11756-006-0051-7 199. Kanner J, Harel S, Granit R (2001) Betalains – a new class of dietary cationized antioxidants. J Agric Food Chem 49:5178–5185. https://doi.org/10.1021/jf010456f

4

Betalains as Antioxidants

87

200. Hadipour E, Taleghani A, Tayarani-Najaran N et al (2020) Biological effects of red beetroot and betalains: a review. Phytother Res 34:1847–1867. https://doi.org/10.1002/ptr.6653 201. Hunyadi A (2019) The mechanism(s) of action of antioxidants: from scavenging reactive oxygen/nitrogen species to redox signaling and the generation of bioactive secondary metabolites. Med Res Rev 39:2505–2533. https://doi.org/10.1002/med.21592 202. Biancardi E, McGrath JM, Panella LW et al (2010) Sugar beet. In: Bradshaw JE (ed) Root and tuber crops, Handbook of plant breeding, vol 7. Springer Science+Business Media LLC, New York, pp 173–219. https://doi.org/10.1007/978-0-387-92765-7_6 203. Kubis S, Heslop-Harrison JS, Schmidt T (1997) A family of differentially amplified repetitive DNA sequences in the genus Beta reveals genetic variation in Beta vulgaris subspecies and cultivars. J Mol Evol 44:310–320. https://doi.org/10.1007/pl00006148 204. Lange W (1999) Taxonomy and cultonomy of beet (Beta vulgaris L.). Bot J Linn Soc 130:81– 96. https://doi.org/10.1111/j.1095-8339.1999.tb00785.x 205. McGrath JM, Saccomani M, Stevanato P et al (2007) Beet. In: Kole C (ed) Vegetables. Springer, Berlin Heidelberg, Berlin, Heidelberg, pp 191–207. https://doi.org/10.1007/978-3540-34536-7_6 206. Slatnar A, Stampar F, Veberic R et al (2015) HPLC-MSn identification of betalain profile of different beetroot (Beta vulgaris L. ssp. vulgaris) parts and cultivars. J Food Sci 80:C1952– C1958. https://doi.org/10.1111/1750-3841.12977 207. McGrath JM, Panella L (2018) Sugar beet breeding. Plant breed rev: 167-218. https://doi.org/ 10.1002/9781119521358.ch5 208. Kujala T, Vienola M, Klika K et al (2002) Betalain and phenolic compositions of four beetroot (Beta vulgaris) cultivars. Eur Food Res Technol 214:505–510. https://doi.org/10.1007/ s00217-001-0478-6 209. Sawicki T, Bączek N, Wiczkowski W (2016) Betalain profile, content and antioxidant capacity of red beetroot dependent on the genotype and root part. J Funct Foods 27:249–261. https:// doi.org/10.1016/j.jff.2016.09.004 210. Choo WS (2018) Betalains: application in functional foods. In: Mérillon JM, Ramawat K (eds) Bioactive molecules in food. Reference Series in Phytochemistry. Springer, Cham, pp 1–28. https://doi.org/10.1007/978-3-319-54528-8_38-2 211. Gengatharan A, Dykes GA, Choo WS (2015) Betalains: natural plant pigments with potential application in functional foods. LWT 64:645–649. https://doi.org/10.1016/j.lwt.2015.06.052 212. Dörnenburg H, Knorr D (1996) Generation of colors and flavors in plant cell and tissue cultures. Crit Rev Plant Sci 15:141–168. https://doi.org/10.1080/07352689.1996.10393184 213. Wu X, Beecher GR, Holden JM et al (2004) Lipophilic and hydrophilic antioxidant capacities of common foods in the United States. J Agric Food Chem 52:4026–4037 214. Váli L, Stefanovits-Bányai É, Szentmihályi K et al (2007) Liver-protecting effects of table beet (Beta vulgaris var. rubra) during ischemia-reperfusion. Nutrition 23:172–178. https://doi.org/ 10.1016/j.nut.2006.11.004 215. Kujawska M, Ignatowicz E, Murias M et al (2009) Protective effect of red beetroot against carbon tetrachloride- and N-nitrosodiethylamine-induced oxidative stress in rats. J Agric Food Chem 57:2570–2575. https://doi.org/10.1021/jf803315d 216. Watts AR, Lennard MS, Mason SL et al (1993) Beeturia and the biological fate of beetroot pigments. Pharmacogen Gen 3:302–311. https://doi.org/10.1097/00008571-19931200000004 217. Tesoriere L, Fazzari M, Angileri F et al (2008) In vitro digestion of betalainic foods. Stability and bioaccessibility of betaxanthins and betacyanins and antioxidative potential of food digesta. J Agric Food Chem 56:10487–10492 218. Ravichandran K, Saw NMMT, Mohdaly AAA et al (2013) Impact of processing of red beet on betalain content and antioxidant activity. Food Res Int 50:670–675. https://doi.org/10.1016/J. Foodres.2011.07.002 219. Stintzing FC, Carle R (2004) Functional properties of anthocyanins and betalains in plants, food, and in human nutrition. Trends Food Sci Technol 15:19–38

88

E. L. Bastos and W. Schliemann

220. Gomez-Maqueo A, Antunes-Ricardo M, Welti-Chanes J et al (2020) Digestive stability and bioaccessibility of antioxidants in prickly pear fruits from the Canary Islands: healthy foods and ingredients. Antioxidants 9:164. https://doi.org/10.3390/antiox9020164 221. Wybraniec S, Platzner I, Geresh S et al (2001) Betacyanins from vine cactus Hylocereus polyrhizus. Phytochemistry 58:1209–1212. https://doi.org/10.1016/S0031-9422(01)00336-3 222. Wybraniec S, Mizrahi Y (2002) Fruit flesh betacyanin pigments in Hylocereus cacti. J Agric Food Chem 50:6086–6089. https://doi.org/10.1021/jf020145k 223. Herbach KM, Stintzing FC, Carle R (2006) Stability and color changes of thermally treated betanin, phyllocactin, and hylocerenin solutions. J Agric Food Chem 54:390–398 224. Guerrero-Rubio MA, Hernandez-Garcia S, Garcia-Carmona F et al (2019) Extension of lifespan using a RNAi model and in vivo antioxidant effect of Opuntia fruit extracts and pure betalains in Caenorhabditis elegans. Food Chem 274:840–847. https://doi.org/10.1016/j. foodchem.2018.09.067 225. Iriel A, Lagorio M (2010) Is the flower fluorescence relevant in biocommunication? Naturwissenschaften 97:915–924. https://doi.org/10.1007/s00114-010-0709-4 226. Lagorio MG, Cordon GB, Iriel A (2015) Reviewing the relevance of fluorescence in biological systems. Photochem Photobiol Sci 14:1538–1559. https://doi.org/10.1039/c5pp00122f 227. Gawlik-Dziki U, Dziki L, Anisiewicz J et al (2020) Leaves of white beetroot as a new source of antioxidant and anti-inflammatory compounds. Plan Theory 9. https://doi.org/10.3390/ plants9080944 228. Gościnna K, Wszelaczyńska E, Pobereżny J (2020) Potential of a new beetroot cultivar ‘Śnieżna kula’ (Beta vulgaris L. ssp.). AIMS Agric Food 5:563–577. https://doi.org/10. 3934/agrfood.2020.4.563 229. Kanner J, Harel S, Granit R (1996) Compositions containing antioxidants and a method for their preparation. Patent WO1998026792A1, 06/25/1998 230. Escribano J, Pedreño M, Garcia-Carmona F et al (1998) Characterization of the antiradical activity of betalains from Beta vulgaris L. roots. Phytochem Anal 9:124–127 231. Zakharova NS, Petrova TA (1998) Relationships between the structure and antioxidant activity of certain betalains. Appl Biochem Microbiol 34:182–185 232. Sekiguchi H, Ozeki Y, Sasaki N (2010) In vitro synthesis of betaxanthins using recombinant DOPA 4,5-dioxygenase and evaluation of their radical-scavenging activities. J Agric Food Chem 58:12504–12509. https://doi.org/10.1021/jf1030086 233. Herbach KM, Stintzing FC, Carle R (2004) Thermal degradation of betacyanins in juices from purple pitaya [Hylocereus polyrhizus (Weber) Britton & Rose] monitored by high-performance liquid chromatography–tandem mass spectometric analyses. Eur Food Res Technol 219:377– 385. https://doi.org/10.1007/s00217-004-0948-8 234. Terradas F, Wyler H (1991) 2,3- and 4,5-Secodopa, the biosynthetic intermediates generated from L-DOPA by an enzyme system extracted from the fly agaric, Amanita muscaria L., and their spontaneous conversion to muscaflavin and betalamic acid, respectively, and betalains. Helv Chim Acta 74:124–140. https://doi.org/10.1002/hlca.19910740115 235. Esatbeyoglu T, Wagner AE, Motafakkerazad R et al (2014) Free radical scavenging and antioxidant activity of betanin: electron spin resonance spectroscopy studies and studies in cultured cells. Food Chem Toxicol 73:119–126. https://doi.org/10.1016/j.fct.2014.08.007 236. Gliszczyńska-Świgło A, Szymusiak H (2007) Molecular insight in the pH-dependent radicalscavenging activity of betanidin. Pol J Food Nutr Sci 4:17–25 237. Allegra M, Carletti F, Gambino G et al (2015) Indicaxanthin from Opuntia ficus-indica crosses the blood-brain barrier and modulates neuronal bioelectric activity in rat hippocampus at dietary-consistent amounts. J Agric Food Chem 63:7353–7360. https://doi.org/10.1021/acs. jafc.5b02612 238. Tesoriere L, Allegra M, Butera D et al (2006) Cytoprotective effects of the antioxidant phytochemical indicaxanthin in beta-thalassemia red blood cells. Free Radic Res 40:753–761 239. Tesoriere L, Attanzio A, Allegra M et al (2014) Indicaxanthin inhibits NADPH oxidase (NOX)-1 activation and NF-κB-dependent release of inflammatory mediators and prevents

4

Betalains as Antioxidants

89

the increase of epithelial permeability in IL-1β-exposed Caco-2 cells. Br J Nutr 111:415–423. https://doi.org/10.1017/S0007114513002663 240. Lee C-H, Wettasinghe M, Bolling BW et al (2005) Betalains, phase II enzyme-inducing components from red beetroot (Beta vulgaris L.) extracts. Nutr Cancer 53:91–103. https:// doi.org/10.1207/s15327914nc5301_11 241. Wybraniec S, Stalica P, Jerz G et al (2009) Separation of polar betalain pigments from cacti fruits of Hylocereus polyrhizus by ion-pair high-speed countercurrent chromatography. J Chromatogr A 1216:6890–6899. https://doi.org/10.1016/j.chroma.2009.08.035 242. Cai Y, Sun M, Corke H (2005) HPLC characterization of betalains from plants in the Amaranthaceae. J Chromatogr Sci 43:454–460. https://doi.org/10.1093/chromsci/43.9.454 243. Nemzer B, Pietrzkowski Z, Spórna A et al (2011) Betalainic and nutritional profiles of pigment-enriched red beet root (Beta vulgaris L.) dried extracts. Food Chem 127:42–53. https://doi.org/10.1016/j.foodchem.2010.12.081 244. Kahkonen MP, Hopia AI, Vuorela HJ et al (1999) Antioxidant activity of plant extracts containing phenolic compounds. J Agric Food Chem 47:3954–3962. https://doi.org/10. 1021/jf990146l 245. Sigurdson GT, Tang P, Giusti MM (2017) Natural colorants: food colorants from natural sources. Annu Rev Food Sci Technol 8:261–280. https://doi.org/10.1146/annurev-food030216-025923 246. Wrolstad RE, Culver CA (2012) Alternatives to those artificial FD&C food colorants. Annu Rev Food Sci Technol 3:59–77. https://doi.org/10.1146/Annurev-Food-022811-101118 247. Gonçalves LCP, Trassi MAdS, Lopes NB et al. (2012) A comparative study of the purification of betanin. Food Chem 131:231–238. https://doi.org/10.1016/j.foodchem.2011.08.067 248. Roy K, Gullapalli S, Chaudhuri UR et al (2004) The use of a natural colorant based on betalain in the manufacture of sweet products in India. Int J Food Sci Tech 39:1087–1091. https://doi. org/10.1111/j.1365-2621.2004.00879.x 249. Ciriminna R, Fidalgo A, Danzi C et al (2018) Betanin: a bioeconomy insight into a valued betacyanin. ACS Sustain Chem Eng 6:2860–2865. https://doi.org/10.1021/acssuschemeng. 7b04163 250. EFSA ANS Panel (2015) Scientific opinion on the re-evaluation of beetroot red (E162) as a food additive. EFSA J 13:4318–4374. https://doi.org/10.2903/j.efsa.2015.4318 251. EFSA ANS Panel (2016) Safety of the proposed extension of use of beetroot red (E162) in foods for special medical purposes in young children. EFSA J 14:4487–4500. https://doi.org/ 10.2903/j.efsa.2016.4487 252. Pasch JH, von Elbe JH (1979) Betanine stability in buffered solutions containing organic acids, metal cations, antioxidants, or sequestrants. J Food Sci 44:72–75 253. Bilyk A, Kolodij MA, Sapers GM (1981) Stabilization of red beet pigments with isoascorbic acid. J Food Sci 46:1616–1617 254. Attoe EL, von Elbe JH (1985) Oxygen involvement in betanine degradation: effect of antioxidants. J Food Sci 50:106–110 255. von Elbe JH, Attoe EL (1985) Oxygen involvement in betalain degradation - measurement of active oxygen species and oxidation redution potentials. Food Chem 16:49–67 256. Attoe EL, von Elbe JH (1984) Oxygen involvement in betanin degradation. Oxygen uptake and influence of metal ions. Z Lebensm Unters For 179:232–236 257. Wattananate K, Thanachayanont C, Tonanon N (2014) ORAC and VIS spectroscopy as a guideline for unmodified red purple natural dyes selection in dye-sensitized solar cells. Sol Energy 107:38–43. https://doi.org/10.1016/J.Solener.2014.05.004 258. Qin CY, Clark AE (2007) DFT characterization of the optical and redox properties of natural pigments relevant to dye-sensitized solar cells. Chem Phys Lett 438:26–30 259. Zhang D, Lanier SM, Downing JA et al (2008) Betalain pigments for dye-sensitized solar cells. J Photochem Photobiol A 195:72–80 260. Gülçin İ (2012) Antioxidant activity of food constituents: an overview. Arch Toxicol 86:345– 391. https://doi.org/10.1007/s00204-011-0774-2

90

E. L. Bastos and W. Schliemann

261. Taira J, Tsuchida E, Katoh MC et al (2015) Antioxidant capacity of betacyanins as radical scavengers for peroxyl radical and nitric oxide. Food Chem 166:531–536. https://doi.org/10. 1016/j.foodchem.2014.05.102 262. Rojo de la Vega M, Krajisnik A, Zhang DD et al. (2017) Targeting NRF2 for improved skin barrier function and photoprotection: focus on the achiote-derived apocarotenoid bixin. Nutrients 9. https://doi.org/10.3390/nu9121371 263. Livrea MA, Tesoriere L (2013) Lipoperoxyl radical scavenging and antioxidative effects of red beet pigments. In: Neelwarne B (ed) Red beet biotechnology: food and pharmaceutical applications. Springer, Boston, pp 105–124. https://doi.org/10.1007/978-1-4614-3458-0_6 264. Tesoriere L, Allegra M, Butera D et al (2004) Absorption, excretion, and distribution of dietary antioxidant betalains in LDLs: potential health effects of betalains in humans. Am J Clin Nutr 80:941–945 265. Tesoriere L, Gentile C, Angileri F et al (2013) Trans-epithelial transport of the betalain pigments indicaxanthin and betanin across Caco-2 cell monolayers and influence of food matrix. Eur J Nutr 52:1077–1087. https://doi.org/10.1007/s00394-012-0414-5 266. Gokhale SV, Lele SS (2014) Betalain content and antioxidant activity of Beta vulgaris: effect of hot air convective drying and storage. J Food Process Pres 38:585–590. https://doi.org/10. 1111/Jfpp.12006 267. Guldiken B, Toydemir G, Memis KN et al (2016) Home-processed red beetroot (Beta vulgaris L.) products: changes in antioxidant properties and bioaccessibility. Int J Mol Sci 17. https:// doi.org/10.3390/ijms17060858 268. Paciulli M, Medina-Meza IG, Chiavaro E et al (2016) Impact of thermal and high pressure processing on quality parameters of beetroot (Beta vulgaris L.). LWT 68:98–104. https://doi. org/10.1016/j.lwt.2015.12.029 269. Gandia-Herrero F, Cabanes J, Escribano J et al (2013) Encapsulation of the most potent antioxidant betalains in edible matrixes as powders of different colors. J Agric Food Chem 61:4294–4302. https://doi.org/10.1021/Jf400337g 270. Kaimainen M, Marze S, Jarvenpaa E et al (2015) Encapsulation of betalain into W/O/W double emulsion and release during in vitro intestinal lipid digestion. LWT 60:899–904. https://doi.org/10.1016/j.lwt.2014.10.016 271. Pagano APE, Khalid N, Kobayashi I et al (2018) Microencapsulation of betanin in monodisperse W/O/W emulsions. Food Res Int 109:489–496. https://doi.org/10.1016/j.foodres.2018.04.053 272. Otalora MC, Carriazo JG, Iturriaga L et al (2015) Microencapsulation of betalains obtained from cactus fruit (Opuntia ficus-indica) by spray drying using cactus cladode mucilage and maltodextrin as encapsulating agents. Food Chem 187:174–181. https://doi.org/10.1016/j. foodchem.2015.04.090 273. Saldanha do Carmo C, Nunes AN, Serra AT et al. (2015) A way to prepare a liposoluble natural pink colourant. Green Chem 17:1510–1518. https://doi.org/10.1039/c4gc01801j 274. Brewer MS (2011) Natural antioxidants: sources, compounds, mechanisms of action, and potential applications. Compr Rev Food Sci Food Saf 10:221–247. https://doi.org/10.1111/j. 1541-4337.2011.00156.x 275. Foti MC (2008) Antioxidant properties of phenols. J Pharm Pharmacol 59:1673–1685 276. Litwinienko G, Ingold KU (2007) Solvent effects on the rates and mechanisms of reaction of phenols with free radicals. Acc Chem Res 40:222–230 277. Ingold KU (1969) Peroxy radicals. Acc Chem Res 2:1–9 278. Leopoldini M, Marino T, Russo N et al (2004) Antioxidant properties of phenolic compounds: H-atom versus electron transfer mechanism. J Phys Chem A 108:4916–4922 279. Viehe HG, Janousek Z, Merenyi R et al (1985) The captodative effect. Acc Chem Res 18:148– 154. https://doi.org/10.1021/ar00113a004 280. Warren JJ, Tronic TA, Mayer JM (2010) Thermochemistry of proton-coupled electron transfer reagents and its implications. Chem Rev 110:6961–7001. https://doi.org/10.1021/cr100085k 281. Foti MC, Amorati R (2009) Non-phenolic radical-trapping antioxidants. J Pharm Pharmacol 61:1435–1448

4

Betalains as Antioxidants

91

282. Foti MC, Daquino C, Geraci C (2004) Electron-transfer reaction of cinnamic acids and their methyl esters with the DPPH• radical in alcoholic solutions. J Org Chem 69: 2309–2314 283. Gryn'ova G, Hodgson JL, Coote ML (2011) Revising the mechanism of polymer autooxidation. Org Biomol Chem 9:480–490. https://doi.org/10.1039/c0ob00596g 284. Apak R (2018) Electron transfer-based antioxidant capacity assays and the cupric ion reducing antioxidant capacity (CUPRAC) assay. In: Apak R, Capanoglu E, Shahidi F (eds) Measurement of antioxidant activity & capacity: recent trends and applications. John Wiley & Sons Ltd, Chichester, pp 57–75 285. Rietjens IM, Boersma MG, Haan L et al (2002) The pro-oxidant chemistry of the natural antioxidants vitamin C, vitamin E, carotenoids and flavonoids. Environ Toxicol Pharmacol 11: 321–333 286. MacLean PD, Chapman EE, Dobrowolski SL et al (2008) Pyrroles as antioxidants: solvent effects and the nature of the attacking radical on antioxidant activities and mechanisms of pyrroles, dipyrrinones, and bile pigments. J Org Chem 73:6623–6635 287. Wybraniec S (2005) Formation of decarboxylated betacyanins in heated purified betacyanin fractions from red beet root (Beta vulgaris L.) monitored by LC-MS/MS. J Agric Food Chem 53:3483–3487 288. Nakagawa S, Tachrim ZP, Kurokawa N et al (2018) pH stability and antioxidant power of cycloDOPA and its derivatives. Molecules 23. https://doi.org/10.3390/molecules23081943 289. Gonçalves LCP, Di Genova BM, Dörr FA et al (2013) Effect of dielectric microwave heating on color and antiradical capacity of betanin. J Food Eng 118:49–55 290. Rodriguez SA, Baumgartner MT (2020) Betanidin pKa prediction using DFT methods. ACS Omega 5:13751–13759. https://doi.org/10.1021/acsomega.0c00904 291. Valero E, Escribano J, Garcia-Carmona F (1988) Reactions of 4-methyl-o-benzoquinone, generated chemically or enzymatically, in the presence of L-proline. Phytochemistry 27: 2055–2061. https://doi.org/10.1016/0031-9422(88)80096-7 292. Tutone M, Lauria A, Almerico AM (2016) Theoretical determination of the pKa values of betalamic acid related to the free radical scavenger capacity: comparison between empirical and quantum chemical methods. Interdiscip Sci Comput Life Sci 8:177–185. https://doi.org/ 10.1007/s12539-015-0101-3 293. Hider RC, Liu ZD, Khodr HH (2001) Metal chelation of polyphenols. In: Packer L (ed) Methods in Enzymology, vol 335. Academic Press, San Diego, pp 190–203. https://doi.org/10. 1016/s0076-6879(01)35243-6 294. Roy K, Popelier PLA (2009) Predictive QSPR modeling of the acidic dissociation constant (pKa) of phenols in different solvents. J Phys Org Chem 22:186–196 295. Hider RC, Hall AD (1991) Two clinically useful chelators of tripositive elements. In: Ellis GP, West GB (eds) Progress in medicinal chemistry, vol 28. Elsevier, Amsterdam, pp 41–173. https://doi.org/10.1016/s0079-6468(08)70363-1 296. Kremer T, Schleyer PV (1997) Charge-localizing effect in alkali-metal enolates and phenolates. Structure and aromaticity of the phenolate anion. Organometallics 16:737–746 297. Stylianou M, Keramidas AD (2010) Drouza C (2010) pH-potentiometric investigation towards chelating tendencies of p-hydroquinone and phenol iminodiacetate copper(II) complexes. Bioinorg Chem Appl. https://doi.org/10.1155/2010/125717 298. Stylianou M, Drouza C, Viskadourakis Z et al (2008) Synthesis, structure, magnetic properties and aqueous solution characterization of p-hydroquinone and phenol iminodiacetate copper(II) complexes. Dalton Trans:6188–6204 299. Atmani D, Chaher N, Atmani D et al (2009) Flavonoids in human health: from structure to biological activity. Curr Nutr Food Sci 5:225–237 300. Dolatabadi JEN (2011) Molecular aspects on the interaction of quercetin and its metal complexes with DNA. Int J Biol Macromol 48:227–233 301. Galleano M, Verstraeten SV, Oteiza PI et al (2010) Antioxidant actions of flavonoids: thermodynamic and kinetic analysis. Arch Biochem Biophys 501:23–30

92

E. L. Bastos and W. Schliemann

302. Wybraniec S, Starzak K, Skopińska A et al (2013) Effects of metal cations on betanin stability in aqueous-organic solutions. Food Sci Technol 22:353–363. https://doi.org/10.1007/s10068013-0088-7 303. Kumorkiewicz A, Szmyr N, Popenda L et al (2019) Alternative mechanisms of betacyanin oxidation by complexation and radical generation. J Agric Food Chem 67:7455–7465. https:// doi.org/10.1021/acs.jafc.9b01168 304. Wybraniec S, Stalica P, Spórna A et al (2011) Antioxidant activity of betanidin: electrochemical study in aqueous media. J Agric Food Chem 59:12163–12170. https://doi.org/10.1021/ jf2024769 305. Wybraniec S, Starzak K, Skopińska A et al (2013) Studies on nonenzymatic oxidation mechanisms in neobetanin, betanin, and decarboxylated betanins. J Agric Food Chem 61: 6465–6476. https://doi.org/10.1021/jf400818s 306. Kumorkiewicz A, Szneler E, Wybraniec S (2018) Conjugation of oxidized betanidin and gomphrenin pigments from Basella alba L. fruits with glutathione. J Agric Food Chem 66: 12815–12826. https://doi.org/10.1021/acs.jafc.8b04941 307. Wybraniec S, Michalowski T (2011) New pathways of betanidin and betanin enzymatic oxidation. J Agric Food Chem 59:9612–9622. https://doi.org/10.1021/jf2020107 308. Krumova K, Cosa G (2016) Overview of reactive oxygen species. In: Nonell S, Flors C (eds) Singlet oxygen: applications in biosciences and nanosciences, vol 1. The Royal Society of Chemistry, Cambridge, pp 1–21. https://doi.org/10.1039/9781782622208-00001 309. Premi S, Wallisch S, Mano CM et al (2015) Photochemistry. Chemiexcitation of melanin derivatives induces DNA photoproducts long after UV exposure. Science 347:842–847. https://doi.org/10.1126/science.1256022 310. Krajisnik A, Perer J, Wondrak GT (2019) Sunscreen-based skin protection against solar insult: molecular mechanisms and opportunities. In: Alberts DS, Hess LM (eds) Fundamentals of cancer prevention, 4th edn. Springer International Publishing, Cham, pp 377–404. https://doi. org/10.1007/978-3-030-15935-1_12 311. Wendel M, Nizinski S, Gierszewski M et al (2016) Chemical quenching of singlet oxygen by betanin. Photoch Photobio Sci 15:872–878. https://doi.org/10.1039/c6pp00037a 312. Bonacin JA, Engelmann FM, Severino D et al (2009) Singlet oxygen quantum yields (ΦΔ) in water using beetroot extract and an array of LEDs. J Braz Chem Soc 20:31–36 313. Nizinski S, Wendel M, Rode MF et al (2017) Photophysical properties of betaxanthins: miraxanthin V - insight into the excited-state deactivation mechanism from experiment and computations. RSC Adv 7:6411–6421. https://doi.org/10.1039/c6ra28110a 314. Wendel M, Szot D, Starzak K et al (2015) Photophysical properties of indicaxanthin in aqueous and alcoholic solutions. Dyes Pigments 113:634–639. https://doi.org/10.1016/j. dyepig.2014.09.036 315. Gandia-Herrero F, Escribano J, Garcia-Carmona F (2009) The role of phenolic hydroxy groups in the free radical scavenging activity of betalains. J Nat Prod 72:1142–1146 316. Guerrero-Rubio MA, Hernández-García S, García-Carmona F et al (2020) Biosynthesis of a novel polymeric chitosan-betaxanthin and characterization of the first sugar-derived betalains and their effects in the in vivo model Caenorhabditis elegans. Carbohydr. Polym. https://doi. org/10.1016/j.carbpol.2020.117141 317. Rice-Evans CA, Miller NJ, Paganga G (1996) Structure-antioxidant activity relationships of flavonoids and phenolic acids. Free Radic Biol Med 20:933–956. https://doi.org/10.1016/ 0891-5849(95)02227-9 318. Stewart AJ, Mullen W, Crozier A (2005) On-line high-performance liquid chromatography analysis of the antioxidant activity of phenolic compounds in green and black tea. Mol Nutr Food Res 49:52–60 319. Pietta P (2000) Flavonoids as antioxidants. J Nat Prod 63:1035–1042 320. Foti M, Ruberto G (2001) Kinetic solvent effects on phenolic antioxidants determined by spectrophotometric measurements. J Agric Food Chem 49:342–348

4

Betalains as Antioxidants

93

321. Schwinn KE (2016) The dope on L-DOPA formation for betalain pigments. New Phytol 210: 6–9 322. Sheehan H, Feng T, Walker-Hale N et al (2019) Evolution of L-DOPA 4,5-dioxygenase activity allows for recurrent specialisation to betalain pigmentation in Caryophyllales. New Phytol. https://doi.org/10.1111/nph.16089 323. Christinet L, Burdet FX, Zaiko M et al (2004) Characterization and functional identification of a novel plant 4,5-extradiol dioxygenase involved in betalain pigment biosynthesis in Portulaca grandiflora. Plant Physiol 134:265–274 324. Chung HH, Schwinn KE, Ngo HM et al (2015) Characterisation of betalain biosynthesis in Parakeelya flowers identifies the key biosynthetic gene DOD as belonging to an expanded LigB gene family that is conserved in betalain-producing species. Front Plant Sci 6:499. https://doi.org/10.3389/fpls.2015.00499 325. Guerrero-Rubio MA, Garcia-Carmona F, Gandia-Herrero F (2020) First description of betalains biosynthesis in an aquatic organism: characterization of 4,5-DOPA-extradioldioxygenase activity in the cyanobacteria Anabaena cylindrica. Microb Biotechnol. https:// doi.org/10.1111/1751-7915.13641 326. Harris N, Javellana J, Davies K et al (2012) Betalain production is possible in anthocyaninproducing plant species given the presence of DOPA-dioxygenase and L-DOPA. BMC Plant Biol 12:34 327. Bean A, Sunnadeniya R, Akhavan N et al (2018) Gain-of-function mutations in beet DODA2 identify key residues for betalain pigment evolution. New Phytol 219:287–296. https://doi.org/ 10.1111/nph.15159 328. Pioli RM, Mattioli RR, Esteves LC et al (2020) Comparison of the effect of N-methyl and Naryl groups on the hydrolytic stability and electronic properties of betalain dyes. Dyes Pigments 183. https://doi.org/10.1016/j.dyepig.2020.108609 329. Graham HN (1992) Green tea composition, consumption, and polyphenol chemistry. Prev Med 21:334–350. https://doi.org/10.1016/0091-7435(92)90041-f

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Selected Species of Medicinal/Arboreal Mushrooms as a Source of Substances with Antioxidant Properties Katarzyna Sułkowska-Ziaja, Agata Fijałkowska, and Bożena Muszyńska

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Antioxidant Properties of Selected Arboreal Medicinal Mushrooms . . . . . . . . . . . . . . . . . . . . . . 2.1 Auricularia auricula-judae . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Fomitopsis betulina . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Fomitopsis officinalis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Ganoderma applanatum . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.5 Hericium erinaceus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.6 Laetiporus sulphureus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.7 Lentinula edodes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.8 Pleurotus ostreatus . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abstract

Keeping the right balance between the production of free radicals and enzymatic/ nonenzymatic antioxidant defense is a necessary condition for the proper functioning of the human body. Exposure to free radicals led to the development of endogenous defense mechanisms to eliminate them from the system. Natural products with antioxidant properties are able to efficiently support this endogenous defense system. The role of antioxidants in the prevention of excessive accumulation of oxidative stress and related diseases has been systematically more understood through the years. Hence, researchers are constantly searching for new, safe, natural sources of antioxidants. Due to their enormous biosynthetic

K. Sułkowska-Ziaja (*) · A. Fijałkowska · B. Muszyńska Faculty of Pharmacy, Department of Pharmaceutical Botany, Jagiellonian University Medical College, Kraków, Poland e-mail: [email protected]; agata.fi[email protected]; [email protected] © Springer Nature Switzerland AG 2022 H. M. Ekiert et al. (eds.), Plant Antioxidants and Health, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-78160-6_38

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potential, arboreal mushrooms are a recognized medicinal raw material utilized primarily in traditional Chinese medicine. Currently, they are appreciated more and more often in modern mycotherapy, as well as in the cosmetics industry. This review includes details on the morphology, ecology, and distribution in the natural environment of selected examples of arboreal medicinal mushroom species. Much attention was paid to the content of bioactive substances present in fruiting bodies and their therapeutic and prohealth applications, in connection with their antioxidant potential. Numerous studies indicate these species are rich sources of antioxidants, such as phenolic compounds, tocopherols, ascorbic acid, and carotenoids, as well as polysaccharides. Bioactive compounds present in the extracts obtained from mushrooms’ fruiting bodies act in a synergistic and additive mode; therefore, these species can be a potential source of substances that can be useful in the prevention of civilization diseases. This review compares the antioxidant potential of the following arboreal, medicinal mushrooms that are important from a medical point of view: Auricularia auricula-judae, Fomitopsis betulina, Fomitopsis officinalis, Ganoderma applanatum, Hericium erinaceus, Laetiporus sulphureus, Lentinula edodes, and Pleurotus ostreatus. Keywords

Arboreal mushrooms · Chemical composition · Civilization diseases · Medicinal mushrooms · Oxidative stress Abbreviations

ABTS BHA BHK-21 cells CAT DPPH DW FRAP GSH IC50 LAP LEM LEPA1, LEPB1, LEPC1 NGF ROS SOD TCM

2,20 -azobis-3-ethylbenzothiazoline-6-sulfonate Butylated hydroxyanisole Baby hamster kidney cells Catalase 2,2-diphenyl-1-picrylhydrazyl Dry weight Ferric reducing antioxidant power assay Px glutathione peroxidase Half of the maximal inhibitory concentration Aqueous precipitate extract from the mycelium Lentinula edodes Fractionated extract from mycelium Lentinula edodes Polysaccharides fraction of Lentinula edodes Nerve growth factor Reactive oxygen species Superoxide dismutase Traditional Chinese medicine

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Introduction

Free oxygen radicals are atoms or molecules with an unpaired electron in a valence orbit. The term reactive oxygen species (ROS) has a broader meaning as it includes singlet oxygen and hydrogen peroxide. The most common ROS are free radicals, i.e., superoxide anionic radical hydroperoxide radical, hydroxyl radical, and nonradical species that exhibit significant activity or may be easily transformed into free radicals, such as singlet oxygen, ozone, or hydrogen peroxide. Active forms of oxygen are formed during oxidative processes (respiration, photosynthesis) in normally functioning cells or under the influence of biotic or abiotic factors. External factors include ionizing radiation, UV radiation, ultrasounds, or environmental stressors causing the so-called “respiratory burst.” ROS cause undesirable and even dangerous effects by reacting with various cellular structures (proteins, membranes, or nucleic acids). Changes in proteins, mainly enzymatic ones (modification of amino acids, oxidation of SH groups), may lead to metabolic disorders. Peroxidation of membrane-building lipids leads to changes in their permeability, instability, or disturbances in the functioning and transmembrane transport [1, 2]. Free radicals are important factors causing many pathological processes in the human body and encourage higher civilization diseases rates. They can damage cell membranes, proteins, enzymes, and DNA, increasing the risk of diseases such as Parkinson’s disease, Alzheimer’s disease, angiocardiopathies, asthma, diabetes, atherosclerosis, eye-degenerative diseases, chronic inflammation, neurodegenerative diseases, and neoplastic diseases [3]. Oxidative stress is a state of imbalance between the production and neutralization of ROS, which leads to their excessive activity. Antioxidants constitute an important element in the defense system against oxidative stress. Antioxidants are chemical compounds that counteract the oxidation processes or even in low concentrations delay the oxidation of substrates. Among the protective mechanisms of antioxidants, we can distinguish factors that prevent the initiation of the chain of free radical production, which include superoxide dismutase, catalase, and glutathione peroxidase [4, 5]. Other important repair mechanisms act by interrupting the chain of reactions at the propagation level. This kind of activity is demonstrated by vitamin A, C, and E, bilirubin, glutathione, uric acid, carnitine, and flavonoids. Finally, some factors remove the products of free radicals by repairing or eliminating damaged molecules. This is how, for example, DNA polymerase works. Small-molecule forms protect against the formation of ROS by directly reacting with them or with indirect metabolites of the redox reaction. Antioxidants are active in the hydrophilic (ascorbic acid) as well as in the hydrophobic (tocopherols, carotenoids) phase. Phenolic compounds can act in both phases, depending on the structure. Understanding the role of antioxidants in the prevention of oxidative stress and related diseases has resulted in the constant search for new, safe, natural sources of antioxidants.

