Biology, Cultivation and Applications of Mushrooms 9811662568, 9789811662560

Citation preview

Arun Arya Katerina Rusevska   Editors

Biology, Cultivation and Applications of Mushrooms

Biology, Cultivation and Applications of Mushrooms

Arun Arya • Katerina Rusevska Editors

Biology, Cultivation and Applications of Mushrooms

Editors Arun Arya Department of Environmental Studies Maharaja Sayajirao University of Baroda Vadodara, India

Katerina Rusevska Mycological Laboratory, Institute of Biology Ss. Cyril and Methodius University Skopje, North Macedonia

ISBN 978-981-16-6256-0 ISBN 978-981-16-6257-7 https://doi.org/10.1007/978-981-16-6257-7

(eBook)

© The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 This work is subject to copyright. All rights are solely and exclusively licensed 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 Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore

Foreword

Mushrooms—the fleshy fungi—are unique organisms of our planet. These constitute an important component for a sustainable forest ecosystem. Mushrooms may occur as saprophytes and help in recycling of minerals, form mycorrhizae and enhance plant growth or behave as a parasite, cause diseases, and damage the plantation. Not only used as food and nutraceuticals, they are an important part of enzymes and the pharmaceutical industry. In the twenty-first century, their role is well recognized by ecologists in providing organic compost, biofertilizers, biocontrol agents, and as bioremediators. Now usually grown in a controlled environment, edible mushrooms are a rich source of potassium, riboflavin, selenium, and vitamin D and are proven to be highly beneficial in building immunity, managing weight, and minimizing the risks of various chronic diseases. Apart from these, various kinds of nonedible mushrooms are also utilized in the pharmaceutical and nutraceutical industries. Mushrooms represent a market of more than 70 billion US dollars per year. Considering the huge potential of mushroom spent the mushroom cultivation may be a part of the circular economy in our agriculture sector. I had a unique chance to work with some of these novel microorganisms, forming mycorrhizae, which were beneficial for plant growth and serve as a boon for mankind. I have seen that a tribal person has a better understanding of mushrooms and their possible applications than a university science graduate. More efforts are needed to educate the common man about the economics and immense potential of mushrooms. The use of mushrooms by diverse cultures was illustrated by R. Gordon Wasson, who proposed that Soma—divine mushroom of immortality as mentioned in Vedic literature—was essentially Amanita muscaria. In spring of 1991, in Italian Alps mountain scientists have found a well-preserved man who died over 5300 years ago. With this man they recovered a flint ax and polypore fungus Piptoporus betulinus and another fungus. The importance of this mushroom is identified as tinder for starting fire, in preventing bleeding, and treating wounds and can serve as immuneenhancer tea. Fascinating fungi are now no more mysterious to the universe. Mycologists have worked to decipher the stories of fairy rings, bioluminescence, their unique v

vi

Foreword

hallucinogenic behavior, and death after consumption. I am sure that the present work by Prof. Arun Arya and Dr. Katerina Rusevska will throw some light on ethnomycology, various mushrooms used as food and medicine. The book strives to narrate new knowledge explored in the subject of mushroom biology and cultivation technology. These new advancements will help to boost the mushroom production in industries. Contributions from eminent national and international mushroom researchers included in the book deal with various aspects of cultivation and environmentrelated issues. I am sure that the volume shall be of immense importance not only to experts, academicians, researchers, and industry personnel but also to common growers and planners. My congratulations to the editors and all the contributors for compiling the focused approaches in the study of mushroom biology. Bilaspur University, Bilaspur, India Atal Bihari Vajpayee University, Bilaspur, India Nagaland Central University, Lumami, India Assam Central University, Silchar, India 5th April 2021

G. D. Sharma

Preface

Apart from the culinary, nutritional, and health benefits of edible mushrooms, its large-scale cultivation is now playing an instrumental role in solving one of the main problems facing mankind in the twenty-first century: the need to feed an everincreasing population such as in case of millions of malnourished population in several developing countries especially in Africa and Asia. The Food and Agriculture Organization (FAO) has also recognized the importance of mushrooms as a rich protein food. Mushroom cultivation has increased many times in the past few decades, and this can be used to solve the environmental problems of stubble burning or increase in greenhouse gases. The wheel of change depends on our economic fortune at any one time. The bounties of nature are unlimited, and the fact we can exploit all available resources at our will is not true presently with increasing population. Fungi and particularly mushrooms attract our attention during the rainy season or in a visit to a garden or a forest ecosystem. These organisms have been an object of curiosity for any child or an aged man’s perception. Once thought as life giving vital food for members of royal families, the hallucinogens were consumed for joy or inducing happiness among youth, also for treating mental disorders. These were objects of worship in ancient times. Splendid color, unusual fast growth, and unique architecture of these beautiful mushrooms leave an everlasting impression on a child mind. Biological approaches based on industrial and environmental biotechnology focus on the development of “clean technologies,” which emphasize on maximum production, reduced waste generation, and treatment and conversion of waste in some useful form. Further, these clean technologies focus on the use of biological methods for the remediation of waste. Mushrooms and other fungi possess enzymatic machinery for the degradation of pollutants and therefore have a large potential. Three primary thoughts triggered our mind to take up the task to edit the present volume on nature’s unique creature popularly termed as mushrooms. 1. There is a need to change our food portfolio and reduce the problems of malnutrition particularly among women, tribal people, and young ones. vii

viii

Preface

2. Mushrooms are considered as a good source of food and medicine and can be exploited similarly to medicinal herbs. During difficult times of the COVID-19 pandemic, these mushrooms can provide enough protein and immunity to keep our body healthy. At the same time, their cultivation will help the mushroom growers financially. 3. The waste generated in agricultural fields as well as bio-waste in kitchen, offices, and industries needs a viable management. These were studied in detail (my students tried these for mushroom cultivation and some good results were obtained), and some results are presented in the volume. The use of mushrooms extends back to Paleolithic times. These unique large fruiting bodies served as a source of delicacies and food for longevity though more by kings or high-ranking people than by peasants. Although Auricularia, Lentinula, Agaricus, and Pleurotus are grown industrially to meet the market requirements, many more are still being collected from wastelands or forests and consumed on a regular basis. The cultivation strategies of many of the mycorrhizal fungi are not well understood. More efforts are needed to develop suitable protocols for their in vitro or in vivo cultivation. There is a fear of unknown death among people when mushrooms are collected and consumed. Proper identification should be promoted among villagers/hunters, amateurs, and especially among people who are collecting mushrooms for their own existence. The use of mushrooms has been mentioned in Ancient Chinese and Indian text Atharva Veda as medicine. It is good for providing nutrition and better health due to the presence of proteins, selenium, and folic acid. Online supplementary annexure is added citing recipes for beginners to try these delicious dishes and promote their use in daily diet. The chapters are classified into three parts. The first part deals with several interesting articles on medicinal uses and cultivation technology of Auricularia, Xylaria, Ganoderma, Lentinula, Lenzites, Agaricus, Pleurotus, Schizophyllum, Trametes, etc. The chapters included in the book deal with a variety of uses, chemicals present, and cultivation protocols standardized in different parts of the world. Nowadays with enormous publications and information, especially concerning the medicinal properties of mushrooms, the chapters in this book represent the reviews of the most important usage of fungi in various fields of human life including diseases like COVID-19. The authors have discussed their uses as food, medicine, nutraceutical, cosmetics, in biodeterioration of wood, and in bioremediation. The second part of the book provides a detailed account of entomopathogenic fungus Cordyceps militaris, the science of mushroom biology, common fungi occurring in an area, problems of wood deterioration, etc. The third section focuses on cultivation aspects of edible and medicinal mushrooms, with the inclusion of mushroom production technology in circular economy to boost the income of farmers. This technology can do miracles in rural parts of the developing countries. Each chapter is interesting, and the authors have designed the content in such a way that it arouses the curiosity of the reader. The growing of mushrooms can help in clearing the agro waste and organic municipal waste, thus reducing global warming and can solve the problem of waste management and environmental pollution due to stubble burning.

Preface

ix

Well-known national and international mycologists, when approached for the book, were willing to share their knowledge on the subject. Dr. Katerina Rusevska, a young and enthusiastic mycologist from Macedonia, took up the challenge and showed her willingness to work with me jointly as editor of the present volume. We highly appreciate Prof. G.D. Sharma, Hon. Vice Chancellor of the University of Science and Technology, Meghalaya, India, for the Foreword and his blessings for the success of publication. Mushrooms are unique. We will have to learn from these lovely, tiny creatures how we can live in harmony in this planet. We thank all the eminent experts working in the field of mushroom biology and for submitting their valuable work in a short possible time. Prof. Arya is grateful to Dr. S.K. Nanda, IAS, Shri S.N. Tyagi, IFS, Prof. Bihari Lal, and Prof. J.J. Shah for their guidance and support. Dr. Katerina would like to thank all her family members for their encouragement and support. We would like to thank Ms. Aakanksha Tyagi and her team at Springer Nature for providing all the help in the publication. Vadodara, India Skopje, North Macedonia 5th June, 2021

Arun Arya Katerina Rusevska

Contents

Part I

Applications and Cultivation of Mushrooms

1

Beauty, Diversity, and Potential Uses of Certain Macrofungi . . . . . Sunanda Mandal

2

Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use Against Covid-19 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . K. K. Hapuarachchi and T. C. Wen

3

Recent Advances in the Discovery of Bioactive Metabolites from Xylaria Hill ex Schrank . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . Sunil K. Deshmukh, Kandikere R. Sridhar, Sanjai Saxena, and Manish Kumar Gupta

3

27

47

4

Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology, and Uses . . . . . . . . . . . . . . . . . . . . . . . . . . . . 117 Gordana Kasom and Sead Hadžiablahović

5

Health Promoting and Pharmacological Compounds from Mushrooms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 149 K. Madhusudhanan, N. K. Shahina, and Angel Mathew

6

The Nutritional and Pharmacological Potential of Medicinal Mushroom “Ganoderma lucidum (Lingzhi or Reishi)” . . . . . . . . . . . 161 Jegadeesh Raman, Hariprasath Lakshmanan, Shin Hyun-Jae, and Kab-yel Jang

7

Anti-Aging Properties of Medicinal Mushrooms in Systemic Aesthetic Medicine . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 185 Paola Angelini, Carolina Elena Girometta, Roberto Venanzoni, and Gianluigi Bertuzzi

xi

xii

Contents

8

Diversity, Chemistry, and Environmental Contamination of Wild Growing Medicinal Mushroom Species as Sources of Biologically Active Substances (Antioxidants, Anti-Diabetics, and AChE Inhibitors) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 203 Maja Karaman, Eleonora Čapelja, Milena Rašeta, and Milana Rakić

9

Edible and Medicinal Mushrooms: Some Aspects and Prospects . . . 259 Chakravarthula Manoharachary

10

Truffles: The Cultivation and Health Benefits . . . . . . . . . . . . . . . . . 285 Fahad Said Khan, Imtiaz Hussain, Muhammad Akram, and Mustafa Nadhim Owaid

11

Auricularia spp.: from Farm to Pharmacy . . . . . . . . . . . . . . . . . . . . 301 Somanjana Khatua, Susmita Sett, and Krishnendu Acharya

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals . . . . . 357 Uzma Altaf, S. A. J. Hashmi, and Yash Pal Sharma

13

Potential Uses of Mushrooms as Dietary Supplement to Enhance Memory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 387 Chitra Arya

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps . . . 403 Arun Arya

Part II

Biology and Occurrence of Mushrooms

15

Citizen for Mushrooms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 435 N. S. K. Harsh

16

Mushroom Biotechnology: Developing Cultivation Protocol for Four Different Mushrooms and Accessing Their Potential in Pollution Management . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 457 Ajinkya G. Deshpande and Arun Arya

17

The Tolimas and the Mushroom: Mycolatry in Pre-Hispanic Colombia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 487 Juan Camilo Rodriguez Martinez

18

Lignocellulosic Waste Management Through Cultivation of Certain Commercially Useful and Medicinal Mushrooms: Recent Scenario . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 497 S. P. Pourush Shrikhandia, Sapna Devi, and Geeta Sumbali

19

Selective and Simultaneous Delignification Capacity of Wood Decay Fungus Trametes pini in Tectona grandis L. f. and Terminalia crenulata (Heyne) Roth . . . . . . . . . . . . . . . . . . . . . . 535 Praveen Kumar Nagadesi, Arun Arya, and Susy Albert

Contents

20

xiii

Biological and Ecological Aspects of Rare Bioluminescent Mushrooms . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 547 Ankita Bhatt, Neha Singh, and Arun Arya

Part III

Advances in Cultivation of Mushrooms

21

Cultivation of Two Edible Mushrooms and Need for Training of Mushroom Production Technology to Enhance Rural Economy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 561 Anup Kumar and Anil Satpathy

22

Cultivation and Medicinal Uses of Cordyceps militaris (L.) Link: A Revolutionary Entomopathogenic Fungus . . . . . . . . . . . . . . . . . . 579 Srishti Johri, Yash Vignesh Nair, and A. Selvapandiyan

23

Cultivation Technology of the Fungus Ganoderma lucidum (Curtis) P. Karst . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 597 Savita Jandaik and Satish Kumar Gupta

24

Problems of Fungal Contaminants and Cultivation Strategies of Certain Medicinal Mushrooms . . . . . . . . . . . . . . . . . . . . . . . . . . 611 Rashmi Mishra

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus florida on Cellulosic Waste of Cotton and Paper . . . . . . . 629 Nisha, Aesha Chhatbar, Harsiddhi Chhatbar, and Arun Arya

Mushroom Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 653 Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 659

Editors and Contributors

About the Editors Arun Arya, Ex-Head, Department of Environmental Studies in The Maharaja Sayajirao University of Baroda, Vadodara, India. He is a botanist, phytopathologist, philatelist, and a popular science writer. He is a fellow of Indian Botanical Society and Indian Phytopathological Society. He is a recipient of Young Scientist award by DST and V. Puri Gold Medal by Indian Botanical Society. He specializes in fungal taxonomy, aerobiology, and mycorrhizae. He has worked on deterioration of Egyptian Mummy and cochaired the session in 12th World Forestry Congress at Canada. He has published 150 papers and 15 books including Management of Fungal Plant Pathogens, published by CABI. Katerina Rusevska is Associate Professor at the Institute of Biology, Faculty of Natural Sciences and Mathematics, UKIM, Macedonia. Her fields of interest include mycology (General Mycology, Fungi of Macedonia), nutritional aspect of mushrooms, medicinal mushrooms, and methods in biology teaching for teachers in primary and secondary schools as well. Since 2019 she is General Secretary of European Mycological Association and Secretary of the scientific journal Biologia Macedonica. An expert on molecular identification, she has guided 13 scientific projects. She has more than 52 research papers in international journals and 10 chapters in books to her credit and has presented 45 papers in conferences.

Contributors Krishnendu Acharya Molecular and Applied Mycology and Plant Pathology Laboratory, Centre of Advanced Study, Department of Botany, University of Calcutta, Kolkata, West Bengal, India

xv

xvi

Editors and Contributors

Muhammad Akram Department of Eastern Medicine, Government College University, Faisalabad, Pakistan Susy Albert Department of Botany, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India Uzma Altaf Department of Botany, University of Jammu, Jammu, Jammu and Kashmir, India Paola Angelini Department of Chemistry, Biology, Biotechnology, University of Perugia, Perugia, Italy Arun Arya Department of Environmental Studies, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India Chitra Arya Environmental Science Programme, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India Gianluigi Bertuzzi Higher School of Systemic Aesthetic Medicine, Tivoli, RM, Italy Ankita Bhatt Department of Environmental Studies, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India Eleonora Čapelja Department of Biology and Ecology, Faculty of Sciences, Trg D. Obradovića 2, University of Novi Sad, Novi Sad, Serbia Aesha Chhatbar Parul Institute of Applied Science, Waghodia, Gujarat, India Harsiddhi Chhatbar Department of Environmental Studies, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India Sunil K. Deshmukh TERI–Deakin Nano Biotechnology Centre, The Energy and Resources Institute, New Delhi, India Ajinkya G. Deshpande UK Centre for Ecology and hydrology, Edinburgh, UK Sapna Devi Department of Botany, University of Jammu, Jammu, India Carolina Elena Girometta Department of Earth and Environmental Sciences, Università degli Studi di Pavia, Pavia, Italy Manish Kumar Gupta SGT College of Pharmacy, SGT University, Gurugram, HR, India Satish Kumar Gupta School of Agriculture, Shoolini, University of Biotechnology and Management Sciences, Solan, Himachal Pradesh, India Sead Hadžiablahović Environmental Podgorica, Montenegro

Protection

Agency

of

Montenegro,

Editors and Contributors

xvii

Kalani K. Hapuarachchi State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, China The Engineering Research Center of Southwest Bio–Pharmaceutical Resources Ministry of Education, Guizhou University, Guiyang, Guizhou Province, China Center of Excellence in Fungal Research, Mae Fah Luang University, Chiang Rai, Thailand The Mushroom Research Centre, Guizhou University, Guiyang, China N. S. K. Harsh Forest Research Institute, Dehradun, India S. A. J. Hashmi Department of Botany, University of Jammu, Jammu, Jammu and Kashmir, India Imtiaz Hussain Department of Food Technology, Faculty of Agriculture, University of Poonch, Rawalakot, Azad Kashmir, Pakistan Shin Hyun-Jae Department of Biochemical and Polymer Engineering, Chosun University, Gwangju, South Korea Savita Jandaik Department of Plant Pathology, Dr. Y S Parmar University of Horticulture and Forestry Nauni, Solan, Himachal Pradesh, India Kab-yel Jang Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, South Korea Srishti Johri Department of Biosciences, Jamia Millia Islamia University, New Delhi, India Maja Karaman Department of Biology and Ecology, Faculty of Sciences, Trg D. Obradovića 2, University of Novi Sad, Novi Sad, Serbia Gordana Kasom Environmental Protection Agency of Montenegro, Podgorica, Montenegro Fahad Said Khan Department of Eastern Medicine, Faculty of Medical and Health Sciences, University of Poonch, Rawalakot, Azad Kashmir, Pakistan Somanjana Khatua Molecular and Applied Mycology and Plant Pathology Laboratory, Centre of Advanced Study, Department of Botany, University of Calcutta, Kolkata, West Bengal, India Department of Botany, Krishnagar Government College, Nadia, West Bengal, India Anup Kumar CSIR-Central Institute of Medicinal and Aromatic Plants (CIMAP), Lucknow, UP, India Hariprasath Lakshmanan Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore, India K. Madhusudhanan Department of Botany and Research Centre, St. Albert’s College (Autonomous), Ernakulam, Kerala, India Sunanda Mandal Nadia, West Bengal, India

xviii

Editors and Contributors

Chakravarthula Manoharachary Department of Botany, Osmania University, Hyderabad, India Juan Camilo Rodriguez Martinez Independent Mycology Research Project, Sociedad Colombiana de Micología, Bogotá, Colombia Angel Mathew Department of Statistics, Maharaja’s College, Ernakulam, Kerala, India Rashmi Mishra Biotechnology, Noida Institute of Technology, Greater Noida, UP, India Swadeshi Science Movement of India, Delhi, India Praveen Kumar Nagadesi Department of Botany, St. Josephs College, Bangalore, Karnataka, India Yash Vignesh Nair Amity Institute of Microbial Technology, Amity University, Noida, Uttar Pradesh, India Nisha Environmental Science Programme, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India Mustafa Nadhim Owaid Department of Heet Education, General Directorate of Education in Anbar, Ministry of Education, Anbar, Iraq Department of Environmental Sciences, College of Applied Sciences, University of Anbar, Anbar, Iraq Milana Rakić Faculty of Sciences, University of Novi Sad, Novi Sad, Serbia Jegadeesh Raman Department of Biochemical and Polymer Engineering, Chosun University, Gwangju, South Korea Milena Rašeta Department of Chemistry, Biochemistry and Environmental Protection, Trg D. Obradovića, Novi Sad, Serbia Anil Satpathy Ma Saabi Mushrooms, Vadodara, Gujarat, India Sanjai Saxena Department of Biotechnology, Thapar Institute of Engineering & Technology (Deemed to be a University), Patiala, Punjab, India AGPharm Bio-Innovations LLP, STEP-TIET, Patiala, Punjab, India A. Selvapandiyan J H Institute of Molecular Medicine, School of Interdisciplinary Studies and Technology, Jamia Hamdard, New Delhi, India Susmita Sett Molecular and Applied Mycology and Plant Pathology Laboratory, Centre of Advanced Study, Department of Botany, University of Calcutta, Kolkata, West Bengal, India N. K. Shahina Department of Botany and Research Centre, St. Albert’s College (Autonomous), Ernakulam, Kerala, India

Editors and Contributors

xix

Yash Pal Sharma Department of Botany, University of Jammu, Jammu, Jammu and Kashmir, India S. P. Pourush Shrikhandia Department of Botany, University of Jammu, Jammu, India Neha Singh Department of Environmental Studies, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India Kandikere R. Sridhar Department of Biosciences, Mangalore University, Mangalore, Karnataka, India Geeta Sumbali Department of Botany, University of Jammu, Jammu, India Roberto Venanzoni Department of Chemistry, Biology, Biotechnology, University of Perugia, Perugia, Italy T. C. Wen State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, China The Mushroom Research Centre, Guizhou University, Guiyang, China

Part I

Applications and Cultivation of Mushrooms

Chapter 1

Beauty, Diversity, and Potential Uses of Certain Macrofungi Sunanda Mandal

Abstract Macrofungi are diverse in their uses as good source of protein in our diet, nutraceuticals, cosmeceuticals medicine, and for making beautiful art pieces. Several species serve as decomposers and many form mycorrhizal associations with plants. The commercial cultivation of several macrofungi has been steadily increasing globally. Cultivation of Cordyceps militaris can be done in a variety of media including silkworm pupae, rice, or liquid nutrition. Macrofungi are diverse with complex and highly varied growth conditions and bioactive constituents, most macro-fungal resources have not yet been fully explored and implicated, leading to an urgent need for appropriate strategies to address the problem. Increasing attention has been paid to the cultivation and application, of these fungi as potential probiotics. The accumulated secondary metabolites in medicinal mushrooms have been widely accepted as sources of safe and effective nutraceuticals, cosmeceuticals, and pharmaceuticals. Various mushrooms are utilized as foods appreciated for their exquisite flavour and are used extensively for their medicinal properties. Recently, we saw how an invisibly small entity an ultramicroscopic virus created a turmoil in dynamic ecosystem of the planet Earth and caused the human societies to grind to a halt. Of course, human lives have pivoted around the metabolic ingenuity of fungi for a long time and these organisms can still be the tools to learn the intricacies of life, their mutualistic behaviour with other organisms and potential to produce a large number of secondary metabolites useful to fight diseases and providing good memory and better health are our present day concerns. Entangled body of tubes can teach the lessons of human survival in this crucial time of Corona pandemic. These macrofungi could modulate immune cell’s response and possess antimicrobial, antioxidants, and anticancer properties. In Western Ghats as well as Himalayan mountain ranges of India, the lush green vegetation supports a variety of naturally occurring macrofungi. Brief details of

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-98116-6257-7_1) contains supplementary material, which is available to authorized users. S. Mandal (*) Sai Apartment, Krishnanagar, West Bengal, India © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_1

3

4

S. Mandal

some of the well-known fungi found in India, Macedonia, and other parts of the world are highlighted in this chapter. Keywords Beauty · Diversity · Uses · Macrofungi · Food · Medicine · Secondary metabolites

1.1

Introduction

Fungi are the most diverse organisms on earth and are defined as a eukaryotic, heterotrophic which is devoid of chlorophyll and obtains its nutrients by absorption and reproduces by means of spores (Taylor et al. 1998). Fungi string their way through the soil, through sulphurous substratum on ocean beds, occurring on coral reefs, inhabiting leaves, roots, and shoots of the plants. Bacteria use its mycelial networks as highways to navigate the bustling wilderness of the soil (Sheldrake 2020). The tiny microbes help in recycling of nutrients through ecosystems using their tubular networks. These can be associated with termites, insects, and can cause human diseases. These smart creatures of nature known as fungi embody the most basic principle of ecology: that of the relationships between organisms. They can live saprobically, parasitically or in mutualistic symbiosis termed as endophytes. Their evolution on earth is a learning lesson for all human beings. Their survival strategies in stressed environment and methods of reproduction are unique. Macro or large fungi are those that form fructifications visible without the aid of the microscope and include members of Basidiomycota and Ascomycota with large observable spore bearing structures (Servi and Akata 2010). Kasischke (2016) wrote about these mushrooms: Mushrooms Like silent naked monks huddled Around an old tree stump, having Spun themselves in the night Out of thought and nothingnessAnd God so pleased with their silence He grants them teeth and tongues Like us How long have you been gone? A child’s hot tears on my bare arms. (www.poemhunter.com/poem/mushrooms-11)

Ecologically, terrestrial macrofungi are saprobes or mycorrhizal symbionts, but some may be pathogenic on plants. Fungi of various taxonomic groups producing conspicuous sporocarps are collectively known as macrofungi. These include “gilled fungi”, “jelly fungi”, “coral fungi”, “stink fungi”, “bracket fungi”, “puffballs”, “truffles”, and “birds nest” (Enow 2013). Mushrooms are widespread in nature and they still remain as the earliest form of fungi known to mankind (Okhuoya

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

5

et al. 2010). Mushrooms can be classified in to four categories; edible mushrooms, medicinal mushrooms, poisonous or toadstools, and other mushrooms. The fleshy or soft mushrooms fall in to the edible mushroom category (Agaricus bisporus (J.E. Lange) Imbach) and mushrooms which possess medicinal properties belong to the medicinal mushrooms (Ganoderma lucidum (Curtis) Karst). Thirdly, mushrooms that are being toxic fall in to poisonous mushrooms (Amanita phalloides (Vaill ex Fr.) Link) and a miscellaneous category that tentatively grouped as other mushrooms (Hawksworth 1974; Chang and Miles 2004). Generally, they use fascinating methods for dispersion of their millions of spores (Purves et al. 1994). Growing of mushrooms in ring is common. It is said that during rains fairies dance with joy and when they are tired they sit on these heavenly structures termed as mushrooms. Famous English poet William Shakespeare (1623) wrote in The Tempest (Shakespeare 2004) entitled—If you see a Fairy Ring: If you see a fairy ring In a field of grass, Very lightly step around, Tiptoe as you pass, Last night fairies frolicked there, And they’re sleeping somewhere near, If you see a tiny fay. Lying fast asleep, Shut your eyes and run away, Do not stay or peep; And be sure you never tell, Or you’ll break a fairy spell.

The fairy ring mushroom (Marasmius oreades (Boltan) Fr.) is an edible species that is associated with fairy ring formation. In the British Isles it was believed that grass inside the fairy ring was poisonous, and animals who grazed there would be struck by disease (Findlay 1982). This concern was even shown up in Shakespeare’s The Tempest: Ye elves of hills, brooks, standing lakes and groves, And ye that on the sands with print less foot Do chase the ebbing Neptune and do fly him When he comes back; you demi-puppets that By moonshine do the green sour ringlets make, Whereof the ewe not bites, and you whose pastime Is to make midnight mushrooms . . . (Shakespeare 2004, originally published in 1623, p. 146)

Mushroom was depicted prominently on the cover page of children’s story book written by Lewis Carroll (1865) (Fig. 1.1). Using plant/macro-fungal species ratio data current estimate of macrofungi is between 53,000 and 110,000 species. This list included 21,679 names of macrofungi compiled by Mueller et al. (2007). The percentage of new inclusions from temperate Asia were 37% and from Australasia 72%. About 3000 species from over 30 genera

6

S. Mandal

Fig. 1.1 Cover page of children’s story book “ Alice in wonder land” written by Lewis Carroll (1865). (Source: Pinterest)

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

7

of these known species are known as prime edible mushrooms. So far, around 100 species were grown experimentally. Among them, about 30 mushrooms have been cultivated on a commercial basis and 60 species were cultivated on economic base concepts. However, only 15 species are exploited on industrial scale (Hawksworth 2001; Lindequist et al. 2005). The traditional use of macrofungi in generating bioactive metabolites has long been established and the experience in ethno medicinal use of macrofungi suggests the greater potential of mushrooms for successful bioprospecting (Lindequist et al. 2005).

1.1.1

What Are Mushrooms?

Mushrooms are foods that are commonly consumed since earliest history; ancient Greeks believed that mushrooms are a source of strength for warriors in battle; the Romans regarded mushrooms as the “Food of the Gods” served them only on festive occasions. For centuries, the Chinese culture has treasured mushroom as a health food, an “elixir of life” (Liu et al. 2012). Mushrooms are originally defined as macrofungi with a distinctive fruiting body, which is large enough to be seen with the naked eye and picked by hand. These are devoid of the green pigment chlorophyll. The enzymes present enable them to degrade complex organic matter into soluble substances, which can be absorbed for nutrition and stored as secondary metabolites. The growth and fruiting of an individual mushroom species on particular substrate will depend upon their ability to produce enzymes that degrade the major component of the substrate such as cellulose, hemicelluloses, and lignin (Lallawmsanga et al. 2018).

1.1.2

Stages in Life Cycle of Basidiomycetous Fungi

The life cycle of basidiomycetes includes special stages such as the alternation ofgenerations (Alexopoulos et al. 1996). Spores from basidium are generally produced for sexual reproduction, rather than asexual reproduction (Gadgil 2005). The club-shaped basidium carries four basidiospores. In the basidium, nuclei of two different mating strains ( and +) fuse (karyogamy), giving rise to a diploid zygote that then undergoes meiosis. The haploid nuclei migrate into basidiospores, which germinate and generate monokaryotic mycelium. The mycelium that results is called a primary mycelium. Mycelia of different mating strains can combine and produce a secondary mycelium that contains haploid nuclei of two different mating strains. This is the dikaryotic stage of the basidiomycetes lifecycle, which also referred to as dominant stage. Poet L.J. Finnigan wrote about Mushrooms.

8

S. Mandal

I am Omega My mycelium creeps Beneath the earth Whatever you are I am less The bottom line To deny it Would be disservice To my essence. . .. . .. . . . (ALF Creations @The Star Heart Café: Omega)

Basidiospores germinate to form a primary mycelium, it meets with another basidiospore or a primary mycelial cell to form a secondary mycelium, which transforms in to a fruiting body termed a basidiocarp. These may protrudes above the soil (epigeous) or formed below the surface as hypogeous macrofungi, like truffles. The basidiocarp bears the basidia on the gills under its cap. In the phylum Basidiomycota, sexual reproduction is often dictated by two independent sets of mating-type specific genes, which control the stages of the sexual cycle. The genes encode premating lipopeptide pheromones and their cognate receptors mediate the recognition of mating partners, cell fusion, and homeodomain transcription factors, which form heterodimers to regulate post-mating behaviour. Sexual reproduction help in promoting the genetic variation, and required adaptations to survive in fluctuating environments (Maia et al. 2015).

1.2

Diversity and Uses of Certain Macrofungi

Many macrofungi colonize organic substrates and wood and this capability has been exploited to produce fruiting bodies for commercial use (Leatham 1982; Zadrazil 1974). Biotechnological approaches have been applied for white-rot fungi shiitake and oyster to degrade hard wood logs (Zabel et al. 2020). The use of pine wood saw dust can be further utilized as feed for animals and has a definite role in circular economy (Grimm and Wosten 2018). A brief account of some of the dominant mushrooms of India and certain other cosmopolitan species are mentioned in the following. Their morphological characters and uses are described.

1.2.1

Agaricus L.

It is an important genus of mushroom containing both edible and poisonous species with over 400 members worldwide (Karunarathna et al. 2016) and 127 from India (Bilgrami et al. 1991; Upadhyay et al. 2017). The genus is named after Agarica district in Sermatica province of Russia, it includes the common button mushroom (Agaricus bisporus (J.E. Lange) Imbach) and field mushroom (Agaricus campestris

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

9

L.). Members of Agaricus are characterized by having a fleshy pileus from the underside gills that produced the naked spores (Yeh et al. 2011). The pileus of basidiocarp is elevated by a stipe and a partial veil protects the gills and later forms a ring on the stalk. Agaricus spp. are also called as button mushroom, white mushroom, table mushroom, champignon mushroom, crimini mushroom, Swiss brown mushrooms, Roman brown mushrooms, and Italian mushroom, etc. Kaur et al. (2017) reported 11 species from Northwest India out of these 5 species were edible, whereas A. blazei was identified as cure for cancer, diabetes, and hepatitis.

1.2.2

Amanita Pers.

The beauty of mushroom Amanita muscaria (L.) Lam is depicted in fairy tale literature of books, pictures on postcards, and images were depicted on silver screen when motion pictures spread across America in 1900s (Fig. 1.4e). It was believed that wherever thunderbolt had stricken the earth, A. muscaria emerged from an egg like body (Lowy 1974). The first published account of the effects of A. muscaria or fly agaric on man was made by von Strahlenburg (1730), a Swedish Colonel. He spent 12 years of his life in Siberia as a prisoner of war. “These accounts were later mentioned by Oliver Goldsmith in his book, Citizen of the World”. In the 1970s, a German botanist named Georg Wilhelm Steller noted that reindeerconsumed A. muscaria and they easily become addicted, and as a result, their flesh would have the chemicals of this mushroom. Amanita shows ecto-mycorrhizal association with birch (Betula utilis) trees in Kedarnath area of Himalaya, Uttarakhand, India. In the Scandinavian Peninsula, the indigenous Sami people used to perform healing rituals using the red-and-white toadstool that they considered holy. So holy, in fact, that the shamans used to dress up like the mushrooms for their visit. What does this storied fungus contain? Unlike “magic mushrooms” which contain psilocybin, the psychoactive components present in A. muscaria were ibotenic acid and muscimol. According to the Erowid Centre, a non-profit dedicated to collecting and disseminating information about psychoactive plants and chemicals, a common dose of Amanita muscaria is approximately between 5 and 10 g (https://erowid.org/general/ announce/monthly_current.shtml June 30th 2021). Also unlike psilocybin, the effects of A. muscaria tend to be slightly less euphoric, and are generally more variable. A. muscaria can be consumed by the Koryak people in Siberia in the urine of shamans who had eaten the mushroom. It should be noted that there are other members of the Amanita genus that are highly toxic and dangerous.