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Macromycetes mushrooms are a source of compounds with multidirectional healing effects, such as anticancer, immunostimulating (glucans, glycoproteins, sesquiterpenoids, and triterpenoids), antiatherosclerotic (chitin, chitosan, and statins), antibacterial and antifungal (antibiotics), and antioxidant (sterols, tocopherols, and carotenoids) [6]. Compounds that can be found in mushroom-fruiting bodies and which exert protective activity against free radical-related diseases are (in order of highest antioxidant activity) phenolic compounds, flavonoids, ascorbic acid, tocopherols, carotenoids, and indole compounds [7, 8]. Mushrooms are recognized as a valuable medicinal raw material due to their ability to rapidly form into fruiting bodies, which can be also obtained by biotechnological methods that allow to optimize the cultivation conditions in order to control the level of active compounds [9]. Most studies on the antioxidant activity of mushrooms have focused so far on edible species, commonly consumed by humans. However, a comprehensive review of research shows that arboreal mushrooms, both edible and used only for medicinal purposes, exhibit stronger antioxidant activity than terrestrial mushrooms [10]. These findings prompted the search for new, natural sources of antioxidants with high therapeutic potential among arboreal species [11]. Scientific studies confirm that phenolic acids are the most common of the phenolic antioxidants present in mushrooms [10]. Their broad spectrum of biological activity is related to their strong antioxidant activity and ability to protect vital structures, i.e., chromosomal DNA, structural proteins, enzymes, LDL, and cell membrane lipids against oxidative damages [12]. Phenolic acids commonly found in arboreal mushrooms, such as gallic acid, parahydroxybenzoic acid, and protocatechuic acid, are characterized by antioxidant, antibacterial, antifungal, and anti-inflammatory properties, that were confirmed in in vitro and in vivo tests [13–15]. Protocatechuic acid also has immunomodulating, spasmolytic, cardioprotective, antithrombotic, and chemopreventive effects [16–25]. The antioxidant activity of mushrooms usually depends on the presence of lowmolecular-weight compounds, especially phenolic derivatives. However, it also depends on the content of terpenes and polysaccharides [10], as well as on the concentration of ergothioneine, which has strong antioxidant activity. Significant amounts of this compound have been determined in arboreal mushrooms [26]. The results of scientific research confirm a high positive correlation between the antioxidant activity of plants and the concentration of phenolic compounds in them [27]. A similar relationship is also observed for edible mushrooms [26]. However, in the case of arboreal mushrooms, a similar correlation is less frequent. Orhan et al. did not observe a significant correlation between the antioxidant activity of arboreal mushrooms and the content of phenolic compounds in ethanol extracts from their fruiting bodies [28]. Other studies on species of arboreal mushrooms also indicate a lack of correlation between the content of phenolic compounds in the extracts and the antioxidant activity (demonstrated in DPPH tests and the hydrogen peroxide-induced chemiluminescence test) [29].

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Turkoglu et al. proved that the antioxidant activity of Laetiporus sulphureus fruiting bodies is related to the presence of phenolic and flavonoid compounds [30]. On the other hand, Karaman et al. showed a high correlation between the total content of phenolic compounds in methanol extracts from fruiting bodies of arboreal mushrooms and the antioxidant activity determined in the DPPH test. However, based on the study of the interdependence of these parameters for chloroform extracts, it was found that other compounds with antioxidant activity are present in mushroom fruiting bodies as well [10]. Despite the commonness of the thesis that phenolic acids and other phenolic derivatives are the quantitatively dominant group of compounds responsible for the antioxidant activity of arboreal mushrooms, lack of a good correlation between these parameters indicates the presence of compounds with a different structure that play a key role in the antioxidant activity of mushrooms [10]. This review focuses on the medicinal, arboreal mushrooms belonging to the Basidiomycota: Auricularia auricula-judae (Bull.) Quél.; Fomitopsis betulina (Bull.) B.K. Cui, M.L. Han & Y.C. Dai); Fomitopsis officinalis (Vill.) Bondartsev & Singer; Ganoderma applanatum (Pers.) Pat.; Hericium erinaceus (Bull.) Pers.; Laetiporus sulphureus (Bull.) Murrill; Lentinula edodes (Berk.) Pegler; and Pleurotus ostreatus (Jacq.) P. Kumm. In the present work, the mycological and ecological characteristics, and an overview of the compounds responsible for the antioxidant properties of selected species of arboreal mushrooms are presented. These species belong to a large group of medicinal mushrooms that have been used in traditional European folk medicine and traditional Chinese medicine (TCM) for many years. Contemporary mycochemical studies based on modern analytical methods prove that the presence of valuable metabolites in the extracts of fruiting bodies, such as polysaccharides, phenolic compounds, or terpenoids, exhibits therapeutic effects, including antioxidant activity. In this study, particular emphasis was placed on the review of current works on the chemical composition of fruiting bodies in connection with the antioxidant effect.

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Antioxidant Properties of Selected Arboreal Medicinal Mushrooms

2.1

Auricularia auricula-judae

Auricularia auricula-judae (Bull.) Quél. belongs to the Auriculariaceae family. The species was described for the first time in 1789 by Bulliard as Tremella auriculajudae. The current name was given in 1886 by Quélet, who classified it to the genus Auricularia. The most common Latin synonyms of this mushroom are Auricularia auricula, Auricularia auricularis, Hirneola auricula, Hirneola auricula-judae, Merulius auricula, Peziza auricula-judae, and Tremella auricula-judae. In English, the species is known as jew’s ear, black wood ear, black fungus, or jelly ear.

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2.1.1 Mycological and Ecological Characteristics This species has a worldwide occurrence, except for high mountain areas. It is a parasite or saprotroph. It grows all year round. The fruiting bodies are most often found in forests, thickets, parks, gardens, and by the roads. It develops on weakened or dead wood of deciduous trees of the genus Acer sp., Alnus sp., and Sambucus nigra. It is considered as an edible species [31]. The fruiting bodies of Auricularia auricula-judae, with a diameter of 2–10 cm, initially form a calyx-shaped and later develop a cup-shaped structure with characteristic vein-ribbed foldings. Their upper surface is brown and matte (Fig. 1). The spores are formed on the lower red-brown surface of the fruiting body, which becomes whitish over time. In wet weather conditions, fruiting bodies have a jellylike consistency. This species does not have a characteristic smell [32, 33]. The basic information of the species (taxonomy, host, and geographic distribution) is tabulated in Table 1. 2.1.2 Traditional and Modern Medicinal Value Auricularia auricula-judae has been used for centuries in Eastern medicine as a medicinal raw material that dilutes the blood, regulates blood pressure, strengthens, detoxifies, soothes coughs or sore throats, and cures hemorrhoids. In Europe, in the sixteenth century, remedies based on milk or beer were recommended for the treatment of sore throats. In the seventeenth century in the British Isles, powdered fruiting bodies were used to treat jaundice. In the eighteenth century, Linnaeus advised infusions from fruiting bodies in colds and eye inflammation. Nowadays, extracts from Auricularia auricula-judae are used to treat ulcers, wounds, inflammations of the throat and eyes, stomach, and intestines. Active ingredients of fruiting bodies represent various chemical groups, including polysaccharides, sterols, and bioelements. Researches have shown that extracts obtained from fruiting bodies exhibit many therapeutic actions including hypoglycemic, antithrombotic, antiatherosclerotic, antibacterial, antiviral, cardioprotective, and antitumor activity [34]. 2.1.3 Chemical Composition and Antioxidant Properties Research on the biological activity of extracts from Auricularia auricula-judae fruiting bodies confirms their significant antioxidant potential. Compounds responsible for this activity profile are mainly polysaccharides present in the fruiting bodies [35]. Results from tests using DPPH (2,2-diphenyl-1-picrylhydrazyl) and ABTS (2,20 -azobis-3-ethylbenzothiazoline-6-sulfonate) radicals showed that polysaccharides had IC50 (half of the maximal inhibitory concentration) value of 3.29 and 1.23 mg/mL, while a reference substance, BHA (butylated hydroxyanisole), had IC50 of 4.45 and 5.78 mg/mL. Polysaccharides have also shown the ability to scavenge the hydroxyl radical and the superoxide radical. Moreover, they had an inhibitory effect on lipid peroxidation in the egg yolk homogenate at the level of IC50 of 0.07 mg/mL and showed significant reductive properties [36]. Researchers also compared the antioxidant activity of Auricularia auricula-judae polysaccharides with polysaccharides obtained from other fungal species. Based on the ability to scavenge the hydroxyl radical and DPPH, it was found that Auricularia auricula-judae polysaccharides have weaker antioxidant properties compared to

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Fig. 1 Selected species of arboreal mushrooms: (a) Auricularia auricula-judae (author: Krzysztof Kujawa); (b) Fomitopsis betulina (author: Krzysztof Kujawa); (c) Fomitopsis officinalis (author: Jacek Piętka); (d) Ganoderma applanatum (author: Krzysztof Kujawa); (e) Hericium erinaceus (author: Grażyna Domian); (f) Laetiporus sulphureus (author: Krzysztof Kujawa); (g) Lentinula edodes (author: Piotr Zięba); and (h) Pleurotus ostreatus (author: Krzysztof Kujawa)

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Table 1 Mycological characteristic of selected arboreal mushrooms Name of species Auricularia auriculajudae Fomitopsis betulina Fomitopsis officinalis

Family Auriculariaceae

Host Sambucus nigra Acer sp., Alnus sp.

Fomitopsidaceae

Betula sp.

Fomitopsidaceae

Larix sp., Abies sp., Cedrus sp., Picea sp., Pinus sp., Pseudotsuga sp.

Ganoderma applanatum

Polyporaceae

Hericium erinaceus Laetiporus sulphureus

Hericiaceae

Lentinula edodes

Omphalotaceae

Pleurotus ostreatus

Pleurotaceae

Acer negundo, Acer platanoides, Aesculus hippocastanum, Alnus glutinosa, Betula pendula, Carpinus sp., Corylus sp., Crataegus sp., Fagus sp., Fraxinus excelsior, Populus tremula, Prunus domestica, Quercus sp., Robinia pseudoacacia, Salix sp., Tilia sp., Ulmus minor Fagus sp., Quercus sp., Malus sp., Juglans regia Aesculu sp., Populus sp., Quercus sp., Larix sp., Taxus sp. Carpinus sp., Castanea sp., Fagus sp., Pasania sp., Quercus sp. Betula sp., Fagus sp., Juglans regia, Robinia pseudoacacia, Salix sp.

Laetiporaceae

Natural distribution A worldwide occurrence, except for high mountain areas Range of occurrence covers the northern hemisphere Range covers a large part of the northern hemisphere, and it has many natural habitats in Africa, North America, and Asia, and in Europe it occurs in old-growth forest A worldwide occurrence, except for high mountain areas

Range of occurrence covers the northern hemisphere A worldwide occurrence

Native to East Asia

A worldwide occurrence, except Antarctica

polysaccharides from Agaricus bisporus, Lentinus edodes, and a reference substance – vitamin C. At the same time, Auricularia auricula-judae polysaccharides had a stronger antioxidant activity than polysaccharides from Flammulina velutipes [37]. The antioxidant potential of polysaccharides from Auricularia auricula-judae was also analyzed in an in vivo model. Mice that were forced to experience physical exertion showed greater resistance to fatigue after oral ingestion of polysaccharides compared to the control group. Moreover, oxidative stress generated by exercise was significantly reduced in mushroom-supplemented mice, which was evidenced by a reduction in the concentration of malonyldialdehyde (one of the main products of lipid peroxidation) and 8-hydroxy-20 -deoxyguanosine (an index of DNA oxidative

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damage) in rodents’ plasma and muscles. At the same time, an increase in the activity of superoxide dismutase, glutathione peroxidase, and catalase in the tissues of the tested animals was observed [38]. A significant increase in the activity of glutathione peroxidase and superoxide dismutase, and a decrease in the level of malonyldialdehyde, was also observed in heart and liver homogenates of mice treated for 30 days with Auricularia auriculajudae polysaccharides (daily doses ranged from 50 to 200 mg/kg). Results from other experiments showed a beneficial effect of polysaccharides on the activity of antioxidant enzymes in animals’ hearts, and a significant increase in left ventricular ejection volume. Polysaccharides also had a positive effect on blood lipid profile, reducing the concentration of triglycerides, total cholesterol, and LDL cholesterol, and increasing the concentration of HDL [39]. The antioxidant activity of Auricularia auricula-judae extracts was also investigated and compared with the activity of other mushrooms: Pleurotus tuber-regium, Termitomyces robustus, Lentinus squarrosulus, Pleurotus ostreatus, and Pleurotus sajor-caju. Auricularia auricula-judae extract not only showed a high reducing power and the ability to scavenge the DPPH radical, but it also inhibited lipid peroxidation at the lowest level [40]. Comparison of Auricularia auricula-judae, Inonotus obliquus, Ganoderma lucidum, Lentinus edodes, and Tremella fuciformis water and methanol extracts showed that Auricularia auricula-judae exhibited the lowest antioxidant activity [41]. On the other hand, the next studies demonstrated that methanol and water extracts had the ability to scavenge free radicals in the DPPH test. Furthermore, the methanol extract showed an ability to complex Fe(II) ions, which is important in preventing the Fenton reaction, generating hydroxyl radical in the body. Researches also established that, when applied to BHK-21 cells (baby hamster kidney cells) treated with hydrogen peroxide, the aqueous extract inhibits plasma lipid peroxidation and protects BHK-21 cells from the damaging effect of hydrogen peroxide [42]. The phenolic compounds present in fruiting bodies, including catechin, para-hydroxybenzoic acid, gallic acid, caffeic acid, carotenoids, ascorbic acid, and melanin, are responsible for the antioxidant activity of Auricularia auricula-judae extracts as well [40, 43–45]. The chemicals compounds with antioxidant properties present in Auricularia auricula-judae were summarized in Table 2.

2.2

Fomitopsis betulina

Fomitopsis betulina (Bull.) B.K. Cui, M.L. Han & Y.C. Dai belongs to the Fomitopsidaceae family. It was described for the first time by Bulliard in 1788 as Boletus betulinus. In 2016, this species was classified as a part of the genus Fomitopsis. The most known Latin synonyms of this mushroom are Fomes betulinus, Piptoporus betulinus, Placodes betulinus, Polyporus betulinus, and Ungularia betulina. In English, it is called birch polypore, birch bracket, or razor strop.

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Table 2 Chemical compounds with antioxidant activity in selected arboreal mushrooms Mushrooms species Auricularia auriculajudae

Fomitopsis betulina

Fomitopsis officinalis

Ganoderma applanatum Hiericium erinaceus Laetiporus sulphureus

Lentinula edodes

Pleurotus ostreatus

Chemical compounds/extracts with antioxidant activity Ascorbic acid Carotenoids Catechin Melanin Phenolic acids Polysaccharides Ascorbic acid Flavonoids Lycopene α-, β-, γ-, δ–tocopherol β-carotene Catechin Flavonoids Phenolic acids Polysaccharides Triterpenes (ganoderic acid A) Phenolic acids Phenolic acids Flavonoids (kaempferol, catechin) Phenolic acids Polysaccharides (laetiporan) Phenolic acids Catechin Tocopherols β-carotene Polysaccharides (LEPA1, LEPB1, LEPC1) Ascorbic acid Flavonoids Phenolic acids Polysaccharides Tocopherols

References [35, 36, 40, 43– 45]

[28, 51, 52]

[55, 56]

[58–60, 62–64]

[77–79]

[90–94]

[101–103]

2.2.1 Mycological and Ecological Characteristics Fomitopsis betulina is a widespread species of arboreal mushroom. Its range of occurrence covers the northern hemisphere. It produces its fruiting bodies from August to November. This species grows in forests with a predominance of deciduous species, in parks, and by roads and prefers high humidity, and shaded places. It is characterized by low variability (differentiation of the characteristics of individuals within one population or species) [31]. Fomitopsis betulina is related with the genus Betula sp. The fruiting bodies are white, with a smooth greyish-brown top surface, while the creamy white underside has pores that contain the spores. The fruiting bodies has a rubbery texture, becoming corky with age. The spores are cylindrical to ellipsoidal in shape (Fig. 1). It significantly accelerates the death of weakened trees, causing the so-called brown rot-chemical decomposition, and the resulting decay of the cell walls of wood. The fruiting bodies can synthesize

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enzymes that enable the utilization of wood components (mainly cellulose, hemicelluloses, and lignin). Fomitopsis betulina is considered an inedible species, but young specimens are considered edible [32, 33].

2.2.2 Traditional and Modern Medicinal Value The oldest evidence of use of Fomitopsis betulina fruiting bodies by humans is the discovery of its fragments near the remains of the “iceman” – Ötzi, who lived around 3300 BC. It is believed that the fruiting bodies of this species were already used for medicinal purposes because of their beneficial effect on the wound-healing process [46–48]. For a very long time, in European folk medicine, infusions of powdered fruiting bodies of Fomitopsis betulina were used due to their strengthening, antibacterial, antiparasitic, laxative, and wound-healing properties. Numerous studies confirmed its traditionally known medicinal properties and also showed new directions in the research of biological activity of extracts obtained from fruiting bodies, including antioxidant, anti-inflammatory, and anticancer properties [34, 49]. 2.2.3 Chemical Composition and Antioxidant Properties Chemically diverse compounds with antioxidant potential are present in the fruiting bodies of Fomitopsis betulina [50]. The analysis of phenolic acids content in fruiting bodies and, comparatively, in mycelial cultures carried out by Sułkowska-Ziaja et al. proved the presence of syringic acid, gallic acid, para-hydroxybenzoic acid, and 3,4-dihydroxyphenylacetic acid. The total content of phenolic acids present in methanol extracts from fruiting bodies was 37.08 mg/100 g DW (dry weight), while the total content of phenolic acids in methanol extracts from biomass obtained from mycelial cultures was 22.56 mg/100 g DW (Table 3). Phenolic acids identified in both fruiting bodies and mycelial cultures exhibit a broad spectrum of biological activity of antioxidant, antibacterial, antiviral, antifungal, and anti-inflammatory character [51] . The presence of β-carotene, lycopene, tocopherols, ascorbic acid, and many compounds from the group of flavonoids and polyphenols was also confirmed in the fruiting bodies. A positive correlation was demonstrated between the antioxidant activity and the total amount of phenolic compounds in methanol-acetone extracts from Fomitopsis betulina collected from the natural environment in Poland. It was found that polyphenols show the ability to neutralize free radicals, prevent lipid oxidation, and stabilize compounds susceptible to oxidation – including vitamin C [28, 52]. The tocopherols identified in fruiting bodies are α-, β-, γ-, and δ-tocopherol, which occurs in the largest amount – 577.62μg/100 g DW. The content of vitamin C was 87.9 mg/100 g DW of DW, β-carotene – 0.09 mg/100 g DW, and lycopene – 0.23 mg/g DW. The total content of flavonoids in fruiting bodies was 6.79 mg/g and phenolic compounds – 34.94 mg/g of the methanol extract. Antioxidant activity of the fruiting bodies was confirmed in the DPPH free radical scavenging test (EC50 ¼ 8.97 mg/mL), as well as by the β-carotene autoxidation inhibition in the β-carotene-linoleic acid system test (EC50 ¼ 1.97 mg/mL) [52]. The chemicals compounds with antioxidant properties present in Fomitopsis betulina were summarized in Table 2.

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Table 3 Phenolic acids and cinnamic acid in selected arboreal mushrooms (the results of own study carried out in the Department of Pharmaceutical Botany UJ CM) Phenolic acids Auricularia auricula-judae Fomitopsis betulina

Fomitopsis officinalis Ganoderma applanatum

Hiericium erinaceus Laetiporus sulphureus

Lentinula edodes

Pleurotus ostreatus

a

Name of species

References

a

3,4-Dihydroxyphenylacetic acid Gallic acid Para-hydroxybenzoic acid Syringic acid Para-hydroxybenzoic acid Gallic acid Para-hydroxybenzoic acid Protocatechuic acid Syringic acid

[51]

[55] [61]

a

Gallic acid Para-hydroxybenzoic acid Protocatechuic acid Caffeic acid Gallic acid Para-hydroxybenzoic acid Protocatechuic acid Vanillic acid Ferulic acid Para-hydroxybenzoic acid Protocatechuic acid Sinapic acid Cinnamic acid

[61]

[95]

[105]

Not analyzed

2.3

Fomitopsis officinalis

Fomitopsis officinalis (Vill.) Bondartsev & Singer belongs to the Fomitopsidaceae family. This species was first described by Villars in 1788 as Boletus officinalis. In 1941, Bondartsev and Singer moved the species to the genus Fomitopsis. The most known Latin synonyms are Boletus officinalis, Polyporus officinalis, Piptoporus officinalis, Cladomeris officinalis, Ungulina officinalis, Fomes officinalis, Laricifomes officinalis, Agaricum officinale, Boletus laricis, Fomes laricis, Boletus purgaricum, and Boletus agaricus. Common English names are agarikon and quinine conk.

2.3.1 Mycological and Ecological Characteristics Fomitopsis officinalis’ range covers a large part of the northern hemisphere. It has many natural habitats in Africa, North America, and Asia. In Europe, it occurs mainly on very old larch trees, in natural forests, and very rarely in artificially renewed stands. It hosts, apart from Larix sp., on species of the genus Abies sp., Cedrus sp., Picea sp., Pinus sp., and Pseudotsuga sp. Fomitopsis officinalis is a parasite that causes intense brown rotting of wood [31]. After several years of growth, fruiting bodies can reach a weight of up to 10 kg. The surface of the fruiting

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body is gray, with some visible cracks. It is attached sideways to the trunk of a tree since it has no stem (Fig. 1). The chalk-like flesh structure has a very bitter taste [32, 33].

2.3.2 Traditional and Modern Medicinal Value Fomitopsis officinalis is considered one of the oldest medicinal mushrooms in Europe and Asia. Therapeutic properties of Fomitopsis officinalis were commonly known in ancient Greece and Rome. It was used as a panacea for many ailments, such as excessive sweating, dizziness, respiratory diseases, tuberculosis, rheumatism, and gastrointestinal complaints. Intensive harvesting of fruiting bodies and uncontrolled deforestation [53] are the reasons for this species’ legal protection in many European countries nowadays. Properties of the raw material are determined by rich chemical composition, the presence of polysaccharides, terpenoids, coumarin flavonoids, and open acids [54]. Studies have shown that raw fruiting body extracts have multidirectional therapeutic effects, including anti-inflammatory, cytotoxic, and antimicrobial activity. 2.3.3 Chemical Composition and Antioxidant Properties The antioxidant potential of Fomitopsis officinalis fruiting body extracts tested by Fijałkowska et al. by DPPH method was 36.0% at a concentration of 225μg/mL of the extract. During the same experiment, the content of para-hydroxybenzoic acid was determined in the amount of 0.07 mg/100 g DW and gallic acid in the amount of 0.09 mg/100 g DW (Table 3). Additionally, the presence of catechin in the amount of 58.37 mg/100 g DW was confirmed [55]. Studies involving the evaluation of the antioxidant effect of the flavonoid fraction isolated from the fruiting bodies of Fomitopsis officinalis carried out in in vivo models using animals have proven that they influence the aging process of the organism. Three groups of rodents were supplemented with different doses of flavonoids that ranged from low – 100 mg/kg body weight, medium – 200 mg/kg body weight, to high – 400 mg/kg body weight. The results of the experiment proved that each of the administered doses can increase the value of the brain index, spleen and thymus index, the activity of glutathione peroxidase (GSH-Px) in brain tissues, catalase (CAT), and superoxide dismutase (SOD) in liver tissues [56]. The chemical compounds with antioxidant properties present in Fomitopsis officinalis were summarized in Table 2.

2.4

Ganoderma applanatum

Ganoderma applanatum (Pers.) Pat. belongs to the Polyporaceae family. The species was first described by Persoon in 1800 as Boletus applanatus, but in 1887 Patouillard changed its name. The most known Latin synonyms are Boletus applanatus, Elfvingia applanate, Fomes applanatus, Fomes vegetus, Ganoderma lipsiense, Polyporus applanatus, and Polyporus vegetus. Common English names are artist’s bracket, artist’s conk, and bear bread.

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2.4.1 Mycological and Ecological Characteristics Ganoderma applanatum is a common species of a wood-decay mushroom. It is easy to be found not only all over the world except in the higher mountain parts, mostly in the forests, but also in parks and along roads. This species is a parasite or saprotroph. The fruiting bodies grow all year round. Ganoderma applanatum grows on living and dead trunks of deciduous or conifers trees such as Acer negundo, Acer platanoides, Aesculus hippocastanum, Alnus glutinosa, Betula pendula, Carpinus sp., Corylus sp., Crataegus sp., Fagus sp., Fraxinus excelsior, Populus tremula, Prunus domestica, Quercus robur, Quercus petrea, Robinia pseudoacacia, Salix sp., Tilia sp., and Ulmus minor [31]. Its fruiting body is flat and semicircular. It is positioned sideways to the trunk since it usually does not form steam. Its size ranges from 10 to 60 cm, and its thickness varies from 2 to 8 cm. The hymenophore consists of whitish, multilayered, blunt tubes. The flesh is soft and elastic in touch and resembles felt when torn (Fig. 1). The spores are rusty brown, oval-spherical, covered with warts. The young fruiting body has a characteristic typical mushroom smell and a burning, bitter taste. It is considered an inedible species [32, 33]. 2.4.2 Traditional and Modern Medicinal Value Ganoderma spp. has been used in traditional Eastern medicine for many years. It has been used to regulate blood pressure, treat chronic bronchitis, improve immunity, and as a stress-reducing agent. This species was also expected to have antitumor, antiviral, and immunomodulatory properties. Contemporary research has proven the following properties: anticancer, immunoregulatory, antioxidant, anti-inflammatory, antiallergic, neuroprotective, hepatoprotective, hypoglycemic, hypotensive, antimicrobial, antiviral, and antimalarial. The most important chemical compounds in Ganoderma spp. are triterpenes (GTs – Ganoderma triterpenes) and polysaccharides. Until now, more than 300 triterpenes and 50 polysaccharides characterized by various chemical structures and biological activity have been isolated [34, 57]. 2.4.3 Chemical Composition and Antioxidant Properties Independently conducted studies of the antioxidant activity of Ganoderma applanatum proved that polysaccharides, triterpenes, and phenolic compounds are responsible for this effect to a different extent [58]. The evaluation of the antioxidant activity of ethanol extract from fruiting bodies showed inhibition of lipid peroxidation and strong activity of scavenging hydroxyl radicals compared to a reference substance (catechin). The IC50 value of the extract was 267μg/mL for the hydroxyl radical scavenging activity and 166μg/mL for lipid peroxidation. Moreover, ethanol extracts increased the production of nitric oxide (742 pmol/mg DW/h) [59]. The antioxidant activity of phenolic compounds from the fruiting bodies of Ganoderma applanatum is based on several different mechanisms. They are assigned the following properties: As reducing compounds, they are capable of donating an electron; as metal ion chelators found in enzymes that initiate oxidation reactions; and as stabilizers of free radicals through their hydrogenation or complexation [60].

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Phenolic compounds present in fruiting bodies are represented mainly by phenolic acids such as gallic acid, para-hydroxybenzoic acid, para-coumaric acid, protocatechuic acid, vanillic acid, caffeic acid, and trans-cinnamic acid [10]. Chemical analysis of biomass from mycelial cultures carried out at the Department of Pharmaceutical Botany UJCM confirmed the presence of gallic acid, parahydroxybenzoic acid, protocatechuic acid, and syringic acid (Table 3) [61]. The lanostane triterpenes present in fruiting bodies were also tested for antioxidant properties. A representative of this group is ganoderic acid A, which has antioxidant and hepatoprotective properties [62, 63]. The antioxidant properties of polysaccharides from this species were evaluated in the DPPH test (77.5–81.9% at concentrations of 0.1–1.0 mg/mL), in the lipid peroxidation test (73.9–74, 3% at a concentration of 5.0–20.0 mg/mL), and in the Fe(II) chelation test (15.7–89.0% at concentrations of 0.1–20.0 mg/mL). The total polysaccharide content in the aqueous extracts was 303 mg/g DW. Another study showed that 35% of the total carbohydrate content was attributable to glucans, of which β-glucans (16.0 g/100 g) were more abundant than α-glucans (6.4 g/100 g) [64]. The chemical compounds with antioxidant properties present in Ganoderma applanatum were summarized in Table 2.

2.5

Hericium erinaceus

Hericium erinaceus (Bull.) Pers. belongs to the Hericiaceae family. This species was first described by Bulliard in 1781 as Hydnum erinaceus. Its current name was given to it by Persoon in 1797, who classified Hydnum erinaceus to the genus Hericium. This species has numerous Latin synonyms: Clavaria conferta, Clavaria erinaceus, Dryodon caput-medusae, Dryodon erinaceus, Hericium caput-medusae, Hericium echinus, Hericium grande, Hericium hystrix, Hydicium unguiculatum, Hydusanum, caputnum-echinum. Erinaceus, Hydnum grande, Hydnum hystricinum, Hydnum hystrix, Hydnum juranum, Hydnum omasum, Hydnum unguiculatum, Manina cordiformis, Martella echinus, Martella hystricinum, Martella hystrix, Merisma hystrix, and Steccherinum quercinum. In English, it is called: lion’s mane mushroom, monkey head mushroom, bearded tooth mushroom, satyr’s beard, bearded hedgehog mushroom, or bearded tooth fungus.

2.5.1 Mycological and Ecological Characteristics Hericium erinaceus is a saprotroph and can be found in the northern hemisphere. It usually grows in deciduous forests with an old tree stand, mainly on tree trunks in their lower part, up to several meters high. This species develops fruiting bodies on the trunks of deciduous trees of the genus Fagus sp., Quercus sp., as well as Malus sp., and Juglans regia [31]. Spherical fruiting bodies, 8–20 cm in size, are initially white, with time becoming creamy white. The fruiting bodies grow to the side or the bulbous part of the tree trunk, which becomes lignified in older specimens. The surface of the fruiting body is densely covered with spines 2–6 cm long and 1.5–2 mm thick. The spines are

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whitish-yellow initially, then yellow-orange to gray-brown. The flesh of the fruiting body is fleshy, elastic, springy, and somewhat fibrous (Fig. 1). It tastes sweet and smells with typical mushroom odor [32, 33].

2.5.2 Traditional and Modern Medicinal Value Hericium erinaceus has a long history of use as a recognized medicinal mushroom in TCM, where it has found use in the treatment of neurasthenia and general weakness [65]. Because of its rich chemical composition of fruiting bodies, many dietary supplements and alternative medicines have been developed. In fruiting bodies, compounds representing a variety of chemical groups are present, including polysaccharides, proteins, lectins, phenolic compounds, and terpenoids. It has been proven that two groups of terpenoid compounds with a diterpene structure called hericenons and erinacins, isolated from both fruiting bodies and mycelial cultures, stimulate the synthesis of NGF (nerve growth factor) [66]. Contemporary research has confirmed many traditional applications and postulates new directions of biological activity, including anticancer, neuroprotective, immunomodulating, hypoglycemic, and hypocholesterolemic effects. 2.5.3 Chemical Composition and Antioxidant Properties Studies have shown strong antioxidant properties of extracts and individual compounds isolated from both, fruiting bodies and mycelium obtained from mycelial cultures of Hericium erinaceus [67–71]. Antioxidant activity is shown, inter alia, by phenolic compounds, lipopolysaccharides, and β-glucans. A study of the phenol fraction from mycelial extracts in hot water has been described to evaluate the in vitro antioxidant activity by Abdullah et al. [9, 72]. Another experiment described the antioxidant properties of phenolic compounds from fruiting bodies and mycelium. The mycelial extracts showed the highest total phenolic content and the highest iron-reducing antioxidant power (FRAP). Both fresh and oven-dried fruiting body extracts contained phenolic compounds with antioxidant properties. However, possibly due to the production and accumulation of Maillard reaction products (MRPs) during dry processing, the potential antioxidant capacity of oven-dried fruiting bodies was higher than that of the freeze-dried extract [73]. Han et al. [74] demonstrated antioxidant activity against oxidative damage to the kidneys induced by reperfusion ischemia in mice. The results of the earlier administration of β-glucans from Hericium erinaceus showed increased enzymatic activity of antioxidant nature, as well as a decreased level of lipid peroxidation. Zhang et al. [75] isolated endopolysaccharides from ethanol extracts of Hericium erinaceus mycelium that had grown on tofu whey. Results showed an extremely strong antioxidant effect in in vitro tests. It suggests that extracts of Hericium erinaceus fruiting bodies may increase the activity of antioxidant enzymes in humans. Xu et al. [76] also proved that β-glucans isolated from Hericium erinaceus showed antiaging activity. This effect was caused by the inhibition of activity of matrix metalloproteinase (MMP-1) and tissue matrix metalloproteinase inhibitor (TIMP-1) in older rat models. The lipopolysaccharides (LPS) present in the mycelium showed a significant antioxidant effect confirmed in an experiment using

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mice derived from the BALB/C strain (albinotic, laboratory strain of domestic mice), which resulted in elevated levels of glutathione in the liver [77]. The chemicals compounds with antioxidant properties present in Hericium erinaceus were summarized in Table 2.

2.6

Laetiporus sulphureus

Laetiporus sulphureus (Bull.) Murrill belongs to the Laetiporaceae family. This species was first described by Bulliard in 1789 as Boletus sulphureus. The present name was given to it by Murrill in 1920, who classified it to the genus Laetiporus. The most famous Latin synonyms of this genus are Agaricus speciosus, Boletus citrinus, Boletus imbricatus, Boletus sulphureus, Ceriomyces aurantiacus, Cladomeris casearius, Daedalea imbricata, Grifola sulphurea, and Leptoporus imbricatum. In English, it is commonly known as forest crab, sulfur polyp, sulfur shelve, and forest chicken.

2.6.1 Mycological and Ecological Characteristics This species is a cosmopolitan arboreal mushroom. Its habitats occur in Europe and North America. It grows in deciduous and mixed forests, parks, gardens, and orchards, along streets and roads. Laetiporus sulphureus attacks and colonizes both, living specimens and dead wood of deciduous species, such as Robinia sp., Aesculus sp., Populus sp., Quercus sp., and less frequently coniferous species, e.g., Larix sp., Taxus sp. Laetiporus sulphureus is a parasitic fungus. It causes the intense brown rotting process of wood [31]. The fruiting bodies consist of fleshy, semicircular fan-shaped hats with a characteristic sulfur-yellow color. The flesh is white to creamy yellow, soft and juicy in young specimens, and tender in older specimens (Fig. 1). The taste is pleasant, slightly sour, with a mushroom aroma. It is classified as a conditionally edible mushroom because only young fruiting bodies after proper preparation are edible [32, 33]. 2.6.2 Traditional and Modern Medicinal Value Laetiporus sulphureus has been used in traditional medicine for centuries in many European countries, where it was valued for its antipyretic, antitussive, and antirheumatic properties. Extensive research on both, extracts and single compounds, confirms formerly known, traditional applications and shows new profiles of biological activity. 2.6.3 Chemical Composition and Antioxidant Properties The fruiting bodies of Laetiporus sulphureus are an important source of compounds with antioxidant activity. It does not have side effects, typical for synthetic compounds with this kind of potential [30]. The total content of phenolic compounds in the methanol and chloromethane extract from the fruiting bodies of Laetiporus sulphureus is approximately 7.25 and 0.33 mg/g DW, respectively. Among the determined phenolic acids, gallic acid was

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the quantitatively dominant compound in the methanol extract, the content of which was 2.06 mg/g DW. In addition to gallic acid, protocatechuic acid was also determined in the amount of 1.21 mg/g DW [10]. In another study, the total content of flavonoids and, separately, phenolic compounds in ethanol extract from fruiting bodies was determined to 14.02μg/mg (based on quercetin concentration) and 63.8μg/mg (based on the concentration of pyrocatechol), respectively [30]. In the extract obtained with the use of ethyl acetate, the content of quercetin compounds (11.37 mg/g), kaempferol (5.01 mg/g,) (+) – catechin 14.04 mg/g, gallic acid (28.57 mg/g), chlorogenic acid (22.61 mg/g), caffeic acid (20.07 mg/g), and para-coumaric acid (18.84 mg/g) was determined [78, 79]. Chemical analysis of biomass from mycelial cultures carried out at the Department of Pharmaceutical Botany UJCM confirmed the presence of gallic acid, para-hydroxybenzoic acid, protocatechuic acid, and syringic acid (Table 3) [61]. Ethanol extracts from the fruiting bodies of Laetiporus sulphureus show antioxidant activity confirmed by many studies, including in the DPPH radical scavenging test, the linolenic acid emulsion stability test, and by measuring the total content of phenolic compounds and flavonoids. The ethanol extract from fruiting bodies in the amount of 320μg showed an antioxidant effect in the DPPH test corresponding to 40μg of α-tocopherol. The antioxidant activity was proportional to the concentration of the extract used and the content of phenolic compounds in it. Another group of researchers isolated water-soluble endopolysaccharides with the structure of glucans, galactans, and glycoproteins from fruiting bodies. They accounted for 3.67% of the mushroom fruiting body mass. The main polysaccharide, which accounted for 0.28% of DW the fruiting body, was a 56-kDa laetiporan – β-1,3-glucan, substituted at the C6 position with a mannose, galactose, fucose, xylose, or rhamnose residue [77]. The galactomannoglucan named laetiporan A, isolated from the fruiting bodies of Laetiporus sulphureus, showed a strong antioxidant effect in vitro, preventing the occurrence of hepatitis in experimental animals treated with carbon tetrachloride [80]. As one of eight species of arboreal mushrooms (Ganoderma lucidum, Ganoderma applanatum, Meripilus giganteus, Laetiporus sulphureus, Flammulina velutipes, Coriolus versicolor, Pleurotus ostreatus, and Panus tigrinus), Laetiporus sulphureus showed the highest ability to scavenge hydroxyl radicals, and in the DPPH test only Ganoderma lucidum fruiting bodies had a stronger antioxidant potential. Methanol extracts from Laetiporus sulphureus inhibited approximately 40% of the lipid peroxidation process in in vitro test [10]. The chemical compounds with antioxidant properties present in Laetiporus sulphureus were summarized in Table 2.

2.7

Lentinula edodes

Lentinula edodes (Berk.) Pegler belongs to the Omphalotaceae family. This species was first described by Berkeley in 1878 as Agaricus edodes. Its current name was given to it by Pegler in 1976, classifying it to the genus Lentinula. Its most famous Latin synonyms are Agaricus edodes, Armillaria edodes, Collybia shiitake,

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Cortinellus shiitake, Lentinus edodes, Lentinus mellianus, Lentinus shiitake, Lentinus tonkinensis, Lepiota shiitake, Mastoleucomyces edodes, and Tricholoma shiitake. The common name is shiitake.

2.7.1 Mycological and Ecological Characteristics Natural distribution Lentinula edodes includes warm and moist climates in Southeast Asia. The fruiting bodies grow in groups on the dead deciduous wood of trees of the genera: Carpinus sp., Castanea sp., Fagus sp., Pasania sp., and Quercus sp. [31]. The brown or brownish fruiting body forms a cap up to 20 cm in diameter and a stem 3–4 cm thick. Its shank has light reddish-brown color with slightly darker scales at the top of the surface. A whitish, dense, and wide hymenophore turns into a reddish blotch with time (Fig. 1). The flesh is white and tastes slightly sour. Lentinula edodes is one of the most often cultivated mushrooms in the world [81]. 2.7.2 Traditional and Modern Medicinal Value The tradition of using Lentinula edodes for medicinal purposes in the Far East countries (China, Japan, and Korea) is several thousand years old. The first mention of this topic dates back to 119 CE. During the Ming Dynasty, shiitake was used as a medicine for diseases of the liver, cardiovascular system, respiratory system, and fatigue. It was also attributed to the property of enhancing vital forces and inhibiting the aging process [82, 83]. Over the past 30 years, Lentinula edodes has become one of the most thoroughly studied species of medicinal mushrooms. A number of compounds have been isolated from fruiting bodies and mycelium, which can be attributed to pharmacological effects, mainly immunomodulatory and anticancer [84]. Significant importance in medicine plays polysaccharide fractions (lentinan) and extracts from mycelium and culture medium: LEM (water extract obtained from mycelium grown on solid media that contains amino acids, vitamins, polysaccharides of various structures, glycoproteins, polyphenols, and ergosterol), LAP (an extract containing many different ingredients, including lentionine and polysaccharide fractions of various structures) [85–87]. Lentinan was isolated in 1970 by Chihara by fractionating water-soluble polysaccharides derived from the cell wall of Lentinula edodes fruiting bodies [88, 89]. The basic structure of the polysaccharide is the β-(1–3)-D-glucan chain with two side branches, every five sugar units, connected to the main chain by β-(1–6)-glycosidic bonds [90]. 2.7.3 Chemical Composition and Antioxidant Properties Polyphenols (gallic acid, protocatechuic acid, and catechin), tocopherols, β-carotene, and polysaccharides are responsible for the antioxidant properties of Lentinula edodes fruiting bodies. It has been found that the antioxidant properties are weaker than that of ascorbic acid [91–94]. Chemical analysis of biomass from mycelial cultures of Lentinula edodes carried out at the Department of Pharmaceutical Botany UJCM confirmed the presence of gallic acid, para-hydroxybenzoic acid, protocatechuic acid, caffeic acid, and vanillic acid (Table 3) [94].

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The antioxidant activity of the polysaccharides was assessed using various extraction techniques and various test methods. Polysaccharides from water extract as well as acidic and basic extracts show antioxidant activity by inhibiting hydroxyl activity, ABTS + radicals, and lipid peroxidation [96]. Polysaccharides present both in the cell wall and intracellularly include soluble polysaccharides (α- and β-glucans, galactans, mannans, and xyloglucans) and waterinsoluble (heteroglycans, polyuronides, and β-glucans). The polysaccharides typical for this species are characterized by multidirectional biological activity, including immunostimulating effects, eliminating the side effects of chemotherapy and radiotherapy, as well as anticancer, antiviral, antibacterial, and antioxidant properties. Polysaccharides with the symbols LEPA1, LEPB1, and LEPC1 were analyzed for antioxidant activity in the hydroxyl scavenging test, the superoxide scavenging test, and the chelating effect on Fe(II). The antioxidant capacity of the above-mentioned fractions was demonstrated in a concentration-dependent manner. Except for the superoxide scavenging test for concentrations from 0.5 to 1 mg/mL, it was shown that the higher the uronic acid content, the stronger the antioxidant activity of LEPA1, LEPB1, and LEPC1. One of the mechanisms involved in antioxidant activity may result from the ability of the molecule to donate hydrogen atoms, which disrupts radical chain reactions and turns free radicals into harmless products [97]. It can be assumed that the more electron-withdrawing groups such as a carboxyl or carbonyl group in a polysaccharide, the more the dissociation energy of the O-H bond can be lowered, and thus the greater the release of hydrogen atoms. Moreover, it was found that compounds containing at least two of the following functional groups: -OH, -SH, -COOH, -PO3, H2, C¼O, -S-, and -O- in a favorable configuration of the structure-function can positively affect the activity of chelating metals [98]. Besides, some other chemical properties of polysaccharides, such as the presence of a protein molecule, monosaccharide composition, and molecular weight, can also influence the antioxidant properties. The chemicals compounds with antioxidant properties present in Lentinula edodes were summarized in Table 2.

2.8

Pleurotus ostreatus

Pleurotus ostreatus (Jacq.) P. Kumm. belongs to the Pleurotaceae family. This species was first described by Jacquin in 1774 as Agaricus ostreatus. The current name was given to him by Kummer in 1871 classifying the species to the genus Pleurotus. The most famous Latin synonyms are Agaricus ostreatus, Agaricus revolutus, Agaricus salignus, Crepidopus ostreatus, Dendrosarcus ostreatus, Dendrosarcus revolutus, Pleurotus revolutus, and Pleurotus salignus. English common names are oyster mushroom, oyster fungus.

2.8.1 Mycological and Ecological Characteristics Pleurotus ostreatus occurs on all continents of the globe except Antarctica. It is not only a saprotroph that grows on dead wood, but also a parasite that attacks live weakened trees. The fruiting bodies appear in late autumn, from the end of October.

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It is a species found on dead wood of deciduous tree species such as Fagus sp., Betula sp., Salix sp., Robinia pseudoacacia, or Juglans regia. It usually grows as clusters of many fruiting bodies, often stuck together, resembling oyster shoals, which is the reason why the species got its name [31]. The fruiting body develops a cap from 5 to 25 cm in diameter that is initially arcuate, with a visibly tucked rim, later shell-shaped or funnel-shaped. The fruiting body grows sideways to the ground. It is soft and springy. The color of the fruiting bodies is quite varied; it can be of various shades of brown, ash-gray, and has dense, deeply converging gills, whitish to gray, purple in older specimens. The flesh is soft and springy in older fruiting bodies. The stem flesh of older fruiting bodies is woody and white (Fig. 1). The taste of fruiting bodies is defined as sour [32, 33].

2.8.2 Traditional and Modern Medicinal Value Oyster mushrooms are one of the most frequently cultivated mushrooms due to their fast mycelium and fruiting bodies growth, short life cycle, disease resistance, high adaptability to growth conditions, and low-cost production [81, 99]. The first cultivation methods were developed in Germany during World War I and then successfully applied on a large scale as a result of the search for new sources of food due to the problem of hunger in Germany. However, it was not until the early 1970s that the oyster mushroom was cultivated on an industrial scale, mainly in Asian countries. Many different cultivation technologies were developed and many varieties were selected, differing mainly in the optimal fruiting temperature [100]. Health benefits of Pleurotus ostreatus include antitumor and anticancer properties, immune support, cholesterol reduction, hypertension treatment, vascular health support, antimicrobial properties, and arthritis treatment. 2.8.3 Chemical Composition and Antioxidant Properties Pleurotus ostreatus extracts showed direct antioxidant activity in DPPH, ABTS, FRAP, and β-carotene bleaching tests, comparable to, among others, BHA and vitamin C [101–103]. Elbatrawny et al. determined the antioxidant effect of extracts obtained with seven different solvents of varying degrees of polarity. The water extract was the most active concerning the DPPH radical [104]. This direction of action is probably associated with the presence of phenolic acids, flavonoids, vitamins C and E, as well as polysaccharides. Chemical analysis of fruiting bodies of Pleurotus ostreatus carried out at the Department of Pharmaceutical Botany UJCM confirmed the presence of ferulic acid, para-hydroxybenzoic acid, protocatechuic acid, sinapic acid, and cinnamic acid (Table 3) [105]. However, oyster mushrooms not only can directly scavenge reactive molecules but also enhance the activity of antioxidant enzymes. This activity has been demonstrated in in vivo studies using rats. A group of animals with the administration of ethanol extract had an increase in the expression of the CAT (catalase) gene in the livers and kidneys. Moreover, a decrease in the level of carbonylated proteins in these organs was observed [106]. Ethanol extract in the group of diabetic rats increased the activity of antioxidant enzymes SOD (superoxide dismutase), CAT (catalase), GPX (glutathione peroxidase), and the level of vitamins

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C and E in the livers, and decreased the level of malonyldialdehyde [107]. The antioxidant effect and the tissue protection against damage were also found after the action of carbon tetrachloride and paracetamol [105, 108, 109]. The chemical compounds with antioxidant properties present in Pleurotus ostreatus were summarized in Table 2.

3

Conclusions

Numerous species of arboreal mushrooms belong to the group of medicinal mushrooms. Their therapeutic potential is related to the presence of a variety of chemical compounds represented by primary and secondary metabolites. An important group of substances present in these species are antioxidants, among which phenolic compounds, tocopherols, ascorbic acid, polysaccharides, and carotenoids show the greatest antioxidant potential. The species in question have a well-established position in traditional Asian (Chinese, Korean, and Japanese) and European medicine. Contemporary research confirms the activities that were known from traditional use and draws attention to new directions of biological activity, including high antioxidant potential, which can be used in the prevention and prophylaxis of many civilization diseases.

References 1. Dad S, Bisby RH, Clark IP, Parker AW (2006) Formation of singlet oxygen from solutions of vitamin E. Free Radic Res 40:333–338 2. Nimse SB, Pal D (2015) Free radicals, natural antioxidants, and their reaction mechanisms. RSC Adv 5:27986–28006 3. Sharifi-Rad M, Anil Kumar NV, Zucca P et al (2020) Lifestyle, oxidative stress, and antioxidants: back and forth in the pathophysiology of chronic diseases. Front Physiol 11:694 4. Sheng Y, Abreu IA, Cabelli DE et al (2014) Superoxide dismutases and superoxide reductases. Chem Rev 114:3854–3918 5. Alfonso-Prieto M, Biarnés X, Vidossich P, Rovira C (2009) The molecular mechanism of the catalase reaction. J Am Chem Soc 131:11751–11761 6. Krishnamurthy P, Wadhwani A (2012) Antioxidant enzymes and human health. In: El-Missiry MA (ed) Antioxidant enzyme. INTECH 7. Vaz JA, Barros L, Martins A et al (2011) Phenolic profile of seventeen Portuguese wild mushrooms. LWT – Food Sci Technol 44:343–346 8. Reis FS, Heleno SA, Barros L et al (2011) Toward the antioxidant and chemical characterization of mycorrhizal mushrooms from Northeast Portugal. J Food Sci 76:C824–C830 9. Ferreira I, Barros L, Abreu R (2009) Antioxidants in wild mushrooms. Curr Med Chem 16: 1543–1560 10. Karaman M, Jovin E, Malbaša R et al (2010) Medicinal and edible lignicolous fungi as natural sources of antioxidative and antibacterial agents. Phytother Res 24:1473–1481 11. Wei S, Van Griensven LJLD (2008) Pro- and antioxidative properties of medicinal mushroom extracts. Int J Med Mushrooms 10:315–324 12. Yeh JY, Hsieh LH, Wu KT, Tsai CF (2011) Antioxidant properties and antioxidant compounds of various extracts from the edible basidiomycete Grifola frondosa (Maitake). Molecules 16: 3197–3211

5

Selected Species of Medicinal/Arboreal Mushrooms as a Source of Substances. . .

117

13. Del Signore A, Romeo F, Giaccio M (1997) Content of phenolic substances in basidiomycetes. Mycol Res 101:552–556 14. Kalyoncu F, Oskay M, Kayalar H (2010) Antioxidant activity of the mycelium of 21 wild mushroom species. Mycology 1:195–199 15. Heleno SA, Martins A, Queiroz MJRP, Ferreira ICFR (2015) Bioactivity of phenolic acids: metabolites versus parent compounds: a review. Food Chem 173:501–513 16. Fernández MA, Sáenz MT, García MD (1998) Anti-inflammatory activity in rats and mice of phenolic acids isolated from Scrophularia frutescens. J Pharm Pharmacol 50:1183–1186 17. Özçelik B, Kartal M, Orhan I (2011) Cytotoxicity, antiviral and antimicrobial activities of alkaloids, flavonoids, and phenolic acids. Pharm Biol 49:396–402 18. Merkl R, Hrádková I, Filip V, Šmidrkal J (2010) Antimicrobial and antioxidant properties of phenolic acids alkyl esters. Czech J Food Sci 28:275–279 19. Gawlik-Dziki U, Szymanowska U, Baraniak B (2007) Characterization of polyphenol oxidase from broccoli (Brassica oleracea var. botrytis italica) florets. Food Chem 105:1047–1053 20. Vaquero MJR, Alberto MR, de Nadra MCM (2007) Antibacterial effect of phenolic compounds from different wines. Food Control 18:93–101 21. Vaquero MJR, Manca De Nadra MC (2008) Growth parameter and viability modifications of Escherichia coli by phenolic compounds and argentine wine extracts. Appl Biochem Biotechnol 151:342–352 22. Gañan M, Martínez-Rodríguez AJ, Carrascosa AV (2009) Antimicrobial activity of phenolic compounds of wine against Campylobacter jejuni. Food Control 20:739–742 23. Czechowska SK, Markiewicz R, Borawska MH (2009) Microbiological activity and cytotoxicity of selected phenolic acids in in vitro tests. Bromat Chem Toksykol 3:959–964 24. Ortiz Urbina JJD, Martin ML, Sevilla MA et al (1990) Antispasmodic activity on rat smooth muscle of polyphenol compounds caffeic and protocathechic acids. Phytother Res 4:71–76 25. Tani M, Shimazu H, Takahashi T, Asakuma S (1978) Gastric response to meat extract stimulation in patients with gastroduodenal ulcer and patients after vagotomy or antrectomy. Jpn J Surg 8:10–18 26. Dubost NJ, Ou B, Beelman RB (2007) Quantification of polyphenols and ergothioneine in cultivated mushrooms and correlation to total antioxidant capacity. Food Chem 105:727–735 27. Kim MY, Seguin P, Ahn JK et al (2008) Phenolic compound concentration and antioxidant activities of edible and medicinal mushrooms from Korea. J Agric Food Chem 56:7265–7270 28. Orhan I, Üstün O (2011) Determination of total phenol content, antioxidant activity and acetylcholinesterase inhibition in selected mushrooms from Turkey. J Food Compos Anal 24:386–390 29. Macáková K, Opletal L, Polášek M et al (2009) Free-radical scavenging activity of some European Boletales. Nat Prod Commun 4:261–264 30. Turkoglu A, Duru ME, Mercan N et al (2007) Antioxidant and antimicrobial activities of Laetiporus sulphureus (Bull.) Murrill. Food Chem 101:267–273 31. Laessoe T, Petersen JH (2019) Fungi of temperate Europe, vol 1. Princeton University Press, Princeton 32. Gumińska B, Wojewoda W (1988) Grzyby i ich oznaczanie. PWRiL, Warszawa 33. Hanna Kwaśna H, Łakomy P (2015) Atlas hub. Multico, Warszawa 34. Dias DA, Urban S, Roessner U (2012) A historical overview of natural products in drug discovery. Metabolites 2:303–336 35. Yang L, Zhao T, Wei H et al (2011) Carboxymethylation of polysaccharides from Auricularia auricula and their antioxidant activities in vitro. Int J Biol Macromol 49:1124–1130 36. Zeng WC, Zhang Z, Gao H et al (2012) Characterization of antioxidant polysaccharides from Auricularia auricular using microwave-assisted extraction. Carbohydr Polym 89:694–700 37. He JZ, Ru QM, Dong DD, Sun PL (2012) Chemical characteristics and antioxidant properties of crude water soluble polysaccharides from four common edible mushrooms. Molecules 17: 4373–4387 38. Zhang H, Wang ZY, Zhang Z, Wang X (2011) Purified Auricularia auricular-judae polysaccharide (AAP I-a) prevents oxidative stress in an ageing mouse model. Carbohydr Polym 84: 638–648

118

K. Sułkowska-Ziaja et al.

39. Hao H (2014) Effect effects of auricularia auricula polysaccharides on exhaustive swimming exercise-induced oxidative stress in mice. Trop J Pharm Res 13:1845–1851 40. Obodai M, Ferreira ICFR, Fernandes  et al (2014) Evaluation of the chemical and antioxidant properties of wild and cultivated mushrooms of Ghana. Molecules 19:19532–19548 41. Zhang N, Chen H, Zhang Y et al (2015) Chemical composition and antioxidant properties of five edible Hymenomycetes mushrooms. Int J Food Sci Technol 50:465–471 42. Oke F, Aslim B (2011) Protective effect of two edible mushrooms against oxidative cell damage and their phenolic composition. Food Chem 128:613–619 43. Bin L, Wei L, Xiaohong C et al (2012) In vitro antibiofilm activity of the melanin from Auricularia auricula, an edible jelly mushroom. Ann Microbiol 62:1523–1530 44. Zou Y, Hu W, Ma K, Tian M (2015) Physicochemical properties and antioxidant activities of melanin and fractions from Auricularia auricula fruiting bodies. Food Sci Biotechnol 24:15–21 45. Zou Y, Xie C, Fan G et al (2010) Optimization of ultrasound-assisted extraction of melanin from Auricularia auricula fruit bodies. Innov Food Sci Emerg Technol 11:611–615 46. Poder R (2005) The Ice Man’s fungi: facts and mysteries. Int J Med Mushrooms 7:357–359 47. Capasso L (1998) 5300 years ago, the Ice Man used natural laxatives and antibiotics. Lancet 352:1864 48. Peintner U, Pöder R, Pümpel T (1998) The Iceman’s fungi. Mycol Res 102:1153–1162 49. Lemieszek MK, Langner E, Kaczor J et al (2009) Anticancer effect of fraction isolated from medicinal birch polypore mushroom, Piptoporus betulinus (Bull.: Fr.) P. Karst. (Aphyllophoromycetideae): in vitro studies. Int J Med Mushrooms 11:351–364 50. Keller C, Maillard M, Keller J, Hostettmann K (2002) Screening of European fungi for antibacterial, antifungal, larvicidal, molluscicidal, antioxidant and free-radical scavenging activities and subsequent isolation of bioactive compounds. Pharm Biol 40:518–525 51. Sułkowska-Ziaja K, Szewczyk A, Galanty A et al (2018) Chemical composition and biological activity of extracts from fruiting bodies and mycelial cultures of Fomitopsis betulina. Mol Biol Rep 45:2535–2544 52. Reis FS, Pereira E, Barros L et al (2011) Biomolecule profiles in inedible wild mushrooms with antioxidant value. Molecules 16:4328–4338 53. Gregori A, Piškur B, Gregori M, Jurc D (2007) Spread of the fungus Fomitopsis officinalis inoculated in stems of living larch in Slovenia. In: The fourth international medicinal mushroom conference, Ljubliana, pp 304–305 54. Muszyńska B, Fijałkowska A, Sułkowska-Ziaja K et al (2020) Fomitopsis officinalis: a species of arboreal mushroom with promising biological and medicinal properties. Chem Biodivers 17:e2000213 55. Fijałkowska A, Muszyńska B, Sułkowska-Ziaja K et al (2020) Medicinal potential of mycelium and fruiting bodies of an arboreal mushroom Fomitopsis officinalis in therapy of lifestyle diseases. Sci Rep 10:20081 56. Sha AL (2016) Effects of the Fomes officinalis flavonoids on anti-senile action in the aging model mice. Chin J Appl Physiol 32:121–123 57. Paterson RRM (2006) Ganoderma – a therapeutic fungal biofactory. Phytochemistry 67:1985– 2001 58. Kozarski M, Klaus A, Nikšić M et al (2012) Antioxidative activities and chemical characterization of polysaccharide extracts from the widely used mushrooms Ganoderma applanatum, Ganoderma lucidum, Lentinus edodes and Trametes versicolor. J Food Compos Anal 26:144–153 59. Acharya K, Samui K, Rai M et al (2004) Antioxidant and nitric oxide synthase activation properties of Auricularia auricula. Indian J Exp Biol 42:538–540 60. Parus A (2013) Przeciwutleniające i farmakologiczne właściwości kwasów fenolowych. Postępy Fitoter 1:48–54 61. Sułkowska-Ziaja K, Grabowska K, Apola A et al (2021) Mycelial culture extracts of selected wood-decay mushrooms as a source of skin-protecting factors. Biotechnol Lett 43:1051–1061 62. Ming DS, Chilton J, Fogarty F, Towers GHN (2002) Chemical constituents of Ganoderma applanatum of British Columbia forests. Fitoterapia 73:147–152

5

Selected Species of Medicinal/Arboreal Mushrooms as a Source of Substances. . .

119

63. Liu Y, Liu Y, Qiu F, Di X (2011) Sensitive and selective liquid chromatography-tandem mass spectrometry method for the determination of five ganoderic acids in Ganoderma lucidum and its related species. J Pharm Biomed Anal 54:717–721 64. Kozarski M, Klaus A, Niksic M et al (2011) Antioxidative and immunomodulating activities of polysaccharide extracts of the medicinal mushrooms Agaricus bisporus, Agaricus brasiliensis, Ganoderma lucidum and Phellinus linteus. Food Chem 129: 1667–1675 65. De Silva DD, Rapior S, Sudarman E et al (2013) Bioactive metabolites from macrofungi: ethnopharmacology, biological activities and chemistry. Fungal Divers 62:1–40 66. Mori K, Obara Y, Hirota M et al (2008) Nerve growth factor-inducing activity of Hericium erinaceus in 1321N1 human astrocytoma cells. Biol Pharm Bull 31:1727–1732 67. James SL, Abate D, Abate KH et al (2018) Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet 392:1789–1858 68. Mau JL, Lin HC, Song SF (2002) Antioxidant properties of several specialty mushrooms. Food Res Int 35:519–526 69. Malinowska E, Krzyczkowski W, Herold F et al (2009) Biosynthesis of selenium-containing polysaccharides with antioxidant activity in liquid culture of Hericium erinaceum. Enzym Microb Technol 44:334–343 70. Fu HY, Shieh DE, Ho CT (2002) Antioxidant and free radical scavenging activities of edible mushrooms. J Food Lipids 9:35–43 71. Mujić I, Zeković Z, Lepojević Ž et al (2010) Antioxidant properties of selected edible mushroom species. J Cent Eur Agric 11:387–391 72. Abdullah N, Ismail SM, Aminudin N et al (2012) Evaluation of selected culinary-medicinal mushrooms for antioxidant and ACE inhibitory activities. Evid-Based Complement Altern Med 2012:464238 73. Wong KH, Sabaratnam V, Abdullah N et al (2009) Effects of cultivation techniques and processing on antimicrobial and antioxidant activities of Hericium erinaceus (Bull.:Fr.) Pers. extracts. Food Technol Biotechnol 47:47–55 74. Han ZH, Ye JM, Wang GF (2013) Evaluation of in vivo antioxidant activity of Hericium erinaceus polysaccharides. Int J Biol Macromol 52:66–71 75. Zhang AQ, Fu L, Xu M et al (2012) Structure of a water-soluble heteropolysaccharide from fruiting bodies of Hericium erinaceus. Carbohydr Polym 88:558–561 76. Xu HM, Xie ZH, Zhang WY (1994) Immunomodulatory function of polysaccharide of Hericium erinaceus. Zhongguo Zhong Xi Yi Jie He Za Zhi 14:427–428 77. Jang JH, Noh KH, Choi JN et al (2010) Effect of Hericium erinaceus mycelia supplementation on the oxidative stress and inflammation processes stimulated by LPS and their mechanisms in BALB/C mice. J Kor Soc Food Sci Nutr 39:227–236 78. Olennikov DN, Tankhaeva LM, Agafonova SV (2011) Antioxidant components of Laetiporus sulphureus (Bull.: Fr.) Murr. fruit bodies. Appl Biochem Microbiol 47:419–425 79. Sułkowska-Ziaja K, Muszyńska B, Motyl P et al (2012) Phenolic compounds and antioxidant activity in some species of polyporoid mushrooms from Poland. Int J Med Mushrooms 14: 385–393 80. Olennikov DN, Agafonova SV, Borovskii GB et al (2009) Water-soluble endopolysaccharides from the fruiting bodies of Laetiporus sulphureus (Bull.:Fr.) Murr. Appl Biochem Microbiol 45:536–543 81. Zięba P, Sękara A, Sułkowska-Ziaja K, Muszyńska B (2021) Culinary and medicinal mushrooms: insight into growing technologies. Acta Mycol 55:1–19 82. Hobbs C (1995) Medicinal mushrooms: an exploration of tradition, healing and culture. Botanica Press, Santa Cruz 83. Wasser SP, Weis AL (1997) Medicinal mushrooms. Lentinus edodes (Berk.). Peledfus Publ. House, Haifa

120

K. Sułkowska-Ziaja et al.

84. Smith J, Rowen N, Sullivan R (2002) Medicinal mushrooms: their therapeutic properties and current medical usage with special emphasis on cancer treatments. Special report commissioned by cancer research UK. The University of Strathclyde in Glasgow 85. Morita K, Kobayashi S (1967) Isolation, structure, and synthesis of lenthionine and its analogs. Chem Pharm Bull 15:988–993 86. Mizuno T (1995) Shiitake, Lentinus edodes: functional properties for medicinal and food purposes. Food Rev Int 11:109–128 87. Mizuno T (1996) Development of antitumor polysaccharides from mushroom fungi. Food Food Ingred J Jpn 167:69–87 88. Chihara G, Maeda Y, Hamuro J et al (1969) Inhibition of mouse sarcoma 180 by polysaccharides from Lentinus edodes (Berk.) sing. Nature 222:687–688 89. Chihara G, Hamuro J, Maeda YY et al (1970) Fractionation and purification of the polysaccharides with marked antitumor activity, especially Lentinan, from Lentinus edodes (Berk.) Sing. (an edible mushroom). Cancer Res 30:2776–2781 90. Sasaki T, Takasuka N (1976) Further study of the structure of lentinan, an anti-tumor polysaccharide from Lentinus edodes. Carbohydr Res 47:99–104 91. Wasser SP, Weis AL (1999) Therapeutic effects of substances occurring in higher basidiomycetes mushrooms: a modern perspective. Crit Rev Immunol 19:65–96 92. Cheung LM, Cheung PCK, Ooi VEC (2003) Antioxidant activity and total phenolics of edible mushroom extracts. Food Chem 81:249–255 93. Yang JH, Lin HC, Mau JL (2002) Antioxidant properties of several commercial mushrooms. Food Chem 77:229–235 94. Kitzberger CSG, Smânia A, Pedrosa RC, Ferreira SRS (2007) Antioxidant and antimicrobial activities of Shiitake (Lentinula edodes) extracts obtained by organic solvents and supercritical fluids. J Food Eng 80:631–638 95. Kała K, Krakowska A, Szewczyk A et al (2021) Determining the amount of potentially bioavailable phenolic compounds and bioelements in edible mushroom mycelia of Agaricus bisporus, Cantharellus cibarius, and Lentinula edodes. Food Chem 352:129456 96. Ziaja-Sołtys M, Radzki W, Nowak J et al (2020) Processed fruiting bodies of Lentinus edodes as a source of biologically active polysaccharides. Appl Sci 10:470 97. Gaitán-Hernández R, López-Peña D, Esqueda M, Gutiérrez A (2019) Review of bioactive molecules production, biomass, and basidiomata of Shiitake culinary-medicinal mushrooms, Lentinus edodes (Agaricomycetes). Int J Med Mushrooms 21:841–850 98. Chen H, Ju Y, Li J, Yu M (2012) Antioxidant activities of polysaccharides from Lentinus edodes and their significance for disease prevention. Int J Biol Macromol 50:214–218 99. Sulistiany H, Sudirman LI, Dharmaputra OS (2016) Production of fruiting body and antioxidant activity of wild Pleurotus. HAYATI J Biosci 23:191–195 100. Sánchez C (2010) Cultivation of Pleurotus ostreatus and other edible mushrooms. Appl Microbiol Biotechnol 85:1321–1337 101. Yim HS, Chye FY, Tan CT et al (2010) Antioxidant activities and total phenolic content of aqueous extract of Pleurotus ostreatus (cultivated oyster mushroom). Malays J Nutr 16:281– 291 102. Arbaayah H, Kalsom U (2013) Antioxidant properties in the oyster mushrooms (Pleurotus spp.) and split gill mushroom (Schizophyllum commune) ethanolic extracts. Mycosphere 4: 661–673 103. Chowdhury HMH, Kubra K, Ahmed RR (2015) Screening of antimicrobial, antioxidant properties and bioactive compounds of some edible mushrooms cultivated in Bangladesh. Ann Clin Microbiol Antimicrob 14:8 104. Elbatrawy EN, Ghonimy EAA, Alassar MM, Wu FS (2015) Medicinal mushroom extracts possess differential antioxidant activity and cytotoxicity to cancer cells. Int J Med Mushrooms 17:471–479

5

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121

105. Muszyńska B, Sułkowska-Ziaja K, Ekiert H (2013) Phenolic acids in selected edible basidiomycota species: Armillaria mellea, Boletus badius, Boletus edulis, Cantharellus cibarius, Lactarius deliciosus and Pleurotus ostreatus. Acta Sci Pol Hortorum Cultus 12:107 106. Jayakumar T, Thomas PA, Isai M, Geraldine P (2010) An extract of the oyster mushroom, Pleurotus ostreatus, increases catalase gene expression and reduces protein oxidation during aging in rats. J Chin Integr Med 8:774–780 107. Tahrani AA, Barnett AH (2010) Dapagliflozin: a sodium glucose cotransporter 2 inhibitor in development for type 2 diabetes. Diabetes Ther 1:45–56 108. Jayakumar T, Sakthivel M, Thomas PA, Geraldine P (2008) Pleurotus ostreatus, an Oyster mushroom, decreases the oxidative stress induced by carbon tetrachloride in rat kidneys, heart and brain. Chem Biol Interact 176:108–120 109. Kała K, Krakowska A, Sułkowska-Ziaja K et al (2017) Kinetics of extracted bioactive components from mushrooms in artificial digestive juices. Int J Food Prop 20:1796–1817

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Antioxidant and Pro-oxidant Activities of Carotenoids Mariana Lucas, Marisa Freitas, Fe´lix Carvalho, Eduarda Fernandes, and Daniela Ribeiro

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Carotenoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.1 Structural Characteristics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.2 Classification . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.3 Natural Sources and Distribution . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2.4 Pharmacokinetics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.1 Astaxanthin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.2 Canthaxanthin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.3 α-Carotene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.4 β-Carotene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.5 β-Cryptoxanthin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.6 Fucoxanthin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.7 Lutein . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.8 Lycopene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3.9 Zeaxanthin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Pro-oxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.1 β-Carotene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4.2 Lycopene . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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M. Lucas · M. Freitas · E. Fernandes (*) · D. Ribeiro (*) LAQV, REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal e-mail: mfl[email protected]; [email protected]; [email protected]; [email protected] F. Carvalho UCIBIO, REQUIMTE, Laboratory of Toxicology, Department of Biological Sciences, Faculty of Pharmacy, University of Porto, Porto, Portugal e-mail: [email protected] © Springer Nature Switzerland AG 2022 H. M. Ekiert et al. (eds.), Plant Antioxidants and Health, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-78160-6_4

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Abstract

Carotenoids are plant pigments widely spread in nature, especially in fruits and vegetables. These compounds have been subject of scientific research due to their several biological activities. Attention has been devoted to their role as antioxidants and/or pro-oxidants. If in one hand carotenoids are postulated to reduce the risk and prevent the development of several diseases associated with oxidative stress, including cancer, cardiovascular, and chronic diseases. On the other hand, due to their potential pro-oxidant action, carotenoids may enhance harmful effects and oxidative damage to biomolecules, like DNA, proteins, and membranes. This chapter provides a general overview of carotenoids and their mechanisms of action, both as anti- and/or pro-oxidants, as evaluated in in vitro non-cellular and cellular models as well as in in vivo systems. Keywords

Carotenes · Xanthophylls · Reactive species · Antioxidant · Pro-oxidant · Oxidative stress Abbreviations

ABTS•+ APPH BCMO1 BCO2 CD36 DCFH-DA DHR 123 DPPH FRAP GPx GSH GST IDL LDL MDA ORAC ORAC-L PCL RNS ROS SCARB1 SOD VLDL

2,20 -Azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) 2,20 -Azobis (2-methylpropionamidine)dihydrochloride β-Carotene-15,150 -monooxygenase β-Carotene-90 ,100 -oxigenase 2 Cluster determinant 36 20 ,70 -Dichlorofluorescein diacetate Dihydrorhodamine 123 2,2-Diphenyl-1-picrylhydrazyl Ferric reducing antioxidant power Glutathione peroxidase Glutathione Glutathione S-transferase Intermediate-density lipoprotein Low-density lipoprotein Malondialdehyde Oxygen-radical absorbance capacity Oxygen radical absorbing capacity for lipophilic compounds Photochemiluminescence Reactive nitrogen species Reactive oxygen species Scavenger receptor class B member 1 Superoxide dismutase Very low-density lipoprotein

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1

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Introduction

Carotenoids are a class of organic fat-soluble pigments widely distributed in nature [1]. These compounds are hydrocarbons that generally contain at least 40 carbons, with a basic tetraterpene structure characterized by a long chain of conjugated double bonds [2]. This double bond system is responsible for the pigmentation of plants, fungi, algae, and bacteria, which can range from yellow to red [3]. Although animals and humans do not have the ability to synthesize carotenoids, they ingest them through the diet [1, 4]. Despite the variety of carotenoids found in nature, only about 40 to 50 are ingested through the human diet, of which only about 20 were found in human blood and tissues, namely, α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein, and zeaxanthin [1, 3, 5]. Carotenoids play several important roles and functions, and are responsible for the beneficial properties of fruits and vegetables and can also interfere with different cellular processes [1, 2]. Thus, there are several reports that refer the biological properties of carotenoids, which include anti- and pro-oxidant activities [6], immune enhancement, anti-inflammatory activity, regression of malignant lesions, inhibition of mutagenesis, modulation of growth factors, among others [1–3, 5]. Despite the various biological activities associated with carotenoids, their role as antioxidants receives great importance, being the subject of several studies. Indeed, carotenoids have been reported to reduce the risk and prevent the development of several diseases associated with oxidative stress, such as cancer, cardiovascular, and chronic diseases [1]. However, some carotenoids have also been associated with pro-oxidant effects that have been directly related to the development and progression of the abovementioned diseases [6, 7]. This chapter provides a general overview of carotenoids and their mechanisms of action both as anti- and/or pro-oxidants.