1.2.3

Bisporella Sacc.

Bisporella (Fig. 1.2a) was originally described by August Batsch (1789) as Peziza citrina. Richard Korf noted that since Bisporella was published by Pier Andrea

10

S. Mandal

Fig. 1.2 Decorative paintings of (a) Bisporella citrina and (b) Craterellus cornucopioides. (Source: Author)

Saccardo in 1884, it had priority over Boudier’s 1885 Calycella. Calycella has since been folded into Bisporella. The specific epithet citrina is derived from the Latin citrin, meaning “lemon yellow”. Common names for the fungus include “yellow fairy cups”, and the British Mycological Society-approved “lemon disco”; the name “disco” is short for Discomycetes. B. citrina, commonly known as yellow fairy cups or lemon discs, is a species of the white spored fungus in the family Helotiaceae. The fungus produces tiny yellow cups on decaying wood without bark. Fruit bodies begin as spherical, closed globules, before expanding. The stalk is broad, pale yellow in colour, and short. Fruit bodies that have dried were wrinkled and have a dull orangish-brown colour. The fruit bodies have no distinctive taste nor odour, and are not edible.

1.2.4

Calocybe Kühner ex Donk

Calocybe indica, or milky-white edible mushroom, native to India, which appears in summer after rainfall in fields, on road sides, and on rich organic matter. It is grown commercially in several Indian states and other tropical countries and traditionally eaten in West Bengal for medicinal purposes (Philips and Roger 2006). The robust mushroom is all-white and has a firm consistency. Its cap is 10–14 cm across, convex initially before flattening out with age. The cuticle can be easily peeled off the cap. The crowded gills are white, with 10 cm cylindrical stipe has no ring or volva. It has a sub-bulbous base. A saprobic mushroom may also form ectomycorrhizae with the roots of the coconut (Cocos nucifera).

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

1.2.5

11

Calvatia Fr. (Giant Puff ball)

Calvacin was the most frequently used natural product derived from a mushroom, which display strong antitumor activity. It has been isolated from the Calvatia gigantea which belongs to giant puffballs. Its activity was found against various experimental tumours, including Sarcoma 180, mammary adenocarcinoma 755, leukaemia L-1210, and HeLa cell lines (Lucas et al. 1957). A village population in Kashmir using puff balls in their diet has never reported any cancer. The discovery of novel antitumor substances from mushrooms has become a matter of great significance (Gao et al. 2002).

1.2.6

Craterellus Sacc

Craterellus cornucopioides (L.) Pers. (Fig.1.2b) is an edible mushroom. These are unattractive but have good flavour, the flavour still improves when dried. These are known as black chanterelle, black trumpet, trompette de lamont (French), trombetta dei morti (Italian) or trumpet of the dead. The Cornucopia, in Greek mythology, referred to the horn of Amalthea’s goat that filled itself with whatever meat or drink its owner requested. It has become the symbol of plenty. The fruiting body is funnel shaped expanded at the top. The upper and inner surface is black or dark grey, and the lower and outer fertile surface is a much lighter shade of grey. Wrinkled fertile surface with two spored basidia. The possible origin for the name trumpet of the dead is that the growing mushrooms were seen as being played as trumpets by dead people under the ground. Apparently these are mycorrhizal; associated with conifers in wet conifer bogs; growing gregariously, often in moss. Cap: 2–6 cm across; shallowly to deeply vaseshaped; bald, or with innate brown fibrils; brown to brownish orange; fading to tan. Stem: 2.5–5.5 cm long; 4–11 mm thick; equal, or tapered slightly toward the base; hollow; bald; lubricous; bright orange; basal mycelium white. KOH negative on cap surface. The mycelium has clamp connections.

1.2.7

Cyathus Haller (Bird’s Nest Fungus)

Saprobic basidiomycetous fungus Cyathus is known as bird’s nest fungus. Although mentioned by Carolus Clusius in 1601 in Rariorum plantarum historia it was named by Swiss scientist A. vanHaller in 1768. Arya (2004) collected trumpet like 10–14 mm size bird’s nest fungi or peridia produced on fallen leaves of bamboo in the arboretum of Botany Department, M.S. University of Baroda. Garnett in 1958 demonstrated that light of less than 530 nm was essential for heterokaryotic mycelium of Cyathus to produce fruiting bodies. The fungus is positively phototropic and

12

S. Mandal

requires proper temperature and moisture. By breaking the epiphragm a membrane the peridioles or the eggs are exposed. Webster and Webster (1997) have described technique to culture C. stercoreous in organic soil. Medicinally important cyathane diterpenes have been isolated from C. africanus (Han et al. 2012) and C. hookeri (Xu et al. 2013) which show antiinflammatory, neuroprotective and anti-cancerous properties.

1.2.8

Ganoderma P. Karst. (Reishi Mushroom)

The genus was named by Karsten in 1881. Growing on trees this woody polypore Ganoderma can be differentiated from others because of double-walled truncate basidiospores. The name Ganoderma is derived from the Greek ganos “brightnesssheen” or “shining” and derma “skin” (Florian et al. 2016). Ganoderma is characterized by basidiocarps that are large, perennial, and brackets like, called as “conks”. They are lignicolous, leathery either with or without a stem. The fruit bodies typically grow in a fanlike or hoof like form on the trunks of living or dead trees. Phylogenetic analysis using DNA sequences derived from mitochondrial Small Subunit (SSU) rDNA has helped in our understanding of the relationships among Ganoderma species. Kozarski et al. (2012) studied the antioxidant and immunomodulatory properties of glucans from G. lucidum and G. applanatum with respect to their potential application in food, and reported a significant free radical scavenging activity and protective action against lipid peroxidation, as well as significant enhancement of interferon synthesis in human blood cells. G. applanatum is very widely distributed and common species, found all year round. It lives as a saprobe on logs, stumps, or as a parasite on living trees of numerous hardwood genera, more rarely on conifers. In the Republic of Macedonia it has generally been found on fallen trunks, rotten wood, logs, and stumps of Fagus, Alnus glutinosa, Pinus nigra, and Abies. It is also registered on Quercus, Acer pseudoplatanus, and Populus tremulae, which are new substrates. It is a very common species, which has been found on more than 20 localities and following ten are new for Macedonia: mountains of Belasica, Gradishki Planini, Karadzica, Karaorman, Korab, Kozjak (between Nidze Mt. and Kozhuf Mt.), Maleshevski Planini, Osogovski Planini, Skopska Crna Gora, and vicinity of city Skopje. Fruiting bodies of G. carnosum are annual laterally to eccentrically stipitate causing white rot on conifers and Abies (Bernicchia et al. 2007). G. lucidum survives as a saprobe, fruiting body is annual, centrally to laterally stipitate with a thin, shiny or varnished crust on the pileus. The G. lucidum group has 220 species (Ryvarden and Gilbertson 1993). G. resinaceum is another parasitic species, growing alone or in groups usually at the base of living broadleaved trees. The basidiocarps are perennial, dimidiate with upper surface having a dull, thin resinous layer.

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

1.2.9

13

Grifola Grey (Maitake Mushroom)

It is a polypore mushroom that grows in clusters of usually oak trees. The greyish brown fruit bodies of mushroom Grifola frondosa (Dicks.) Grey are usually of the size of 60 cm. The under surface of each cap bears approximately 1–3 pores per mm with the tubes rarely deeper than 3 mm. The milky-white stipe (stalk) has a branchy structure and becomes tough as the mushroom matures. G. frondosa is a perennial fungus that often grows in the same place for a number of years in succession. It is prized in traditional Chinese and Japanese herbology. Most Japanese find it tasty and the texture is enormously appealing, though the mushroom has been alleged to cause allergic reactions in rare cases and becomes inedible such as all polypores when they are older because it is too tough to eat (Yeh et al. 2011).

1.2.10 Lentinus Fr. (Shiitake) This macrofungi belong to the family Marasmiaceae of Polyporales widely spread in subtropical regions. The name, Lentinus (syn. Lentinula), is derived from the Latin word lent, meaning “pliable”, and inus, meaning “resembling”. Lentinus spp. possess extracellular enzymes and thus act as wood-decaying basidiomycetes, gregarious on fallen wood of a wide variety of deciduous trees such as Shiia, oak, chestnut, beech, maple, sweetgum, cotton, alder, hornbeam, and mulberry in a warm or moist climate (Pegler 1983). The geographic distribution of L. edodes (Berk.) Singer in nature is widely extended through the various continents such as Asia, Europe, Australia, Africa, and America, and often time it is utilized as a medicinal mushroom. Pegler (1983) correlated morphological differences with geographic distribution of Shiitake: Lentinula lateritia in Southeast Asia and Australasia and L. novaezelandieae in New Zealand. Other species of Lentinus include: L. crinitus and L. tigrinus (Stamets 2000). Lentinus is valued for its lantinan content useful in cancer and HIV cures. Krüzselyia et al. (2020) reported that peel and gills contain more antioxidant quality than inner peel and stipe. Log cultivation of the mushroom was known in China during the Sung Dynasty (960–1127 AD). Synthetic log cultivation method was suggested by Arya and Arya (2003). Japan accounts for 80% of worldwide shiitake production; China exports considerably more than Japan now. The city of Qingyuan is said to produce 50% of the world’s shiitake mushroom (Halpern 2007).

1.2.11 Lenzites Fr. Lenzites a genera of wood-decay fungi of the class Agariomycetes, in Aphyllophorales, was circumscribed by Elias Magnus Fries in 1835 and was

14

S. Mandal

reported from the parts of Europe, Asia, and Africa (Kirk 2016). The species is a white-rot pathogen living on woods; it has corky fruiting bodies in the shape of semicircular plates formed on the trunks of several types of deciduous trees. The pore surface is white to tan at initial stage but as the fruit body matures, some of the pore walls break down, forming slits with blunt partitions. This results in the characteristic of a maze like (daedaloid or labyrinthine/labyrinthiform) appearance. The tube walls are 10–30 mm long with thick walls. The smooth and elliptical basidiospores are 6–8 μm (Bhattacharjee et al. 1993). Known as bioremidiator Lenzites spp. have many medicinal properties, i.e. antioxidant, antimicrobial, antitumor, and immunosuppressive activities, but only few species such as L. betulina and L. warnieri have been examined and documented (Barros et al. 2008).

1.2.12 Morchella Dill. ex Pers. Morel mushrooms are ascocarps of Morchella spp. After truffles these are second most sought after edible mushroom. The yellow or brown morels, i.e. M. esculenta, M. deliciosa, and M. crassipes have conical 2–8 cm high cap or pileus with a short hollow stalk. The distortions of pileus increase the surface area for the production of asci. In temperate climate the black morels (M. angusticeps) are more common. Bodies develop from sclerotia when environmental conditions are favourable. It is said the trenches, where bombing occurred during World War more morels were produced. Life cycle of morels was proposed by Thomas and Leonard (1990). Morels may have mycorrhizal association. According to Stamets (2000) the conditions of fire or floods reduces the nutrient levels as well as other competitors. There is an increase in potassium, calcium, and other minerals which promote sclerotia formation and these later on produce fruiting when suitable environmental conditions (Temp. 4–10  C and humidity 85–90%) are present.

1.2.13 Mycena (Pers.) Roussel The name Mycena comes from the Greek word “mykes” meaning mushroom. Species in the genus Mycena and in Hemimycena are commonly known as bonnets. These are small saprophytic mushrooms (Fig. 1.3a, b) with white spore print. The pileus is small conical or bell shaped with a fragile stipe, usually grey or brown but few species are coloured or bioluminescent creating a glow. Bioluminescent fungi usually attract insects. Some species are edible, while others contain a toxin, called muscarine. According to Smith (1947) the monograph of Mycena included 232 spp, which has now increased to about 500 spp. Most have a translucent and striate cap, which rarely has an incurved margin. The gills are attached and usually have cystidia. Some species, like M. haematopus exude latex and few have chlorine like odour.

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

15

Fig. 1.3 Decorative paintings of (a) Mycena leaina and (b) Mycena leaiana var. australis. (Source: Author)

1.2.14 Phellinus Quel. The name Phellinus means cork. It is a genus of the family Hymenochaetaceae. Arya (2004) reported the seven species of wood deteriorating fungi from Gujarat, India, Phellinus nilgheriensis (Mont.) Cunn. was one of these. The tough and woody or cork-like, large, brown basidiocarps of the fungi were reported by Nagadesi and Arya (2014) Phellinus sp. produce a number of natural chemicals which include phenol and bioactive phelligridins, and phellinins. In Australia, the tribe’s use Phellinus fruit bodies medicinally. The smoke produced from burning the fruit bodies was inhaled by those having sore throats. Aqueous extract made from scrapings of the slightly charred fruit bodies was taken to treat coughing, sore throats, bad chests, fevers and diarrhoea. There is some uncertainty about which species of Phellinus were used for which ailment. So importantly, polyphenolic substances isolated from mushrooms have been recognized to possess strong anticancer properties. For instance, hispolon and its derivatives were isolated from the fungus P. igniarius and have been reported to have apoptosis effect on human epidermoid KB cells (Mo et al. 2003).

1.2.15 Pleurotus (Fr.) P. Kumm. (Oyster Mushroom) Pleurotus ostreatus (Jacq.) Kummer or the pearl oyster mushroom (Fig. 1.4d) was first cultivated in Germany during World War I (Stamets 2005) and is now commercially grown around the world for food. It is relative to the similarly cultivated king oyster mushroom. This yellow oyster mushroom (P. citrinopileatus) has the bitter-sweet aroma of benzaldehyde (Stamets 2000). P. ostreatus is easily recognized

16

S. Mandal

Fig. 1.4 Decorative paintings and pictures of beautiful mushrooms. (a) A lady with mushrooms: Sketch by author (Ms. Sunanda Mandal). (b) Painting showing certain mushrooms and insectsrecollected by a common human mind (mushrooms and human head–A painting by author). (c) Painting by German Artist Fritz Baumgarten (1883–1966). (d) Fruiting in Pleurotus florida (Picture

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

17

by the way it grows on wood in shelf-like clusters; its relatively large size; its whitish gills that run down a stubby, nearly absent stem. The mushroom has a broad, fan, or oyster-shaped cap of 5–25 cm size; natural specimens range from white to grey or tan to dark-brown; the margin is enrolled when young, and is smooth and often somewhat lobed or wavy. P. ostreatus and P. eryngii var. ferulae were used as a dietary supplement, in medicine, and formulated feeds for animals (Rathore et al. 2017).

1.2.16 Russula Pers. Christian Hendrik Persoon first described the genus Russula in his 1796 work Observationes Mycologicae, and it was characterized by the fleshy fruit bodies, depressed cap, and equal gills. Like the genus Lactarius, Russulas have fleshy gills and the stipe, and which normally makes them immediately recognizable. They have no veil and the gills are brittle except in a few cases, and cannot be bent parallel with the cap without breaking. They have brittle or splitting gills and do not exude a milky substance at cut surfaces, contrary to the Lactarius. Presence of large spherical cells, “sphaerocysts”, in the stipe is an important characteristic feature to distinguish the members of Russulaceae from other mushrooms. In Russula, the stipe breaks like the flesh of an apple, while in others it breaks into fibres. The spore powder varies from white to cream or even orange. Among the Indian Russulaceous mushrooms few like R. cyanoxantha and R. virescens are more delicious (Atri et al. 2010). R. emetica is another mushroom which is dried and used as substitute for chilli powder (Arora 1986). Carboxylic acid was found in R. cyanoxantha (Ribeiro et al. 2008). A peptide extracted from R. paludosa has been reported to show HIV-1 reverse transcriptase inhibitory activity (Wang et al. 2007), and antitumor activity by R. lepida (Atri et al. 2016).

1.2.17 Termitomyces R. Heim We are familiar how ancient women collected few grains and grew them in their backyards during rainy season year after year and thus the practice of agriculture was evolved by man. But you will be surprized to note that a group of termite called Macrotermitinae (Termitidae) practices the cultivation of fungi Termitomyces for its food. It is a mushroom forming fungi. The Macrotermitinae and their  ⁄ Fig. 1.4 (continued) by A. Arya). (e) Uploaded by WEIRDLAND TV Mushroom postcards by German artist, Heinz Geilfus (1890–1956) a painting of Amanita. (f) Beautiful basidiocarp of Trametes versicolor

18

S. Mandal

associated fungi are mutually dependent on each other, because free-living representatives of both partners have never been found. The termites provide a suitable, highly regulated growth environment for the fungi, even they sprinkle water to make the environment humid in a termite hole. The termites propagate the fungi in largescale monoculture, via asexual spores inoculated in their faeces. The fungi help in providing the food for the termites (Rouland-Lefèvre and Bignell 2001). The symbiotic fungi descend from a single domestication some 30 million years ago in central tropical Africa. The ecologically highly successful association has allowed the colonization of savannas and several members migrated from Africa to Asia. The detailed symbiotic interactions and genetics of Termitomyces is studied by Nobre et al. (2011). Termitomyces titanicus is the world’s largest mushroom according to Guinness Book of records. It has a pileus of the size of 1 m, although other species T. microcarpus may be as small as 2 cm. Twenty-three edible species of Termitomyces are reported from 35 countries. The genus is highly esteemed and many species are widely consumed with high nutritional value. The mushrooms are collected throughout Africa and are used widely in Asia. Notable species include T. clypeatus, T. microporus, and T. striatus. The species are medicinally important and are regarded good for enhancing memory (Wei and Yao 2003).