2

Carotenoids

2.1

Structural Characteristics

Carotenoids are lipid-soluble plant pigments that belong to the tetraterpenes family and have a long carbon chain, usually with 40 carbons, formed from eight isoprene (C5H8) units (Fig. 1) [2, 4]. Certain bacteria can also produce, via different intermediates, carotenoids with 30 and 50 carbons [4]. The basic structure of carotenoids is characterized by a system of conjugated double bonds that can be linear or have a cyclic hydrocarbon at one or both ends of the molecule, and, generally, the structure presents a near bilateral symmetry around the central double bond (Fig. 1) [2, 8]. The system of conjugated double bonds endows carotenoids their typical isomerism and their pigment characteristics, which can range from yellow to red, since the π-electrons are extensively delocalized over the length of the polyene chain what enables these compounds to absorb visible light [3, 10, 11]. On the other hand, such

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Fig. 1 Chemical structures of a isoprene unit, astaxanthin, with the respective common numbering system, and lycopene [9]

structures are highly susceptible to attack by electrophilic substances, due to their electron-rich system, which gives them greater instability toward oxidation [10]. Carotenoids can be found in the E or Z configurations, which, despite some exceptions, correspond to the trans and cis forms. The trans-isomers are more prevalent in nature due to its higher stability. The cis-isomers are less thermodynamically stable, due to the steric hindrance between adjacent hydrogens and methyl groups. Moreover, there is rotation around the single carbon-carbon bond, which implies that carotenoids can be found in several shapes. The cis-isomers are not linear and have different molecular geometries, while the trans-isomers are linear and rigid, presenting an extended conjugated double bond system. Thus, cis-isomers can be more readily absorbed and transported within cellular compartments due to their greater solubility, when compared to trans-isomers [11]. In addition to the isomerism and the rotation around the single carbon-carbon bond, the type of end groups and the modifications in the base structure caused by the cyclization of those end groups contribute to the diversity of existing carotenoids. These modifications also affect the polarity of these compounds, which consequently influences the carotenoid-membrane interaction, location and orientation. Generally, their hydrophobic characteristics favor the interaction with the hydrophobic areas of cells [1, 11, 12].

2.2

Classification

Carotenoids can be classified based on different criteria. According to their chemical structure, carotenoids can be divided into carotenes and xanthophylls (Fig. 2). Carotenes are made up only of carbon and hydrogen atoms, without any functional group

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Fig. 2 Chemical structures of the carotenoids, and their classification into carotenes and xanthophylls, with the identification of pro-vitamin A carotenoids (marked in blue), that will be further discussed in this chapter [9]

(e.g., lycopene, α-carotene and β-carotene), while xanthophylls contain oxygen in addition to carbon and hydrogen atoms (e.g., astaxanthin, canthaxanthin, lutein, and zeaxanthin). Carotenoids can also be divided into pro-vitamin A (e.g., α-carotene, β-carotene and β-cryptoxanthin) and non-pro-vitamin A (e.g., lutein, lycopene, and zeaxanthin), depending on whether or not they are precursors of vitamin A. Carotenoids are considered pro-vitamin A when by enzymatic and non-enzymatic cleavage mechanisms, they originate vitamin A and its metabolites [2, 8]. Vitamin A is essential for visual function, immune system function, cell growth, and differentiation, among other physiological functions and processes [3, 13]. Among the pro-vitamin A carotenoids, β-carotene is the most well-characterized, being the most used to exemplify the mechanism of conversion of pro-vitamin A carotenoids into vitamin A. After ingestion, and during its metabolism in intestinal epithelia and other tissues, β-carotene and other pro-vitamin A carotenoids are converted into vitamin A. Considering β-carotene, the 15-150 cleavage generates two molecules of retinaldehyde that can be reduced to retinol, which is the alcohol form of vitamin A, or oxidized to retinoic acid, which is the biologically active form of vitamin A [3, 8]. Bearing in mind the basic structure of carotenoids, differences in the end groups, as well as in the substitution pattern can be observed. Thus, bicyclic carotenoids can be found, where both terminal rings are hydroxylated (e.g., lutein and zeaxanthin,

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Fig. 2) but there are also other examples where both end rings are simple hydrocarbons, without any functional group (e.g., α-carotene and β-carotene, Fig. 2). Bicyclic carotenoids in which the terminal rings have keto-groups can also be found, with or without hydroxy groups as substituents on these rings (e.g., astaxanthin and canthaxanthin, respectively, Fig. 2). This type of carotenoid, with two terminal rings joined by the chain of conjugated double bonds, is the most widely distributed in nature. In addition to these, there are other less common structures, such as bicyclic carotenoids, where the two end rings are aromatic rings (e.g., synechoxanthin), and monocyclic carotenoids (e.g., torulene) [4, 9]. Furthermore, acyclic carotenoids, without a terminal ring system, can also be found (e.g., lycopene, Fig. 2, and phytoene) [14].

2.3

Natural Sources and Distribution

Carotenoids were first identified in primitive organisms, where they probably acted as lipid molecules with the function of strengthening membranes, a feature conferred by their conjugated double-bond backbone that confers rigidity to the molecule [4]. Carotenoids comprise more than 700 known structures and can be synthesized by plants and microorganisms, while animals and humans do not have this ability [1, 4]. Indeed, phototropic and non-phototrophic organisms (except animals) are great sources of carotenoids. Thus, these compounds can be synthesized by algae, fungi, and plants (eukarya domain), as well as by organisms from archaea and bacteria domains [4]. Carotenoids, due to their pigment character, are responsible for the colors found in foods, such as fruits and vegetables, but also for the bright colors of birds, mammals, fish, crustaceans, among others [4, 12]. Among the small variety of carotenoids ingested in the human diet only about 20 (e.g., α-carotene, β-carotene, β-cryptoxanthin, lycopene, lutein, and zeaxanthin) has already been found in human blood and tissues [1, 3, 5]. The consumption of pigmented fruits, vegetables, and natural juices are one of the biggest sources of carotenoids in the human diet [1]. Table 1 summarizes some common diet sources of the carotenoids that will be further discussed in this chapter. For more details regarding carotenoid biosynthesis and sources of carotenoids in the human diet see references [4, 12].

2.4

Pharmacokinetics

The presence of carotenoids in several human organs and tissues was first reported in 1990. Since then, the presence of carotenoids and their metabolites in human organs and tissues, as well as their effects on the organism, has been widely studied. Indeed, carotenoids have already been detected in several human organs as in the liver, breast, lung, and skin, at levels that range from ng to μg·g1 [18]. As mentioned above, carotenoids are abundantly present in food, but despite their inclusion in the human diet, their bioavailability and effectiveness are influenced by numerous factors: type and amount of carotenoids, and the medium in which they are

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Table 1 Examples of dietary sources of carotenoids that will be further discussed in this chapter Carotenoid Astaxanthin Bixin Canthaxanthin α-Carotene β-Carotene β-Cryptoxanthin Fucoxanthin

Lutein Lycopene Zeaxanthin

Dietary sources Marine animals (e.g., crustaceans and fish) Annatto (Bixa orellana) Koi carp, crustacean, egg yolks, salmon Carrots, lettuce, spinach, apricots Carrots, pumpkins, sweet potatoes, tomato, papaya, apricots, red grapes, watermelon, spinach, green collard, broccoli, cantaloupe, beet green Tangerines, papaya, oranges, peaches, marine sources (e.g., the green alga, Nanochlorum eucaryotum) Brown seaweeds [e.g., wakame (Undaria pinnatifida), brown algae (Hijikia fusiformis, Laminaria japonica, and Sargassum fulvellum)] Spinach, green collard, beet, broccoli, green peas Tomato, papaya, apricots, watermelon, red grapes Green leafy vegetables, orange, corn, eggs, honeydew melon

References [15] [12] [16] [1, 12] [1, 12]

[1, 17] [17]

[1] [1, 12] [12, 17]

incorporated (e.g., food matrix) [5, 19]. In addition, there are other factors that influence the bioavailability of carotenoids, such as dietary factors (e.g., fat and fiber ingested in the meals), interactions among carotenoids and/or with other compounds, and genetic factors, which are reviewed in references [5, 19, 20]. The fact that carotenoids are highly hydrophobic leads to less bioavailability, since their solubilization is significantly affected, which consequently influences their intestinal absorption. After ingestion, carotenoids are released from the food matrix and are dispersed with aid of bile and solubilized in mixed-micelles, allowing their absorption in the intestinal epithelium. Absorption occurs by simple diffusion, depending on the concentration gradient along the membranes [3]. In addition to simple diffusion, there are other absorption mechanisms, such as through the scavenger receptor class B member 1 (SCARB1) and the cluster determinant 36 (CD36) [3, 20]. After ingestion, carotenoids are also incorporated into the hydrophobic nucleus of several lipoproteins, such as chylomicrons, very low-density lipoprotein (VLDL), low-density lipoprotein (LDL), intermediate-density lipoprotein (IDL), along with other lipids (e.g., retinyl esters and cholesteryl esters), being subsequently secreted in the lymph and circulated in the body in this form [8]. Carotenoids’ metabolism is mediated by two cleavage enzymes: β-carotene-15,150 -monooxygenase (BCMO1), which can be found in the intestinal mucosa, and β-carotene-90 ,100 -oxygenase 2 (BCO2), which is highly expressed in hepatocytes. The metabolism of pro-vitamin A and non-pro-vitamin A carotenoids has some differences. In the case of pro-vitamin A carotenoids metabolism, the BCMO1 cleaves carotenoids forming retinal, which subsequently can be irreversibly oxidized into retinoic acid or reversibly reduced to retinol. BCO2 is involved in the asymmetrical cleavage of carotenoids, originating retinal and β-100 -carotenals, which can be metabolized into retinoic acid or short-chain carbonyl molecules [3, 19, 21, 22]. Notwithstanding, BCOM1 fails to catalyze the cleavage of non-pro-vitamin A carotenoids; however,

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BCO2 is able to metabolize this class of carotenoids [21]. The existing published studies raise the hypothesis that carotenoids are metabolized and stored in the liver [23]. Indeed, there are few studies on the tissue storage and excretion of carotenoids, due to their atypical metabolism in humans and also to the lack of animal models that mimic the respective human metabolism (ferret and the Mongolian gerbil are considered the best animal models) [22]. Despite the scarcity of information, the main excretion pathway described is through the feces [9, 20, 22, 24]. The carotenoids’ absorption, distribution, metabolism and excretion process is detailed elsewhere [3, 20].

3

Antioxidant Activity

Carotenoids are described in the literature as powerful antioxidants. An antioxidant is defined as any compound that have the ability to prevent or delay the oxidation of a substrate, even at low concentrations [25]. Carotenoids may exert their antioxidant activity through multiple mechanisms: electron transfer, hydrogen abstraction, radical addition, metal chelation, quenching of molecular oxygen, scavenging reactive species [e.g., reactive oxygen and nitrogen species (ROS and RNS, respectively)], or lipid peroxidation prevention [13]. Thus, as exogenous antioxidants, carotenoids play a fundamental role in the body’s redox balance, decreasing the incidence of several diseases as diabetes, cancer, cardiovascular diseases, and photosensitivity disorders [5, 13]. This antioxidant activity is influenced by multiple factors dictated by carotenoids’ chemical structure and interaction with biological membranes and with co-antioxidants (e.g., vitamin E and C) [17]. The number of conjugated double bonds, the end groups (cyclic or acyclic), and the nature of substituents in the carotenoids containing cyclic end groups are factors that influence the quenching activity of these compounds [26]. As carotenoids are hydrophobic compounds, they can adopt distinct locations and orientations within biological membranes, also affecting their reactive species scavenging activity [11]. The lipophilic character of carotenoids incites the scientific research to find the mechanisms able to surpass their low bioavailability, as their incorporation in liposomes and LDLs, which is reviewed in references [13, 27]. The antioxidant effects and mechanisms of action, clearly demonstrated in the literature, of the most reported carotenoids will be presented and discussed. Thus, for each carotenoid, it is presented some general information (classification, color and distribution), and the mechanisms of antioxidant action in in vitro non-cellular and cellular and in vivo systems.

3.1

Astaxanthin

Astaxanthin belongs to the xanthophyll class, and it characteristically red pigmentation, and it is widely found in nature, namely in birds, crustaceans, fish, and marine bacteria [17, 28]. This carotenoid is predominantly found as an all-trans isomer,

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(all-E)-astaxanthin, and it is broadly described in the literature as a highly effective antioxidant [28, 29]. Astaxanthin is described as having an antioxidant potency 10-fold greater than lutein, canthaxanthin, and β-carotene [17]. Astaxanthin displays singlet oxygen (1O2) quenching activity, with a capacity 500-fold greater than vitamin E, contributing to the prevention of lipid peroxidation in biological membranes [30]. Indeed, astaxanthin, due to its orientation across the membrane, leads to a more effective protective ability against the oxidation by peroxyl radicals (ROO•) [11]. Astaxanthin and some derivatives can inhibit hydrogen peroxide (H2O2)-mediated activation of transcription factor nuclear factor kappa B and to scavenge superoxide anion radical (O2•) [17]. The scavenging properties of astaxanthin are described against several other reactive species [H2O2, hydroxyl radical (HO•), hypochlorous acid, peroxynitrite anion (ONOO), nitric oxide radical (NO•), and lipid hydroperoxides] [30]. More recently, natural astaxanthin (3–50 μg·mL1), extracted from shrimp shells, was also studied, showing ability to quench 1O2 and prevent β-carotene bleaching. It also demonstrated antioxidant effects against the non-physiological radicals 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,20 -azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid) (ABTS•+) [31]. Nonetheless, in a previous study to assess the relative antioxidant activity of some carotenoids (astaxanthin, canthaxanthin, α-carotene, β-carotene, β-cryptoxanthin, lutein, lycopene, and zeaxanthin), astaxanthin (≈ 100 μM) revealed a negligible ability in the ABTS•+ scavenging assay [32]. The discrepancies observed in these two studies regarding ABTS•+ scavenging may be explained by the different methodologies used and by the distinct sources of astaxanthin. As astaxanthin may exist under different isomers, it is of interest to understand their possible variable activities. (9Z)- and (13Z)-Astaxanthin and (all-E)-astaxanthin isomers were evaluated for their antioxidant activity by oxygen radical absorbing capacity for lipophilic compounds (ORAC-L), DPPH radical scavenging, and in photochemiluminescence (PCL) assays [29]. Generally, the (E)-isomer showed less activity than the two (Z)-isomers of astaxanthin. Interestingly, in the DPPH radical scavenging assay, (9Z)-astaxanthin showed a better effect than (13Z)-isomer, while in PCL and ORAC-L assays, (13Z)-astaxanthin had higher antioxidant ability than (9Z)-isomer. The antioxidant activity of these isomers (0.6 μM) was also evaluated in vitro using two intestinal cell lines in co-culture: clone of heterogeneous human epithelial colorectal adenocarcinoma (Caco-2/BBe1) and human colon adenocarcinoma (HT-29). For that purpose, authors used the cellular antioxidant assay (CAA), where the antioxidant activity is assessed through the ability of compounds to prevent the oxidation of 20 ,70 -dichlorofluorescein diacetate (DCFH-DA) to dichlorofluorescein, by 2,20 -azobis (2-methylpropionamidine)dihydrochloride (APPH)-generated ROO•. The (13Z)astaxanthin isomer showed high activity in the CAA assay, being superior to the (all-E)- and (9Z)-isomers. (9Z)-Astaxanthin displayed a much lower activity when compared to the other isomers, in this assay [29]. Astaxanthin (3 μM) also decreased the ROS production induced by light exposure, in a murine cone cell line derived from mouse retinal tumors (661 W cell line) that was subjected to light irradiation [33]. More recently, this effect of astaxanthin was observed in another study, using the same methodology, using a concentration range between 0 and 50 μM. Astaxanthin inhibited

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the production of ROS in a concentration-dependent manner, particularly at higher concentrations (20 and 50 μM) [34]. Astaxanthin (50, 100, and 150 μM) also showed antioxidant effects in human LS-180 colorectal cancer cell line, since it increased the activity of antioxidant enzymes [superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx)] and decreased the malondialdehyde (MDA) levels in astaxanthintreated cells [35]. The effects of astaxanthin have also been studied in in vivo models. It was reported that astaxanthin exhibits a neuroprotective effect in mouse brain associated with its antioxidant properties, since an increased catalase and SOD activities, and glutathione (GSH) levels were observed [17]. In a recent in vivo study, it was suggested that the antioxidant activity of astaxanthin contributes to its potential anti-arthritic activity against complete Freund’s adjuvant-induced arthritis in rats. Complete Freund’s adjuvant-induced arthritis rats suffered from a significant decrease in serum GSH, SOD, and catalase activities, and a significant increase in serum nitrite and MDA levels. The oral administration of astaxanthin (25–100 mg·kg1) to female Wistar rats, for 14 consecutive days, was able to reverse these effects [36]. In another in vivo study, astaxanthin demonstrated to protect mice heart from ochratoxin A-induced oxidative stress. In this study, there was a group treated with astaxanthin alone (100 mg·kg1), a group treated with ochratoxin alone (5 mg·kg1), and another group treated with astaxanthin and ochratoxin A, where ochratoxin A (5 mg·kg1) was administered 2 h after the administration of astaxanthin (100 mg·kg1). The C57 male mice were treated for 7 days followed by 2 days of rest, being repeated for a total of 27 days. GSH, SOD, and catalase enzymes were used as antioxidant markers for cardiac injury, while MDA was used as an index of lipid peroxidation. Ochratoxin A increased the concentration of MDA and decreased the levels of SOD, GSH, and catalase. Astaxanthin decreased the concentration of MDA and increased the levels of the three enzymes, and the same result was observed in the group treated with astaxanthin and ochratoxin A [37]. This protective effect of astaxanthin was also observed against ochratoxin A-induced kidney injury to C57BL/J mice [38]. Both studies show that astaxanthin exerts a protective action against ochratoxin A-induced injury, and its potential to be applied in the prevention and treatment of oxidative damage to organs, through its antioxidant properties [37, 38]. Astaxanthin also showed a protective effect against photoaging in an in vivo assay with HR-1 hairless mice. Astaxanthin (100 mg·kg1) was orally administered and the mice (dorsal skin) were exposed to ultraviolet lamp for 8 weeks, three times per week, with a gradual increase in the exposure intensity. Astaxanthin inhibited ROS generation in the epidermis and capillary vessels in the mice’s dorsal skin [39].

3.2

Canthaxanthin

Canthaxanthin is a red-orange xanthophyll non-pro-vitamin A carotenoid. This carotenoid is responsible, for example, for the color of crustacean shell and flamingo feathers [16, 40].

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The studies on the antioxidant activity of canthaxanthin are scarce. In a study to assess the relative antioxidant activity of some carotenoids, canthaxanthin (≈ 100 μM) showed a negligible activity on the scavenging of the non-physiological free radical ABTS•+, as also described for astaxanthin [32]. However, in a more recent review of Siems and coworkers [10], canthaxanthin was described as having the ability to quench 1O2. In fact, more recently, in a review from Esatbeyoglu and coworkers [16], it becomes clear that canthaxanthin has the ability to scavenge ROS, but did not seem to achieve the same effect on ONOO. And similarly to what has been demonstrated for astaxanthin, isomerization also seems to influence the radical scavenging activity of canthaxanthin, since (9Z )-canthaxanthin has been shown to be more effective at scavenging O2• than (all-E)-canthaxanthin [16]. Further, some in vitro cellular and in vivo (e.g., rats and mice) studies demonstrated canthaxanthin antioxidant activity. In in vivo studies it demonstrated several antioxidant effects, namely decreased lipid peroxidation and increased catalase, SOD, and GPx activities [16].

3.3

α-Carotene

α-Carotene is a carotenoid that belongs to the carotene class, which acts as provitamin A. It is less abundant than β-carotene and can be found in vegetables and fruits, such as carrots, lettuces, spinach, and apricots [12, 41]. The antioxidant activity of α-carotene is poorly studied. Nonetheless, α-carotene (≈100 μM) demonstrated to scavenge the nonphysiological free radical ABTS•+ [32]. In a review from Siems and coworkers [10], α-carotene was described as having quenching activity against 1O2. In another study, α-carotene showed the ability to scavenge ONOO. The interaction between ONOO and α-carotene was evaluated with the probe dihydrorhodamine (DHR) 123 and in human LDL isolated from plasma. α-Carotene (0.5 μM) avoided the oxidation of DHR 123 by ONOO, being one of the most active among the tested carotenoids (β-carotene, β-cryptoxanthin, lutein, lycopene, and zeaxanthin); and, in the presence of human LDL, α-carotene (60  15 nmol·g LDL protein1) reacted with ONOO [42]. α-Carotene and β-carotene crystals (0.001–0.1%, w·v1), isolated from crude palm oil, showed a dual behavior, as anti- and pro-oxidants [41]. In DPPH radical scavenging, metal chelating, and O2• scavenging assays, these carotenoids (0.001%, w·v1) proved to be effective radical scavengers. However, the same was not observed for the prevention of lipid peroxidation, ABTS•+ scavenging, and reducing activity assays, where effects were only shown at the highest tested concentration (0.1%, w·v1). In fact, α-carotene and β-carotene, at higher concentrations, showed high reducing activity, while the inverse behavior was observed for their radical scavenging activity. Authors also reported that higher concentrations of carotenoids resulted in pro-oxidant effects, which were observed in the metal chelating, and DPPH radical and O2• scavenging assays. The results obtained in this study indicate that depending on the carotenoids’ concentration, they can act as antioxidants or pro-oxidants [41].

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β-Carotene

β-Carotene is a carotenoid that belongs to the carotene class and has an orange color. This carotenoid is the main precursor of vitamin A and is very often found in the human diet. β-Carotene can be found in orange, yellow, and green fruits and vegetables, such as carrots, pumpkins, spinach, among others [43, 44]. β-carotene is one of the most studied carotenoids, its antioxidant properties being widely described. β-Carotene (≈ 100 μM) exhibits the ability to scavenge the nonphysiological free radical ABTS•+ [32]. As described for other carotenoids, the antioxidant properties of β-carotene in in vitro membrane systems are affected by its location and orientation in the biological membranes. In general, β-carotene is oriented inside the biological membranes and parallel to their surfaces, which reduces its protective effect against ROO• and may explain the differences between its antioxidant potential in in vitro non-membranar and membranar systems [11]. Similarly to astaxanthin and canthaxanthin, isomerization also seems to influence its radical scavenging activity. In in vitro assays, (all-E)-β-carotene and (Z )-isomers (9Z, 13Z, and 15Z ) (10 μM) showed ABTS•+ bleaching activity and ROO• scavenging activity, but they did not show ferric reducing activity. No significant differences were noted between (all-E)-β-carotene and (Z )-isomers (9Z and 13Z) in bleaching the ABTS•+ or in ROO• scavenging. However, (15Z )-β-carotene was less active than the other isomers in both assays. (all-E)-β-Carotene and (Z )-isomers were more effective than α-tocopherol, which was used as reference compound [45]. Focusing in the physiological reactive species, in a review from Raposo and coworkers [30], the antioxidant activity of β-carotene was clearly described against 1 O2, ONOO, nitrogen dioxide (NO2), and peroxynitrous acid (ONOOH). Additionally, in the study of Kikugawa and coworkers [46], β-carotene (100 μM) showed a strong scavenging activity against NO2 and ONOOH/ONOO, but did not appear to react with NO•. β-Carotene (0–0.1 mM) also showed ability to scavenge O2• and HO•, being more efficient against HO•. Trevithick-Sutton and coworkers [47] indicated a possible scavenging mechanism of HO• through a bond formation between the HO• and one of the double bonds in the carotenoid, since these double bonds are more susceptible to radical addition [47]. As β-carotene has a lipophilic nature, it is commonly studied when incorporated in lipidic systems. When incorporated into a soybean phosphatidylcholine liposome system, β-carotene (0.38 mol %), in the presence of oxygen, partially suppressed lipid peroxidation [48]. Authors indicated that β-carotene antioxidant efficiency is affected by oxygen pressure, that is, when the oxygen pressure increases above the physiological value, there is a decrease in β-carotene antioxidant efficiency [48]. Everett and coworkers [49] showed that β-carotene (10 μM) interferes with lipid peroxidation by scavenging free radicals [•NO2, thiyl (RS•), and thiyl-sulfonyl (RSO•2)] involved in its development and progression. The authors referred that these radicals interfere with β-carotene by different mechanisms. The reaction of • NO2 with β-carotene occurs exclusively by electron transfer, generating [β-carotene]+• through a process of bimolecular charge transfer decays. RS• undergoes rapid addition reactions, generates [RS-β-carotene]•. RSO•2, adding an

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electron to the poly-conjugated double bonds, generates [RSO2-β-carotene]•, or abstracting an electron, generating a polyene radical-cation [49]. Following the lipophilic rationale of β-carotene distribution in the human body, several in vitro models of LDL have been used. In a review from Boon and coworkers [43], it was indicated that β-carotene contributes to the prevention of cardiovascular diseases by reducing platelet aggregation and protecting LDL from oxidation, which seems to be related to its reactive species scavenging properties [43]. Panasenko and coworkers [42] also showed the ability of β-carotene to scavenge ONOO. β-carotene (0.5 μM) avoids the oxidation of the probe DHR 123 by ONOO; and in the presence of human LDL, β-carotene (130  30 nmol·g LDL protein1) reacted with ONOO, as described for α-carotene [42]. The β-carotene preventive effects of oxidative damage have also been described in in vitro cellular models. Chisté and coworkers [50] studied the potential of some carotenoids (β-carotene, β-cryptoxanthin, lutein, lycopene, and zeaxanthin) (0.1–3 μM) to inhibit lipid peroxidation, oxidation of hemoglobin, and the depletion of GSH, in freshly isolated human erythrocytes. β-Carotene inhibited lipid peroxidation, in a concentration-dependent manner, when it was induced by APPH, whereas when tert-butyl hydroperoxide was used, β-carotene was much less efficient. β-carotene also proved to be an efficient antioxidant by inhibiting hemoglobin oxidation, but it was not able to inhibit the ROO•-induced GSH depletion in erythrocytes, at the highest tested concentration (3 μM) [50]. In a very recent study with several in vitro cellular models, β-carotene demonstrated antioxidant activity by inhibiting ONOO-induced lipid peroxidation. In this study, β-carotene (0–3 μM) was assessed for its ability to scavenge or model reactive species production in human whole blood and human neutrophils, but it did not reveal any relevant activity. The effects of β-carotene (0–3 μM) on lipid peroxidation were also evaluated in a synaptosomal model from rat brain tissue. In this assay, ONOO and H2O2 were used as lipid peroxidation inducers; β-carotene was only able to inhibit ONOO-induced lipid peroxidation [51]. In in vivo studies, β-carotene demonstrated a nephroprotective effect against bromobenzene in female Wistar albino rats [52]. Bromobenzene caused an increase of lipid peroxidation and a decrease on the antioxidant enzymes [SOD, catalase, GPx, glutathione S-transferase (GST), reduced glutathione]. The oral pretreatment with β-carotene (10 mg·kg1) for 9 days, before the administration of bromobenzene, allowed the reversion of these effects, leading to an increased activity of the five antioxidant enzymes and decreased levels of thiobarbituric acid reactive substances in kidney tissues [52].

3.5

β-Cryptoxanthin

β-Cryptoxanthin is a carotenoid of the xanthophyll class, which acts as pro-vitamin A. Despite being a carotenoid commonly found in the human blood, it only occurs at high concentrations in a small number of foods. The best diet source of

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β-cryptoxanthin is citrus fruits but it can also be found in pumpkins, peaches, papayas, among others [17, 22]. Studies on the antioxidant activity of β-cryptoxanthin are scarce and their antioxidant activity is controversial. In a review from Burri and coworkers [22], the differences in the effects exerted by non-pro-vitamin A and pro-vitamin A carotenoids are emphasized. Generally, the non-pro-vitamin carotenoids (e.g., lycopene), in most circumstances, are able to protect against DNA damage, whereas pro-vitamin A carotenoids (e.g., β-cryptoxanthin) have a dual effect: in some cases, they protect against DNA damage while in other they increase DNA damage, mostly when present at high concentrations. In the case of β-cryptoxanthin, as it tends to be present in tissues at low concentrations when compared to other antioxidants, it is indicated as an important antioxidant, protecting against DNA damage [22]. β-Cryptoxanthin (≈ 100 μM) exhibits the ability to scavenge the non-physiological radical, ABTS•+, being one of the carotenoids with higher activity when compared to the previously mentioned α-carotene and β-carotene [32]. In a study from Quesada-Gómez and coworkers [53], β-cryptoxanthin exhibited antioxidant effects in in vitro non-cellular and cellular models. The antioxidant activity of β-cryptoxanthin (0.01, 0.1 and 1 μM) was evaluated by ABTS•+ and oxygen-radical absorbance capacity (ORAC) assays, reflecting two antioxidant mechanisms: electron transfer and hydrogen-donating. In addition, human umbilical vein endothelial cells were treated with β-cryptoxanthin (0.01, 0.1 or 1 μM). In this assay, the effect of β-cryptoxanthin on intracellular ROS levels was evaluated in the presence and absence of H2O2, used as oxidative stress inducer. This carotenoid decreased peroxide levels both in the presence and absence of H2O2, reducing oxidative stress [53]. β-cryptoxanthin (0.5 μM) prevented the oxidation of DHR 123 by ONOO; and, in the presence of human LDL isolated from plasma, β-cryptoxanthin (61  12 nmol·g LDL protein1) reacted with ONOO, as happened for α-carotene and β-carotene [42]. In another in vitro cellular study, using human erythrocytes, β-cryptoxanthin (0.1–3 μM) prevented lipid peroxidation induced by tert-butyl hydroperoxide. However, it was unable to inhibit hemoglobin oxidation, as well as total GSH depletion, at the highest tested concentration (3 μM). Additionally, and as previously mentioned, β-carotene was more efficient than β-cryptoxanthin in preventing APPH-induced lipid peroxidation and hemoglobin oxidation [50].

3.6

Fucoxanthin

Fucoxanthin is a non-pro-vitamin A carotenoid that belongs to the xanthophylls class. This carotenoid is found in edible brown seaweeds, such as Undaria pinnatifida, Hijikia fusiformis, Laminaria japonica, and Sargassum fulvellum. Fucoxanthin has a unique structure and chirality, being considered unstable, which together with an allenic bond seems to be responsible for its antioxidant properties [17, 54, 55]. These properties were already reviewed and summarized by Raposo and coworkers [30] and Peng and coworkers [56]. In more detail, in 2017, purified

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fucoxanthin from Himanthalia elongata seaweed was able to scavenge the DPPH radical (EC50 ¼ 12.9  1.04 μg·mL1) and showed reducing power (15.2  1.21 μg trolox equivalent), exhibiting an activity similar to the commercial fucoxanthin [57]. In another in vitro study, fucoxanthin (0–100 μM) exhibited high reactive species scavenging activity, being able to scavenge DPPH, ABTS•+, HO•, 1O2, and O2•. Fucoxanthin proved to be a more efficient HO• scavenger than α-tocopherol, but a weaker quencher of 1O2 than β-carotene [54]. Fucoxanthin also demonstrated to scavenge ROO•, when evaluated by the ORAC method (fucoxanthin, 1–4 μM) and by electron spin resonance (fucoxanthin, 50 μM) [58]. The effects of fucoxanthin have also been studied in in vitro cellular models. This carotenoid demonstrated protective effect against tributyltin-induced oxidative stress in the human hepatoma cell line HepG2 [59]. Tributyltin stimulates the generation of ROS inside the cells, increases the accumulation of MDA, and decreases SOD activity. Treatment of cells with fucoxanthin (3 μM) reversed the effects induced by tributyltin, as a decrease on intracellular ROS and MDA (lipid peroxidation marker) levels were observed, as well as an increase on the intracellular SOD activity [59]. More recently, fucoxanthin demonstrated to prevent ethanol-induced hepatotoxicity, by avoiding the excessive oxidation of mouse hepatocytes caused by alcohol intake, attenuating alcohol-induced oxidative stress, and increasing the antioxidant capacity. In this study, alcohol supplemented with fucoxanthin (10, 20 and 40 mg·kg1) was orally administered to male ICR mice for 7 days. In the groups of mice treated with fucoxanthin, there was an increase of the liver total antioxidant capacity as well as an increase of SOD, catalase, and GPx activities and a decrease in MDA levels [60].