1.2.18 Tremella Pers. Tremella name comes from the Latin tremere means “to tremble”. Linnaeus placed Tremella in the algae including seaweeds, cyanobacteria, and myxomycetes as well as fungi, but Persoon revised Tremella in 1794 and 1801. He repositioned and considered Tremella as a genus from the originally created by Linnaeus (Tremella L.). Tremella Pers. has now been conserved under the International Code of Botanical Nomenclature with T. mesenterica as a type species (Masuda et al. 2008). Species of Tremella are parasites of other wood rotting fungi and most of these produce anamorphic yeast states, when basidiocarps are produced; they are gelatinous and colloquially classed among the “jelly fungi”. Over 100 species of Tremella are currently recognized worldwide. It is polyphyletic. Two species, namely T. fuciformis and T. aurantialba are commercially cultivated for food (Deng et al. 2009). Although considered bland and flavourless, the fungus is edible. T. mesenterica produces various biologically active compounds (Regulo et al. 2013).

1.3

Medicinal Uses of Macrofungi

Several biologically active compounds such as polysaccharides (β 1–3, 1–4, 1–6 glucans, hetero-β glucans, proteo-glucans), krestin, lentinan, coriolan, schyzophillan, sesquiterpenes, quinones, hydrophobins, galectins, sterols,

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

19

ergothionin, tri-teripenes, sterols, germanium, nucleotide, drosophilin, armillasin, amphalone, eloporoside, and volatile (skatole) were reported in medicinal mushrooms (Lindequist et al. 2005). Mushrooms are the producers of extracellular proteolytic enzymes with fibrinolytic and thrombolytic activities (El-Batal et al. 2015). The presence of wide biomolecules in medicinal mushrooms has been attributed to different therapeutic effects such as antibacterial, antifungal, cytotoxic, anti-inflammatory, insecticidal, nematocidal, and antioxidant (Zhang et al. 2016). Mushrooms are known to contain substances such as antibacterial, antifungal, anti-inflammatory, anticancer, antiviral, antiparasitic, antioxidant, antiproliferative, cytotoxic, antidiabetic, anti-HIV, hypocholesterolemic, anticoagulant, and hepatoprotective compounds (Thatoi and Singdevsachan 2014; Mau et al. 2004). Some ordinary bioactive compounds isolated from the macrofungi encompass glycolipids, flavonoids, aromatic phenols, compounds derived from shikimic acid, polyketides, fatty acid derivatives, polyacetylamine, sesterterpenes, and nucleosides (Lorenzen and Anke 1998).

1.3.1

Isolation and Characterization of Secondary Metabolites

A variety of secondary metabolites are produced by macrofungi in response to external stimuli including nutritional or climatic alterations (Calvo et al. 2002). Majority of the biomasses produced by macrofungi are naturally available in the form of inert, insoluble, and as polymeric material (Ghisalberti 1993). Highly lipophilic components are extracted using hexane or chloroform, whereas highpolarity solvents such as alcohols yield a spectrum of non-polar and polar compounds from the matrix (Ghisalberti 1993). Secondly, desired components are separated from the crude extract. This is performed using liquid–liquid partition or by a number of low-resolution chromatography methods such as size exclusion and normal phase column chromatography. The final purification steps will be facilitated by concentrating the components of interest. Generally, isolation of active compounds from extracts is carried out via bioassay guided fractionations where fractions obtained after each chromatographic or solvent–solvent fractionation is subjected to the relevant bio assays to locate the active fractions which were used for the next fractionation steps (Marston and Hostettmann 1991). The third stage of the procedure includes a high-resolution method to separate the preferred compounds. The optimization of the separation method becomes vital to accomplish adequate resolution in the final preparative isolation. Commonly, the final step is performed using high-pressure liquid chromatography (HPLC), droplet counter-current chromatography (DCCC), countercurrent chromatography (CCC), and centrifugal partition chromatography (CPC) (Marston and Hostettmann 1991). One- and two-dimensional NMR experiments, proton NMR (1H-NMR), 13C-NMR, Distortion less Enhancement Polarization

20

S. Mandal

Transfer 13C NMR (DEPT13C-NMR), H–H Correlation Spectroscopy (COSY), Heteronuclear Multiple Quantum Correlation (HMQC), Heteronuclear Multiple Bond Correlation (HMBC), and Nuclear Overhauser Effect Spectroscopy (NOESY) are used to determine chemical structures of the targeted compounds (Elsa et al. 2007). Mass spectrometric methods such as High-Resolution Electrospray Ionization Mass Spectrometry (HREIMS) are used to obtain the highresolution mass spectrum of the compound. NMR spectroscopy provides detailed information regarding the chemical structure, molecular dynamics, reaction state of the molecules, and chemical environment of targeted molecules (Pople et al. 1957).

1.4

Mcrofungi Used as Nutraceuticals

Mushrooms contain the amino acids, vitamins, macro, microelements, and a substantial amount of dietary fibres. Higher Basidiomycetes have much insoluble dietary fibre bound with chitin, hemicellulose, mannans, glucans, glycogen, and trehalose in their cell wall. Cheung (2010) has reported the use of dietary fibres in prevention of constipation, colon disease, and haemorrhoids in lowering blood glucose, and strengthens immune system with antitumor activity. Mushrooms are known to possess complexes of polysaccharides and protein, which enhance innate and cell-mediated immune responses and exhibit antitumor activities in animals and humans (Lallawmsanga et al. 2016). Medicinal mushrooms contain considerable amount of essential and nonessential amino acids. Essential fatty acid (linoleic acid), a precursor of 1-octen-3-ol, has been the principal active compound that contributed to the aroma and flavour of mushrooms. The bioavailability of mineral in medicinal mushrooms, except sodium in low concentrations, has made edible mushrooms choice of food that regulate blood pressure, maintain cellular function, and promote the availability of metalloenzymes, and metabolic growth (Kim et al. 2009).

1.5

Other Uses of Macrofungi

Mushrooms are considered as dietary supplement, designers’ foods, super food, nutraceuticals as well as functional foods (Childs and Poryzees 1997). Mushrooms have short oligosaccharides which are classified as prebiotics (Thatoi and Patra 2018). Gibson and Roberfroid (1995) coined this term to non-digestible food which selectively enhances growth of microbial flora in gut. Mushrooms act as a source of enzymes, flavour ingredients (Rajarathnam and Sashirekha 2003). A Japanese proverb states that the Tricholoma matsutake is noted for its aroma and Lyophyllum shimeji is noted for its taste. The aroma components of T. matsutake are matsutakeol and methyl cinnamate. A sulphur-containing compound, lenthinic acid present in fresh L. edodes is flavourless, but it is converted by heat to lenthionin, which is responsible for the specific flavour, when L. edodes is dried. Mushrooms

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

21

are rich in protein have vitamins and tocopherol which acts as antiaging chemicals. Mushrooms are also known for their B-complex vitamins (niacin, thiamine, and B12) and folic acid. Mushrooms such as Truffles (Tuber aestivum) from France, Morels (Morchella deliciosa and M. esculenta) from Kashmir, India, and Boletus edulis from Europe are delicious. Hundreds of scent molecules waft off fresh truffles which are hypogean and once taken out will degenerate within 10 days. Truffles have peculiar smell due to 5 α- androstanol and dimethyl sulphide. Fossils of certain fungi like Mycena are known (Taylor et al. 2015). Bioluminescent fungi are investigated by Desjardin et al. (2010). These fungi are dispersed by members of arthropods, which are attracted by luminescence. Ecto-mycorrhizal mushrooms act as bioremediators and remove heavy metals by hyper-accumulation, volatilization, and biostabilization of heavy metals. Huang et al. (1997) observed hyper-accumulation of heavy metals in the presence of EDTA. In an experiment, where Pleurotus sajor-caju in modified Asthana and Hawker’s medium “A” can remediate heavy metals at lower concentrations. At higher levels of metal concentration cell membranes can damage, enzyme specificity may change, cellular functions are disturbed, and DNA structure gets damaged (Bruins et al. 2000). The mushroom biomass (living or dead) is used to immobilize and treat polluted water having heavy metals (Barr and Aust 1994). These macrofungi can easily degrade lignin and cellulose from dead plants thus help in recycling of minerals in soil. Mushroom spent left after cultivation can be used as compost (Polat et al. 2009). Mushroom cultivation is a part of circular economy and a variety of uses of spent mushroom substrates have been suggested by Grimm and Wosten (2018). Concentration of mushroom production units in a geographical area may lead to environmental problems hence avoided (Leiva et al. 2015). The hard sporophores after treatment and polishing can be utilized aesthetically as decorative pieces. Mushroom art has attracted the attention of many art lovers and its use can be seen in paintings (Fig. 1.4a–f), in porcelain kettle (Fig. 1.4e) and even mushroom shaped lamp stand (Fig. 1.4f).

1.6

Conclusions

In the last few decades, much attention has been paid to utilize the bioactive compounds present in mushrooms. Compounds such as polysaccharides may be present in carpophores, mycelium, sclerotia, or filtrates. One of the most promising features of polysaccharide-protein compounds present in fungi is its potential activity in immune-stimulating and in cancer cure. However, certain mechanisms of the activity are not yet well understood. The opinion that the mentioned compounds interact with the different immunological cells, which can cause cascade transduction of signals responsible for immunological system reaction, finds acceptance. Many macromolecules can also show the direct, cytostatic interaction with cancer causing cells, and inhibiting the process of uncontrolled growth. It is possible that

22

S. Mandal

both types of activity may be complementary. The relevance of medicinal mushrooms in modern-day pharmaceuticals and nutraceuticals is an innovative concept. This could be also a means to diversify the food produce to solve the food insecurity, malnutrition as well as possible cure for a number of diseases. The beauty of mushrooms has drawn the attention of artists and find place in a variety of products and paintings.

References Alexopoulos CJ, Mims CW, Blackwell MM (1996) Introductory mycology, 4th edn. Wiley, New York Arora D (1986) Mushrooms demystified: a comprehensive guide to the fleshy fungi. Ten Speed Press, Berkeley, p 936 Arya A (2004) In: Srivastava PC (ed) Vistas in palaeobotany and plant morphology: evolutionary and environmental perspectives, Prof D D Pant Memorial Vol. UP Offset, Lucknow, pp 321–327 Arya C, Arya A (2003) Effect of acid hydrolysis of substrate on the yield of oyster mushroom (Pleurotus sajor-caju (Fr.) Singer). Mushroom Res 12(1):35–38 Atri NS, Saini SS, Gupta AK, Kaur A, Kour H, Saini SS (2010) Documentation ofwild edible mushrooms and their seasonal availability in Punjab. In: Mukerji KG, Manoharachary C (eds) Taxonomy and ecology of Indian fungi. I.K. International Publishing House Pvt. Ltd., New Delhi, pp 161–169 Atri NS, Sharma S, Saini MK, Das K (2016) Researches on Russulaceous mushrooms-an appraisal. Kavaka 47:63–82 Barr DP, Aust SD (1994) Mechanisms white rot fungi use to degrade pollutants. Environ Sci Technol 28(2):78A–87A Barros L, Cruz T, Baptista P, Estevinho LM, Ferreira ICFR (2008) Wild and commercial mushrooms as source of nutrients and nutraceuticals. Food Chem Toxicol 46:2742–2747 Bernicchia A, Savino E, Gorjón SP (2007) Aphyl-lophoraceous wood-inhabiting fungi on Pinus spp. in Italy. Mycotaxon 101:5–8 Bhattacharjee B, Roy A, Majumder AL (1993) Carboxymethyl cellulase from Lenzites saepiaria, a brown-rotter. Int J Biochem Mol Biol 30(6):1143–1152 Bilgrami KS, Jamalludin, Rizvi AM (1991) Fungi of India. Today and Tomorrow’s Printers and Publishers, New Delhi, p 798 Bruins MR, Kapil S, Oehme FW (2000) Microbial resistance to metals in the environment. Ecotoxicol Environ Saf 45(3):198–207. https://doi.org/10.1006/eesa.1999.1860 Calvo AM, Wilson RA, Bok JW, Keller NP (2002) Relationship between secondary metabolism and fungal development. Microbiol Mol Biol Rev 66:4470–4459 Carroll L (1865) Alice in Alice’s Adventures in Wonderland (1865). Simon & Schuster, New York Chang ST, Miles PG (2004) Mushroom: cultivation, nutritional value, medicinal effect, and environmental impact, Boca Raton, CRC Press, p 451 Cheung PCK (2010) The nutritional and health benefits of mushrooms. Nutr Bull 35:292–299 Childs NM, Poryzees GH (1997) Foods that help prevent disease; consumer attitudes and public policy implications. Br Food J 9:419–426 Deng G, Lin H, Seidman A (2009) A phase I/II trial of polysaccharide extracts from Grifola frondosa (Maitake mushroom) in breast cancer patients: immunological effects. J Cancer Res Clin Oncol 135(9):1215–1221

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

23

Desjardin DE, Perry BA, Lodge DJ, Luquillo Stevani CV, Nagasawa E (2010) Luminescent Mycena: new and noteworthy species. Mycologia 102(2):459–477. https://doi.org/10.3852/ 09-197#2010 El-Batal AI, El-Kenawy NM, Yassin AS, Amin MA (2015) Laccase production by Pleurotus streatus and its application in synthesis of gold nanoparticles. Biotechnol Rep 5:31–39 Elsa C, Gerald SR, Eve T, Serge GSA, Tenailleau E, Akoka S (2007) Precise and accurate quantitative 13C NMR with reduced experimental time. Talanta 71:1016–1021 Enow E (2013) Diversity and distribution of macrofungi (mushrooms) in the Mount Cameroon Region. J Ecol Nat Environ 5(10):318–334 Findlay WPK (1982) Fungi: folklore, fiction, & fact. Mad River Press, Eureka Florian H, Zakaria C-A, Tim L, Jose GM-V, Helge BB, Meike P (2016) Distinguishing commercially grown Ganoderma lucidum from Ganoderma lingzhi from Europe and East Asia on the basis of morphology, molecular phylogeny, and triterpenic acid profiles. Phytochemistry 127: 29–37 Gadgil PD (2005) Fungi on trees and shrubs in New Zealand. In: Fungi of New Zealand, fungal diversity research series 16, vol 4. Fungal Diversity Press, Hong Kong, pp 437–458 Gao YH, Zhou SF, Chen GL, Dai XH, Ye JX (2002) A phase I/II study of a Ganoderma lucidum extract (Ganopoly) in patients with advanced cancer. Int J Med Mushrooms 4:207–214 Ghisalberti EL (1993) Detection and isolation of bioactive natural products. In: Colegate SM, Molyneux RJ (eds) Bioactive natural products: detection, isolation and structural determination. CRC, Boca Raton Gibson GR, Roberfroid MB (1995) Dietary modulation of the human colonic microbiota. Introducing the concept of prebiotics. Nutrition 125:1401–1412 Grimm D, Wosten AB (2018) Mushroom cultivation in circular economy. Appl Microbiol Biotechnol 102:7795–7803. https://doi.org/10.1007/s00253-018-9226-8 Halpern GM (2007) Heeling mushrooms : ancient wisom for better health. Squaew One Publishers, New York, 185p Han J, Chen Y, Li B, Yang X, Liu D, Li S, Zhao F, Liu H (2012) Anti-inflammatory and cytotoxic cyathane diterpenoids from the medicinal fungus Cyathus africanus. Fitoterapia 84:22–31. https://doi.org/10.1016/j.fitote.2012.10.001. Epub 2012 Oct 14 Hawksworth DL (1974) Mycologist’s handbook. Commonwealth Agricultural Bureau, Slough, p 231 Hawksworth DL (2001) Mushrooms: the extent of the unexplored potential. Int J Med Mushrooms 3:1–5 Huang JW, Chen J, Berti WR, Cunningham SD (1997) Phytoremediation of lead contaminated soils: role of synthetic chelates in lead phytoextraction. Environ Sci Technol 31:800–805 Karunarathna SC, Chen J, Mortimer PE, Xu JC, Zhao RL, Callac P, Hyde KD (2016) Mycosphere essay 8: a review of genus Agaricus in tropical and humid subtropical regions of Asia. Mycosphere 7(4):417–439 Kasischke L (2016) The infinitesimals. Copper Canyon Press. www.laurakasischke.com/ Kaur H, Kaur M, Malik NA (2017) New additions to the genus Agaricus (Agaricaceae, Agaricales) from Northwest India. Kavaka 48(2):84–94 Kim DJ, Ferrin DL, Rao HR (2009) Trust and satisfaction, the two wheels for successful e-commerce transactions: a longitudinal exploration. Inf Syst Res 20(2):237–257 Kirk PM (2016) Species fungorum. In: Species 2000 and integrated taxonomic information system (ITIS), catalogue of life. Version 23rd. Naturalis, Leiden, pp 107–111 Kozarski M, Klaus A, Niksic M, Vrvic MM, Todorovic N, Jakovljevic D, van Griensven LJLD (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 Krüzselyia D, Ágnes M, Móricza M, Vetter J (2020) Comparison of different morphological mushroom parts based on the antioxidant activity. Food Sci Technol 127:109436. https://doi. org/10.1016/j.lwt.2020.109436