3.7

Lutein

Lutein belongs to the xanthophyll class, and acts as non-pro-vitamin A. This carotenoid can be found in spinach, broccoli, green peas, beet, among others [1]. In biological membranes, lutein adopts a parallel position to the surface, being effectively anchored along one side of the membrane, due to its ability to freely rotate the end-group around the C6-C7 single bond. Thus, lutein may exhibit less protective ability against oxidation by ROO• than astaxanthin (oriented across the membrane) [11, 14]. Lutein (≈ 100 μM) displays a relative ability to scavenge the non-physiological free radical ABTS•+, an activity already described for other carotenoids as α-carotene, β-carotene, and β-cryptoxanthin [32]. In the review of Siems and coworkers [10], lutein was described as having quenching activity against 1O2; however, it was the least active among the tested carotenoids (astaxanthin, canthaxanthin, α-carotene, β-carotene, γ-carotene, lutein, lycopene, and zeaxanthin) [10]. Lutein (0–0.1 mM) also showed ability to scavenge of O2• and HO•, being more efficient against HO•; as happened with β-carotene. As above mentioned for β-carotene, the authors indicated a possible scavenging of HO•, through bond formation between the HO• and one of the

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double bonds in the carotenoid [47]. Lutein (0.5 μM) also demonstrated the ability to avoid the oxidation of DHR 123 by ONOO, although it was the least effective among the tested carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lycopene, and zeaxanthin). In the presence of human LDL isolated from plasma, lutein (9  4 nmol·g LDL protein1) was able to react with ONOO, as described for α-carotene, β-carotene, and β-cryptoxanthin [42]. Lutein may exist under different isomerization states, leading to variations in its activity. (all-E)-Lutein and (9Z )- and (13Z )-lutein isomers (20–130 μg·mL1) were evaluated for their antioxidant activity by ORAC-L, ferric reducing antioxidant power (FRAP), and DPPH radical scavenging assay. In the three assays, the (13Z )-isomer showed a higher activity when compared to the other isomers. Moreover, in the FRAP and ORAC-L assays, (9Z)-lutein showed a better effect than (all-E)-isomer; while in DPPH radical scavenging assay, (all-E)-lutein had higher antioxidant ability than (9Z )-isomer. The antioxidant activity of these isomers (2.5 μM) was also evaluated in vitro by CAA assay, using Caco-2 human intestinal cell line. The three isomers showed good activities in the CAA assays and no significant differences were observed among them [61]. In another in vitro cellular study, using freshly human erythrocytes, lutein (0.1–3 μM) was able to inhibit APPH-induced lipid peroxidation, in a concentration-dependent manner, being more effective than the other tested carotenoids (β-carotene, β-cryptoxanthin, lycopene, and zeaxanthin). However, when evaluating tert-butyl hydroperoxide-induced lipid peroxidation, total GSH depletion induced by ROO•, and hemoglobin oxidation, lutein was not so active. The authors reported that lutein was less efficient than β-cryptoxanthin in preventing tert-butyl hydroperoxide-induced lipid peroxidation, while more effective than β-carotene. However, lutein was less efficient than β-carotene and more effective than β-cryptoxanthin at inhibiting hemoglobin oxidation [50]. Lakshminarayana and coworkers [62, 63] reported the effects of lutein (5–10 μg.mL1) on the inhibition of lipid peroxidation in human cervical carcinoma cell lines (HeLa), decreasing MDA and GSH levels, but also on the scavenging of DPPH radical. Sindhu and coworkers [64] evaluated the antioxidant potential of lutein in in vitro and in vivo models. In in vitro assays, lutein (1–100 μg) proved to be an effective scavenger of DPPH, NO•, O2•, and HO•, and inhibited lipid peroxidation, in a concentration-dependent manner. Lutein was also able to scavenge ABTS•+, but less effectively. In what concerns in vivo studies, lutein (50, 100, and 250 mg·kg1) was orally administered to male Swiss albino mice, for 30 days. Catalase, SOD, GSH and glutathione reductase activities increased in the blood and liver of mice treated with lutein. Hepatic GPx and GST activities also increased. Lutein also inhibited O2• generation in mice peritoneal macrophages [64]. Besides its antioxidant activity, lutein also proved to ameliorate lung and liver damage associated with cyclophosphamide administration. In another in vivo study lutein (40 and 100 mg·kg1) was orally administered to male Swiss albino mice, for 5 days, before and after cyclophosphamide administration (injection of 50 mg·kg1). The lutein treatment increased SOD activity and GSH levels and decreased MDA concentration in lung and liver of cyclophosphamide-intoxicated mice [65].

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In Sprague-Dawley Wistar female rats, lutein supplementation was able to protect the ovariectomized rats against oxidative stress. Lutein (50 mg·kg1) was administered for 4 weeks and demonstrated ability to reverse the effects of ovariectomization. Thus, lutein reduced lipid peroxidation and oxidative stress, and increased serum GSH levels [66]. In Wistar albino female rats, lutein administration ameliorated the ovarian ischemia-reperfusion injury. Lutein (1 mg·kg1) was orally administered 1 h before the application of reperfusion and significantly decreased the MDA levels and ameliorated the total GSH levels in the ovarian tissue [67].

3.8

Lycopene

Lycopene is a non-pro-vitamin A carotenoid that belongs to the carotene class. This carotenoid is responsible for the red color of fruits such as tomatoes. In fact, tomatoes and tomato products are one of the biggest sources of lycopene in the human diet, where it is found in relatively high concentrations [68]. The antioxidant properties of lycopene are known and are broadly described in literature. Siems and Sthal [68], in their review, describe lycopene as the most efficient 1O2 quencher of the natural carotenoids, having high quenching rate constants. These authors also refer the potential of lycopene as ROO• scavenger. It has been suggested that the presence of two additional non-conjugated double bonds in the lycopene structure provides an increase in its reactivity [68]. In a study with the nonphysiological free radical ABTS•+, lycopene (≈ 100 μM) exhibited the ability to scavenge this radical, being the most active among tested carotenoids (astaxanthin, canthaxanthin, α-carotene, β-carotene, β-cryptoxanthin, lutein, and zeaxanthin) [32]. In what concerns reactive species that can be physiologically found, Siems and coworkers [10], in their review, indicate that lycopene has quenching activity against 1 O2 [10]. Additionally, lycopene (0–0.1 mM) also show ability to scavenge O2• and HO•, being more efficient against HO•; as happened with β-carotene and lutein. As mentioned for β-carotene and lutein, the authors indicated a possible scavenging mechanism for HO•, through bond formation between the HO• and one of the double bonds in the carotenoid [47]. Moreover, lycopene (0.5 μM) prevented the oxidation of DHR 123 by ONOO, being more effective than the other tested carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein, and zeaxanthin); and, in the presence of human LDL, lycopene (75  19 nmol·g LDL protein1) was also able to react with ONOO, as described for α-carotene, β-carotene, β-cryptoxanthin, and lutein [42]. Lycopene (10 μM), as astaxanthin, demonstrated ROS quenching ability by the reduction of ROS production induced by light exposure, in a murine cone cell line derived from mouse retinal tumors (661 W cell line) [33]. In freshly isolated human erythrocytes, Chisté and coworkers [50] studied the potential of lycopene (0.1–3 μM) to inhibit lipid peroxidation, the oxidation of hemoglobin, and the depletion of GSH. Lycopene inhibited lipid peroxidation in a concentrationdependent manner when it was induced by tert-butyl hydroperoxide, being the

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most efficient among tested carotenoids (β-carotene, β-cryptoxanthin, lutein, and zeaxanthin). However, it was unable to inhibit hemoglobin oxidation, as well as total GSH depletion, at the highest tested concentration (3 μM), as happened with β-cryptoxanthin [50]. Lycopene exhibits cytoprotective effects against H2O2induced oxidative damage in bovine mammary epithelial cells. The treatment of cells with lycopene (0.5–2 μM) reversed the effects induced by H2O2, namely the increase of intracellular ROS and MDA levels and the decrease of SOD, catalase, and GPx activities [69]. The effects of lycopene have also been studied in in vivo models, namely in male Wistar albino rats, where lycopene was shown to be able to prevent aflatoxin B1-induced hepatotoxicity. The group of rats orally treated with aflatoxin B1 (0.5 mg·kg1), for 7 days, recorded an increase in MDA levels and a decrease in the antioxidant enzymes (SOD, catalase, GSH, GPx, GST) levels in the liver tissues. The group of rats orally treated with lycopene alone (5 mg·kg1), for 15 days, decreased the concentration of MDA and increased the levels of the antioxidant enzymes in the liver tissues. Additionally, a group of rats was treated with both aflatoxin B1 (0.5 mg·kg1) and lycopene (5 mg·kg1) from day 1, the first one was daily administered for 7 days and the latter was daily administered for 15 days [70]. Lycopene was also able to inhibit aflatoxin B1-induced oxidative stress in male Kunming mice spleen. In this case, oral administration of lycopene (5 mg·kg1), for 30 days, decreased the levels of ROS and MDA, and increased the total antioxidant capacity and the SOD and catalase activities [71]. Lycopene also demonstrated antioxidant effects in bisphenol A-induced hepatic oxidative stress in female Wistar rats. Lycopene (10 mg·kg1), daily administered, for 30 days reversed the bisphenol A-induced increase in MDA levels and decrease in the activities of SOD and GPx [72]. Finally, lycopene showed neuroprotective effects against oxaliplatin-induced central and peripheral neuropathy in rats. Lycopene (2 or 4 mg·kg1) was orally administered to Sprague Dawley rats on 1st, 2nd, 4th, and 5th days before intraperitoneal administration of oxaliplatin (4 mg·kg1). Oxaliplatin increased MDA levels and decreased antioxidant enzymes activities (SOD, catalase, and GPx) and GSH levels. These effects were reversed with the administration of lycopene, being most effective at the highest tested concentration (4 mg·kg1) [73].

3.9

Zeaxanthin

Zeaxanthin is a xanthophyll and a non-pro-vitamin A carotenoid that can be found in several dietary sources such as eggs, oranges, and green leafy vegetables. In addition to dietary sources, zeaxanthin can also be found in marine sources (e.g., Gramella oceani sp. bacteria, Rhodophyta spp. algae, among others) [17]. The antioxidant properties of zeaxanthin have been studied over the years. As example, Gammone and coworkers [17] described that zeaxanthin can act as a direct and indirect antioxidant, since it can regulate the synthesis and levels of GSH, improving the intracellular redox status upon oxidative stress. Moreover, this carotenoid can also decrease the susceptibility to cell death induced by H2O2 [17].

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As occurred with other carotenoids (α-carotene, β-carotene, β-cryptoxanthin, lutein, and lycopene), zeaxanthin (≈ 100 μM) also exhibited the ability to scavenge ABTS•+ [32]. In addition, Siems and coworkers [10], in their review, indicated that zeaxanthin is also able to quench 1O2, like canthaxanthin, α-carotene, lutein, and lycopene [10]. Zeaxanthin (0–0.1 mM) is a scavenger of O2• and HO•, being more efficient against HO•, like β-carotene, lutein, and lycopene, through the already mentioned mechanisms [47]. Additionally, zeaxanthin (0.5 μM) avoids the oxidation of the probe DHR 123 by ONOO; and, in the presence of human LDL isolated from plasma, zeaxanthin (8  4 nmol·g LDL protein1) reacted with ONOO; as happened with α-carotene, β-carotene, β-cryptoxanthin, lutein, and lycopene [42]. In another study, zeaxanthin (5 μM), incorporated in liposomes, slowly reacted with ONOO. This reaction is a second-order reaction and the formation of hydrogen bonds between distal hydroxy groups of zeaxanthin and ONOOH can limit the rate of the reaction [74]. In freshly isolated human erythrocytes, Chisté and coworkers [50] observed that zeaxanthin (0.1–3 μM) inhibited APPH induced-lipid peroxidation in a concentration-dependent manner. However, this carotenoid was much less efficient when lipid peroxidation was induced by tert-butyl hydroperoxide. Zeaxanthin was also effective in inhibiting hemoglobin oxidation, but has not been able to inhibit the ROO•-induced GSH depletion in erythrocytes. In the same study, and as previously mentioned, other carotenoids, namely β-carotene, β-cryptoxanthin, lutein, and lycopene, were also evaluated and the effects observed for zeaxanthin were similar to those shown by β-carotene [50]. In what concerns in vivo studies, zeaxanthin exhibited protective effects on acetic acid-induced colitis in rats. The male Sprague Dawley rats were pre-treated with zeaxanthin (50 mg·kg1), for 14 days, by oral administration and then colitis was induced (transrectal administration of 3% acetic acid). Zeaxanthin decreased the MDA levels and increased the levels of GSH, and SOD and catalase activities [75].

4

Pro-oxidant Activity

The pro-oxidant term defines any xenobiotic or endobiotic agent with the potential to induce oxidative stress. Oxidative stress can occur by inhibition of antioxidant systems and/or generation of reactive species, which results in an increase of the oxidative damage to biomolecules, such as lipid oxidation and DNA damage [7, 76]. Noteworthy, some antioxidants can also behave as pro-oxidants, as they can show distinct activities under specific conditions [76]. Carotenoids are an example of antioxidant compounds that may also have pro-oxidant activity, but this issue is still controversial [6, 7]. As example, Young and Lowe [14], in their review, consider that carotenoids did not act as true pro-oxidants in biological systems, since the observed effects are related to the loss of effectiveness as antioxidants [14]. Indeed, it is difficult to make a concrete separation between the carotenoids’ classification as anti- or pro-oxidants, and some studies address the two types of activities for the same carotenoid [6, 41].

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The pro-oxidant activity of carotenoids can be influenced by several factors such as oxygen tension, carotenoid concentration, interaction with other antioxidants, and their possible autoxidation [7, 14]. In the literature, it is indicated that at low oxygen pressures carotenoids act as chain-breaking antioxidants. However, for high oxygen pressures, it is described that carotenoids show pro-oxidant effects possibly due to their autoxidation. This behavior was observed in homogeneous lipid solutions, membrane models, and intact cells [7, 77]. Edge and Truscott [78] suggested, based on pulsed radiation techniques, that alternation between anti- and pro-oxidant activity occurs as a function of oxygen levels, and that the antioxidant activity of carotenoids results from the synergistic effect with other compounds as vitamins E and C [78]. High concentrations of carotenoids seem to be directly related with their pro-oxidant effect, which may be related to the faster rate of carotenoid autoxidation and/or to the formation of ROO• [7]. As already stated for vitamins E and C, the interaction of carotenoids with other antioxidants is also described in the literature as a determining factor in the duality between anti- and pro-oxidant activities of carotenoids. It is suggested that the presence of other antioxidants may affect the involvement of carotenoids in oxidative processes. Carotenoids, in the presence of high concentrations of other antioxidants, usually have antioxidant effects. However, when these other antioxidants are exhausted, the behavior of carotenoids can change to pro-oxidant [7]. Shin and coworkers [79], in their review, summarized the pro-oxidant effects of some carotenoids, namely astaxanthin, bixin, β-carotene, β-cryptoxanthin, fucoxanthin, lutein, and lycopene; and pointed out mechanisms of pro-oxidant action including some of the already mentioned: increase of ROS and MDA levels, DNA damage, and decrease of GSH levels [79]. Below, the pro-oxidant effects of β-carotene and lycopene will be further presented and discussed, since their pro-oxidant effects are the most reported and clearly demonstrated in the literature.

4.1

β-Carotene

Siems and coworkers [10], in their review, reported the antioxidant and pro-oxidant activity of β-carotene, depending on the concentration tested. Lower concentrations of β-carotene scavenged 1O2, nonetheless higher concentrations induced the generation of ROO•[10]. Previously, these authors reported a possible mechanism of pro-oxidant activity of β-carotene and carotenoid cleavage products, where they proposed that under heavy oxidative stress conditions, β-carotene is degraded, forming high amounts of pro-oxidant products [80]. The pro-oxidant effects of β-carotene in cell cultures were reviewed by Palozza and coworkers [81]. In this review the oxidative markers indicative of the pro-oxidant activity of β-carotene were also analyzed: increase in ROS production, as a result of the autoxidation of carotenoid metabolites; changes in cell antioxidant defenses, in the activity of cytochrome P450 enzymes and in iron levels; increase in lipid oxidation; modulation of redox-sensitive genes and transcription factors; increase in DNA oxidation, due to lack of DNA protection from oxidative damage;

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impairment of cell antioxidant status through the modulation of antioxidant enzymes activities (SOD, catalase, and GPx); increase of oxidized GSH; decrease of GSH levels; increase of α-tocopherol consumption, since it can protect β-carotene from oxidation and/or the formation of β-carotene-derived ROO•; and increase in protein oxidation [81]. These authors also refer that the pro-oxidant effects of β-carotene are observed under certain conditions: high oxygen tension, unbalanced intracellular redox status, and high carotenoid concentration [81]. Additionally, these authors also addressed the interaction of β-carotene with antioxidants, such as α-tocopherol, referring that the presence of antioxidants may limit the pro-oxidant effects of carotenoids. For example, α-tocopherol is able to inhibit the increase in lipid peroxidation in cell membranes, resulting from high β-carotene concentrations, which shows that α-tocopherol can reverse the pro-oxidant effects of β-carotene [81].

4.2

Lycopene

The studies on the pro-oxidant activity of lycopene are scarce. However, lycopene (50 μM) exhibited pro-oxidant effects in in vitro cellular assays with several cancer cell lines [human prostate cancer (PC-3), human alveolar epithelial adenocarcinoma (A549), human cervical cancer (HeLa), human breast adenocarcinoma (MCF-7), human epidermoid carcinoma (A431), and human hepatocellular carcinoma (HepG2)]. Lycopene also induced a decrease of cell viability; however, its effects on viability vary according to the concentration used and the cell type. Treatment of MCF-7, PC-3, and HeLa cell lines with lycopene led to increased MDA levels and GSH depletion, as well as increased ROS production [82].

5

Conclusion

In this chapter, it is evident the enormous variety of studies that report the antioxidant activity of carotenoids, which include in vitro non-cellular and cellular studies, as well as in vivo studies. Carotenoids have been shown to be antioxidants, mainly acting as reactive species scavengers, in both in vitro non-cellular and cellular assays, which were the most common models used to evaluate the potential antioxidant activity of carotenoids. In in vivo studies, carotenoids demonstrate to exert their antioxidant effects as modulators of the activity of antioxidant enzymes and GSH levels, as well as acting as inhibitors of lipid peroxidation. However, it is difficult to fully characterize the mechanism of action that is involved or the most promising carotenoid, especially in the effects observed in vivo, where there are an enormous variety of factors that can influence the observed results. As depicted in this chapter, the pro-oxidant activity of carotenoids is still a controversial subject and needs further studies, since the mechanism by which these effects are exerted is still unclear. Figure 3 systematizes the carotenoids with antioxidant and/or pro-oxidant activities mentioned along this chapter, and the effects associated with these activities.

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Fig. 3 Summarized representation of the carotenoids’ antioxidant and/or pro-oxidant activities and the effects associated with these activities, mentioned along this chapter

In conclusion, and despite the number and diversity of the existing studies, only a small group of carotenoids has been thoroughly studied, remaining a large number of compounds for which biological activities still need to be better understood. Acknowledgments This work received financial support from PT national funds (FCT/MCTES, Fundação para a Ciência e Tecnologia and Ministério da Ciência, Tecnologia e Ensino Superior) through grant UIDB/50006/2020 (LAQV-REQUIMTE Associate Laboratory) and from the European Union (FEDER funds through COMPETE POCI-01-0145-FEDER-029253). Marisa Freitas acknowledges the financial support from the European Union (FEDER funds through COMPETE POCI-01-0145-FEDER-029248).

References 1. Rao AV, Rao LG (2007) Carotenoids and human health. Pharmacol Res 55(3):207–216 2. Milani A, Basirnejad M, Shahbazi S, Bolhassani A (2017) Carotenoids: biochemistry, pharmacology and treatment. Br J Pharmacol 174(11):1290–1324 3. Nagao A (2014) Bioavailability of dietary carotenoids: intestinal absorption and metabolism. Jpn Agric Res Q 48(4):385–391

6

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4. Walter MH, Strack D (2011) Carotenoids and their cleavage products: biosynthesis and functions. Nat Prod Rep 28(4):663–692 5. Fiedor J, Burda K (2014) Potential role of carotenoids as antioxidants in human health and disease. Nutrients 6(2):466–488 6. El-Agamey A, Lowe GM, McGarvey DJ, Mortensen A, Phillip DM, Truscott TG, Young AJ (2004) Carotenoid radical chemistry and antioxidant/pro-oxidant properties. Arch Biochem Biophys 430(1):37–48 7. Palozza P (1998) Prooxidant actions of carotenoids in biologic systems. Nutr Rev 56(9):257–265 8. Shete V, Quadro L (2013) Mammalian metabolism of β-carotene: gaps in knowledge. Nutrients 5(12):4849–4868 9. Ribeiro D, Freitas M, Silva AMS, Carvalho F, Fernandes E (2018) Antioxidant and pro-oxidant activities of carotenoids and their oxidation products. Food Chem Toxicol 120:681–699 10. Siems W, Wiswedel I, Salerno C, Crifò C, Augustin W, Schild L, Langhans C-D, Sommerburg O (2005) β-carotene breakdown products may impair mitochondrial functions – potential side effects of high-dose β-carotene supplementation. J Nutr Biochem 16(7):385–397 11. Jomova K, Valko M (2013) Health protective effects of carotenoids and their interactions with other biological antioxidants. Eur J Med Chem 70:102–110 12. Namitha KK, Negi PS (2010) Chemistry and biotechnology of carotenoids. Crit Rev Food Sci Nutr 50(8):728–760 13. Pérez-Gálvez A, Viera I, Roca M (2020) Carotenoids and chlorophylls as antioxidants. Antioxidants 9(6):1 14. Young AJ, Lowe GM (2001) Antioxidant and prooxidant properties of carotenoids. Arch Biochem Biophys 385(1):20–27 15. Tapiero H, Townsend DM, Tew KD (2004) The role of carotenoids in the prevention of human pathologies. Biomed Pharmacother 58(2):100–110 16. Esatbeyoglu T, Rimbach G (2017) Canthaxanthin: from molecule to function. Mol Nutr Food Res 61(6):1600469 17. Gammone MA, Riccioni G, D’Orazio N (2015) Marine carotenoids against oxidative stress: effects on human health. Mar Drugs 13(10):6226–6246 18. Khachik F, Carvalho L, Bernstein PS, Muir GJ, Zhao D-Y, Katz NB (2002) Chemistry, distribution, and metabolism of tomato carotenoids and their impact on human health. Exp Biol Med 227(10):845–851 19. Priyadarshani AMB (2017) A review on factors influencing bioaccessibility and bioefficacy of carotenoids. Crit Rev Food Sci Nutr 57(8):1710–1717 20. Bohn T, Desmarchelier C, Dragsted LO, Nielsen CS, Stahl W, Rühl R, Keijer J, Borel P (2017) Host-related factors explaining interindividual variability of carotenoid bioavailability and tissue concentrations in humans. Mol Nutr Food Res 61(6):1600685 21. Wu L, Guo X, Wang W, Medeiros DM, Clarke SL, Lucas EA, Smith BJ, Lin D (2016) Molecular aspects of β, β-carotene-90 , 100 -oxygenase 2 in carotenoid metabolism and diseases. Exp Biol Med 241(17):1879–1887 22. Burri BJ, La Frano MR, Zhu C (2016) Absorption, metabolism, and functions of β-cryptoxanthin. Nutr Rev 74(2):69–82 23. Caris-Veyrat C, Schmid A, Carail M, Böhm V (2003) Cleavage products of lycopene produced by in vitro oxidations: characterization and mechanisms of formation. J Agric Food Chem 51(25):7318–7325 24. Burri BJ, Clifford AJ (2004) Carotenoid and retinoid metabolism: insights from isotope studies. Arch Biochem Biophys 430(1):110–119 25. Pisoschi AM, Pop A (2015) The role of antioxidants in the chemistry of oxidative stress: a review. Eur J Med Chem 97:55–74 26. Stahl W, Sies H (1996) Lycopene: a biologically important carotenoid for humans? Arch Biochem Biophys 336(1):1–9 27. Black HS, Boehm F, Edge R, Truscott TG (2020) The benefits and risks of certain dietary carotenoids that exhibit both anti- and pro-oxidative mechanisms-a comprehensive review. Antioxidants 9(3):264

146

M. Lucas et al.

28. Nishino A, Maoka T, Yasui H (2016) Analysis of reaction products of astaxanthin and its acetate with reactive oxygen species using LC/PDA ESI-MS and ESR spectrometry. Tetrahedron Lett 57(18):1967–1970 29. Yang C, Zhang L, Zhang H, Sun Q, Liu R, Li J, Wu L, Tsao R (2017) Rapid and efficient conversion of all-E-astaxanthin to 9Z- and 13Z-isomers and assessment of their stability and antioxidant activities. J Agric Food Chem 65(4):818–826 30. Raposo MFJ, de Morais AMMB, de Morais RMSC (2015) Carotenoids from marine microalgae: a valuable natural source for the prevention of chronic diseases. Mar Drugs 13(8):5128–5155 31. Chintong S, Phatvej W, Rerk-Am U, Waiprib Y, Klaypradit W (2019) In vitro antioxidant, antityrosinase, and cytotoxic activities of astaxanthin from shrimp waste. Antioxidants 8(5):128 32. Miller NJ, Sampson J, Candeias LP, Bramley PM, Rice-Evans CA (1996) Antioxidant activities of carotenes and xanthophylls. FEBS Lett 384(3):240–242 33. Inoue Y, Shimazawa M, Nagano R, Kuse Y, Takahashi K, Tsuruma K, Hayashi M, Ishibashi T, Maoka T, Hara H (2017) Astaxanthin analogs, adonixanthin and lycopene, activate Nrf2 to prevent light-induced photoreceptor degeneration. J Pharmacol Sci 134(3):147–157 34. Lin C-W, Yang C-M, Yang C-H (2020) Protective effect of astaxanthin on blue light lightemitting diode-induced retinal cell damage via free radical scavenging and activation of PI3K/ Akt/Nrf2 pathway in 661W cell model. Mar Drugs 18(8):387 35. Hormozi M, Ghoreishi S, Baharvand P (2019) Astaxanthin induces apoptosis and increases activity of antioxidant enzymes in LS-180 cells. Artif Cells Nanomed Biotechnol 47(1):891–895 36. Kumar A, Dhaliwal N, Dhaliwal J, Dharavath RN, Chopra K (2020) Astaxanthin attenuates oxidative stress and inflammatory responses in complete Freund-adjuvant-induced arthritis in rats. Pharmacol Rep 72(1):104–114 37. Cui G, Li L, Xu W, Wang M, Jiao D, Yao B, Xu K, Chen Y, Yang S, Long M, Li P, Guo Y (2020) Astaxanthin protects ochratoxin A-induced oxidative stress and apoptosis in the heart via the Nrf2 pathway. Oxidative Med Cell Longev 2020:7639109 38. Li L, Chen Y, Jiao D, Yang S, Li L, Li P (2020) Protective effect of astaxanthin on ochratoxin A-induced kidney injury to mice by regulating oxidative stress-related NRF2/KEAP1 pathway. Molecules 25(6):1386 39. Li X, Matsumoto T, Takuwa M, Ali MSES, Hirabashi T, Kondo H, Fujino H (2020) Protective effects of astaxanthin supplementation against ultraviolet-induced photoaging in hairless mice. Biomedicine 8(2):18 40. Mordi RC, Walton JC (2016) Identification of products from canthaxanthin oxidation. Food Chem 197:836–840 41. Sen Gupta S, Ghosh M (2013) In vitro antioxidative evaluation of α- and β-carotene, isolated from crude palm oil. J Anal Methods Chem 2013:351671 42. Panasenko OM, Sharov VS, Briviba K, Sies H (2000) Interaction of peroxynitrite with carotenoids in human low density lipoproteins. Arch Biochem Biophys 373(1):302–305 43. Boon CS, McClements DJ, Weiss J, Decker EA (2010) Factors influencing the chemical stability of carotenoids in foods. Crit Rev Food Sci Nutr 50(6):515–532 44. Sommerburg O, Langhans C-D, Arnhold J, Leichsenring M, Salerno C, Crifò C, Hoffmann GF, Debatin K-M, Siems WG (2003) β-Carotene cleavage products after oxidation mediated by hypochlorous acid – a model for neutrophil-derived degradation. Free Radic Biol Med 35(11):1480–1490 45. Mueller L, Boehm V (2011) Antioxidant activity of β-carotene compounds in different in vitro assays. Molecules 16(2):1055–1069 46. Kikugawa K, Hiramoto K, Tomiyama S, Asano Y (1997) β-Carotene effectively scavenges toxic nitrogen oxides: nitrogen dioxide and peroxynitrous acid. FEBS Lett 404(2–3):175–178 47. Trevithick-Sutton CC, Foote CS, Collins M, Trevithick JR (2006) The retinal carotenoids zeaxanthin and lutein scavenge superoxide and hydroxyl radicals: a chemiluminescence and ESR study. Mol Vis 12:1127–1135

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Antioxidant and Pro-oxidant Activities of Carotenoids

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48. Kennedy TA, Liebler DC (1992) Peroxyl radical scavenging by β-carotene in lipid bilayers. Effect of oxygen partial pressure. J Biol Chem 267(7):4658–4663 49. Everett SA, Dennis MF, Patel KB, Maddix S, Kundu SC, Willson RL (1996) Scavenging of nitrogen dioxide, thiyl, and sulfonyl free radicals by the nutritional antioxidant β-carotene. J Biol Chem 271(8):3988–3994 50. Chisté RC, Freitas M, Mercadante AZ, Fernandes E (2014) Carotenoids inhibit lipid peroxidation and hemoglobin oxidation, but not the depletion of glutathione induced by ROS in human erythrocytes. Life Sci 99(1):52–60 51. Ribeiro D, Sousa A, Nicola P, Ferreira de Oliveira JMP, Rufino AT, Silva M, Freitas M, Carvalho F, Fernandes E (2020) β-Carotene and its physiological metabolites: effects on oxidative status regulation and genotoxicity in in vitro models. Food Chem Toxicol 141:111392 52. Akkara PJ, Sabina EP (2020) Pre-treatment with beta carotene gives protection against nephrotoxicity induced by bromobenzene via modulation of antioxidant system, pro-inflammatory cytokines and pro-apoptotic factors. Appl Biochem Biotechnol 190(2):616–633 53. Quesada-Gómez JM, Santiago-Mora R, Durán-Prado M, Dorado G, Pereira-Caro G, MorenoRojas JM, Casado-Díaz A (2018) β-Cryptoxanthin inhibits angiogenesis in human umbilical vein endothelial cells through retinoic acid receptor. Mol Nutr Food Res 62(2):1700489 54. Sachindra NM, Sato E, Maeda H, Hosokawa M, Niwano Y, Kohno M, Miyashita K (2007) Radical scavenging and singlet oxygen quenching activity of marine carotenoid fucoxanthin and its metabolites. J Agric Food Chem 55(21):8516–8522 55. Zhang H, Tang Y, Zhang Y, Zhang S, Qu J, Wang X, Kong R, Han C, Liu Z (2015) Fucoxanthin: a promising medicinal and nutritional ingredient. Evid Based Complementary Altern Med 2015:723515–723515 56. Peng J, Yuan J-P, Wu C-F, Wang J-H (2011) Fucoxanthin, a marine carotenoid present in brown seaweeds and diatoms: metabolism and bioactivities relevant to human health. Mar Drugs 9(10):1806–1828 57. Rajauria G, Foley B, Abu-Ghannam N (2017) Characterization of dietary fucoxanthin from Himanthalia elongata brown seaweed. Food Res Int 99:995–1001 58. Taira J, Sonamoto M, Uehara M (2017) Dual biological functions of a cytoprotective effect and apoptosis induction by bioavailable marine carotenoid fucoxanthinol through modulation of the Nrf2 activation in RAW264.7 macrophage cells. Mar Drugs 15(10):305 59. Zeng J, Zhang Y, Ruan J, Yang Z, Wang C, Hong Z, Zuo Z (2018) Protective effects of fucoxanthin and fucoxanthinol against tributyltin-induced oxidative stress in HepG2 cells. Environ Sci Pollut Res 25(6):5582–5589 60. Zheng J, Tian X, Zhang W, Zheng P, Huang F, Ding G, Yang Z (2019) Protective effects of fucoxanthin against alcoholic liver injury by activation of Nrf2-mediated antioxidant defense and inhibition of TLR4-mediated inflammation. Mar Drugs 17(10):552 61. Yang C, Fischer M, Kirby C, Liu R, Zhu H, Zhang H, Chen Y, Sun Y, Zhang L, Tsao R (2018) Bioaccessibility, cellular uptake and transport of luteins and assessment of their antioxidant activities. Food Chem 249:66–76 62. Lakshminarayana R, Sathish UV, Dharmesh SM, Baskaran V (2010) Antioxidant and cytotoxic effect of oxidized lutein in human cervical carcinoma cells (HeLa). Food Chem Toxicol 48(7):1811–1816 63. Lakshminarayana R, Aruna G, Sathisha UV, Dharmesh SM, Baskaran V (2013) Structural elucidation of possible lutein oxidation products mediated through peroxyl radical inducer 2,20 -azobis (2-methylpropionamidine) dihydrochloride: antioxidant and cytotoxic influence of oxidized lutein in HeLa cells. Chem Biol Interact 203(2):448–455 64. Sindhu ER, Preethi KC, Kuttan R (2010) Antioxidant activity of carotenoid lutein in vitro and in vivo. Indian J Exp Biol 48(8):843–848 65. El-Kholy AA, Elkablawy MA, El-Agamy DS (2017) Lutein mitigates cyclophosphamide induced lung and liver injury via NF-κB/MAPK dependent mechanism. Biomed Pharmacother 92:519–527

148

M. Lucas et al.

66. Li H, Huang C, Zhu J, Gao K, Fang J, Li H (2018) Lutein suppresses oxidative stress and inflammation by Nrf2 activation in an osteoporosis rat model. Med Sci Monit 24:5071–5075 67. Turkler C, Kulhan NG, Ata N, Kiremitli T, Cimen FK, Suleyman H (2018) The ameliorative effect of lutein on ovarian ischemia-reperfusion injury in rats. Bratisl Lek Listy 119(11): 713–717 68. Sies H, Stahl W (1998) Lycopene: antioxidant and biological effects and its bioavailability in the human. Proc Soc Exp Biol Med 218(2):121–124 69. Sun X, Jia H, Xu Q, Zhao C, Xu C (2019) Lycopene alleviates H2O2-induced oxidative stress, inflammation and apoptosis in bovine mammary epithelial cells via the NFE2L2 signaling pathway. Food Funct 10(10):6276–6285 70. Karaca A, Yilmaz S, Kaya E, Altun S (2019) The effect of lycopene on hepatotoxicity of aflatoxin B1 in rats. Arch Physiol Biochem 1–8. Online ahead of print 71. Xu F, Wang P, Yao Q, Shao B, Yu H, Yu K, Li Y (2019) Lycopene alleviates AFB1-induced immunosuppression by inhibiting oxidative stress and apoptosis in the spleen of mice. Food Funct 10(7):3868–3879 72. Abdel-Rahman HG, Abdelrazek HMA, Zeidan DW, Mohamed RM, Abdelazim AM (2018) Lycopene: hepatoprotective and antioxidant effects toward bisphenol A-induced toxicity in female wistar rats. Oxid Med Cell Longev 2018:5167524 73. Celik H, Kucukler S, Ozdemir S, Comakli S, Gur C, Kandemir FM, Yardim A (2020) Lycopene protects against central and peripheral neuropathy by inhibiting oxaliplatin-induced ATF-6 pathway, apoptosis, inflammation and oxidative stress in brains and sciatic tissues of rats. Neurotoxicology 80:29–40 74. Scheidegger R, Pande AK, Bounds PL, Koppenol WH (1998) The reaction of peroxynitrite with zeaxanthin. Nitric Oxide 2(1):8–16 75. El-Akabawy G, El-Sherif NM (2019) Zeaxanthin exerts protective effects on acetic acidinduced colitis in rats via modulation of pro-inflammatory cytokines and oxidative stress. Biomed Pharmacother 111:841–851 76. Rahal A, Kumar A, Singh V, Yadav B, Tiwari R, Chakraborty S, Dhama K (2014) Oxidative stress, prooxidants, and antioxidants: the interplay. Biomed Res Int 2014:761264 77. Eghbaliferiz S, Iranshahi M (2016) Prooxidant activity of polyphenols, flavonoids, anthocyanins and carotenoids: updated review of mechanisms and catalyzing metals. Phytother Res 30(9):1379–1391 78. Edge R, Truscott TG (1997) Prooxidant and antioxidant reaction mechanisms of carotene and radical interactions with vitamins E and C. Nutrition 13(11–12):992–994 79. Shin J, Song M-H, Oh J-W, Keum Y-S, Saini RK (2020) Pro-oxidant actions of carotenoids in triggering apoptosis of cancer cells: a review of emerging evidence. Antioxidants 9(6):1–17 80. Siems W, Sommerburg O, Schild L, Augustin W, Langhans C-D, Wiswedel I (2002) Betacarotene cleavage products induce oxidative stress in vitro by impairing mitochondrial respiration. FASEB J 16(10):1289–1291 81. Palozza P, Serini S, Di Nicuolo F, Piccioni E, Calviello G (2003) Prooxidant effects of β-carotene in cultured cells. Mol Asp Med 24(6):353–362 82. Arathi BP, Sowmya PR-R, Kuriakose GC, Vijay K, Baskaran V, Jayabaskaran C, Lakshminarayana R (2016) Enhanced cytotoxic and apoptosis inducing activity of lycopene oxidation products in different cancer cell lines. Food Chem Toxicol 97:265–276

7

Selenium: Prospects of Functional Food Production with High Antioxidant Activity Nadezhda Golubkina, Viktor Kharchenko, and Gianluca Caruso

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Plants Biofortification with Selenium . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Microgreens and Sprouts . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Edible Mushrooms, New Functional Food Products . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Natural Selenium Accumulators with High Antioxidant Activity . . . . . . . . . . . . . . . . . . . . . . . . . 6 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abstract

The essentiality of selenium for mammals including human beings, its powerful antioxidant properties, and synergism with other natural antioxidants elicit intensive investigations in agricultural and medicinal crop products with high levels of selenium, phenolics, and other antioxidants. The present chapter demonstrates the most interesting results of such studies revealing high possibilities of selenium biofortification, increase in soil selenium bioavailability via arbuscular mycorrhizal fungi (AMF) and Se-dependent bacteria application, and discovery of new medicinal plants – Se accumulators with high antioxidant activity. Moreover, special attention has been paid to the production of functional food with artificially high selenium and antioxidant content: sprouts and microgreens fortified with selenium, medicinal mushrooms. N. Golubkina (*) Laboratory Analytical Department, Federal Scientific Center of Vegetable Production, Moscow, Russia V. Kharchenko Laboratory of Selection and Seed Production of Green, Spice and Flower Crops, Federal Scientific Center of Vegetable Production, Moscow, Russia G. Caruso Department of Agricultural Sciences, University of Naples Federico II, Naples, Italy © Springer Nature Switzerland AG 2022 H. M. Ekiert et al. (eds.), Plant Antioxidants and Health, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-78160-6_3

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Keywords

Selenium · Biofortification · Antioxidants · Medicinal plants · Functional food Abbreviations

AMF AOA DW GAE Se

1

Arbuscular mycorrhizal fungi Total antioxidant activity Dry weight Gallic acid equivalent Selenium

Introduction

Since the discovery of Se essentiality for humans (1974) the interest to this trace element has been increasing constantly. The main features of the modern Se studies are investigations of Se in nutritional food chain (soil, plants, insects, animals, human beings) [1–3], biogeochemical cycling [4, 5], Se toxicity and deficiency [6, 7], Se status mapping of the world territory [8], biofortification of agricultural crops [9], protection against heavy metals and other abiotic stresses [10, 11], and production of functional food products and supplements rich with selenium [12]. Indeed, during 2020 at least seven Se reviews were published [13–19]. In 2019 the international journal Plants organized a special issue devoted to “Se metabolism and accumulation in plants,” where three Se reviews were published [20–22]. That indicates that up to now not all nutritional and medicinal potential of Se has been fully explored. Furthermore, the phenomenon of Se protection against viral diseases [23–25] is being widely discussed in the frame of coronavirus pandemic [13, 26], suggesting that selenium supplementation may open new prospects in COVID treatment, considering that the epidemiological data in China revealed significantly lower COVID morbidity and mortality in provinces with high selenium status [27]. Taking into account the low Se status in many countries worldwide and the possibility of future Se deficiency increase [7], selenium-enriched products may gain special importance. Moreover, wide discussions are being achieved on the possibility of cardiovascular, cancer risk decrease, improvement of human fertility and mental activity due to selenium utilization [2, 28]. Nevertheless, it should be noted that with regard to Se, little attention is being paid to the significance of the complex Se/natural antioxidants effects on human organisms. Being a natural antioxidant, selenium actively participates in antioxidant defense both in humans and in all other living beings including plants [20]. From a practical point of view, that means that products with high content of Se and other natural antioxidants may benefit the human health more greatly than the sole high levels of this microelement in food. That may also be important in case of human protection against viral diseases, as the latest investigations indicate high prospects of COVID protection under utilization of medicinal plants polyphenols [29, 30].

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Furthermore, compared to food additives plants rich in selenium and other antioxidants may provide additional benefits via synergism of natural antioxidants effect, multiplicity of biologically active compounds, and lack of side effects often connected to food supplements [31]. In this context, Se biofortification programs attain incremental importance, as Se-enriched food crops give a higher contribution in nutritional components including antioxidants, compared to Se supplements, thus providing more benefits to consumers. There are several aspects relevant to plant selenium utilization. Firstly, the global increase of selenium levels in all agricultural crops successfully achieved in Finland [9] led to human Se status optimization. Despite the intensive regular monitoring of Se plants-human transfer during this program implementation, no information is still available regarding the changes in other antioxidant levels in plants and their possible role in the improvement of human health. The latter topic sounds particularly interesting, as Se biofortification is known to improve phenolics and other plant antioxidants accumulation [19, 32]. Since the beginning of Se containing fertilizers utilization in 1980, the mortality from cardiovascular diseases and cancer dramatically decreased in Finland. In the latter respect, the scientific community suggested other possible unknown factors showing a beneficial effect on human health in addition to Se in that country. The improvement of plant antioxidant levels might explain this phenomenon. A second aspect connected to plant Se use is the development and implementation of technologies directed to production of functional food with high selenium/ antioxidants levels, which is still in progress. Thirdly, little attention has been paid to the natural plant sources of selenium and phenolics (antioxidants) useful for human organism protection. In particular, medicinal plants potential as an important source of both ordinary antioxidants (polyphenols, glucosinolates, flavonoids, carotenoids, etc.) and selenium has not been fully exploited so far. The present chapter aims to indicate the most interesting aspects of functional food production based on plants selenium biofortification and discoveries of appropriate natural reserves.

2

Plants Biofortification with Selenium

The opportunities of exploiting the utilization potential of plants as valuable sources of selenium and antioxidants are presented in Scheme 1. The data reveal several important stages regarding human knowledge development. Large-scale biofortification of plants via selenium-fertilizers utilization aimed exclusively to the human selenium status optimization, included selenium enrichment of forage grasses, cereals, and vegetables. This approach was first used nationwide in Finland [9], and later it was introduced in several other countries, such as Great Britain, New Zealand, Australia, and Malawi [33]. During this period little attention was paid to the relationship between selenium and other antioxidants. On the other hand, seeds of wheat, rice, and legumes, determining the human selenium status in most world countries, are characterized by low antioxidant

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Se enriched vegetables

Global Se biofortification of plants

Se enriched sprouts Super functional food

Se enriched microgreens Se-enriched staple crops (cereals, legumes)

Se-enriched mushrooms Medicinal plants Se-accumulators

Scheme 1 Potential opportunities of functional food production with high levels of selenium and antioxidants

Fig. 1 Shelford’s law of tolerance [34]

content, while vegetable crops as significant sources of antioxidants in wide-scale utilization of selenium-containing fertilizers are not fully exploited because of significant variations in plant tolerance to selenium and of frequent sub-optimal conditions for achieving the highest selenium and other antioxidant concentrations. Indeed, each plant species and even variety demonstrate individual tolerance level to selenium supply, which is in accordance with the well-known Shelford ecological law (Fig. 1). In the latter respect, the optimization of selenium biofortification conditions for agricultural crops entails the directed production of selenium-enriched functional food with high antioxidant activity. At the same time, the antioxidant and selenium status of mature plants, grown in the field conditions, is affected by several factors,

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such as genetic peculiarities, meteorological conditions, soil characteristics, presence of arbuscular mycorrhizal fungi, plant hormonal status and growth stimulators, antioxidant stress intensity, dose, method of supply, and chemical form of selenium formulate. In this regard, special efforts are necessary to standardize the quality of the product obtained. The effect of biogeochemical peculiarities on plant growth and development may be manifested at the mountainous areas due to soil geological variability. In fact, significant differences in selenium and antioxidants accumulation were recorded in wild garlic sprouts (Allium ursinum L.) gathered in forests of 10 regions in the Chechen Republic (Russia), the values varying from 40 to 1775 μg Se·kg
1 DW and from 39.6 to 67.1 mg GAE·g
1 DW respectively [35]. The morphological peculiarities of plants may also affect the aforementioned parameters, especially selenium accumulation level. Indeed, the foliar sodium selenate application to parsley varieties grown in field conditions (25 mg·L
1) resulted in the highest biofortification level in curly parsley, cultivar Krasotka, which showed the largest leaf area and the highest level of total antioxidant activity (AOA) (Fig. 2). The lowest values were recorded for Mitsuba parsley with the lowest plant foliage. In these conditions, the biofortification significantly increased the AOA only in leaves of root parsley (cultivar Zolushka) and Japanese parsley Mitsuba (Fig. 3). Both in mammals and in plants, the efficiency of Se accumulation depends greatly on the hormonal status of an organism [36, 37]. In the latter respect, the most significant examples of hormonal interaction with Se in plants include Se participation in downregulating auxin and ethylene biosynthesis [38], predominant accumulation of Se in female spinach forms compared to male representative [37], and selenium increase in female cannabis forms as a result of sodium selenite treatment of plants [39]. Effect of sodium selenate application on spinach was also manifested in predominant accumulation of iodine and ascorbic acid in female forms and polyphenols in the male ones [37]. 60000 Leaves area, mm2

50000

y = - 58015+994.56x R² = 0.86

Krasotka

40000 Moskvichka

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70 AOA, mg GAE g-1 DW

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Fig. 3 Total antioxidant activity of control and Se-fortified parsley

The effect of arbuscular mycorrhizal fungi on selenium and antioxidants accumulation is of special interest [40, 41]. Selenium accumulation in plants is known to be governed by plant genetic tolerance to high concentrations of this toxic microelement, climate, biogeochemical characteristics of the growing area and in particular by the amount of bioavailable selenium in soil [42]. In most cases, selenium plant/ soil Se transfer factor (TF) for plant secondary Se accumulators and non-accumulators is very low, which entails the need of enhancing TF. Apart from hormonal regulation [37] and transgenic modifications [42], the soil inoculation with arbuscular mycorrhizal fungi (AMF) may be the most efficient approach to the problem solution. Indeed, the widespread symbiosis of AMF with most of terrestrial plants provides enormous enhancements of root surface due to fungi hyphae, thus improving mineral nutrition (predominantly N, P, and K), root accessibility to water, and stress resistance. Research in this field revealed that AMF is also beneficial in microelements accumulation and enhancement of plants antioxidant status [43]. As far as selenium is concerned, the latest results demonstrated that AMF is also beneficial in improving selenium accumulation. The latter may be due to the phenomenon of sulfate and phosphate transporters decoding by AMF genome [44–46], thus improving the accumulation of sulfur, phosphorous, and also selenium (as selenates are accumulated via sulfate transporters, while selenites via phosphate transporters). According to Ye et al. [17], the following mycorrhizal fungi improve selenium accumulation in host-plants: Glomus claroideum, G. fasciculatum, G. intraradices, G. mosseae, G. versiform, Rhizophagus intraradices, Funneliformis mosseae, Alternaria seleniiphila, Alternaria astragali, Aspergillus leporis, Fusarium acuminatum, and Trichoderma harzianum. AMF is able to increase selenium accumulation in plants either in ordinary conditions of low environmental selenium (onion, garlic) or under selenium supply [47]. In the latter respect, Se biofortification of asparagus with sodium selenite under AMF utilization increased Se concentration and antioxidant activity of plants by

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1.3 times [48]. Biofortification of A. cepa with selenium under AMD supply enhanced total antioxidant activity and flavonoid content by 1.37 and 1.69 times respectively [47]. The enhancement of Se and antioxidants content under AMF supply was recorded also in shallot plants [49]. The production of functional food enriched with selenium and iodine was also demonstrated in the case of I/Se biofortification of chickpea [50], where a significant increase of both phenolics content and total antioxidant activity was also recorded; interestingly, the improvement of plant antioxidant status took place both without and under I and/or Se supply. The antioxidant properties of iodine, its close relationship with selenium metabolism, and the difficulties of plant joint biofortification with iodine and selenium reveal the significance of these results as a new technology tool in production of functional food with high antioxidants, selenium and iodine status [50]. Utilization of plant growth-promoting rhizobacteria for plant biofortification with microelements is another method for improving plant selenium status. Successful investigations in this field were carried out on wheat [51, 52], lettuce [53], and Indian mustard [54, 55]. The utilization of plant growth-promoting bacteria may be beneficial not only for improving the selenium status, but also for enhancing protection against environmental stress factors. Special focus should be given to the highest beneficial effect of AMF and Se application recorded in stress conditions. In this respect, one of the paradoxical examples may be short-term exposure to stressful conditions (high temperature and humidity, as a result of sample transport in hermetically closed polyethylene bags during 24 h) of the aromatic plants lavender, hyssop, and tarragon (A. dracunculus), grown without and with AMF utilization [56]. In normal conditions, control plants and those inoculated with AMF did not differ in AOA and phenolics content, whereas the stress application resulted in significant changes not only of biochemical parameters, that is antioxidant defense, but also in terms of plant appearance (Fig. 4). The improvement of plant antioxidant status under environmental stress may become useful for producing functional food not only in the case of AMF application by also in ordinary vegetation conditions: for instance, water stress increased phenolics content in basil [57]. The intensive protective effect of selenium against reactive oxygen species was also recorded in rape seedlings and marine algae under significant oxidant stress, contrary to the low efficiency of Se antioxidant defense in non-stressed conditions [58, 59].

3

Microgreens and Sprouts

Early stages of plant development give powerful opportunities to produce functional food with anomalously high antioxidant activity and bioavailable selenium compounds, as well as the following biochemical processes: activation of hydrolytic enzymes, intensive biosynthesis of biologically active compounds, including vitamins and polyphenols [60, 61], glucosinolates, hydrolysis of proteins with formation of bioavailable amino acids, accumulation of essential linoleic acid and microelements, high levels of enzymes [62], and production of water-soluble selenium

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Fig. 4 Effect of AMF application on aromatic plant tolerance to abiotic stress [56]

derivatives [28]. Moreover, the nutritional value of the product is reportedly effective in cancer prevention and immunity optimization [62]. The determination of selenium biofortification efficiency of seed sprouts of 28 plant species belonging to 10 families revealed that the predominant chemical forms of selenium in sprouts are methylated forms of selenium-containing amino acids [63] known to be powerful anti-carcinogens. The level of these compounds in Allium sprouts reaches more than 96% of the total amount of absorbed selenium [64]. The investigation of Kurian and Megha [65] demonstrated that total antioxidant activity and phenolic content in Vigna radiata and Cicer arietinum decrease according to the following sequence: microgreens>sprouts>seeds. In general, biofortification of microgreens and sprouts with selenium results in production of functional food with high biological activity [66–68]. The high prospect of such an approach is also connected with the extremely short vegetation period and the possibility to standardize both cultivation conditions and the products quality, which is difficult to achieve with mature plants [69]. Sprouts have been investigated more intensively than microgreens and, currently, the most popular plant sprouts belong to wheat [70], rice [60], and other cereals [71], soybean [72], broccoli [73], radish, alfalfa, and white mustard [74], Brassicaceae sprouts [75], A. cepa and mung beans [76], amaranthus [77], and wild garlic [35]. Studies on the production of selenium-biofortified broccoli sprouts demonstrated that the content of carotenoids, soluble sugars, soluble proteins, vitamin C, total antioxidant activity, total phenolics, total flavonoids, glucosinolates, and organic selenium were significantly improved through Se supply and a combination of red,

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blue, and green light using light-emitting diodes (LED), without negatively affecting the sprout fresh weight [78]. Furthermore, environmental shocks were proved to be highly efficient in improving antioxidant status not only of mature plants but especially of sprouts [79]. Experiments on alfa-alfa, broccoli, and radish sprouts revealed that high light and chilling may increase phenolic content by 1.5–2 times. Despite the high antioxidant activity in such sprouts, the selenium content in most cases is rather low without artificial Se supplementation and is priority determined by the chemical composition of nutrition solution. In fact, stable results are more available in the case of artificial selenium biofortification of sprouts grown in hydroponics. A positive effect of selenium biofortification was recorded (broccoli, cauliflower, green cabbage, Chinese cabbage, kale, and Brussels sprouts) on the content of glucosinolates in Brassicaceae plant sprouts [80, 81]. These antioxidants show anti-cancer activity, as also done by the methylated forms of selenium-containing amino acids, that is the main chemical forms of selenium in Brassicaceae sprouts. Investigation of Allium sprouts biofortification with selenium [82] led to some peculiar results. Indeed, the sprout biofortification with selenium had little or no effect on antioxidant activity and phenolic content in unfertilized seeds showing relatively low values of the mentioned parameters; differently, when the control sprouts had high antioxidants content, the total antioxidant activity and phenolics significantly increased by 26–27% and 32–35% respectively (Fig. 5). Furthermore, the study revealed that phenolics content in selenium-fortified sprouts was positively correlated with the level of selenium biofortification (r ¼ 0.95 at P < 0.001). For perennial and Allium cepa sprouts a positive correlation between selenium content and total antioxidant activity (r ¼ 0.90 at p < 0.001) was recorded, which gives an opportunity to indicate the best promising varieties with the highest

АОА, mg GAE g –1 DW

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y = 1.6849 + 1.3849x

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R² = 0.93

y = 3.6862 + 0.9148x

9 R² = 0.72

7 4

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6 7 8 9 10 –1 Polyphenol content, mg GAE g DW

11

Fig. 5 Relationship between AOA and phenolics content in Allium sprouts, fortified (r ¼ 0.97 at P < 0.001) and not fortified with selenium (r ¼ 0.85 at P < 0.004) [82]

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selenium and antioxidants content. It is significant that the sprouts of all Allium species investigated were characterized by similar high level of water-soluble Se derivatives (about 65.5%), indicating the high bioavailability of selenium in sprouts. Not so many data are available regarding the effect of selenium biofortification of microgreens. The popularity of these functional food products has increased dramatically during the last years [83, 84]. Depending on the plant species, the microgreens production period does not exceed 7–21 days since the moment of sowing. Much higher levels of biologically active compounds including antioxidants and microelements, compared to mature plants, suggest the important nutritional significance and beneficial effect of these products on human health [84]. The microgreens biofortification with selenium provides not only new products with high level of this essential microelement, but also enhances the content of antioxidant and other biologically active compounds such as proteins and carbohydrates [85]. In this respect, hydroponics appears to be the most suitable technological approach providing functional product standardization, guaranteeing safety and quality [86, 87]. On the other hand, it should be highlighted that the selenium biofortification of microgreens has been studied rather fragmentarily [83], with the main targeted species being buckwheat [88], wheat [85], and basil [87]. The only exception is the work of Kyriacou et al. [84] who were able to determine phenolics in plant microgreens belonging to 13 genotypes and 5 families. The authors recorded the highest polyphenol levels in coriander, basil, and tatsoi. The highest selenium biofortification of tatsoi and coriander resulted in 95% and 21% increase of polyphenols levels in the corresponding microgreens respectively. In particular, rutin level in coriander increased by 33%, and kaempferol glycoside concentration increased by 157% in tatsoi, whereas the total amount of phenolics in green basil augmented by 32%. Notably, phenolic profile in these conditions may vary depending on species, variety, and developmental stage. Among other factors affecting phenolic content in microgreens, UV and blue light led to significant increase of these compounds content in soybean microgreens [89], whereas enhancing total light intensity encouraged polyphenol synthesis in chia microgreens [90].

4

Edible Mushrooms, New Functional Food Products

The tolerance of mushrooms to high concentrations of selenium and the wide spectrum of their biological activity, including anti-cancer, antioxidant, anti-bacterial, cardioprotective, hypoglycemic, constantly attract the researchers attention [91– 93]. Mushrooms are a good source of proteins, vitamins (С, D, Е), polyphenols, polysaccharides of powerful anti-cancer effect, food fiber and minerals, mainly potassium [94]. The evaluation of the most common chemical forms of selenium in mushrooms revealed selenomethionine both as a free compound and inside proteins, methylated forms of Se-containing amino acids and selenium-containing polysaccharides [93] (Scheme 2).

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The main chemical forms of Se in Se-enriched mushrooms

Selenomethionine Selenocystine

Seleno-polysaccharides Selenomethyl selenocysteine

Scheme 2 The main chemical forms of selenium in mushrooms

All these compounds are easily absorbed by human organism and are significantly less toxic compared to inorganic derivatives [95]. Besides, all these forms demonstrate high antioxidant activity and are powerful anti-carcinogens [93]. Investigations of selenium accumulating ability of mushrooms [96, 97] showed several species of selenium hyperaccumulators: representatives of Boletus and Agaricus family [96], Lycoperdon, Clitocybe nuda, and Rozites caperata [28]. The above-mentioned species are ordinarily able to accumulate from 1 to 30 mg Se kg
1 DW without Se supply, differently from most edible mushrooms, including the artificially grown ones, which in similar environmental conditions contain about 50– 150 μg Se kg
1 DW. On the other hand, Se accumulation level in edible mushrooms is greatly influenced by bioavailable soil Se. For instance, Se level in Russula species in conditions of contrasting anthropogenic supply is characterized by a wide concentrations range, from 0.16 to 5.51 mg kg
1 DW, in the region of mineral fertilizers production in Voskresensk and phosphogypsum storage site in Moscow region. Similar results were recorded for P. involutus with the typical concentration range of 0.46–2.04 mg/kg DW [98]. Notably, both genetic factors and biogeochemical characteristics of sampling place affect greatly the Se accumulation extent in mushrooms. The total antioxidant activity and phenolic content in mushrooms have not been studied to a high extent and predominantly in conditions of cultivated mushrooms species biofortified with Se [93]. One of the works carried out was devoted to antioxidant activity of wild mushrooms in India [94], but no data on the Se accumulation were reported. The latter authors found significant differences in the total antioxidant activity of 23 wild mushrooms species, indicating Termitomyces heimii and Helvella crispa as the richest with polyphenols and other antioxidants. The evaluation of Se accumulation in fruiting body of Helvellа crispa grown in Moscow region, revealed a low Se accumulation ability of this species (about 100–150 μg kg
1 DW). According to Puttaraju et al. [94], white mushroom (Boletus) is also rich with antioxidants, which is in agreement with our personal data relevant to Butyriboletus appendiulatus and Boletus queletil Schulzer, sampled in the mountainous Crimea (Table 1). At present, the species belonging to Boletus genera have proved to be the richest sources of selenium and polyphenols, though the different methods used for extraction in the examined investigations make it difficult to perform appropriate comparisons. In our studies, the utilization of 70% ethanol resulted in higher levels of antioxidant activity than in the case of water extraction [98]. Figure 6 shows the comparisons between polyphenol contents of several mushrooms Se accumulators (Boletus) and non-accumulators (Russula) gathered in similar ecological conditions near the Black sea coast.

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Table 1 Se accumulation levels, total antioxidant activity, and phenolics content in edible mushrooms of the mountainous Crimea Sampling place Inner Crimean mountains

Karadag Nature reserve

a

Species Butyriboletus appendiulatus Boletus queletil Schulzer Russula foetens Pers. Lactarius insulsus (Fr.) Fr. Xerocomus subtomentosus Russula decolorans Russula amoenolens Romagn Russula aeruginea Lindlad ex Fr Russula medullata Romagn Russula delica Fr Agaricus bisporus Calocybe gambosa Clitocybe nuda Lepista nuda

Аntioxidant activitya (mg GAE·g
1 DW) 43.3  1.2a

Phenolics (mg GAE·g
1 DW) 17.6  0.5b

Se (μg·kg
1 DW) 584  4

37.7  1.1b

19.0  0.6a

423  28

33.2  1,1c

12.0  0.2c

236  12

25.0  0,8d

12.5  0.3c

1200 6 123

23.8  0.8d

11.3  0.2d

319 6 14

24.5  0.8d

9.5  0.1e

431  12

23.9  0.8d

12.0  0.2c

338  46

19.9  0.7e

7.2  0.1f

540  44

16.6  0.6f

8.4  0.1g

326  53

13.0  0.5h 23.5  0.8d

5.7  0.1 12.2  0.2c

316  13 2394  242

20.9  0.7e

7.9  0.1

664  25

20.6  0.7e 13.5  0.5h

13.1  0.2 7.4  0.1f

716  53 979  64

The antioxidant activity was detected using the reaction with K2MnO4 (Golubkina et al. 2020h)

Notably, the analysis of the literature reports on Se and polyphenols accumulation as well as total antioxidant activity in edible mushrooms indicates no relationships between Se and antioxidants in natural conditions, which significantly obstructs the identification of the best promising species capable to accumulate high concentrations of both Se and polyphenols. On the other hand, different mushrooms species grown in similar ecological conditions demonstrated a direct correlation between total antioxidant activity and phenolics content (Fig. 7). Furthermore, a positive correlation between Se dose applied and antioxidants has been recorded in the conditions of Se biofortification. The variability of antioxidant status parameters in mushrooms may reflect the sampling place, growth phase (mycelium, young or old mushrooms), and extraction method [100]. Interestingly, among different mushrooms species Paxillus involutus is known to accumulate the highest levels of heavy metals and the lowest of selenium, contrary to other species

Phenolics, mg GAE g DW

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Selenium: Prospects of Functional Food Production with High Antioxidant Activity

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25 20 15

** *

*

10

** **

*

** ** **

*

5

*

*

**

*

0

Phenolics, mg GAE g –1 DW

Fig. 6 Phenolics content in fruiting body of mushrooms: Se accumulators (Boletus) and nonaccumulators (Russula) gathered at the Turkish shore of the Black Sea (* [99]) or in Crimean mountains (**; own data, 2020)

20 y = 1.6487 + 0.391x

18 16

R² = 0.770

14 12 10 8 6 4 10

15

20

25 30 35 АОА, mg GAE g –1 DW

40

45

Fig. 7 Relationship between AOA and phenolics content in mushrooms of Crimean mountains (r ¼ +0.880; р < 0.001)

with high ability to concentrate both heavy metals and selenium [98]. Analysis of the total antioxidant activity of Paxillus involutus showed unexpectedly high values of AOA reaching 35 mg GAE·g
1 DW, which may be connected with the antioxidant’s participation in defense against heavy metals uptake. The biofortification of mushrooms with selenium is of special significance in production of functional food and biologically active food additives, rich with both selenium and natural antioxidants. The prospects of such investigations are connected with the positive correlation between polyphenol level in mushrooms and selenium dose

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Mushroom biofortification with selenium

A.bisporus

Pleurotus (n=9)

Lentula edodes

Ganoderma lucidum

Cordyceps militaris

Volvariella

Calocybe

volvacea

indica

Coriolus versicolor (mycelia) Hericium erinaceum

Scheme 3 Main mushrooms species successfully fortified with selenium

applied [101], and with the possibility of mushroom biosynthesis of active organic selenium derivatives. In the latter respect, a two-fold increase in the total antioxidant activity of Lentinus edodes mycelium, and a 29% and 40% increase in phenolics and protein content, respectively, were recorded under exogenic selenium supply [101]. A similar phenomenon was demonstrated in selenium biofortification of Ganoderma lucidum [102, 103], Calocybe indica [104], Lentinula edodes [101], Pleurotia [105– 107], Volvariella [105], Cordyceps militaris [108], and Hericium erinaceum [109]. The selenium biofortification was also achieved in species widely used in artificial cultivations: Pleurotus spp., Agaricus bisporus, Calocybe indica, Volvariella volvacea [105, 106]. Moreover, special investigations have been aimed at fortifying mushrooms which are highly valuable particularly in medicine, such as Lentula edodesa, Ganoderma lucidum, Coriolus versicolor [110]. The main mushroom species used in selenium biofortification are presented below (Scheme 3). Some examples of medicinal mushrooms utilization are: Coriolus versicolor [110] is widely used in traditional Chinese medicine to strengthen the liver and spleen, remove toxins, as a cardio-stimulator, valuable in the treatment of hepatitis, upper respiratory tract infections, prostate cancer, ovarian cancer, bladder, esophagus, lung cancer, leukemia, brain cancer, metastases; Hericium erinaceum is used for treatment of chronic hepatitis, esophageal and stomach cancer and leukemia [78]; reisha Ganoderma lucidus [102, 103] is effective in risk decrease of cardiovascular diseases and shows neuroprotective effect [93, 111]; shiitake Lentinula edodes is known for its anti-carcinogenic properties [101, 112]. The biological activity of medicinal mushrooms is strongly connected with their antioxidant properties both in ordinary production conditions and under selenium supply. The latest research indicates that mushrooms may provide strong positive effects on human health. Selenium biofortification [105] and dietary supplementation of selenized mushrooms are efficient tools to retard chemically induced tumors [113]. In another cytotoxicity study against lung cancer cell line A549, the application of hexane fractions of Se-fortified button, oyster, and paddy straw mushroom species highly inhibited the ill cell proliferation in comparison with unfortified control mushrooms [105].

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The dietary intake of Se-fortified mushrooms as a functional food aids in the treatment and prevention of various health-affecting conditions such as HIV infection, cancer, aging, cardiovascular, neurodegenerative, and immunological diseases [114].

5

Natural Selenium Accumulators with High Antioxidant Activity

Summarizing literature data, it can be inferred that the natural potential of new selenium accumulators with high antioxidant status has not been studied extensively, while monitoring herbs with regard to Se accumulation and AOA levels and phenolics content may provide unique possibilities for human health improvement. Up to date, the aforementioned parameters have not been discussed simultaneously, but leaving the leading place to the total antioxidant activity (AOA) and polyphenols content in medicinal herbs [115–120]. An exception is represented by the work of Sotek et al. [121] who investigated the selenium accumulation and AOA of seven herb species, harvested in territories of Lithuania, Poland, and Ukraine. Unfortunately, all the three latter regions are selenium deficient, while none of the species studied belongs to either Se hyperaccumulators or secondary Se accumulators (indicators). In this respect, a significantly higher interest is directed to natural Se hyperaccumulators capable to accumulate more than 1 g Se·kg
1 DW [21], and secondary Se accumulators or Se indicators, accumulating up to 0.1–1 g Se·kg
1 DW [42, 122]. Nevertheless, it is necessary to mention that in ordinary vegetation conditions, that is in selenium-deficient soils, a significant Se accumulation without exogenous Se supplementation occurs only for Se hyperaccumulators. The production of functional food with high Se and antioxidant status is more efficient using wild species of medicinal plants, as wild relatives of agricultural crops often contain higher levels of antioxidants [123]. In the latter respect, wild chervil (A. silvestris) showed 1.5–2 times higher AOA compared to garden chervil (A. cerefolium) in the conditions of Moscow region [124] (Fig. 8). Notably, the capacity of wild medicinal plants to accumulate selenium has not been studied intensively. There are several families among angiosperms, such as Asteraceae, Brassicaceae, Chenopodiaceae, Fabaceae, Rubiaceae, Orobanchaceae, often containing Se hyperaccumulators species [42, 122] which highly deserve to be scanned for searching the possible association with a high antioxidant activity. However, it is expected that identifying new Se hyper- and secondary accumulators showing high concentrations of phenolics may be achieved most successfully under Se supply. In natural habitats, there are coastal areas characterized by intensive selenium transfer with aerosols from the sea surface. In fact, monitoring Se content and total antioxidant activity of 91 medicinal plant species collected in Karadag Nature Reserve (Crimea), allowed to identify about 10% of Se hyperaccumulators among herbs and 7.7% among deciduous trees and bushes, showing a total AOA from 21 to 256 mg GAE·g
1 DW [125] (Fig. 9).

164

b 20

60 50

Flavonoids, mg-eq quercetin g-1 DW

Phenolics, AOA, mg GAE g-1 DW

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N. Golubkina et al.