24

S. Mandal

Lallawmsanga LVV, Passari AK, Mishra VK, Leo VV, Singh BP, Meyyappan GV (2016) Antimicrobial potential, identification and phylogenetic affiliation of wild mushrooms from two sub-tropical semi-evergreen Indian forest ecosystems. PLoS One 11(11):e0166368 Lallawmsanga LVV, Passari AK, Muniraj IK, Uthandi S, Hashem A, Abd-Allah EF (2018) Elevated levels of laccase synthesis by Pleurotus pulmonarius BPSM10 and its potential as a dye decolorizing agent. Saudi J Biolo Scie 26(3):464–468 Leatham GF (1982) Cultivation of shiitake, the Japanese forest mushroom, on logs: a potential industry for the United States. For Prod J 32:29–35 Leiva FJ, Saenz-diez JC, Martinez E, Jimenez E, Blanco J (2015) Environmental impact of Agaricus bisporus cultivation process. Eur J Agron 71:141–148 Lindequist U, Niedermeyer T, Jülich W (2005) The pharmacological potential of mushrooms. Evid Based Complement Alternat Med 2(3):285–299 Liu K, Wang JL, Gong WZ, Xiao X, Wang Q (2012) Antioxidant activities in vitro of ethanol extract and fractions from mushroom, Lenzites betulina. J Food Biochem 37(6):687–693 Lorenzen K, Anke T (1998) Basidiomycetes as a source for new bioactive natural products. Curr Organ Chem 2:329–364 Lowy B (1974) Amanita muscaria and the thunderbolt legend in Guatemala and Mexico. Mycologia 66(1):188–191 Lucas EH, Montesano R, Pepper MS, Hafner M, Sablon E (1957) Tumor inhibitors in Boletus edulis and other holobasidiomycetes. Antibiot Chemother 7:1–4 Maia LC, Aníbal A, de Carvalho Júnior AA (2015) Diversity of Brazilian fungi. Rodriguésia 66(4): 1033–1045. https://doi.org/10.1590/2175-7860201566407. http://rodriguesia.jbrj.gov.br Marston A, Hostettmann K (1991) Modern separation methods. Nat Prod Rep 8:391–413 Masuda Y, Murata Y, Hayashi M, Nanba H (2008) Inhibitory effect of MD-fraction on tumor metastasis: involvement of NK cell activation and suppression of intercellular adhesion molecule (ICAM)-1 expression in lung vascular endothelial cells. Biol Pharm Bull 31(6):1104–1124 Mau JL, Chang CN, Huang SJ, Chen CC (2004) Antioxidant properties of methanolic extracts from Grifola frondosa, Morchella esculenta and Termitomyces albuminosus mycelia. Food Chem 87: 111–118 Mo S, Wang S, Zhou G, Yang Y, Li Y, Chen X (2003) Phelligridins C-F:cytotoxic pyrano[4,3-c][2] benzopyran-1,6-dione and furo[3,2-c]pyran-4-one derivatives from the fungus Phellinus igniarius. J Nat Prod 67:823–828 Mueller GM, Schmit JP, Leacock PR, Buyck B, Cifuentes DJ, Kurt H, Teresa I, Karl-Henrik LD, Jean L, Tom WM, David M, Mario R, Scott AR, Leif R, James MT, Roy W, Qiuxin W (2007) Global diversity and distribution of macrofungi. Biodivers Conserv 16:37–48 Nagadesi PK, Arya A (2014) New records of Lignicolous Fungi from Ratanmahal wildlife sanctuary, Gujarat, India. International Letters of Natural Sciences, 3 Nobre T, Fernandes C, Boomsma JJ, Korb J, Aanen DK (2011) Farming termites determine the genetic population structure of Termitomyces fungal symbionts. Mol Ecol 20:2023–2033. https://doi.org/10.1111/j.1365-294X.2011.05064.X Okhuoya J, Akpaja E, Osemwegie O, Oghenekaro A, Ihayere C (2010) Nigerian mushrooms: underutilized non-wood forest resources. J Appl Sci Environ Manag 14(1):43–54 Pegler DN (1983) The genus Lentinula (Tricholomataceae tribe Collybieae). Sydowia 36:227–239 Philips N, Roger F (2006) Mushrooms, 6th edn. Macmillan, London, 266p Polat E, Uzun H, Topcuo B, Onal K, Onus AN (2009) Effect of spent mushroom compost on quality and productivity of cucumber (Cucumis sativus L.) grown in greenhouses. Afr J Biotechnol l8: 176–180 Pople JA, Bernstein HJ, Schneider WG (1957) The analysis of nuclear magnetic resonanace spectra. Can J Chem 35:65–81 Purves WK, Orians GH, Heller HCR (1994) Life: the science of biology, 4th edn. Sinauer Associates Rajarathnam S, Sashirekha MN (2003) Use of wild mushrooms. In: Mushrooms and truffles/use of wild mushrooms. Elsevier, Amsterdam, pp 4048–4054

1 Beauty, Diversity, and Potential Uses of Certain Macrofungi

25

Rathore H, Prasad S, Sharma S (2017) Mushroom nutraceuticals for improved nutrition and better human health: a review. Pharma Nutr 5:35–46. https://doi.org/10.1016/j.phanu.2017.02.001 Regulo CLH, Michele LL, Anne Marie F, Marie FO, Nathalie F, Catherine RR (2013) Potential of European wild strains of Agaricus subrufescens for productivity and quality on wheat straw based compost. World J Microbiol Biotechnol 29(7):1243–1253 Ribeiro B, Lopes R, Andrade PB, Seabra RM, Goncalves RF, Baptista P, Quelhas I, Valentao P (2008) Comparative study of phytochemicals and antioxidant potential of wild edible mushroom caps and stipes. Food Chem 110:47–56 Rouland-Lefèvre C, Bignell DE (2001) Cultivation of symbiotic fungi by termites of the subfamily Macrotermtinae. In: Seckbach J (ed) Symbiosis: mechanisms and model systems. Kluwer Academic, Dordrecht, pp 731–756 Ryvarden, Gilbertson RL (1993) European polypores (2 vols). ISBN 82-00724-12-8 (pt 1) Servi H, Akata IBC (2010) Macrofungal diversity of bolu abant nature park (Turkey). Afr J Biotechnol 9(24):3622–3628 Shakespeare W (2004) In: Mowat BA, Werstine P (eds) The Tempest. Simon & Schuster, New York (originally pub. 1623) Sheldrake M (2020)Fungi’s lessons for adapting to life on a damaged planet (Sheldrake M in conversation with Macfarlane R) Literary Hub, 12 May 2020 Smith AH (1947) North American species of Mycena. University of Michigan Press, Ann Arbor Stamets P (2000) Growing gourmet and medicinal mushrooms, 3rd edn. Ten Speed Press, Berkeley, CA, pp 259–276 Stamets P (2005) Notes on nutritional properties of culinary-medicinal mushrooms. Int J Med Mushrooms:103–110 Taylor DJ, Green NPO, Stout GW, Soper R (1998) Text book of biological science. University Press, Cambridge, p 984 Taylor TN, Krings M, Tayor EL (2015) Fossil fungi. Academic, Burlington Thatoi H, Patra JK (2018) Prebiotics and their production from unconventional raw materials (mushrooms). In: Therapeutic, probiotic, and unconventional foods Thatoi H, Singdevsachan SK (2014) Diversity nutritional composition and medicinal potential of Indian mushrooms: a review. Afr J Biotechnol 13:523–545 Thomas JV, Leonard TJ (1990) Cytology of the life cycle of Morchella. Mycol Res 94:399–406 Upadhyay RC, Verma B, Sood S, Atri NS, Lakhanpal TN, Sharma VP (2017) Documentary of Agaricomycetous mushrooms of India. Jaya Publishing House, New Delhi, 193p Wang J, Wang HX, Ng TB (2007) A petide with HIV-I reverse transcriptase inhibitory activity from the medicinal mushroom Russula paludosa. Peptides 28(3):560–565 Webster J, Webster RS (1997) Teaching techniques for mycology I. The bird’s nest fungus Cyathus stercoreus. Mycologist 11(3):103–105 Wei TZ, Yao YJ (2003) Literature review of Termitomyces species in China. Fungal Sci 22:39–54 www.poemhunter.com/poem/mushrooms-11 Xu Z, Yan S, Bi K, Han J, Chen Y, Wu Z, Chen Y, Hongwei Liu H (2013) Isolation and identification of a new anti-inflammatory cyathane diterpenoid from the medicinal fungus Cyathus hookeri Berk. Fitoterapia 86:159–162. https://doi.org/10.1016/j.fitote.2013.03.002. Epub 2013 Mar 14 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 Zabel RA, Jeffrey J, Morrell JJ (2020) Introduction to wood microbiology. In: Wood microbiology, 2nd edn. Academic Press, Boca Raton, pp 1–18. https://doi.org/10.1016/B978-0-12-819465-2. 00001-2 Zadrazil F (1974) Mushroom science IX (part I). In: Proceedings of the 9th international scientic congress on the cultivation of edible fungi, Tokyo, pp 621–652 Zhang JJ, Li Y, Zhou T (2016) Bioactivities and health benefits of mushrooms mainly from China. Molecules 21(7):938

Chapter 2

Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use Against Covid-19 K. K. Hapuarachchi and T. C. Wen

Abstract Disease outbreaks have devastated mankind throughout history, altering the course of history and, in some cases, marking the end of entire civilizations. Those incidents have had a profound impact on human civilization’s economic, political, and social importance, with consequences that may last for centuries. Today, the 2019 novel coronavirus (SARS-CoV-2) (COVID-19) spreads rapidly across the world, causing a great threat to public health and global economies. By 2021, several vaccines were produced for the battle against the COVID-19 and simultaneously more vaccine candidates are in the process of development. Despite many advancements in science, there were several reports on complications and side effects after vaccination. Furthermore, continuous emergence of new variants through mutation, lack of well-designed in vivo tests, and randomized controlled clinical studies made COVID-19 vaccination processes less effective. However, many researchers believe that mushroom-based therapeutic approaches would greatly benefit for the COVID-19 patients. Medicinal mushrooms had been used since ancient times for longevity and better health. They are used in multiple therapeutic activities as well as dietary supplements to prevent and treat many

K. K. Hapuarachchi State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, China The Engineering Research Center of Southwest Bio-Pharmaceutical Resources Ministry of Education, Guizhou University, Guiyang, Guizhou Province, China Center of Excellence in Fungal Research, Mae Fah Luang University, Chiang Rai, Thailand The Mushroom Research Centre, Guizhou University, Guiyang, China T. C. Wen (*) State Key Laboratory Breeding Base of Green Pesticide and Agricultural Bioengineering, Key Laboratory of Green Pesticide and Agricultural Bioengineering, Ministry of Education, Guizhou University, Guiyang, China The Engineering Research Center of Southwest Bio-Pharmaceutical Resources Ministry of Education, Guizhou University, Guiyang, Guizhou Province, China The Mushroom Research Centre, Guizhou University, Guiyang, China © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_2

27

28

K. K. Hapuarachchi and T. C. Wen

diseases. Several epidemiological and clinical studies have shown that mushrooms and mushroom-derived supplements can boost the efficiency of our innate and adaptive immune responses to a range of pathogens including viruses. Some of the medicinal mushrooms have shown anti-microbial activity against viral agents in vitro and in vivo. Here, we review anti-viral and anti-inflammatory properties of selected medicinal mushrooms and their potential as a candidate to combat health issues against COVID-19. Keywords Anti-viral activity · Medicinal properties · Global pandemic · Immunomodulation

2.1

Introduction

Novel coronavirus disease (COVID-19) is caused by a pathogenic virus that targets mostly the human respiratory system, developing a severe acute respiratory syndrome and has swiftly become a serious threat to public health (Shereen et al. 2020). The spread of the disease has been exceptionally rapid and the primary mode of human to human transmission of SARS-CoV-2 has been identified to be through respiratory droplets (Rothe et al. 2020). It was originally found in Wuhan, Hubei Province, China and the most challenging threat facing the global community today (Dong et al. 2020). Symptoms of COVID-19 virus appear approximately 2–14 days after the virus infection, high fever, chills, dry cough, dyspnea, weakness, joint, muscle, head and throat pains, loss of taste and smell, nasal congestion and runny, nausea and vomiting, diarrhea are observed (Coronavirus Pandemic; Worldometer: USA, 2021). COVID-19 is currently affecting millions of lives and continues to spread worldwide. Over 185 M cases have been confirmed across 220 countries and territories, and more than 4 M deaths being reported globally (COVID-19 Coronavirus Pandemic; Worldometer: USA 2021, accessed 7 July 2021).With the aid of evolutionary analyses of the human genome, researchers have found evidence of a coronavirus epidemic that broke out more than 20,000 years ago in East Asia, and which the coronavirus plague occurred separately among different regions and spread across East Asia as an epidemic (Souilmi et al. 2021). Coronaviruses are belong to the Coronaviridae family, of which there are four subgroups: alpha (α), beta (β), gamma (γ), and delta (δ) (Shahzad et al. 2020). Among these subgroups, β-coronaviruses were the deadliest and cause many fatalities in human population in history (Velavan and Meyer 2020). Within the last two decades, two extremely pathogenic β-coronaviruses have been found in humans named Middle East respiratory syndrome (MERS)-CoV and severe acute respiratory syndrome (SARS)-CoV which have significantly caused great threat to human beings (Milne-Price et al. 2014; Hamid et al. 2020). Unlike the SARS and MERS epidemics in 2003 and 2012 (Lee and Hsueh 2020), COVID-19 is a record-breaking and highly contagious disease. The new coronavirus SARS-CoV-2 has been classified as a β-coronavirus based on its genomic structure and phylogenetic relationships (Guo et al. 2020). However, α variant which was originally detected in UK, disables

2 Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use. . .

29

the first line of immune defense in human bodies and caused many fatalities (WHO 2020). Despite that, the COVID-19δ variant, which was first discovered in India, is now spreading rapidly over the world. This strain had been detected in more than 80 countries and becoming the dominant strain in some countries, such as the UK, and is expected to do so in others (WHO 2020). Furthermore, it continues to mutate as it spread and around 60% more transmissible than the “alpha” variant, and appears to be provoking a different range of symptoms, according to experts (WHO 2021). Not only that, a novel coronavirus strain, the Lambda (Λ) variant was first detected in Peru in August 2020. On June 15, 2021, the World Health Organization (WHO) classified it “as a variant of interest” at the global level, which implies it possesses mutations with known or suspected implications for its transmissibility and severity, and it has been found in several countries (WHO June 2021). While it is unknown whether this new variant is more transmissible, scientists say the Lambda strain contains a number of changes that could contribute to greater transmissibility or resistance to the antibodies supplied by a COVID-19 vaccination or past viral exposure (WHO June 2021). Hence, there will be more epidemics in the future until an efficient vaccine is developed or individuals gain herd immunity by infecting the majority of the world’s population (about 60% to 70%) (Brett and Rohani 2020). Symptoms of COVID-19 virus appear approximately 2–14 days after the virus infection, high fever, chills, dry cough, dyspnea, weakness, joint, muscle, head and throat pains, loss of taste and smell, nasal congestion and runny, nausea and vomiting, diarrhea are observed (Coronavirus Pandemic; Worldometer: USA 2021). Many researchers have developed potential vaccines and therapeutic agents that are effective against COVID-19; nevertheless, herbal drugs should not be ignored (Shahzad et al. 2020). Because there has not been much research on natural agents against COVID-19, expanding research in this area could help to uncover the potential of such extracts (Shahzad et al. 2020). While the vaccination campaign is rolling out in some countries, it is still important to determine drugs and agents to combat the pandemic. Other than vaccination, very few specific anti-viral agents have been suggested and still the virus remains a serious global health risk. On this account, medicinal mushrooms offer a lot of potential as preventative or therapeutic add-on treatments in COVID-19 infection, together with immunological overreaction and harmful inflammation that happens with COVID-19 attack (Hetland et al. 2021). Mushrooms has been recognized as medicine for over 2000 years ago(Yuen and Gohel 2005;Hapuarachchi et al. 2016a). They hold an immense structural and chemical diversity which is unparalleled to any synthetic library (Hapuarachchi et al. 2016b). Medicinal mushrooms (Fig. 2.1) including Agaricus (almond mushroom), Ganoderma (lingzhi/reishi), Grifola (maitake), Hericium (lion’s mane/pompom), and Lentinus (Shiitake) are usually consumed in China, Japan, Korea, and Thailand as an immune response modulators for cancer prevention, as a dietary supplement during chemotherapy, and for chronic inflammatory illnesses such as hepatitis and other diseases (Mohiuddin 2021). Since they can easily bind to multiple cell receptors, natural polysaccharides from mushrooms could be used for the production of vaccines (Barbosa and de Carvalho Jr. 2021). Agaricus bisporus,

30

K. K. Hapuarachchi and T. C. Wen

Fig. 2.1 Medicinally important mushrooms. (a) Ganoderma applanatum, (b) Inonotus obliquus, (c) Lentinula edodes, (d) Agaricus sp., (e) Cordyceps sp. (Photographs by TC Wen and HD Young)

A. subrufescens, Boletus edulis, Ganoderma spp., Grifola, Lentinula edodes, Pleurotus spp., Phallus, and Trametes versicolor can be found in markets worldwide (Ruthes et al. 2016). Furthermore, utilization of isolated polysaccharides and the foods rich in biologically active polysaccharides assist individuals with expanding invulnerability, diminishing the danger of a confounded clinical condition whenever tainted with SARS-CoV-2 (Barbosa and de Carvalho Jr. 2021). Since, these mushrooms have enormous potential for to become actual medications, yet they are mainly used as dietary supplements or functional food (Mohiuddin 2021). However,

2 Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use. . .