AOA Phenolics

40 30 20 10 0 A.cerefolium

A.silvestris

18 16 14 12 10 8 6 4

2 0

A.cerefolium A.silvestris

Fig. 8 Differences in AOA, phenolics (a) and flavonoids (b) content in A. cerefolium and A. silvestris [124]

The data shown in Fig. 10 indicate complex relationships between Se accumulation levels and total antioxidant activity of herbs and deciduous plants, with several peculiarities. The comparison between AOA and Se medians for the investigated species revealed higher values for deciduous plants (Fig. 10a). Conversely, the frequency of concurrent high levels of Se and antioxidants was recorded more often in herbs than in deciduous plants (Fig. 10b). On the other hand, Se hyperaccumulator herb plants (Lg [Se] >3) showed relatively moderate AOA, with the lg [AOA] concentration ranging between 1.60 and 1.75 (Fig. 10a). They are Anthemis transcheliana, Tragopogon dubius, Cota tinctoria belonging to the family Asteraceae; Astragalus amacantha to Fabaceae; Limonium gerberi to Plumbaginaceae. Unusually high AOA levels in herbs are typical of non-Se-accumulator plants with Lg [Se] of 1.36–2.12, such as: Agrimonia eupatoria in Rosaceae family; Rumex confertus in Polygonaceae; Melissa officinalis and Salvia nemorosa in Lamiaceae; Hypericum perforatum in Hypericaceae; Artemisia taurica, A. santonica, A. dracunculus, and A. scoparia belonging to Asteraceae; Ruscus hypoglossum and R. aculeatus to Asparagaceae. Artemisia species, belonging to Asteraceae family, draw special attention. These plants demonstrate an extremely high adaptability, thus residing in most world areas [126]. They are rather tolerant to high concentrations of Se, being able to accumulate up to 60 mg Se·kg
1 DW at the territory affected by Volcano eruption, such as Redoubt Volcano eruption in Alaska [127]. In Wyoming, Artemisia tridentata accumulated from 100 to 700 μg Se kg
1 DW [128]. Se excretion by roots of Se hyperaccumulators (Astragalus bisulcatus and Stanleya pinnata) stimulated the growth and development of A. ludoviciana, thus increasing Se accumulation levels

a 90

b Mean AOA, mg GAE g-1 DW

Selenium: Prospects of Functional Food Production with High Antioxidant Activity

Mean Se levels, μkg-1 DW

7

80

70

60

50

165

80

70

60

50

40 Herbs

Deciduous

Herbs

Deciduous

% of hyperaccumulators

c 12 11 10 9 8 7 6 5 4 3

Se

Herbs

AOA

Deciduous

Fig. 9 Median of Se (a), AOA (b) levels, and % of Se and antioxidants hyperaccumulators (c), among herbs and deciduous plants collected at the southern coast of Crimea [125]

up to 1–2 mg·kg
1 DW [129]. Se biofortification of A. dracunculus resulted in the selenium concentration of 16.5 mg Se·kg
1 DW in this herb [130] and this accumulation level is much higher than that recorded in Lipidium sativum, Allium porrum L., Ocimum basilicum L., Mentha arvensis L., Allium cepa L., and Raphanus sativus L. Wang et al. [131] reported that Se-fortified A. sphaerocephala provided selenium incorporation into polysaccharides, increasing the anti-tumor activity of herb. High AOA as well as Se tolerance of many Artemisia species suggests great prospects in the production of the related herbs fortified with selenium and enriched with antioxidants. Besides, Se is known to stimulate not only phenolics but also essential oil production in aromatic plants, thus establishing a powerful antioxidant defense [132]. It should also be highlighted that Artemisia species belong to Asteraceae family, containing a significant number of selenium hyperaccumulators. As for deciduous trees and bushes, they demonstrate lower ability to hyperaccumulate antioxidants and selenium (Figs. 10a and 10b), but the concurrent high

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Lg {AOA]

a 2.5

2

1.5

Herbs 1 1

1.5

2

2.5

3

3.5

4

3.5

4

Lg[Se}

Lg [AOA]

b 2.5

2

1.5

Deciduous 1 1

1.5

2

2.5

3

Lg [Se] Fig. 10 Relationships between total antioxidant activity and selenium content in herbs (a) and deciduous plants (b) [125]

values of AOA and Se are much more frequent than in herbs, which allows to identify plants with Lg AOA exceeding 2 and Lg Se being in the range of 2.1–2.27, such as Pistacia atlantica and Cotinus coggygria in Anacardiaceae family and Cornus mas in Cornaceae family (Fig. 2b). Furthermore, among deciduous plants, Tamarix species show unusually high levels of both Se and AOA (Lg values ranging between 3.79 and 2.33 respectively). Another Se hyperaccumulator, Paliurus spinachristi Mill, demonstrated 3.8-time lower levels of AOA than Tamarix species. However, both species are highly valuable in traditional medicine as powerful sources of antioxidants with anti-bacterial, anti-inflammation, and cardioprotective activities [133–136] and their high Se accumulation abilities may become a valuable reference for their future utilization. The descriptions regarding selenium/antioxidants accumulator species, based on the related investigations carried out, provide an interesting source for further research and promising human health-beneficial applications.

7

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Conclusions

Despite the investigations carried out on the most important sources of selenium and antioxidants among fortified and non-fortified plants, the relationships between selenium and other antioxidants still remain very complex to be clearly explained. Selenium substitutes sulfur in different organic compounds, especially in plants known to be good sulfur-accumulators (Allium and Brassica species in particular), thus promoting the biosynthesis of more powerful anti-cancer agents than sulfur analogs (Se glucosinolates, methylated forms of selenium-containing amino acids). By affecting nitrogen metabolism, selenium indirectly stimulates the synthesis of polyphenols, the most powerful antioxidants in plants. The stimulation of carbohydrate biosynthesis by selenium fortification may lead to the production of selenium-derivative polysaccharides which increase plant anti-cancer activity. The selenium participation in photosynthesis encourages the formation of photosynthetic pigments including carotenoids, thus increasing the total antioxidant activity in leaves and fruits. The lack of significant correlation between Se levels and antioxidant activity in wild herbs and the controversial data relevant to Se compounds and AOA determination in Se-enriched black and green tea extracts by Sentkowska and Pyrzyńska [137] suggest the need of further studies in seleniumantioxidants interaction as well as the development of powerful technologies for producing food with high Se/antioxidants potential.

References 1. Lyons MP, Papazyan TT, Surai P (2007) Selenium in food chain and animal nutrition: lessons from nature – review. Asian Australasian J Anim Sci 20(7):1135–1155. https://doi.org/10. 5713/ajas.2007.1135 2. Rayman MP (2008) Food-chain selenium and human health: emphasis on intake. Br J Nutr 100(2):254–268. https://doi.org/10.1017/S0007114508939830 3. Golubkina N, Sheshnitsan S, Kapitalchuk M (2014) Ecological importance of insects in selenium biogenic cycling. Int J Ecol 2014(3):1–6. https://doi.org/10.1155/2014/835636 4. Natasha N, Shahid M, Niazi NK, Khalid S, Murtaza B, Bibi I, Rashid MI (2018) A critical review of selenium biogeochemical behavior in soil-plant system with an inference to human health. Environ Pollut 23:915–934. https://doi.org/10.1016/j.envpol.2017.12.019 5. Winkel LHE, Vriens B, Jones GD, Schneider LS, Pilon-Smits E, Bañuelos GS (2015) Selenium cycling across soil-plant-atmosphere interfaces: a critical review. Nutrients 7(6): 4199–4239. https://doi.org/10.3390/nu7064199 6. Dos Reis AR, El-Ramady H, Santos EF, Gratão PL, Schomburg L (2017) Overview of selenium deficiency and toxicity worldwide: affected areas, selenium-related health issues, and case studies. In: Pilon-Smits E, Winkel L, Lin ZQ (eds) Selenium in plants, Plant ecophysiology, vol 11. Springer, Cham. https://doi.org/10.1007/978-3-319-56249-0_13 7. Jones GD, Droz B, Greve P, Gottschalk P, Poet D, McGrath SP (2017) Selenium deficiency risk predicted to increase under future climate change. Proc Natl Acad Sci U S A 114:2848– 2853. https://doi.org/10.1073/pnas.1611576114 8. Oldfield JE (1999) Selenium Se world atlas. Selenium-Tellurium Development Association, UK 9. Alfthan G, Eurola M, Ekholm P, Venäläinen ER, Root T, Korkalainen K, Hartikainen H, Salminene P, Hietaniemi V, Aspila P, Aro A (2015) Effects of nationwide addition of selenium to fertilizers on foods, and animal and human health in Finland: from deficiency to optimal

168

N. Golubkina et al.

selenium status of the population. J Trace Elem Med Biol 31:142–147. https://doi.org/10. 1016/j.jtemb.2014.04.009 10. Feng R, Wei C, Tu S (2013) The roles of selenium in protecting plants against abiotic stresses. Environ Exp Bot 87:58–68. https://doi.org/10.1016/j.envexpbot.2012.09.002 11. Chauhan R, Awasthi S, Srivastava S, Dwivedi S, Pilon-Smits EAH, Dhankher OP (2019) Understanding Se metabolism in plants and its role as a beneficial element. Crit Rev Environ Sci Technol 49(21):1937–1958. https://doi.org/10.1080/10643389.2019.1598240 12. Kieliszek M (2019) Selenium–fascinating microelement, properties and sources in food molecules. 24(7):1298. https://doi.org/10.3390/molecules24071298 13. Kieliszek M, Lipinski B (2020) Selenium supplementation in the prevention of coronavirus infections (COVID-19). Med Hypotheses 143:109878. https://doi.org/10.1016/j.mehy.2020. 109878 14. Adebayo AH, Yakubu OF, Bakare-Akpata O (2020) Uptake, metabolism and toxicity in tropical plants. Intechopen, London, UK. https://doi.org/10.5772/intechopen.90295 15. Rizwan M, Ali S, Zia-ur-Rehman M, Ok YS (2020) Effects of selenium on the uptake of toxic trace elements by crop plants: a review. Crit Rev Environ Sci Technol. https://doi.org/10.1080/ 10643389.2020.17965 16. D’Amato R, Regni L, Falcinelli B, Mattioli S, Benincasa P, Dal Bosco A, Pacheco P, Proietti P, Troni E, Santi C, Businelli D (2020) Current knowledge on selenium biofortification to improve the nutraceutical profile of food: a comprehensive review. J Agric Food Chem 68 (14):4075–4097. https://doi.org/10.1021/acs.jafc.0c00172 17. Ye Y, Qu J, Pu Y, Rao S, Xu F, Wu C (2020) Selenium biofortification of crop food by beneficial microorganisms. Fungi 6:59. https://doi.org/10.3390/jof6020059 18. Hasanuzzaman M, Bhuyan MHMB, Raza A, Hawrylak-Nowak B, Matraszek-Gawron R, Al Mahmud J, Nahar K, Fujita M (2020) Se in plants: boom or bane? Environ Exp Bot 178: 104170. https://doi.org/10.1016/j.envexpbot.2020.104170 19. Schiavon M, Nardi S, dalla Vecchia F, Ertani A (2020) Selenium biofortification in the 21st century: status and challenges for healthy human nutrition. Plant Soil 453:245–270. https:// doi.org/10.1007/s11104-020-04635-9 20. Mechora Š (2019) Selenium as a protective agent against pests: a review. Plants 8(8):262. https://doi.org/10.3390/plants8080262 21. Pilon-Smits EAH (2019) On the ecology of selenium accumulation in plants. Plants 8(7):197. https://doi.org/10.3390/plants8070197 22. Ponton DE, Graves SD, Fortin C, Janz D, Amyot M, Schiavon M (2020) Selenium interactions with algae: chemical processes at biological uptake sites, bioaccumulation, and intracellular metabolism. Plants 9(4):528. https://doi.org/10.3390/plants9040528 23. Nelson HK, Shi Q, Van Dael P, Schiffrin EJ, Blum S, Barclay D, Levander OA, Beck MA (2001) Host nutritional selenium status as a driving force for influenza virus mutations. FASEB J 15(10):1846–1848. https://doi.org/10.1096/fj.01-0115fje 24. Steinbrenner H, Al-Quraishy S, Dkhil MA, Wunderlich F, Sies H (2015) Dietary selenium in adjuvant therapy of viral and bacterial infections. Adv Nutr 6(1):73–82. https://doi.org/10. 3945/an.114.007575 25. Harthill M (2011) Review: micronutrient selenium deficiency influences evolution of some viral infectious diseases. Biol Trace Elem Res 143(3):1325–1336. https://doi.org/10.1007/ s12011-011-8977-1 26. Zhang J, Taylor EW, Bennett K, Saad R, Rayman MP (2020) Association between regional selenium status and reported outcome of COVID-19 cases in China. Am J Clin Nutr 111(6): 1297–1299. https://doi.org/10.1093/ajcn/nqaa095 27. Zhang L, Liu Y (2020) Potential interventions for novel coronavirus in China: a systematic review. J Med Virol 92:479–490. https://doi.org/10.1002/jmv.2570 28. Golubkina NA, Papazyan TT (2006) Selenium in Nutrition. Plants, animals, human beings. Moscow- Pechatny Gorod (in Russ) 29. Haq FU, Roman M, Ahmad K, Rahman SU, Shah SMA, Suleman N, Ullah S, Ahmad I., Ullah W (2020) Artemisia annua: trials are needed for COVID-19. Phytother Res 1–2. https://doi. org/10.1002/ptr.6733

7

Selenium: Prospects of Functional Food Production with High Antioxidant Activity

169

30. Chojnacka K, Witek-Krowiak A, Skrzypczak D, Mikula K, Młynarz P (2020) Phytochemicals containing biologically active polyphenols as an effective agent against Covid-19-inducing coronavirus. J Funct Foods 73:104146. https://doi.org/10.1015/j.jff.2020.104146 31. Golubkina NA, Nadezhkin SM, Loseva TA, Sokolova AJ (2012) Global ecological crisis. Problems and decisions. Moscow Vniissok (in Russ.) 32. Malagoli M, Schiavon M, dall’Acqua S, Pilon-Smits EAH (2015) Effects of selenium biofortification on crop nutritional quality. Front Plant Sci 6:280. https://doi.org/10.3389/ fpls.2015.00280 33. Ebrahimi N, Stoddard FL, Hartikainen H, Seppänen MM (2019) Plant species and growing season weather influence the efficiency of selenium biofortification. Nutr Cycl Agroecosyst 114(2B):111–124. https://doi.org/10.1007/s10705-019-09994-z 34. Shelford VE (1931) Some concepts of bioecology. Ecology 12(3):455–467. https://doi.org/10. 2307/1928991 35. Amagova Z, Golubkina N, Matsadze V, Elmurzaeva F, Muligova R, Caruso G (2020) Biochemical characteristics of Allium ursinum L. sprouts from mountain forests of Caucasus as affected by growing location in Chechen republic. Italus Hortus 27:66–81. https://doi.org/ 10.26353/j.itahort/2020.2.6681 36. Golubkina NA (2012) Selenium biorhythms and hormonal regulation. In: Aomori C, Hokkaido M (eds) Selenium sources, functions and health effects. Nova Science Publishers, Inc., New York 37. Golubkina N, Kosheleva O, Krivenkov LV, Dobrutskaya H, Nadezhkin S, Caruso G (2017) Intersexual differences in plant growth, yield, mineral composition and antioxidants of spinach (Spinacia oleracea L.) as affected by selenium form. Sci Hortic 225:350–358. https://doi.org/ 10.1016/j.scienta.2017.07.001 38. Malheiros RSP, Costa LC, Ávila RT, Pimenta TM, Teixeira LS, Brito FAL, Zsögön A, Araújo WL, Ribeiro DM (2019) Selenium downregulates auxin and ethylene biosynthesis in rice seedlings to modify primary metabolism and root architecture. Planta 250(1):333–345. https:// doi.org/10.1007/s00425-019-03175-6 39. Soldatov SA, Khryanin BN (2006) Effect of sodium selenite on phytohormonal status and sexual appearance of cannabis dioecious plants. Doklady RAS 2:13–17. (in Russ.) 40. Chen M, Arato M, Borghi L, Nouri E, Reinhardt D (2018) Beneficial services of arbuscular mycorrhizal fungi – from ecology to application. Front Plant Sci 9:1270. https://doi.org/10. 3389/fpls.2018.01270 41. Golubkina N, Krivenkov L, Sekara A, Vasileva V, Tallarita A, Caruso G (2020) Prospects of arbuscular mycorrhizal fungi utilization in production of Allium plants. Plants 9:279. https:// doi.org/10.3390/plants9020279 42. White FJ (2016) Selenium accumulation by plants. Ann Bot 117(2):217–235. https://doi.org/ 10.1093/aob/mcv180 43. Kapoor R, Singh N (2017) Arbuscular mycorrhiza and reactive oxygen species//chapter 10. In: Wu Q-S (ed) Arbuscular mycorrhizas and stress tolerance of plants. Springer, Singapore. https://doi.org/10.1007/978-981-10-4115-0_10 44. Carrino-Kyker SR, Kluber LA, Coyle KP, Burke DJ (2017) Detection of phosphate transporter genes from arbuscular mycorrhizal fungi in mature tree roots under experimental soil pH manipulation. Simbiosis 72:123–133. https://doi.org/10.1007/s13199-016-0448-1 45. Higo M, Tatewaki Y, Iida K, Yokota K, Isobe K (2020) Amplicon sequencing analysis of arbuscular mycorrhizal fungal communities colonizing maize roots in different cover cropping and tillage systems. Sci Rep 10:6093. https://doi.org/10.1038/s41598-020-58942-3 46. Wang M, Yang W, Zhou F, Du Z, Xue M, Chen T, Liang D (2019) Effect of phosphate and silicate on selenite uptake and phloem-mediated transport in tomato (Solanum lycopersicum L.). Environ Sci Pollut Res 26:20475–20484. https://doi.org/10.1007/s11356-019-04717-x 47. Golubkina N, Amagova Z, Matsadze V, Caruso G (2020) Effects of arbuscular mycorrhizal fungi on yield, biochemical characteristics and elemental composition of garlic and onion under selenium supply. Plants 9:84. https://doi.org/10.3390/plants9010084 48. Conversa G, Lazzizera C, Chiaravalle E (2019) A Elia Selenium fern application and arbuscular mycorrhizal fungi soil inoculation enhance Se content and antioxidant properties

170

N. Golubkina et al.

of green asparagus (Asparagus officinalis L.) spears. Sci Hortic 252:176–191. https://doi.org/ 10.1016/j.scienta.2019.03.056 49. Golubkina N, Zamana S, Seredin T, Poluboyarinov P, Sokolov S, Baranova H, Krivenkov L, Pietrantonio L, Caruso G (2019) Effect of selenium biofortification and arbuscular mycorrhizal fungi on yield, quality and antioxidant properties of shallot bulbs. Plants 102(8). https://doi. org/10.3390/plants8040102 50. Golubkina N, Gomez L, Kekina H, Hallam R, Tallarita A, Cozzolino E, Torino V, Koshevarov A, Cuciniello A, Maiello R, Cenvinzo V, Caruso G (2020) Joint selenium-iodine supply and arbuscular mycorrhizal fungi inoculation affect yield and quality of chickpea seeds and residual biomass. Plants 9:804. https://doi.org/10.3390/plants9070804 51. Durán P, Acuñab JJ, Jorquera MA, Azcónc R, Borie F, Cornejo P, Mora ML (2013) Enhanced selenium content in wheat grain by co-inoculation of selenobacteria and arbuscular mycorrhizal fungi: a preliminary study as a potential Se biofortification strategy. J Cereal Sci 57(3):275– 280. https://doi.org/10.1016/j.jcs.2012.11.012 52. Luo W, Li J, Ma X, Niu H, Hou S, Wu F (2019) Effect of arbuscular mycorrhizal fungi on uptake of selenate, selenite, and selenomethionine by roots of winter wheat. Plant Soil 438:71– 83. https://doi.org/10.1007/s11104-019-04001-4 53. Durán P, Acuña JJ, Armada E, López-Castillo OM, Cornejo P, Mora ML, Azcón R (2016) Inoculation with selenobacteria and arbuscular mycorrhizal fungi to enhance selenium content in lettuce plants and improve tolerance against drought stress. J Soil Sci Plant Nutr 16(1). https://doi.org/10.4067/S0718-95162016005000017 54. Souza MP, Chu D, Zhao M, Zayed AM, Ruzin SE, Schichnes D, Terry N (1999) Rhizosphere bacteria enhance selenium accumulation and volatilization by Indian mustard. Plant Physiol 119:565–574. https://doi.org/10.1104/pp.119.2.565 55. Yasin M, El Mehdawi AF, Jahn CE, Anwar A, Turner MF, Faisal M, Pilon-Smits EA (2015) Seleniferous soils as a source for production of selenium-enriched foods and potential of bacteria to enhance plant selenium uptake. Plant Soil 386:385–394. https://doi.org/10.1007/ s11104-014-2270-y 56. Golubkina N, Logvinenko L, Novitsky M, Zamana S, Sokolov S, Molchanova A, Shevchuk O, Sekara A, Tallarita A, Caruso G (2020) Yield, essential oil and quality performances of Artemisia dracunculus, Hyssopus officinalis and Lavandula angustifolia as affected by arbuscular mycorrhizal fungi under organic management. Plants 9(3):375. https://doi.org/10. 3390/plants9030375 57. Luna MC, Bekhradi F, Ferreres F, Jordán MJ, Delshad M, Gil MI (2015) Effect of water stress and storage time on anthocyanins and other phenolics of different genotypes of fresh sweet basil. J Agric Food Chem 63(42):9223–9231. https://doi.org/10.1021/acs.jafc.5b04131 58. Kumar M, Bijo AJ, Baghel RS, Reddy CRK, Jha B (2012) Selenium and spermine alleviates cadmium induced toxicity in the red seaweed Gracilaria dura by regulating antioxidant system and DNA methylation. Plant Physiol Biochem 51:129–138. https://doi.org/10.1016/j.plaphy. 2011.10.016 59. Filek M, Keskinen R, Hartikainen H, Szarejko I, Janiak A, Miszalski Z, Golda A (2008) The protective role of selenium in rape seedlings subjected to cadmium stress. J Plant Physiol 165 (8):833–844. https://doi.org/10.1016/j.jplph.2007.06.006 60. D'Amato R, Fontanella MC, Falcinelli B, Beone GM, Bravi E, Marconi O, Benincasa P, Businelli D (2018) Selenium biofortification in rice (Oryza sativa L.) sprouting: effects on Se yield and nutritional traits with focus on phenolic acid profile. J Agric Food Chem 66(16): 4082–4090. https://doi.org/10.1021/acs.jafc.8b00127 61. Falcinelli B, Famiani F, Paoletti A, D’Egidio S, Stagnari F, Galieni A, Benincasa P (2020) Phenolic compounds and antioxidant activity of sprouts from seeds of citrus species. Agriculture 10:33. https://doi.org/10.3390/agriculture10020033 62. Márton M, Mandoki ZS, Csapó-Kiss ZS, Csapó J (2010) The role of sprouts in human nutrition. A review. Acta Univ Sapientiae, Alimentaria 3:81–117

7

Selenium: Prospects of Functional Food Production with High Antioxidant Activity

171

63. Sugihara S, Kondo M, Chihara Y, Yuji M, Hattori H, Yoshida M (2004) Preparation of selenium-enriched sprouts and identification of their selenium species by high-performance liquid chromatography-inductively coupled plasma mass spectrometry. Biosci Biotechnol Biochem 68(1):193–199. https://doi.org/10.1271/bbb.68.193 64. Larsen JC, Mortensen A (2009) Scientific opinion of the panel on food additives and nutrient sources added to food on Se-Methyl-L-Selenocysteine as a source of selenium added for nutritional purposes to food supplements following a request from the European Commission. EFSA J 1067:1–23 65. Kurian MS, Megha PR (2020) Assessment of variation in nutrient concentration and antioxidant activity of raw seeds, sprouts and microgreens of Vigna radiata (L.) Wilczek and Cicer arietinum L. AIP Conf Proc 2263:030005. https://doi.org/10.1063/5.0018781 66. Penas E, Gomez R, Frias J, Vidal-Valverde C (2008) Application of high-pressure on alfalfa (Medigo sativa) and mung bean (Vigna radiata) seeds to enhance the microbiological safety of their sprouts. Food Control 19:698–705. https://doi.org/10.1016/j.foodcont.2007.07.010 67. Sangronis E, Machado CJ (2007) Influence of germination on the nutritional quality of Phaseolus vulgaris and Cajanus cajan. LWT Food Sci Technol 40:116–120. https://doi.org/ 10.1016/j.lwt.2005.08.003 68. Zakarova A, Seo JY, Kim HY, Kim JH, Shin J-H, Cho KM, Lee CH, Kim J-S (2014) Garlic sprouting is associated with increased antioxidant activity and concomitant changes in the metabolite profile. J Agric Food Chem 62(8):1875–1880. https://doi.org/10.1021/jf500603v 69. El-Ramady H, Alshaal T, Abdalla N, Prokisch J, Sztrik A, Fári M, Domokos-Szabolcsy É (2015) Selenium and nano-selenium biofortified sprouts using micro-farm systems. The 4th international conference on Selenium in the environment and human health, Sao Paulo, Brazil, 18–21 October 2015. https://doi.org/10.13140/RG.2.1.1065.9925 70. Perni S, Calzuola I, Caprara GA, Gianfranceschi GL, Marsili V (2014) Natural antioxidants in wheat sprout extracts. Curr Org Chem 18(23). https://doi.org/10.2174/138527281966 6140923221446 71. Lintschinger J, Fuchs N, Moser J, Kuehnelt D, Goessler W (2000) Selenium-enriched sprouts. A raw material for fortified cereal-based diets. J Agric Food Chem 48(11):5362–5368. https:// doi.org/10.1021/jf000509 72. Kim MA, Kim MJ (2020) Isoflavone profiles and antioxidant properties in different parts of soybean sprout. J Food Sci 85(3):689–695. https://doi.org/10.1111/1750-3841.15058 73. Rychlik J, Olejnik A, Olkowicz M, Kowalska K, Juzwa W, Myszka K, Dembczyński R, Moyer MP, Grajek W (2015) Antioxidant capacity of broccoli sprouts subjected to gastrointestinal digestion. J Sci Food Agric 95(9):892–902. https://doi.org/10.1002/jsfa.6895 74. Woch W, Hawrylak-Nowak B (2019) Selected antioxidant properties of alfalfa, radish, and white mustard sprouts biofortified with selenium. Acta Agrobot 72(2):1768. https://doi.org/10. 5586/aa.1768 75. Zagrodzki P, Paśko P, Galanty A, Tyszka-Czochara M, Wietecha-Posłuszny R, Rubió PS, Bartoń H, Prochownik E, Muszyńska B, Sułkowska-Ziaja K, Bierła K, Łobiński R, Szpunar J, Gorinstein S (2020) Does selenium fortification of kale and kohlrabi sprouts change significantly their biochemical and cytotoxic properties? J Trace Elem Med Biol 59:126466. https:// doi.org/10.1016/j.jtemb.2020.126466 76. Arscott S, Goldm I (2012) Biomass effects and selenium accumulation in sprouts of three vegetable species grown in selenium-enriched conditions. Am Soc Horticult Sci 47:497–502. https://doi.org/10.21273/HORTSCI.47.4.497 77. Tyszka-Czochara M, Pasko P, Zagrodzki P, Gajdzik E, Wietecha-Posluszny R, Gorinstein S (2016) Selenium supplementation of amaranth sprouts influences. Betacyanin content and improves anti-inflammatory properties via NFκB in Murine RAW 264.7 macrophages. Biol Trace Elem Res 169:320–330. https://doi.org/10.1007/s12011-015-0429-x 78. He X, Wang X, Fang J, Chang Y, Ning N, Guo H, Huang L, Huang X, Zhao Z (2017) Structures, biological activities, and industrial applications of the polysaccharides from

172

N. Golubkina et al.

Hericium erinaceus (Lion’s Mane) mushroom: a review. Int J Biol Macromol 97:228–237. https://doi.org/10.1016/j.ijbiomac.2017.01.040 79. Oh M-M, Rajashekar C (2009) Antioxidant content of edible sprouts: effects of environmental shocks. J Sci Food Agric 89(13):2221–2227. https://doi.org/10.1002/jsfa.3711 80. Àvila FW, Yang Y, Faquin V, Ramos SJ, Guilherme LRG, Thannhauser TW, Li L (2014) Impact of selenium supply on Se-methylselenocysteine and glucosinolate accumulation in selenium-biofortified Brassica sprouts. Food Chem 165:578–586. https://doi.org/10.1016/j. foodchem2014.05.134 81. Bachiega P (2018) Biofortification of broccoli seedlings with selenium: influence on bioactive compounds and in vivo toxicity- thesis, Piricicaba-2018 University of São Paulo “Luiz de Queiroz” College of Agriculture. https://doi.org/10.11606/T.11.2019.tde-01112018-164508 82. Golubkina NA, Seredin TM, Baranova HV, Startseva LV, Agafonov AF, Ushakova OV, Kovalsky JG (2018) Prospects of production of Allium sprouts fortified with selenium. Veg Crops Russia 6:50–54. https://doi.org/10.18619/2072-9146-2018-6-50-54. (in Russ.) 83. Pannico A, El-Nakhel C, Graziani G, Kyriacou MC, Giordano M, Soteriou GA, Zarrelli A, Ritieni A, De Pascale S, Rouphael Y (2020) Selenium biofortification impacts the nutritive value, polyphenolic content and bioactive constitution of variable microgreens genotypes. Antioxidants 9:272. https://doi.org/10.3390/antiox9040272 84. Kyriacou MC, El-Nakhel C, Graziani G, Pannico A, Soteriou GA, Giordano M (2019) Functional quality in novel food sources: genotypic variation in the nutritive and phytochemical composition of thirteen microgreens species. Food Chem 277:107–118. https://doi.org/10. 1016/j.foodchem.2018.10.098 85. Islam MZ, Park BJ, Kang HM, Lee YT (2020) Influence of selenium biofortification on the bioactive compounds and antioxidant activity of wheat microgreen extract. Food Chem 309: 125763. https://doi.org/10.1016/j.foodchem.2019.125763 86. Puccinelli M, Malorgio F, Rosellini I, Pezzarossa B (2017) Uptake and partitioning of selenium in basil (Ocimum basilicum L) plants grown in hydroponics. Sci Hortic 225:271– 276. https://doi.org/10.1016/j.scienta.2017.07.014 87. Puccinelli M, Malorgio F, Rosellini I, Pezzarossa B (2019) Production of selenium-biofortified microgreens from selenium-enriched seeds of basil. J Sci Food Agric 99:5601–5605. https:// doi.org/10.1002/jsfa.9826 88. Germ M, Stibilj V, Šircelj H, Jerše A, Krofliˇc A, Golob A, Maršić NK (2019) Biofortification of common buckwheat microgreens and seeds with different forms of selenium and iodine. J Sci Food Agric 99:4353–4362. https://doi.org/10.1002/jsfa.9669 89. Zhang X, Bian Z, Li S, Chen X, Lu C (2019) Comparative analysis of phenolic compound profiles, antioxidant capacities, and expressions of phenolic biosynthesis-related genes in soybean microgreens grown under different light spectra. J Agric Food Chem 67(49): 13577–13588. https://doi.org/10.1021/acs.jafc.9b05594 90. Mlinaric S, Gvozdic V, Vukovic A, Varga M, Vlašiˇcek I, Cesar V, Begovic L (2020) The effect of light on antioxidant properties and metabolic profile of Chia Microgreens. Appl Sci 10:5731. https://doi.org/10.3390/app10175731 91. Valverde ME, Hernández-Pérez T, Paredes-López O (2015) Edible mushrooms: improving human health and promoting quality life. Int J Microbiol 2015:376387. https://doi.org/10. 1155/2015/376387 92. Ogidi CO, Oyetayo VO, Akinyele BJ (2020) Wild medicinal mushrooms: potential applications in phytomedicine and functional foods, an introduction to mushroom, Ajit Kumar Passari and Sergio Sánchez, IntechOpen. https://doi.org/10.5772/intechopen.90291 93. Kora AJ (2020) Nutritional and antioxidant significance of selenium-enriched mushrooms. Bull Nat Res Center 44:34. https://doi.org/10.1186/s42269-020-00289-w 94. Puttaraju NG, Venkateshaiah SU, Dharmesh SM, Urs SMN, Somasundaram R (2007) Antioxidant activity of indigenous edible mushrooms. J Agric Food Chem 54:9764–9772. https:// doi.org/10.1021/jf0615707

7

Selenium: Prospects of Functional Food Production with High Antioxidant Activity

173

95. Witkowska AM (2014) Selenium-fortified mushrooms – candidates for nutraceuticals? Austin Ther 1(2):4 96. Falandysz J (2008) Selenium in edible mushrooms. J Environ Sci Health C 26:256–299. https://doi.org/10.1080/10590500802350086 97. Kozarski M, Klaus A, Jakovljevic D, Todorovic N, Vunduk J, Petrović P, Niksic M, Vrvic MM, van Griensven L (2015) Antioxidants of edible mushrooms. Molecules 20:19489– 19525. https://doi.org/10.3390/molecules201019489 98. Golubkina NA, Mironov VU (2018) Element composition of mushrooms in contrasting anthropogenic loading. Geochem Int 56(12):1263–1275. https://doi.org/10.1134/ S0016702918100087 99. Keleş A, Koca İ, Gençcelep H (2011) Antioxidant properties of wild edible mushrooms. J Food Process Technol 2:130. https://doi.org/10.4172/2157-7110.1000130 100. Srajuć M, Vukojević J, Knežević A, Lausević DS, Milovanović I (2013) Antioxidant protective effect of mushrooms metabolites. Curr Top Med Chem 13:2660–2676. https://www. researchgate.net/publication/257299199 101. Turło J, Gutkowska B, Herold F (2010) Effect of selenium enrichment on antioxidant activities and chemical composition of Lentinula edodes (Berk.) Pegl. mycelial extracts. Food Chem Toxicol 48:1085–1091. https://doi.org/10.1016/j.fct.2010.01.030 102. Zhao I, Zhao G, Du M, Zhao Z, Xiao I, Hu X (2008) Effect of selenium on increasing free radical scavenging activities of polysaccharide extracts from a Se-enriched mushroom species of the genus Ganoderma. Eur Food Res Technol 226:499–505. https://doi.org/10.1007/ s00217-007-0562-7 103. Du M, Zhao I, Li C, Zhao G, Hu X (2007) Purification and characterization of a novel fungi Se-containing protein from Se-enriched Ganoderma Lucidum mushroom and its Se-dependent radical scavenging activity. Eur Food Res Technol 224:659–665. https://doi.org/10.1007/ s00217-006-0344-4 104. Rathore Y, Sharma A, Prasad S, Sharma S (2018) Selenium bioaccumulation and associated nutraceutical properties in Calocybe indica mushrooms cultivated on Se-enriched wheat straw. J Biosci Bioeng 126(4):482–487. https://doi.org/10.1016/j.jbiosc.2018.04.010 105. Bhatia P, Prakash R, Prakash NT (2014) Enhanced antioxidant properties as a function of selenium uptake by edible mushrooms cultivated on selenium-accumulated waste post-harvest wheat and paddy residues. Int J Recycl Org Waste Agric 3:127–132. https://doi.org/10.1007/ s40093-014-0074-y 106. Gąsecka M, Mleczek M, Siwulski M, Niedzielski P (2016) Phenolic composition and antioxidant properties of Pleurotus ostreatus and Pleurotus eryngii enriched with selenium and zinc. Eur Food Res Technol 242:723–732. https://doi.org/10.1007/s00217-015-2580-1 107. Fasoranti OF, Ogidi CO, Oyetayo VO (2019) Nutrient content and antioxidant properties of Pleurotus spp. Cultivated on substrate fortified with selenium. Cur Res Environ Appl Mycol 9 (1):66–76. https://doi.org/10.5943/cream/9/1/7 108. Hu T, Liang Y, Zhao G, Wu W, Li H, Guo Y (2019) Selenium biofortification and antioxidant activity in Cordyceps militaris supplied with selenate, selenite, or selenomethionine. Biol Trace Elem Res 187(2):553–561. https://doi.org/10.1007/s12011-018-1386-y 109. Malinowska F (2008) Biosynthesis of selenium containing polysaccharides with antioxidant activity in liquid culture of Hericium erinaceum. Enzym Microb Technol 44:334–343. https:// doi.org/10.1016/j.enzmictec-2008.12.003 110. Miletíć D, Turło J, Podsadni P, Pantić M, Nedović V, Lević S, Nikšić M (2019) Selenium-enriched Coriolus versicolor mushroom biomass: potential novel food supplement with improved selenium bioavailability. J Sci Food Agric 99:5122–5130. https://doi.org/10.1002/jsfa.9756 111. Siwulski M, Budzynska S, Rzymski P, Gąsecka M (2019) The effect of germanium and selenium on growth, metalloid accumulation and ergosterol: experimental study in Pleurotus osteitis and Ganoderga lucidus. Eur Food Res Technol 245:1799–1810. https://doi.org/10. 1007/s00217-019-03299-9

174

N. Golubkina et al.

112. Nunes RGFL, da Luz JMR, de Freitas RB, Higuchi A, Kasuya MCM, Vanetti MCD (2012) Selenium bioaccumulation in shiitake mushrooms: a nutritional alternative source of this element. J Food Sci 77(9):C983–C986. https://doi.org/10.1111/j.1750-3841.2012.02837.x 113. Spolar MR, Schaffer EM, Beelman RB, Milner JA (1999) Selenium-enriched Agaricus bisporus mushrooms suppress 7,12-dimethlybenz [a] anthracenebioactivation in mammary tissue. Cancer Lett 138:145–150. https://doi.org/10.1016/S0304-3835(99)00003-8 114. Cremades O, MarDiaz-Herrero M, Carbonero-Aguilar P, Gutierrez-Gil JF, Fontiveros E, Rodríguez-Morgado B, Parrado J, Bautista J (2012) Preparation and characterisation of selenium-enriched mushroom aqueous enzymatic extracts (MAEE) obtained from the white button mushroom (Agaricus bisporus). Food Chem 133:1538–1543. https://doi.org/10.1016/j. foodchem.2012.02.046 115. Sytar O, Hemmerich I, Zivcak M, Rauh C, Brestic M (2018) Comparative analysis of bioactive phenolic compounds composition from 26 medicinal plants. Saudi J Biol Sci 25(4):631–641. https://doi.org/10.1016/j.sjbs.2016.01.036 116. Ivanova D, Gerova D, Chervenkov T, Yankova T (2005) Polyphenols and antioxidant capacity of Bulgarian medicinal plants. J Ethnopharmacol 96(1–2):145–150. https://doi.org/10.1016/j. jep.2004.08.033 117. Checkouri E, Reignier F, Da Silva CR, Meilhac O (2020) Evaluation of polyphenol content and antioxidant capacity of aqueous extracts from eight medicinal plants from Reunion Island: protection against oxidative stress in red blood cells and preadipocytes. Antioxidants 9:959. https://doi.org/10.3390/antiox9100959 118. Duda-Chodak A, Tarko T, Rus M (2011) Antioxidant activity and total polyphenol content of selected herbal medicinal products used in Poland. Kerva Polonika 57(1):48–57 119. Kacem R, Hemissi Y, Talbi S, Bouguatosha S (2013) Total polyphenol content and assessment of antioxidant activity of selected medicinal plants. Planta Med 79:PJ22. https://doi.org/10. 1055/s-0033-1352226 120. Najjaa H, Abdelkarim BA, Doria E, Boubakri A, Trabelsi N, Falleh H, Tlili H, Neffati M (2020) Phenolic composition of some Tunisian medicinal plants associated with anti-proliferative effect on human breast cancer MCF-7 cells. Eur Biotech J 4(2). https://doi. org/10.2478/ebtj-2020-0012 121. Sotek Z, Białecka B, Pilarczyk B, Drozd R, Pilarczyk R, Tomza-Marciniak A, Kruzhel B, Lysak H, Bąkowska M, Vovk S (2019) Antioxidant activity and selenium and polyphenols content from selected medicinal plants natives from various areas abundant in selenium (Poland, Lithuania, and Western Ukraine). Processes 7(12):878. https://doi.org/10.3390/ pr7120878 122. Gupta M, Gupta S (2017) An overview of selenium uptake, metabolism and toxicity in plants. Front Plant Sci 7:2074. https://doi.org/10.3389/fpls.2016.02074 123. Berni R, Cantini C, Romi M, Hausman J-F, Guerriero G, Cai G (2018) Agrobiotechnology goes wild: ancient local varieties as sources of bioactives. Int J Mol Sci 19:2248. https://doi. org/10.3390/ijms19082248 124. Kharchenko VA, Moldovan AI, Golubkina NA, Gins MS, Shafigullin DR (2020) Comparative evaluation of several biologically active compounds content in Anthriscus sylvestris (L.) HOFFM and Anthriscus cerefolium (L.) Hoffm. Veg Crops Russia 5:89–95. (in Russ.) 125. Golubkina NA, Logvinenko LA, Molchanova AV, Caruso G (2020) Genetic and environmental influence on macro- and micro-elements accumulation in plants of Artemisia species. Chapter 17. In: Afthab T, Hakeem K (eds) Plant micronutrients. Deficiency and toxicity. Elsevier, Cham, pp 389–417 126. Golubkina N, Lapchenko V, Ryff L, Lapchenko H, Naumenko T, Bagrikova N, Krainuk K, Kosheleva O, Caruso G (2020) Medicinal plants as sources of selenium and natural antioxidants. Banat’s J Biotechnol 11(22). https://doi.org/10.7904/2068-4738-XI(22)-48 127. Severson RC, Fisher S, Gough LP (1990) The eruption of Redoubt volcano, Alaska, – 1989 – August 31. U.S. Government Printing Office

7

Selenium: Prospects of Functional Food Production with High Antioxidant Activity

175

128. Vicklund LE, Vance GF, “Mickey” Steward DG, Spackman LK, Luthe JG (1995) Selenium and mining in the powder river basin, Wyoming: phase I – vegetation analysis. Proc Am Soc Min Reclam 317, 3332; https://doi.org/10.21000/JASMR95010317 129. El Mehdawi AF, Quinn CF, Pilon-Smits EAH (2011) Selenium hyperaccumulators facilitate selenium-tolerant neighbors via phytoenrichment and reduced herbivory. Curr Biol 21:1440– 1449. https://doi.org/10.1016/j.cub.2011.07.033 130. Shariatpanahi M, Anderson AC, Mather F (1986) Trace metal uptake by garden herbs and vegetables. Biol Trace Elem Res 11(1):177–183. https://doi.org/10.1007/BF02795533 131. Wang J, Li Q, Bao A, Liu X, Zeng J, Yang X, Yao J, Zhang J, Lei Z (2016) Synthesis of selenium-containing Artemisia sphaerocephala polysaccharides: Solution conformation and anti-tumor activities in vitro. Carbohydr Polym 152:70–78. https://doi.org/10.1016/j.carbpol. 2016.06.090 132. Skrypnik L, Novikova A, Tokupova E (2019) Improvement of phenolic compounds, essential oil content and antioxidant properties of sweet Basil (Ocimum basilicum L.) Depending on type and concentration of selenium application. Plants 8:458. https://doi.org/10.3390/ plants8110458 133. Ksouri R, Falleh H, Megdiche W, Trabelsi N, Mhamdi B, Chaieb K, Bakrouf A, Magne C, Abdelly C (2009) Antioxidant and antimicrobial activities of the edible medicinal halophyte Tamarix gallica L. and related polyphenolic constituents. Food Chem Toxicol 47:2083–2091. https://doi.org/10.1016/j.fct.2009.05.040 134. Bahransoltani R, Kalkhorani M, Abbas Zaidi SM, Farzaei MH, Rahimi R (2020) The genus Tamarix: traditional uses, phytochemistry, and pharmacology. J Ethnopharmacol 246:112245. https://doi.org/10.1016/j.jep.2019.112245 135. Dafni A, Levy S, Lev L (2005) The ethnobotany of Christ’s Thorn Jujube (Ziziphus spinachristi) in Israel. J Ethnobiol Ethnomed 1:8. https://doi.org/10.1186/1746-4269-1-8 136. Sen A (2018) Antioxidant and anti-inflammatory activity of fruit, leaf and branch extracts of Paliurus spina-christi P. Mill. Marmara Pharm J 22(2):328–333. https://doi.org/10.12991/mpj. 2018.71 137. Sentkowska A, Pyrzyńska K (2019) Investigation of antioxidant activity of selenium compounds and their mixtures with tea polyphenols. Mol Biol Rep 46:3019–3024. https://doi.org/ 10.1007/s11033-019-04738-2

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Antioxidant Activity and Fresh Goat Cheese Leticia Herna´ndez Gala´n, Rosa Vazquez-Garcia, and Sandra T. Martín del Campo

Contents 1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2 Antioxidant Peptides and Their Importance in Health . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Goat Milk as a Source of Antioxidant Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4 Antioxidant Capacity of Fresh Goats Cheeses . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5 Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

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Abstract

Currently, the study of food goes beyond evaluating not only its nutritional quality but also its functionality. Most food products are known to contain substances that can improve the consumer’s health. Milk is an example of these products having not only nutritional importance but also functional activity. Milk, as raw material, has been shown to have antihypertensive, antioxidant, antibacterial, and immunomodulatory qualities. Transformation of milk into different products such as cheese could preserve this functionality. Nevertheless, most of the dairy products present higher biological activities than milk. The objective of this chapter is to make a count of the studies that have demonstrated the presence of antioxidant compounds in fresh goat’s cheeses. This chapter starts with goat milk, its nutritional components, as well as its fucntional compounds. Then the chapter focuses on fresh cheeses, considering animal feeding, cheese coagulation system, and the starter and adjoint cultures.

L. H. Galán Zentrela Inc., Hamilton, ON, Canada R. Vazquez-Garcia · S. T. Martín del Campo (*) School of Science and Engineering, Tecnologico de Monterrey, Querétaro, Qro, Mexico e-mail: [email protected] © Springer Nature Switzerland AG 2022 H. M. Ekiert et al. (eds.), Plant Antioxidants and Health, Reference Series in Phytochemistry, https://doi.org/10.1007/978-3-030-78160-6_6

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Keywords

Fresh goat cheese · Antioxidant activity · Bioactive peptides · Goat milk · Casein’s hydrolysis

1

Introduction

The presence of reactive oxygen species in cells causes affectations in the organism that can lead to diseases such as cancer, obesity, insulin resistance, and other diseases that have become major epidemics in various areas of the planet [1]. Many authors have recommended the prevention of these diseases by consuming more antioxidant products, which can be obtained from a wide variety of foods [2, 3]. Among them is milk, which naturally contains peptides that have antioxidant activity and can be found in derived products such as fresh and ripened cheese [4, 5]. Various studies have shown that the antioxidant capacity of goat’s milk, which has been widely reported, is increased by casein precipitation process by enzymatic hydrolysis during cheese making. Studies have shown that the formation of peptides in the production of cheese increases the antioxidant capacity of fresh cheeses, and this same quality increases during a ripening process [6].

2

Antioxidant Peptides and Their Importance in Health

In recent decades, the study of food has become a success due to its recognition as a major agent for prevention or cure in chronic diseases like cancer, cardiovascular diseases, insulin resistance, and obesity. This knowledge has made it possible the development of new aliments that, beyond a nutritional value, have components that provide health benefits to consumers, resulting in attractive and healthy foods called “functional food,” which are defined as those foods that can present one or more physiological benefits that reduce the risk of developing any disease [7]. In this regard, milk and dairy products have attracted significant attention due to its content of multiple molecules with specific biological activity. Thus, the antioxidant potential of food has been associated with health benefits of the consumers, and the search for novel antioxidant sources has increased considerably in the last few decades. The oxidative metabolism is crucial for the survival of human cells, though this metabolism produces free radicals and reactive oxygen species that cause oxidative changes. Cells maintain complex systems of multiple types of antioxidants such as glutathione, vitamin C, and vitamin E, as well as enzymes such as catalase, superoxide dismutase, and various peroxidases. However, when free radicals and reactive oxygen species are present in higher amounts than the endogenous antioxidant systems, an imbalance in the redox state of the cell is produced, causing toxic effects through the production of peroxide and free radicals start chain reactions. This oxidative stress is involved in many diseases like Parkinson’s disease, Alzheimer’s disease, or even cancer [1].

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Antioxidants stop these chain reactions by removing free radical intermediates and inhibit other oxidation reactions through their oxidation. Compounds that can act as antioxidants can be found in foods and microorganisms that can produce them. It has been shown that peptides derived from certain foods such as milk, cereals, and fermented products possess some properties that favor the health of consumers. One of these biological properties is the antioxidant activity [8]. At present, it has been determined that many foods contain compounds that have antioxidant activity. However, only few foods of animal origin have been studied. Several authors have mentioned that the matrix of foods of animal origin is very complex to determine the source of antioxidant activity. In this area, dairy products have been widely studied since the milk of different mammals has shown the presence of bioactivity [2, 4, 9, 10]. Many authors have determined the presence of various biological activities in the milk of various mammals such as cow, goat, buffalo, or camel. The biological activities include antihypertensive, immunomodulatory, antibacterial, and antioxidant effects [11, 12].

3

Goat Milk as a Source of Antioxidant Compounds

Milk contains several antioxidant factors like peptides, lactoferrin, conjugated linoleic acid, coenzyme Q10, vitamins (C, E, A, and D3), uric acid, carotenoids, enzymatic systems, mainly superoxide dismutase, catalase, and glutathione peroxidase [9]. Also, some of the peptides released from the milk caseins have attracted special interest for their antioxidant capacity [13–15]. In this regard, cow’s milk has been shown to contain large amounts of biologically active peptides, as observed by Català-Clariana et al. [16]. The latter observed antihypertensive, immunomodulatory, antithrombotic, and antioxidant activities in infant milk. Another example is that of sheep’s milk, which has also been shown to have an antioxidant activity after hydrolysis using microbial proteases [17]. The ingestion of goat’s milk has also been shown to have positive effects on enzymatic oxidation processes, which lead to diseases if reactive oxygen species are present during oxidation. Díaz-Castro et al. [18] observed that the continuous consumption of goat milk could inhibit the production of superoxide dismutase, an important enzyme in the production of reactive oxygen species. These studies directly demonstrate the antioxidant capacity of goat’s milk. In this sense, milk has shown great antioxidant qualities in in vitro studies. Using DPPH radical scavenging test in goat and other ruminant milk, El-Fattah et al. [5] observed that the activity is strong in whole and raw milk. It was also shown that after the pasteurization process, the activity decreases but does not disappear, and finally it was determined that sterilization tends to increase the antioxidant capacity. The goat is one of the animals that has accompanied humanity, and its milk is highly valued in various cultures (Fig. 1). In recent years, goat’s milk has attracted important attention due to its multiple benefits, becoming a suitable source of nutrients for infants with allergy to cow milk or even neonates when human milk is lacking [19]. In this regard, Almaas et al. [20] determined that raw goat’s milk was

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Fig. 1 The goat: an important animal in human nutrition

digested much faster than pasteurized cow’s milk, in in vitro digestions using human proteolytic enzymes. Most of the antioxidant compounds are directly derived from animal diet; thus, the origin of the milk is determinant in the antioxidant capacity [21]. In this way, Alyaqoubi et al. [22] observed that the antioxidant activity is also widely related to the breed of the animal, observing that the milk of Jamnapari goats breed has a high antioxidant capacity. The traditional goat farming using pastoral systems leads to uncontrolled consumption of natural browsing plants that could be carriers of several health-promoting compounds including antioxidants [23]. Sanlidere Aloglu and Öner [24] measured and compared the antioxidant activity of traditional and commercial yogurt and found that the traditional product had the highest scavenging activity against the ABTS radical among all the tested samples. Ahmed et al. [25] determined antioxidant activity due to peptide release in both goats caseins and whey proteins. The antioxidant peptides are present after hydrolysis of caseins and generally remain after precipitation with pepsin in cheese production, finally, it was concluded that these peptides could be obtained in a better way from the production of goat cheese. However, the composition of goat’s milk, including antioxidant compounds, varies, which depends on factors like breed, diet, stage of lactation, season, environment, and processing (i.e., mechanical, thermal, and fermentative) [15, 26–28]. In this regard, Alyaqoubi et al. [29] and Alyaqoubi et al. [30] studied the effect of the lactation period and pasteurization treatment on the antioxidant capacity of goat milk collected from different farms in Malaysia. The authors observed differences between farms, attributed to the type of breed. They also found that raw milk collected during the first lactation exhibited a higher total phenol content, ferric-reducing antioxidant content, and 2,2-diphenyl-1-picrylhydrazyl of antioxidant activity. Grassland changes its chemical and nutritional composition seasonally (maybe due to variations in rainfall levels). When goats are feed with freerange grazing, pasture

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whith different nutritional properties, and flavors during the year-round season, the content on antioxidant compounds variates [21]. Chávez-Servín et al. [27] compared the total phenolic compounds (TPC) present in raw and pasteurized milk from goats fed in free-range grazing against goats fed on permanent confinement, during the dry and rainy seasons. The authors found that the TPC was higher in raw milk from dry season than in pasteurized milk from the rainy season. Also, milk from goats fed on free-range grazing had a significantly higher concentration of phenolic compounds and higher antioxidant activity. Environmental factors had the same impact on the biological activity of milk by-products, where TPC and antioxidant capacity were higher in cheese than in milk and whey, highlighting the importance of the dairy matrix on the concentration of antioxidant compounds. Antioxidant capacity in goats milk can be increased by including in the diet specific crops like Acacia farmesiana, a type of leguminous capable of providing nutrients to domestic herbivores [31]. Delgadillo-Puga et al. [32] evaluated the effect of feeding supplementation with A. farmesiana pods on the antioxidant capacity and polyphenol content in goat milk and found that this crop increased the presence of phenolic acid and flavonoids (catechin) responsible of the antioxidant activity. These authors also confirmed previous findings of Chávez-Servín et al. [27] and concluded that grazing produces a healthier profile of bioactive compounds in milk and by-products than indoor feeding.

4

Antioxidant Capacity of Fresh Goats Cheeses

The antioxidant capacity of dairy products can be enhanced not only by phytochemical supplementation on the animal’s diet but also by the release of bioactive compounds through hydrolysis caused by commercial enzymes or during fermentation [33]. Furthermore, some Lactobacillus strains have a direct contribution to the antioxidant activity of fermented products due to its high level of glutathione and its ability to express manganese superoxide dismutase (Mn-SOD) [34]. The type of dairy matrix also regulates the total antioxidant capacity due to the difference in compound concentrations [9, 21]. Cheese is, without a doubt, the most known dairy product produced by the action of proteolytic and lipolytic enzymes on the dairy proteins. This biochemical process is influenced by the milk origin, manufacturing practices, starter, and nonstarter microorganisms, ripening time, etc., resulting in a unique peptide profile characteristic of each variety of cheese [35]. Cheese production starts with hydrolysis of caseins by a residual coagulant, plasmin, cathepsin D, and other somatic cell proteinases, releasing large and intermediate-sized peptides, which are subsequently degraded by the enzymes from the starter and nonstarter flora of the cheese. Even though cheese proteolysis starts when the coagulant is added, it continues during the coagulation process, draining, salting, and pressing (Fig. 2) for both fresh and ripened cheeses. For fresh cheeses, the higher extent of proteolysis is produced during cold storage or in ripening chambers (Fig. 3). Primary proteolysis for fresh goat cheeses was reported

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Fig. 2 Traditional cheese manufacturing using a press

Fig. 3 Fresh goat cheeses inside a ripening chamber

by El Galiou et al. [36]. These authors found significant differences in the proteolytic index water-soluble nitrogen (WSN) and nonprotein nitrogen (NPN) only in 5 ripening days, even in cheeses prepared without starter cultures. In the case of ripened cheese, there is secondary proteolysis by the action of bacterial proteinases and peptidases that generates small peptides and free amino acids [37]. An example of enzymes that can lead to enzymatic hydrolysis is those reported by Awad et al. [38]. They observed the hydrolysis process with chymosin and porcine pepsin on caseins from buffalo, cow, and goat milk, obtaining good results over β-casein in the presence of sodium chloride. Despite the type of cheese, the main objective of proteolysis is the degradation of complex proteins into smaller peptides and amino acids, where some of these peptides have antioxidant properties [14, 25, 39]. These peptides have a length of 5–11 amino acids with hydrophobic properties and aromatic residues. The presence of proline,

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phenylalanine, histidine, tyrosine, and tryptophan has been correlated with the antioxidant capacity [40]. There are only a few works that focused on the evaluation of functional properties fresh goat cheeses since most of the goat cheeses produced in the world have a ripening step. This ripening process could take some days to some weeks. Hernández-Galán et al. [41] evaluated the antioxidant activity in fresh goat cheese fabricated without starters and with raw and pasteurized milk from different seasons. These authors compared antioxidant activity in nonprotein nitrogen (NPN) and soluble in acid (ASN) protein fractions. The NPN fraction exhibited significantly higher antioxidant activity than ASN, probably due to the smaller size of the peptides in the NPN fraction. However, the authors did not find significant differences between cheeses due to heat treatment or milk season. Starter and adjoint cultures have an important role in the production of antioxidant compounds in fresh and ripened cheeses. Kocak et al. [42] reported antioxidant activities (DPPH method) of about 30% on day 1 for brined ripened goat cheeses added with different adjoint cultures. Revilla et al. [43] reported important antioxidant activity from month 0 in ripened cheeses (>5500 μmol of Trolox/mg of cheese) made with summer and winter goats milk. On the other hand, important antioxidant activity has also been observed for goat cheeses with a short ripening time. Sulejmani et al. [44] reported important antioxidant activity in traditional goats cooked paste cheeses ripened in brine for two months with or without the addition of herbs. Barać et al. [45] analyzed the antioxidant capacity of water-soluble and water-insoluble protein fractions from white-brined cheese prepared with overheated goat milk and ripened for 50 days. These authors attributed the antioxidant activity in the water-soluble fraction (WSF) of fresh cheese (day 0) to the peptides that originated from weakly bound whey proteins and products of thermolysis and primary proteolysis. The water-soluble fraction of fresh cheese had almost three times more total antioxidant capacity than the water-insoluble fraction. Meanwhile, the antioxidant capacity of the water-insoluble fraction was related to the proteins incorporated into the gel matrix. The antioxidant activity of both fractions increased during ripening. For the water-soluble protein fraction, the increase in antioxidant capacity was positively correlated with the content of water-soluble nitrogen, meaning that low molecular weight nitrogen compounds, a product of the secondary proteolysis, are significant contributors of the antioxidant capacity of this fraction. Barać et al. [12] probed that in vitro digestion of the water-insoluble protein fraction of goat cheese can significantly improve antioxidant activity. Even though the antioxidant activity observed in fresh goat cheeses is attributed to the peptides released during clotting and storage, there are other compounds present in minor concentrations that come from the milk [21, 28, 32]. DelgadilloPuga et al. [32] reported that milk from grazing goats showed a higher polyphenol content (mg of gallic acid equivalents/L of milk) than the milk from indoor goats fed with a conventional diet. However, this concentration increased when Acacia farnesiana (AF) pods were added to the conventional diet. Nevertheless, DPPH assay showed that antioxidant activity remained significantly higher in gazing goats’ milk despite the AF proportion in animal diet. On the other hand, oxygen radical

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absorbance capacity (ORAC) assay showed similar antioxidant capacity for milk obtained from gazing goats fed with 30% AF. Cuchillo Hilario et al. [21] evaluated the antioxidant capacity of polyphenol extracts from fresh soft goat cheeses made with grazing goats’ milk and indoor goats’ milk. These authors found significant differences in the antioxidant capacity between cheese extracts; cheeses from grazing goat’s milk showed higher antioxidant capacity and a higher concentration of total polyphenols. Both works conclude that antioxidant capacity in the milk as well as in the cheese could be increased by modifying the animal feeding system.

5

Conclusions

Fresh goat cheeses are an important product for human nutrition, not only due to the nutritional facts but also because of the functional activity they show. Most of the fresh goat cheeses are produced in small quantities, but they have a regional impact. Antioxidant activity, associated with health benefits, is present in fresh goat cheeses, despite the lower extent of proteolysis in this kind of cheeses. Fresh goat cheeses contain a wide range of bioactive peptides and polyphenols responsible for the antioxidant capacity. Even if fresh cheeses show lower activities than ripened cheeses, the activity is significant to obtain health benefits. Acknowledgments The second author, Vazquez-Garcia, R gratefully acknowledges Consejo Nacional de Ciencia y Tecnología (CONACyT) for granting scholarship (No. 260794).

References 1. Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, antioxidants, and the degenerative diseases of aging. Proc Natl Acad Sci 90:7915–7922 2. Carlsen MH, Halvorsen BL, Holte K et al (2010) The total antioxidant content of more than 3100 foods, beverages, spices, herbs and supplements used worldwide. Nutr J 9:3 3. Korhonen H, Pihlanto A (2007) Technological options for the production of health-promoting proteins and peptides derived from milk and colostrum. Curr Pharma Des 13:829–843 4. Cloetens L, Panee J, Åkesson B (2013) The antioxidant capacity of milk-the application of different methods in vitro and in vivo. Cell Mol Biol (Noisy-le-grand) 59:43–57 5. El-Fattah AA, Azzam M, Elkashef H et al (2020) Antioxidant properties of milk: effect of milk species, milk fractions and heat treatments. Science 15:1–9 6. Moreno-Fernandez J, Alférez MJ, López-Aliaga I et al (2019) Protective effects of fermented goat milk on genomic stability, oxidative stress and inflammatory signalling in testis during anaemia recovery. Sci Rep 9:1–11, Moreno-Montoro M, Olalla-Herrera M, Rufián-Henares JÁ et al (2017) Antioxidant, ACE-inhibitory and antimicrobial activity of fermented goat milk: activity and physicochemical property relationship of the peptide components. Food Funct 8:2783–2791 7. Toldra F (2019) Dairy foods and positive impact on the consumer’s health. In: Toldra F (ed) Advances in food and nutrition research, Elsevier Science, London, Martínez OA, Martínez EdVM (2006) Proteins and peptides in enteral nutrition. Nutricion hospitalaria 21:1–13, 11–14 8. Korhonen H, Pihlanto A (2003) Food-derived bioactive peptides – opportunities for designing future foods. Curr Pharma Des 9:1297–1308

8

Antioxidant Activity and Fresh Goat Cheese

185

9. Fardet A, Rock E (2018) In vitro and in vivo antioxidant potential of milks, yoghurts, fermented milks and cheeses: a narrative review of evidence. Nutr Res Rev 31:52–70 10. Haque E, Chand R, Kapila S (2008) Biofunctional properties of bioactive peptides of milk origin. Food Rev Int 25:28–43 11. Abdel-Hamid M, Otte J, De Gobba C et al (2017) Angiotensin I-converting enzyme inhibitory activity and antioxidant capacity of bioactive peptides derived from enzymatic hydrolysis of buffalo milk proteins. Int Dairy J 66: 91–98, Choi J, Sabikhi L, Hassan A et al. (2012) Bioactive peptides in dairy products. Int J Dairy Technol 65:1–12, Ibrahim HR, Ahmed AS, Miyata T (2017) Novel angiotensin-converting enzyme inhibitory peptides from caseins and whey proteins of goat milk. J Adv Res 8:63–71 12. Barać M, Pešić M, Vučić T et al (2017) White cheeses as a potential source of bioactive peptides. Mljekarstvo/Dairy 67:3 13. Meira SMM, Daroit DJ, Helfer VE et al (2012) Bioactive peptides in water-soluble extracts of ovine cheeses from Southern Brazil and Uruguay. Food Res Int 48:322–329, El-Salam MHA, El-Shibiny S (2012) Bioactive peptides of buffalo, camel, goat, sheep, mare, and yak milks and milk products. Food Rev Int 29:1–23, El-Sayed M, Awad S (2019) Milk bioactive peptides: antioxidant, antimicrobial and anti-diabetic activities. Biochemistry 7:22–23, Khan IT, Bule M, Rahman Ullah MN et al (2019) The antioxidant components of milk and their role in processing, ripening, and storage: Funct Food. Vet World 12:12 14. Abadía-García L, Cardador A, Martín del Campo ST et al (2013) Influence of probiotic strains added to cottage cheese on generation of potentially antioxidant peptides, anti-listerial activity, and survival of probiotic microorganisms in simulated gastrointestinal conditions. Int Diary J 33:191–197 15. Hernández Galán L, Cardador Martínez A, López del Castillo Lozano M et al (2017) Antioxidant and angiotensin-converting enzyme inhibitory activity in fresh goat cheese prepared without starter culture: a preliminary study. CyTA – J Food 15:49–57 16. Català-Clariana S, Benavente F, Giménez E et al (2013) Identification of bioactive peptides in hypoallergenic infant milk formulas by CE-TOF-MS assisted by semiempirical model of electromigration behavior. Electrophoresis 34:1886–1894 17. Corrêa APF, Daroit DJ, Coelho J et al (2011) Antioxidant, antihypertensive and antimicrobial properties of ovine milk caseinate hydrolyzed with a microbial protease. J Sci Food Agric 91:2247–2254 18. Díaz-Castro J, Pérez-Sánchez LJ, López-Frías MR et al (2012) Influence of cow or goat milk consumption on antioxidant defence and lipid peroxidation during chronic iron repletion. Br J Nutr 108:1–8 19. Atanasova J, Ivanova I (2010) Antibacterial peptides from goat and sheep milk proteins. Biotechnol Biotechnol Equip 24:1799–1803, Park Y (1994) Hypo-allergenic and therapeutic significance of goat milk. Small Ruminant Res 14:151–159 20. Almaas H, Casses A, Devold TG et al (2006) In vitro digestion of bovine and caprine milk by human gastric and duodenal enzymes. Int Dairy J 16:961 21. Cuchillo Hilario M, Delgadillo Puga C, Navarro Ocaña A et al (2010) Antioxidant activity, bioactive polyphenols in Mexican goats’ milk cheeses on summer grazing. J Dairy Res 77:20–26 22. Alyaqoubi S, Abdullah A, Samudi M et al (2015) Physicochemical properties and antioxidant activity of milk samples collected from five goat breeds in Malaysia. Adv J Food Sci Technol 7:235–241 23. Sepe L, Argüello A (2019) Recent advances in dairy goat products. Asian-Australas J Anim Sci 32:1306–1320 24. Sanlidere Aloglu H, Öner Z (2011) Determination of antioxidant activity of bioactive peptide fractions obtained from yogurt. J Dairy Sci 94:5305–5314 25. Ahmed AS, El-Bassiony T, Elmalt LM et al (2015) Identification of potent antioxidant bioactive peptides from goat milk proteins. Food Res Int 74:80–88 26. Guo MR, Park YW, Dixon PH et al (2004) Relationship between the yield of cheese (Chevre) and chemical composition of goat milk. Small Ruminant Res 52:103–107

186

L. H. Gala´n et al.

27. Chávez-Servín JL, Andrade-Montemayor HM, Velázquez Vázquez C et al (2018) Effects of feeding system, heat treatment and season on phenolic compounds and antioxidant capacity in goat milk, whey and cheese. Small Ruminant Res 160:54–58 28. Kukovics S (2018) Goat science. In: Kukovics S (ed) Goat science. IntechOpen, London 29. Alyaqoubi S, Abdullah A, Addai ZR (2014) Antioxidant activity of goat’s milk from three different locations in Malaysia. AIP Conf Proc 1614:198–201 30. Alyaqoubi S, Abdullah A, Samudi M et al (2014) Effect of different factors on goat milk antioxidant activity. Int J ChemTech Res 6:3091–3196 31. Aganga AA, Tsopito CM (1998) A note on the feeding behaviour of domestic donkeys: a Botswana case study. Appl Anim Behav Sci 60:235 32. Delgadillo-Puga C, Cuchillo-Hilario M, León-Ortiz L et al (2019) Goats’ feeding supplementation with Acacia farnesiana pods and their relationship with milk composition: fatty acids, polyphenols, and antioxidant activity. Animals 9:515 33. De Gobba C, Espejo-Carpio FJ, Skibsted LH et al (2014) Antioxidant peptides from goat milk protein fractions hydrolysed by two commercial proteases. Int Dairy J 39:28–40, MorenoFernandez J, Diaz-Castro J, Alférez MJ et al. (2017) Fermented goat milk improves antioxidant status and protects from oxidative damage to biomolecules during anemia recovery. J Sci Food Agric 97:1433–1442, Silva S, Pihlanto A, Malcata F (2006) Bioactive peptides in ovine and caprine cheeselike systems prepared with proteases from Cynara cardunculus. J Dairy Sci 89:3336–3344 34. Kullisaar T, Zilmer M, Mikelsaar M et al (2002) Two antioxidative lactobacilli strains as promising probiotics. Int J Food Microbiol 72:215–224 35. Buffa M, Guamis B, Pavia M et al (2001) Lipolysis in cheese made from raw, pasteurized or high-pressure-treated goats’ milk. Int Dairy J 11:175–179, Beermann C, Hartung J (2012) Current enzymatic milk fermentation procedures. Eur Food Res Technol 235:1–12, Calvo MM, Balcones E (1998) Influence of heat treatment on rennet clotting properties of mixtures of cow’s, ewe’s, and goat’s milk and on cheese yield. J Agric Food Chem 46:2957–2962, Gomes AMP, Silva M, Malcata FX (1998) Caprine cheese with probiotic strains: the effects of ripening temperature and relative humidity on proteolysis and lipolysis. Z Lebensm Unters Forsch A-Food Res Technol 207:386–394, Jin YK, Park YW (1995) Effects of aging time and temperature on proteolysis of commercial goat milk cheeses produced in the United States. J Dairy Sci 78 36. El Galiou O, Zantar S, Bakkali M et al (2013) Lipolysis and proteolysis during the ripening of fresh moroccan goats’ milk cheese. World J Dairy Food Sci 8:201–206 37. Fox P, McSweeney P (1996) Proteolysis in cheese during ripening. Food Rev Int 12:457–509, Carretero C, Trujillo A-J, Mor-Mur M et al. (1994) Electrophoretic study of casein breakdown during ripening of goat’s milk cheese. J Agric Food Chem 42:1546–1550, Gatti M, Fornasari ME, Mucchetti G et al (1999) Presence of peptidase activities in different varieties of cheese. Lett Appl Microbiol 28:368–372 38. Awad S, Lüthi-Peng QQ, Puhan Z (1998) Proteolytic activities of chymosin and porcine pepsin on buffalo, cow, and goat whole and b-casein fractions. J Agric Food Chem 46:4997–5007 39. Bezerra VS, Campos JF, da Silva RA et al (2013) Biotechnological richness of the northeastern semi-arid region: antioxidant activity of casein hydrolysates from Moxotó goat milk (Capra hircus Linnaeus, 1758) obtained by papain action. Food Sci Technol 33:513–520, Gupta A, Mann B, Kumar R et al (2009) Antioxidant activity of Cheddar cheeses at different stages of ripening. Int J Dairy Technol 62:339–347, De Simone C, Picariello G, Mamone G et al (2009) Characterisation and cytomodulatory properties of peptides from Mozzarella di Bufala Campana cheese whey. 15:251, Timón ML, Parra V, Otte J et al (2014) Identification of radical scavenging peptides (