31

to explore them as dietary supplement, preclinical and clinical trials and also legal authorization are required. Some of the medicinal mushrooms have been shown anti-microbial activity against viral agents, Gram-positive and Gram-negative bacteria, and parasites in vitro and in vivo (Hetland et al. 2021). Previous researches into the anti-viral properties of certain mushrooms have been done effectively (Linnakoski et al. 2018). With the Covid-19 outbreaks on the rise, immunity supplement sales were climbed by 51% in 2020 alone. There has also been a growing interest already in using immune-boosting functional mushrooms such as Ganoderma, Inonotus, and Cordyceps to combat against Covid-19 (Nutrition Business Journal 2020). However, the efficiency of medicinal mushrooms in clinical treatments should be substantiated with more biomedical research and their true impact assessed on human health with more standardized clinical evaluations so that the feasibility of biologically active extracts of medicinally important mushroom species in alternative treatments can be recommended (Hapuarachchi et al. 2017; Hyde et al. 2019). COVID-19 causes a variety of disorders, some of which are symptomatic and others which are not (Long et al. 2020). The most well-known manifestation of COVID-19 is immunological dysregulation (cytokine storm) (Long et al. 2020). As a result, regulation of the weakened immune system has been a focus area in the fight against COVID-19. Immunomodulation is a regulatory process that keeps the immune system balanced by preventing all immune cells from being activated at the same time. Food and nutraceuticals-based approaches can enhance immune protection and modify impaired immunity against COVID-19 (Rao et al. 2020). This review has demonstrated the therapeutic potential of some medicinal mushrooms as natural anti-viral anti-inflammatory agents against COVID-19.

2.2 2.2.1

Potential Medicinal Mushrooms and Bioactive Compounds as Treatment For COVID-19 Cordyceps sp. (Caterpillar Fungus)

Cordyceps sinensis is an entomophagous medicinal mushroom with a long history in Chinese traditional medicine to improve longevity and health (Arora 2008). This fungus is endemic to the Tibetan Plateau including the borders in high elevation regions (Winkler 2009). Cordyceps sinensis has been widely used in multiple therapeutic activities as well as dietary supplements to prevent and treat many diseases (Panicker 2017; Samarasinghe and Waisundara 2020; Bhetwal et al. 2021). Several classes of bioactive substances have been isolated and identified from C. sinensis, such as polysaccharides, nucleosides, sterols, fatty acids, proteins, metals, and vitamins (Kaymakci and Guler 2020; Bhetwal et al. 2021). These bioactive constituents are reported to be responsible for the anti-cancer, antiinflammatory, anti-tumor, anti-oxidant, immunomodulatory, immunodeficiency,

32

K. K. Hapuarachchi and T. C. Wen

anti-diabetic, anti-microbial, anti-hypertensive, anti-atherosclerotic, and anti-aging (Wang et al. 2016; Mehra et al. 2017; Bhetwal et al. 2021). In the current COVID-19 pandemic, sustaining immunity and strong immune system is a challenge, thus many questions emerge on the need and benefits of boosting the immunity. During the 2003 outbreak of SARS virus in China, C. sinensis has been gained huge attention (Chen et al. 2013). Similarly, this fungus could be used for the treatment of the COVID-19 for reducing inflammation and fibrosis, increasing immune response and anti-viral effect (Chen et al. 2013). Researchers suggest that it may be a better option to use traditional and wellstudied therapeutic agents rather than discovering new ones for COVID-19 treatment (Kaymakci and Guler 2020; Salvia and Singh 2021). However, in-depth future studies are needed to elucidate the bioactive compounds present in Cordyceps and its therapeutic potential. Cordycepin (30 -deoxyadenosine) from Cordyceps species has been shown to inhibit viral replication in a number of studies (Lei et al. 2018). It also shows strong anti-inflammatory activity and has been shown to actively protect the lungs from acute injury due to the type of inflammatory immune response (Xia et al. 2014) seen in more serious Covid-19 viral infections. Cordycepin (30 -deoxyadenosine), isolated from C. militaris, exerts an anti-viral effect through a protein kinase inhibitory mechanism (Jin et al. 2012). Also, its inhibitory role toward RNA synthesis has been implicated in influenza virus multiplication (Mahy et al. 1973). The epigenetic mode of anti-viral effects has also been linked with Cordycepin (Ryu et al. 2014). C. sinensis and C. militaris were effective in the prevention and treatment of COVID-19 by immunomodulating, reducing the pro-inflammatory cytokines, preventing lung fibrosis, improving tolerance to hypoxemia, and inhibiting the viral enzymes (Kaymakci and Guler 2020).

2.2.2

Ganoderma sp. (Lingzhi/Reishi)

HIV-1 protease inhibitors, tipranavir, saquinavir, ritonavir, nelfinavir, lopinavir, indinavir, darunavir, atazanavir, and amprenavir, have been approved for clinical applications by the Food and Drug Administration (FDA) and, are extensively used to deactivate 3-chymotrypsin-like protease (3CLpro.) (Liu et al. 2020; Suwannarach et al. 2020). Thus, they have been identified as potential drugs in the treatment of CoV infections. However, several HIV-1 protease inhibitor drugs have already been made available in the human clinical use of Coronaviruses (Fernández-Montero et al. 2019; Pokorná et al. 2009; Liu et al. 2020; Lim et al. 2020; Wang et al. 2020a, b; Xu et al. 2020). Furthermore, HIV-1 protease inhibitors have been isolated from Ganodermalucidum including ganolucidic acid A, 3β-5α-dihydroxy-6β-methoxyergosta-7,22-diene, ganoderic acid A–C, ganoderic acid β, ganodermanondiol, ganodermanontriol, and lucidumol B (El-Mekkawy et al. 1998; Min et al. 1998; Martinez-Montemayor et al. 2019). Six colossolactones, ganomycin I, and ganomycin B isolated from G. colossum have displayed antiHIV-1 protease activity (El Dine et al. 2008; El Dine et al. 2009). Moreover,

2 Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use. . .

33

Ganoderic acid GS-2, 20-hydroxylucidenic acid N, 20(21)-dehydrolucidenic acid N and ganoderiol F isolated from G. sinense, exhibited a high potential to inhibit HIV-1 protease activity (Sato et al. 2009). Recent studies show that selenium and zinc play particular roles in cardiovascular conditions, suggesting their beneficial roles against COVID-19. The biofortified, dried fruiting bodies of Ganoderma lucidum may serve as a nutritional source of these essential elements (Jayawardena et al. 2020; Thota et al. 2020; Rahman et al. 2021a, b; Yanuck et al. 2020). Ganoderone A, ganoderol B, lucialdehyde B, lucidadiol, lucialdehyde, amantadine sulfate applanoxidic acid G, and ergosta-7,2, 2-diene-3β-ol isolated from G. pfeifferi have shown anti-viral effects against influenza A virus (Mothana et al. 2003). Except to (HIV)-1 protease inhibitors permitted by the U.S. Food and Drug Administration, RNA-dependent RNA polymerase inhibitors (remdesivir and favilavir) have been applied as COVID-19 treatment in different countries (Wang et al. 2020a, b). Three triterpenoids, colossolactone VIII, colossolactone E, and colossolactone G, found in Ganoderma species were identified as potential candidates for anti-SARCoV-2 agents using molecular docking study since these compounds show protease inhibitory activity (Rangsinth et al. 2021). Hence, those triterpenoids could be used and further developed as an alternative or complementary medicine for COVID-19 treatment (Rangsinth et al. 2021). Moreover, G. lucidum water extract showed promising anti-SARS-CoV-2 effects in Vero E6 cell-based assays (Jan et al. 2021). Since the safety and pharmacological characteristics of these drugs were formely researched, the preclinical and clinical evaluation of the bioactive compounds is expected to be quicker. Consequently, it can reduce the time, effort, and cost for further development of these agents against COVID-19 (Jan et al. 2021). Triterpenes from G. lucidum have strong anti-inflammatory activity and have been shown to inhibit viral replication and viral binding (Hapuarachchi et al. 2017; Wang et al. 2020a, b). Both triterpenes and proteins from this fungus have also been shown to inhibit angiotensin-converting enzyme activity, blocking conversion of ACE-1 to ACE-2 the form of the enzyme through which Covid-19 virus enters cells (Ansor et al. 2013; Ni et al. 2020). A recent study found that G. lucidum extract has a great significant role in reducing the COVID-19 malicious effect under controlled hematological parameters (AL-jumaili et al. 2020).The RNA-dependent RNA polymerase (RdRp) is a key enzyme responsible for both positive and negative-strand RNA synthesis and G. lucidum extract inhibited SARS-CoV RdRp in a dose-dependent manner (Fung et al. 2011; Yang et al. 2020). Ganoderma sp. showed inhibitory effects for two of its triterpenoids—ganoderic acid T-Q and TR—against neuraminidases in the H5N1 and H1N1 virus strains (Zhu et al. 2015). Hence, Ganoderma sp. appear to be promising in protease inhibition-based anti-viral treatment methods when compared to other mushroom species. A study evaluated the anti-inflammatory effects of triterpene extract of G. lucidum in lipopolysaccharide- (LPS-) stimulated macrophages (Dudhgaonkar et al. 2009). The triterpene extract significantly suppressed the secretion of inflammatory cytokine tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6),

34

K. K. Hapuarachchi and T. C. Wen

inflammatory mediators nitric oxide (NO) and prostaglandin E2 (PGE2), from LPS-stimulated murine RAW 264.7 cells (Dudhgaonkar et al. 2009). Recently WHO announced that interleukin-6 receptor blockers, a class of drugs that can save lives in COVID-19 patients who are extremely or critically ill, especially when combined with corticosteroids. Since WHO suggested corticosteroids in 2020, these are the first medications confirmed to be effective against COVID-19 (WHO 2021). Hence, G. lucidum triterpene extract has a potential to develop as a treatment for COVID-19. Biocomponents derived from Ganoderma (Ganocompounds) have been found effective in thwarting HIV-1 protease, which corroborates utilization of these against SARS-CoV-2. Ganocompounds, which are biocomponents produced from Ganoderma, have been proven to be effective in blocking HIV-1 protease, corroborating Ganocompounds’ use against SARSCoV-2.

2.2.3

Inonotus obliquus (Chaga Mushroom)

Inonotus obliquus commonly grows in Asia, Europe, and North America and has a long history of use as therapeutics for a wide variety of diseases, including viruses (Hyun et al. 2006; Balandaykin and Zmitrovich 2015; Szychowski et al. 2020). Extracts from this mushroom have been used for its anti-tumor, anti-oxidant, hepatoprotective, and anti-inflammatory properties (Lemieszek et al. 2011). Moreover, in vivo animal experiments have demonstrated that bioactive constituents of this mushroom have immunomodulatory, anti-microbial, and anti-viral properties as well (Wold et al. 2020). Because of their parasitic mode of life, I. obliquus possess strong enzymatic and defense systems(Shibnev et al. 2011) and have shown promising results in attenuation of inflammatory responses that have been associated with COVID-19 (Shahzad et al. 2020). Hence, I. obliquus can be considered as a potential candidate against the SARS-COV-2 virus. In silico study showed I. obliquus terpenoid compounds possessed some promising binding affinities to the Receptor Binding Domain (RBD) of the SARSCoV-2 spike protein (Basal et al. 2021). Furthermore, betulinic acid and inonotusane C bound to the SARS-CoV-2 spike protein at a region close to the ACE2 recognition site, which may affect the binding of ACE2 to the virus spike protein and therefore viral recognition of the host cell (Basal et al. 2021). Thus, future in vitro research should be carried out by testing the binding dynamics to clarify whether the repurposing of I. obliquus might be an effective therapy for COVID-19 (Basal et al. 2021). Inonotus obliquus polysaccharides inhibit RNA and/or DNA in cat feline viruses; calcivirus, herpes virus 1, influenza, infectious peritonitis, and panleukopenia (Glamoclija et al. 2015). In addition, this mushroom suppresses the infectivity of pandemic influenza virus in mice and it was observed that I. obliquus is comparable to Tamiflu, an anti-viral drug that resists viral reproduction (Filippova et al. 2013). Hence, well planned research should be developed in order to confirm I. obliquus polysaccharides as an effective therapy for COVID-19. Furthermore, it was reported

2 Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use. . .

35

that I. obliquus polysaccharides can inhibit the induction of Nitric oxide (NO) and other similar cytokines including TNF-α, IL-1β, IL-6 (Van et al. 2009), which is a phenomenon that has been associated with COVID-19 (Shahzad et al. 2020). Moreover, patients infected with COVID-19 showed inflammatory responses through activation of CD4+ T cells by possessing significant levels of plasma cytokines and leucocytes (Aras et al. 2018). Since polysaccharides of I. obliquus have shown promising results in treating various viral diseases, the potential of this mushroom to treat COVID-19 should be further studied (Shahzad et al. 2020).

2.2.4

Lentinula edodes (Shiitake Mushroom)

Beta-glucans are sugars that are commonly found in the cell walls of certain saprophytes, lichens, and plants, and used to treat heart diseases and high cholesterol levels (Murphy et al. 2020). β-glucans from the edible Lentinula edodes exhibit a defensive reaction to a wide range of viral infections and may potentially reduce key cytokines involved in cytokine storm observed in severe cases of COVID-19 (Murphy et al. 2020). Ergosterol found in L. edodes possesses protease inhibitory activity and was identified as effective bioactive compound against Covid-19 using molecular docking study (Rangsinth et al. 2021). A novel lentinan (LNT-1) extracted from L. edodes showed down regulation in the expression of pro-inflammatory cytokines such as TNF-α, IL-2, and IL-11, while also upregulating the expressions of IFN-1 and IFN-γ, cytokines that are known to induce anti-viral, anti-proliferative, and immunomodulatory effects (Vilček and Le 1998; Ren et al. 2018). The natural immune response is a critical factor for COVID-19 disease severity and disease outcome. COVID-19 patients exhibit high concentration of inflammatory cytokines and henceforth the effects of LNT-1 could be used against SARS-COV-2 (Ren et al. 2018). Mushroom extracts from Lentinula edodes mycelia (AHCC) are extensively studied for their immuno-stimulant effects against various viruses and could have therapeutic effects against COVID-19 (Di Pierro et al. 2020).

2.3

Other Mushrooms with Anti-Viral Activities, Bioactive Compounds and Their Mechanisms of Actions Relevant to COVID-19

Crude extracts of Lignosus rhinocerus (tiger milk mushroom) showed HIV-1 protease inhibitory activity on Coronavirus infected cells (Sillapachaiyaporn and Chuchawankul 2019). Heliantriol F and velutin extracted from L. rhinoceros and Flammulina velutipes, respectively, could carry HIV-1 protease inhibitory activity and were identified as effective agents in Covid-19 using insilico study (Rangsinth et al. 2021). A study involving influenza virus type A (serotype H1N1) found that

36

K. K. Hapuarachchi and T. C. Wen

Pleurotus ostreatus (oyster mushroom), F.velutipes (enokitake), Trametes versicolor (turkey tail), and Phellinus baumii, all provided effective inhibition against the neuraminidases in the H5N1, H1N1, and H3N2 influenza virus strains (Krupodorova et al. 2014; Hwang et al. 2015). Aqueous extracts of Daedaleopsis confragosa, Datroniamollis, Ischnoderma benzoinum, Trametes gibbosa, T. versicolor, Laricifomes officinalis, and Lenzites betulina showed anti-viral activity against Influenza virus type A (Teplyakova et al. 2012). Therefore, these mushrooms could be suggested as promising new anti-viral agents against flu strains including Covid-19 virus. The anti-viral activity of lectins from mushrooms is a trending research area but their mechanism of action is not well understood yet (Rahaie and Kazemi 2010). Lectins could inhibit the viral activity through binding glycoproteins in virus surface, blocking the host receptor or inhibit viral polymerase enzyme being binding to its active site (Zhao et al. 2009; Keyaerts et al. 2007). Agrocybeaegerita lectin (AAL) could be used as a non-toxic and effective adjuvant with influenza vaccine against H9N2 viruses in mice (Ma et al. 2017). Furthermore, Galectin AAL specifically binds to β-galactose and then boost the humoral immunity towards influenza virus (Feng et al. 2010). Inulin specific lectin which can be extracted from Agaricus bitorquis dried fruiting bodies suppresses the reverse transcriptase activity in HIV-1 and leukemia cell proliferation (Suwannarach et al. 2020). Furthermore, lectins from mushrooms can act as immunomodulators by activating T-lymphocyte or stimulating dendrites or cytokines (Huang et al. 2020). The transport of Ca2+ by SARS-CoV has been documented to activate inflammasome stimulation. During viral infection, cytokines and chemokines play an important role in human immunity and immunopathology. They are the front line of defense for innate immunity in the fight against viral infection (Abbas and Muddukrishnaiah 2021). Ergosterol has been reported as an anti-inflammatory agent (Sun et al. 2019; Liu et al. 2020). This compound can be extracted from Auricularia polytricha and Flammulina velutipes (Tong et al. 2014;Sillapachaiyaporn et al. 2019) and identified as effective agent by molecular docking study for the treatment of Covid-19 (Rangsinth et al. 2021). The porcine delta coronavirus (PDCoV) is a newly identified swine enteropathogenic coronavirus which distributed all over the world. An in vitro study found that ergosterol peroxide from Cryptoporus volvatus has effective antiPDCoV properties (Duan et al. 2021). Ergosterol peroxide inhibited PDCoVinduced apoptosis and increased tight junction protein expression in the small intestine, preserving intestinal barrier integrity (Duan et al. 2021). Furthermore, this compound had an immunomodulatory effect by inhibiting PDCoV-induced pro-inflammatory cytokines and NF-B p65 activation, as well as upregulating IFN-I expression (Duan et al. 2021). Ergosterol peroxide decreased PDCoV replication and alleviated PDCoV-induced apoptosis via the p38/MAPK signaling pathway, implying that ergosterol peroxide inhibited PDCoV replication and alleviated PDCoV-induced apoptosis. Hence, ergosterol peroxide could be developed as a potential treatment and control method for PDCoV infection (Duan et al. 2021). Since they can easily bind to multiplecell receptors, natural polysaccharides from mushrooms could be used for the production of vaccines (Barbosa and de Carvalho

2 Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use. . .

37

Jr. 2021). Agaricus bisporus, A. subrufescens, Boletus edulis, Ganoderma spp., Grifola, Lentinula edodes, Pleurotus spp., Phallus, and Trametes versicolor can be found in markets worldwide (Ruthes et al. 2016). Furthermore, utilization of isolated polysaccharides and the foods rich in biologically active polysaccharides assist individuals with expanding invulnerability, diminishing the danger of a confounded clinical condition whenever tainted with SARS-CoV-2 (Barbosa and de Carvalho Jr. 2021). Renin angiotensin system (RAS) dysregulation has been considered as a pathophysiological factor of COVID-19 led acute lung injury and acute respiratory distress syndrome. In RAS, angiotensin-converting enzyme (ACE) converts angiotensin (Ang) I to AngII and ACE2 converts AngII to angiotensin 1–7 (Rahman et al. 2021a, b). Since impaired ACE/ACE2 ratio has been associated with the COVID-19 pathomechanism, treatment strategies targeting this ratio have received huge attention. ACE inhibitory proteins have been isolated from different edible and medicinal mushrooms; Agrocybe spp., Auricularia auricula-judae, Ganoderma lucidum, Grifola frondosa, Hericium erinaceus, Hypsizygus marmoreus, Pleurotus cystidiosus, P. eryngii, P. flabellatus, P. florida, P. sajor-caju, Schizophyllum commune, Tricholoma giganteum, and Volvariella volvaceae (Ansor et al. 2013, Choi et al. 2001, Lee et al. 2004, Abdullah et al. 2012, Kang et al. 2013, Lau et al. 2013). Besides, peptides and proteins, ACE inhibitory triterpenes have also been extracted from G. lucidum (Morigawa et al. 1986). The ACE inhibitory effect of these mushrooms can restore the ACE/ACE2 ratio indirectly and thus provide a COVID-19-ameliorating effect. Furthermore, by allowing less conversion of AngI to AngII through ACE inhibition, these mushrooms could be effective in COVID-19 treatments. However, chemically synthesized ACE inhibitors have side effects such as dry cough(Yahaya et al. 2014). Also, increasing ACE2 levels would also increase the susceptibility of SARS-CoV-2 binding to host cells (Rahman et al. 2021a, b). Hence, an alternative medicinal approach incorporating mushrooms seem promising and further research is needed. Except to (HIV)-1 protease inhibitors permitted by the U.S. Food and Drug Administration, RNA-dependent RNA polymerase inhibitors (remdesivir and favilavir) have been applied as COVID-19 treatment in different countries (Wang et al. 2020a, b). Different protease inhibitors have been isolated from edible and medicinal mushrooms such as G. lucidum, G. colossum, G. sinense, Lignosus rhinoceros, A. polytricha, Russula paludosa, Cordyceps militaris, and Agaricus bisporus (El-Mekkawy et al. 1998, Min et al. 1998, Martinez-Montemayor et al. 2019, El Dine et al. 2008, 2009, Sato et al. 2009, Sillapachaiyaporn and Chuchawankul 2019, Sillapachaiyaporn et al. 2019, Wang et al. 2007, Jiang et al. 2011, Gallego et al. 2019). A fungal immunomodulatory protein (FIP) -fve was isolated from Flammulina velutipes and it could suppress replication of respiratory syncytial virus, one of bronchiolitis agent (Chang et al. 2014). FIP also inhibited NF-B translocation, which reduced IL-6 expression and inflammation (Chang et al. 2014). Trained immunity (TRIM) is a modified and epigenetic innate immune response capable of establishing antibody-free pathogen memory that lasts for months (Pradeu and Du

38

K. K. Hapuarachchi and T. C. Wen

Pasquier 2018). β-D-glucan has been implicated in enhancing TRIM through epigenetic mechanisms and metabolic regulation (Keating et al. 2020). COVID-19 symptoms raise the risk of respiratory tract infections, particularly lung infections (Rahman et al. 2021a, b). Mushroom-derived β-glucan has been shown to help with upper and lower respiratory infections, as well as enhance the immunity (Fuller et al. 2017, Dharsono et al. 2019, Jesenak et al. 2013). COVID-19 is characterized by common cold or flu-like symptoms. In randomized, double-blind, placebo-controlled studies, oral dose of β-glucan was demonstrated to reduce common cold occurrences by one-fourth (Graubaum et al. 2012, Auinger et al. 2013). It was revealed that β-D-glucan level is reported to be high in G. lucidum (McCleary and Draga 2016). In H1N1 and H5N1 virus-induced influenza model rats, a hot water extract of G. lucidum was reported to reduce influenza (Zhu et al. 2020). Polysaccharides, terpenoids, phenolics, glycerides, and other low molecular weight compounds have been identified from Basidiomycetes mushrooms as antiinflammatory biocomponents (Paterson and Lima 2014, Hetland et al. 2020, Wasser 2017). Reduced cytokine-induced NF-B activation and decreased pro-inflammatory cytokine production (TNF-, IL-8, IL-2, IL-6, IL-22) was indicated by β-D-glucan isolated from Lentinus edodes in human alveolar epithelial A549 cells. Early and late apoptosis mediated by oxidative stress (Murphy et al. 2020). Thus, modulation of the cytokine storm through β-glucan-mediated controlled expression of pro- and antiinflammatory cytokines could aid in withstanding COVID-19 pathogenesis (Hetland et al. 2020, Murphy et al. 2020). Most patients affected with COVID-19 are over 65 years (WHO, 2020). Most of the people in this age range suffer from Alzheimer’s disease, cardiovascular diseases, diabetes mellitus, hypercholesterolemia, hypertension and they are common comorbidities of COVID-19 (Sanyaolu et al. 2020, Alshaikh et al. 2021, Rahman et al. 2021a, b). In order to fight SARS-CoV-2 and maintain homeostasis, patients with COVID-19 and comorbidities require nutritional supplements (Wang et al. 2020c). Both edible and medicinal mushrooms are particularly successful in replenishing nutritional deficiency as a functional food (Chang and Wasser 2012, Rahman and Abdullah 2014, Rahman et al. 2016, 2018, 2020). Polysaccharides (β-D-glucan), polyphenols, triterpenes, proteins, vitamins, and minerals found in mushrooms could aid in the treatment of COVID-19 and comorbidities in patients (Rahman et al. 2021a, b). Supplying mushroom powder to patients with COVID-19 and comorbidities in different regions of the world would also be less difficult for relief agencies because mushroom powder processing is straightforward and does not require specialized handling and preservation techniques (Rahman et al. 2021a, b). Hence, World Health Organization (WHO) and other health-care management organizations could take necessary steps to promote mushroom-based treatment and preventive approach against SARS-CoV-2 (Rahman et al. 2021a, b).

2 Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use. . .

2.4

39

Conclusion

Some in vitro and in vivo studies of medicinal mushrooms appear to be promising, but careful investigation and accurate scientific evidences needed for establishing the safe and efficient use against COVID-19. Ganoderma stands out among mushroom species as the most effective COVID-19 preventive and therapeutic agents. Further research, scientific support, and a deeper scientific understanding of the mechanisms are needed to confirm these effects. Hence, well designed in vivo tests and randomized controlled clinical studies with potential mushrooms can provide statistically significant results to confirm the efficacy and safety of mushroom applications. Furthermore, standardization and quality control of mushroom species, cultivation processes, extracts, and commercial formulations are needed to accept these species as natural product for potential use in the prevention and treatment of various diseases. Experimental, epidemiological, and clinical studies should be carried out on identification of the molecular targets and investigate the association between mushroom intake and disease risk. Moreover, the efficacy dosage, efficacy of the drug, and safety, alone or in combination with chemotherapy or radiotherapy should also be researched in the future.

References Abbas H, Muddukrishnaiah K (2021) Lectins are the sparkle of hope for combating coronavriuses and global COVID 19: a review. Advanced Pharmaceutical Bulletin, 27 March 2021 Abdullah N, Ismail SM, Aminudin N, Shuib AS, Lau BF (2012) Evaluation of selected culinarymedicinal mushrooms for antioxidant and ACE inhibitory activities. Evid Based Complement Alternat Med 2012:464238 Al-Jumaili MM, Al-Dulaimi FK, Ajeel MA (2020) The role of Ganoderma lucidum uptake on some hematological and immunological response in patients with coronavirus (COVID-19). Syst Rev Pharm 11(8):537–541 Alshaikh MK, Alotair H, Alnajjar F, Sharaf H, Alhafi B, Alashgar L, Aljuaid M (2021) Cardiovascular risk factors among patients infected with COVID-19 in Saudi Arabia. Vasc Health Risk Manage 17:161–168. https://doi.org/10.2147/VHRM.S300635. PMID: 33907410; PMCID: PMC8071203 Ansor NM, Abdullah N, Aminudin N (2013) Anti-angiotensin converting enzyme (ACE) proteins from mycelia of Ganoderma lucidum (Curtis) P. Karst. BMC Complement Altern Med 13:256 Aras A, Khalid G, Jabeen S, Farooqi A, Xu B (2018) Regulation of cancer cell signaling pathways by mushrooms and their bioactive molecules: overview of the journey from benchtop to clinical trials. Food Chem Toxicol 119:206–214 Arora RK (2008) Collection, isolation and characterization of caterpillar mushroom-Cordyceps sinensis (Berk.) Sacc. of Uttarakhand. Doctoral dissertation, PhD thesis, GovindBallabh Pant University of Agriculture and Technology, Uttarakhand, p 160 Auinger A, Riede L, Bothe G, Busch R, Gruenwald J (2013) Yeast (1,3)-(1,6)-beta-glucan helps to maintain the body’s defence against pathogens: a double-blind, randomized, placebo-controlled, multicentric study in healthy subjects. Eur J Nutr 52:1913–1918

40

K. K. Hapuarachchi and T. C. Wen

Balandaykin ME, Zmitrovich IV (2015) Review on chaga medicinal mushroom, Inonotus obliquus (higher Basidiomycetes): realm of medicinal applications and approaches on estimating its resource potential. Int J Med Mushrooms. 17(2):95–104 Barbosa JR, de Carvalho Junior RN (2021) Polysaccharides obtained from natural edible sources and their role in modulating the immune system: biologically active potential that can be exploited against COVID-19. Trends Food Sci Technol 108:223–235 Basal WT, Elfiky A, Eid J (2021) Chaga medicinal mushroom inonotus obliquus (agaricomycetes) terpenoids may interfere with SARS-CoV-2 spike protein recognition of the host cell: a molecular docking study. Int J Med Mushrooms 23(3):1–14 Bhetwal S, Chatterjee S, Samrat RR, Rana M, Srivastava S (2021) Cordyceps sinensis: peculiar caterpillar mushroom, salutary in its medicinal and restorative capabilities. Pharma Innov J 10(4):1045–1054 Brett TS, Rohani P (2020) Transmission dynamics reveal the impracticality of COVID-19 herd immunity strategies. Proc Natl Acad Sci U S A 117:25897–25903 Chang ST, Wasser SP (2012) The role of culinary-medicinal mushrooms on human welfare with a pyramid model for human health. Int J Med Mushrooms 14(2):95–134 Chang YC, Chow YH, Sun HL (2014) Alleviation of respiratory syncytial virus replication and inflammation by fungal immuno-modulatory protein FIP-fve from Flammulina velutipes. Antivir Res 110:124–131 Chen PX, Wang S, Nie S, Marcone M (2013) Properties of Cordyceps sinensis: a review. J Funct Foods 5(2):550–569 Choi HS, Cho HY, Yang HC, Ra KS, Suh HJ (2001) Angiotensin I-converting enzyme inhibitor from Grifola frondosa. Food Res Int 34(2–3):177–182 Dharsono T, Rudnicka K, Wilhelm M, Schoen C (2019) Effects of yeast (1,3)-(1,6)-beta-glucan on severity of upper respiratory tract infections: a double-blind, randomized, placebo-controlled study in healthy subjects. J Am Coll Nutr 38(1):40–50 Di Pierro F, Bertuccioli A, Cavecchia I (2020) Possible therapeutic role of a highly standardized mixture of active compounds derived from cultured Lentinula edodes mycelia (AHCC) in patients infected with 2019 novel cororonavirus. Minerva Gastroenterol Dietol 66(2): 172–176. https://doi.org/10.23736/S1121-421X.20.02697-5 Dong E, Du H, Gardner L (2020) An interactive web-based dashboard to track COVID-19 in real time. Lancet Infect Dis 20(5):533–534 Duan C, Wang J, Liu Y, Zhang J, Si J, Hao Z, Wang J (2021) Antiviral effects of ergosterol peroxide in a pig model of porcine deltacoronavirus (PDCoV) infection involves modulation of apoptosis and tight junction in the small intestine. Vet Res 52(1):86. https://doi.org/10.1186/ s13567-021-00955-5. PMID: 34127062; PMCID: PMC8201433 Dudhgaonkar S, Thyagarajan A, Sliva D (2009) Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum. Int Immunopharmacol 9(11): 1272–1280 El Dine RS, El-Halawany A, Ma CM, Hattori M (2009) Inhibition of the dimerization and active site of HIV-1 protease by secondary metabolites from the Vietnamese mushroom Ganoderma colossum. J Nat Prod 72:2019–2023 El Dine RS, Halawany AME, Ma CM, Hattori M (2008) Anti-HIV1-protease activity of lanostane triterpenes from the Vietnamese mushroom Ganoderma colossum. J Nat Prod 71:1022–1026 El-Mekkawy S, Meselhy MR, Nakamura N, Tezuka Y, Otake T (1998) Anti-HIV-1 and anti-HIV1-protease substances from Ganoderma lucidum. Phytochemistry 49:1651–1657 Feng L, Sun H, Zhang Y, Li DF, Wang DC (2010) Structural insights into the recognition mechanism between an antitumor galectin AAL and the Thomsen-Friedenreich antigen. FASEB J 24:3861–3868. https://doi.org/10.1096/fj.10-159111 Fernandez-Montero A, Torrecillas S, Izquierdo M, Caballero MJ, Milne DJ, Secombes CJ et al (2019) Increased parasite resistance of greater amberjack (Seriola dumerili Risso 1810) juveniles fed a cMOS supplemented diet is associated with upregulation of a discrete set of immune genes in mucosal tissues. Fish Shellfish Immunol 86:35–45

2 Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use. . .

41

Filippova EI, Mazurkova NA, Kabanov AS, Teplyakova TV, Ibragimova ZB (2013) Antiviral properties of aqueous extracts isolated from higher basidiomycetes as respect to pandemic influenza virus a(IIIIII). Biol Sci 29:284–290 Fuller R, Moore MV, Lewith G, Stuart BL, Ormiston RV, Fisk HL (2017) Yeast-derived beta-1,3/ 1,6 glucan, upper respiratory tract infection and innate immunity in older adults. Nutrition 39– 40:30–35 Fung KP, Leung PC, Tsui KW, Wan CC, Wong KB, Waye MY et al (2011) Immunomodulatory activities of the herbal formula Kwan Du Bu Fei Dang in healthy subjects: a randomised, double-blind, placebo-controlled study. Hong Kong Med J 17(suppl 2):41–43 Gallego P, Rojas A, Falcón G, Bautista JD (2019) Water-soluble extracts from edible mushrooms (Agaricus bisporus) as inhibitors of hepatitis C viral replication. Food Funct 10:3758–3767 Glamoclija J, Ciric A, Nikolic M, Fernandes A et al (2015) Chemical characterization and biological activity of Chaga (Inonotus obliquus), a medicinal “mushroom”. J Ethnopharmacol 162:323 Graubaum HJ, Busch R, Stier H, Gruenwald J (2012) A double-blind, randomized, placebocontrolled nutritional study using an insoluble yeast beta-glucan to improve the immune defense system. Food Nutr Sci 3:738–746 Guo YR, Cao QD, Hong ZS, Tan YY et al (2020) The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak—an update on the status. Mil Med Res 7:11 Hamid S, Mir MY, Rohela GK (2020) Novel coronavirus disease (COVID-19): a pandemic (epidemiology, pathogenesis and potential therapeutics). New Microb New Infect 35:100679 Hapuarachchi KK, Cheng CR, Wen TC, Jeewon R et al (2017) Mycosphere essays 20: therapeutic potential of Ganoderma species: insights into its use as traditional medicine. Mycosphere 8: 1653–1694. https://doi.org/10.5943/mycosphere/8/10/5 Hapuarachchi KK, Wen TC, Jeewon R, Wu XL et al (2016a) Mycosphere essays 7: Ganoderma lucidum – are the beneficial anti-cancer properties substantiated? Mycosphere 7:305–332. https://doi.org/10.5943/mycosphere/7/3/6.1046 Hapuarachchi KK, Wen TC, Jeewon R, Wu XL et al (2016b) Mycosphere essays 15: Ganoderma lucidum – are the beneficial medical properties substantiated? Mycosphere 7:687–715. https:// doi.org/10.5943/mycosphere/7/6/1 Hetland G, Tangen J-M, Mahmood F, Mirlashari MR et al (2020) Antitumor, anti-inflammatory and antiallergic effects of Agaricus blazei mushroom extract and the related medicinal basidiomycetes mushrooms, Hericium erinaceus and Grifola frondosa: a review of preclinical and clinical studies. Nutrients 12(5):1339. https://doi.org/10.3390/nu12051339 Hetland G, Johnson E, Bernardshaw SV, Grinde B (2021) Can medicinal mushrooms have prophylactic or therapeutic effect against COVID-19 and its pneumonic superinfection and complicating inflammation? Scand J Immunol 93(1):e12937. https://doi.org/10.1111/sji.12937 Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y (2020) Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China Lancet 395:497–506. https://doi.org/10.1016/S01406736(20)30183-5 Hwang BS, Lee IK, Choi HJ, Yun BS (2015) Anti-influenza activities of polyphenols from the medicinal mushroom Phellinus baumii. Bioorg Med Chem Lett 25(16):3256–3260 Hyde KD, Xu J, Rapior S, Jeewon R et al (2019) The amazing potential of fungi: 50 ways we can exploit fungi industrially. Fungal Divers 1:1–36 Hyun K, Jeong S, Lee D, Park J, Lee J (2006) Isolation and characterization of a novel platelet aggregation inhibitory peptide from the medicinal mushroom, Inonotus obliquus. Peptides 27: 1173–1178 Lim WZ, Cheng PG, Abdulrahman AY, Teoh TC (2020) The identification of active compounds in Ganoderma lucidum var. antler extract inhibiting dengue virus serine protease and its computational studies. J Biomol Struct Dyn 38(14):4273–4288. https://doi.org/10.1080/07391102. 2019.1678523 Long QX, Tang XJ, Shi QL et al (2020) Clinical and immunological assessment of asymptomatic SARS-CoV-2 infections. Nat Med 26:1200–1204. https://doi.org/10.1038/s41591-020-0965-6

42

K. K. Hapuarachchi and T. C. Wen

Jan J, Cheng T, Juang Y et al (2021) Identification of existing pharmaceuticals and herbal medicines as inhibitors of SARS-CoV-2 infection. Proc Natl Acad Sci U S A. https://doi.org/10.1073/pnas. 2021579118 Jayawardena R, Sooriyaarachchi P, Chourdakis M, Jeewandara C, Ranasinghe P (2020) Enhancing immunity in viral infections, with special emphasis on COVID-19: a review. Diabet Metab Syndr 14(4):367–382. https://doi.org/10.1016/j.dsx.2020.04.015 Jesenak M, Majtan J, Rennerova Z, Kyselovic J, Banovcin P, Hrubisko M (2013) Immunomodulatory effect of pleuran (b-glucan from Pleurotus ostreatus) in children with recurrent respiratory tract infections. Int Immunopharmacol 15:395–399 Jiang Y, Wong J, Fu M, Ng TB, Liu Z, Liu F (2011) Isolation of adenosine, iso-sinensetin and dimethylguanosine with antioxidant and HIV-1 protease inhibiting activities from fruiting bodies of Cordyceps militaris. Phytomedicine 18:189–193 Jin ML, Park SY, Kim YH, Park G, Son HJ, Lee SJ (2012) Suppression of α-MSH and IBMXinduced melanogenesis by cordycepin via inhibition of CREB and MITF, and activation of PI3K/Akt and ERK-dependent mechanisms. Int J Mol Med 29(1):119–124 Kang MG, Kim YH, Bolormaa Z, Kim MK, Seo GS, Lee JS (2013) Characterization of an antihypertensive angiotensin I-converting enzyme inhibitory peptide from the edible mushroom Hypsizygus marmoreus. Biomed Res Int 2013:283964 Kaymakci MA, Guler EM (2020) Promising potential pharmaceuticals from the genus Cordyceps for COVID-19 treatment: a review study. Bezmialem Sci 8(3):140–144 Keating ST, Groh L, van der Heijden C, Rodriguez H, Dos Santos JC, Fanucchi S (2020) The set7 lysine methyltransferase regulates plasticity in oxidative phosphorylation necessary for trained immunity induced by β-glucan. Cell Rep 31:107548 Keyaerts E, Vijgen L, Pannecouque C, Van Damme E (2007) Plant lectins are potent inhibitors of coronaviruses by interfering with two targets in the viral replication cycle. Antivir Res 75:179– 187. https://doi.org/10.1016/j.antiviral.2007.03.003 Krupodorova T et al (2014) Antiviral activity of Basidiomycete mycelia against influenza type A (serotype H1N1) and herpes simplex virus type 2 in cell culture. Virol Sin 29(5):284–290 Lau CC, Abdullah N, Shuib AS (2013) Novel angiotensin I-converting enzyme inhibitory peptides derived from an edible mushroom, Pleurotus cystidiosus O.K. Miller identified by LC-MS/MS. BMC Complement Altern Med 13:313 Lee HD, Kim HJ, Park SJ, Choi JY, Lee SJ (2004) Isolation and characterization of a novel angiotensin I-converting enzyme inhibitory peptide derived from the edible mushroom Tricholoma giganteum. Peptides 25(4):621–627 Lee PI, Hsueh PR (2020) Emerging threats from zoonotic coronaviruses-from SARS and MERS to 2019-nCoV. J Microbiol Immunol Infect 53:365–367 Lei J, Wei Y, Song P, Li Y, Zhang T, Feng Q, Xu G (2018) Cordycepin inhibits LPS-induced acute lung injury by inhibiting inflammation and oxidative stress. Eur J Pharmacol 818:110–114 Lemieszek M, Langner E, Kaczor J, Kandefer-Szerszén M et al (2011) Anticancer effects of fraction isolated from fruiting bodies of Chaga medicinal mushroom, Inonotus obliquus (Pers.:Fr.) Pilát (Aphyllophoromycetideae): in vitro studies. Int J Med Mushrooms 13:131–114 Linnakoski R, Reshamwala D, Veteli P, Cortina-Escribano M, Vanhanen H, Marjomäki V (2018) Antiviral agents from fungi: diversity, mechanisms and potential applications. Front Microbiol 9:2325. https://doi.org/10.3389/fmicb.2018.02325. PMID: 30333807; PMCID: PMC6176074 Liu C, Zhao S, Zhu C et al (2020) Ergosterol ameliorates renal inflammatory responses in mice model of diabetic nephropathy. Biomed Pharmacother 128:110252 Ma L-B, Bao X, Min H, Lvhui S, Qing Y, Yi-Jie C et al (2017) Adjuvant effects mediated by the carbohydrate recognition domain of Agrocybe aegerita lectin interacting with avian influenza H9N2 viral surface glycosylated proteins. J Zhejiang Univ Sci B 18:653–661. https://doi.org/10. 1631/jzus.B1600106 Mahy BW, Cox NJ, Armstrong SJ, Barry RD (1973) Multiplication of influenza virus in the presence of cordycepin, an inhibitor of cellular RNA synthesis. Nat New Biol 243(127): 172–174

2 Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use. . .

43

Martinez-Montemayor M, Ling T, Suárez-Arroyo IJ, Ortiz-Soto G, Rivas F (2019) Identification of biologically active Ganoderma lucidum compounds and synthesis of improved derivatives that confer anti-cancer activities in vitro. Front Pharmacol 10:115 McCleary BV, Draga A (2016) Measurement of β-glucan in mushrooms and mycelial products. J AOAC Int 99(2):364–373 Mehra A, Zaidi KU, Mani A, Thawani V (2017) The health benefits of Cordyceps militaris—a review. KAVAKA 48(1):27–32 Milne-Price S, Miazgowicz K, Munster V (2014) The emergence of the Middle East Respiratory Syndrome coronavirus (MERS-CoV). Pathog Dis 2014:71 Min BS, Nakamura N, Miyashiro H, Bae KW, Hattori M (1998) Triterpenes from the spores of Ganoderma lucidum and their inhibitory activity against HIV-1 protease. Chem Pharm Bull 46: 1607–1612 Mohiuddin AK (2021) Can medicinal mushrooms fight against SARS-CoV-2/COVID-19? J Int Med Sci Art 2:23–24 Morigawa A, Kitabatake K, Fujimotot Y, Ikekawa N (1986) Angiotensin converting enzymeinhibitory triterpenes from Ganoderma lucidum. Chem Pharm Bull 34:3025–3028 Mothana RA, Awadh Ali NA, Jansen R, Wegner U, Mentel R, Lindequist U (2003) Antiviral lanostanoid triterpenes from the fungus Ganoderma pfeifferi. Fitoterapia 74(1–2):177–180 Murphy EJ, Masterson C, Rezoagli E et al (2020) β-Glucan extracts from the same edible shiitake mushroom Lentinus edodes produce differential in-vitro immunomodulatory and pulmonary cytoprotective effects - implications for coronavirus disease (COVID-19) immunotherapies. Sci Total Environ 732:139330. https://doi.org/10.1016/j.scitotenv.2020.139330 Ni W, Yang X, Yang D, Bao J, Li R (2020) Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Crit Care 24(1):1 Panicker S (2017) Cordyceps the fungal gold-a review. Adv Res 30:1–6 Paterson R, Lima N (2014) Biomedical effects of mushrooms with emphasis on pure compounds. Biom J 37:357–368. https://doi.org/10.4103/2319-4170.143502. Corpus ID: 15575411 Pokorna J, Machala L, Rezacova P, Konvalinka J (2009) Current and novel inhibitors of HIV protease. Viruses 1:1209–1239 Pradeu T, Du Pasquier L (2018) Immunological memory: what’s in a name? Immunol Rev 283(1): 7–20 Rahaie M, Kazemi SS (2010) Lectin-based biosensors: as powerful tools in bioanalytical applications. Biotechnology 9. https://doi.org/10.3923/biotech.2010.428.443 Rahman MA, Abdullah N (2014) Inhibitory effect on in vitro LDL oxidation and HMG Co-A reductase activity of the liquid-liquid partitioned fractions of Hericiumerinaceus (Bull.) Persoon (lion’s mane mushroom). Biomed Res Int 2014:828149 Rahman MA, Abdullah N, Aminudin N (2016) Interpretation of mushroom as a common therapeutic agent for Alzheimer’s disease and cardiovascular diseases. Crit Rev Biotechnol 36(6): 1131–1142 Rahman MA, Abdullah N, Aminudin N (2018) Evaluation of the antioxidative and hypocholesterolemic effects of lingzhi or reishi medicinal mushroom, Ganoderma lucidum (Agaricomycetes), in ameliorating cardiovascular disease. Int J Med Mushrooms 20(10): 961–969 Rahman MA, Hossain S, Abdullah N, Aminudin N (2020) Lingzhi or reishi medicinal mushroom, Ganoderma lucidum (Agaricomycetes) ameliorates spatial learning and memory deficits in rats with hypercholesterolemia and Alzheimer’s disease. Int J Med Mushrooms 22(1):93–103 Rahman MA, Rahman MS, Bashir NM, Mia R, Hossain A, Saha SK, Kakon AJ, Sarker NC (2021a) Rationalization of mushroom-based preventive and therapeutic approaches to COVID-19. Int J Med Mushrooms 23(5):1–11 Rahman MM, Mosaddik A, Alam AK (2021b) Traditional foods with their constituents antiviral and immune system modulating properties. Heliyon 7(1):e05957. https://doi.org/10.1016/j. heliyon.2021.e05957

44

K. K. Hapuarachchi and T. C. Wen

Rao KS, Suryaprakash V, Senthilkumar R, Preethy S et al (2020) Role of immune dysregulation in increased mortality among a specific subset of COVID-19 patients and immune-enhancement strategies for combatting through nutritional supplements. Front Immunol. https://doi.org/10. 3389/fimmu.2020.01548 Rangsinth P, Sillapachaiyaporn C, Nilkhet S, Tencomnao T, Ung AT, Chuchawankul S (2021) Mushroom-derived bioactive compounds potentially serve as the inhibitors of SARS-CoV-2 main protease: an in silico approach. J Tradit Complement Med 11(2):158–172. https://doi.org/ 10.1016/j.jtcme.2020.12.002 Ren G, Xu L, Lu T, Yin J (2018) Structural characterization and antiviral activity of lentinan from Lentinusedodes mycelia against infectious hematopoietic necrosis virus. Int J Biol Macromol 115:1202 Rothe C, Schunk M, Sothmann P, Bretzel G, Froeschl G, Wallrauch C et al (2020) Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. N Engl J Med 382(10):970– 971. https://doi.org/10.1056/NEJMc2001468 Ruthes AC, Smiderle FR, Iacomini M (2016) Mushroom heteropolysaccharides: a review on their sources, structure and biological effects. Carbohydr Polym 136:358–375. https://doi.org/10. 1016/j.carbpol.2015.08.061 Ryu E, Son M, Lee M, Lee K, Cho JY, Cho S et al (2014) Cordycepin is a novel chemical suppressor of Epstein-Barr virus replication. Oncoscience 1(12):866–881. https://doi.org/10. 18632/oncoscience.110 Salvia T, Singh LS (2021) Covid-19 pandemic, significance of reimagining immunity and relevance of medicinal plants to combat SARS-CoV-2 infection: a perspective. Acta Sci Microbiol 4 (1):33–41 Samarasinghe K, Waisundara VY (2020) Therapeutic properties and anti-Lipidemic activity of Cordyceps sinensis. In: Apolipoproteins, triglycerides and cholesterol. IntechOpen, London Sanyaolu A, Okorie C, Marinkovic A, Patidar R et al (2020) Comorbidity and its impact on patients with COVID-19. SN Compr Clin Med 25:1–8. https://doi.org/10.1007/s42399-02000363-4. PMID: 32838147; PMCID: PMC7314621 Sato N, Zhang Q, Ma CM, Hattori M (2009) Anti-human immunodeficiency virus-1 protease activity of new lanostane-type triterpenoids from Ganoderma sinense. Chem Pharm Bull 57: 1076–1080 Shahzad F, Anderson D, Najafzadeh M (2020) The antiviral, anti-inflammatory effects of natural medicinal herbs and mushrooms and SARS-CoV-2 infection. Nutrients 12(9):2573. https://doi. org/10.3390/nu12092573 Shereen M, Khan S, Kazmi A, Bashir N, Siddique R (2020) COVID-19 infection: origin, transmission, and characteristics of human coronaviruses. J Adv Res 24:91–98 Shibnev VA, Mishin DV, Garaev TM, Finogenova NP, Botikov AG, Deryabin PG (2011) Antiviral activity of Inonotus obliquus fungus extract towards infection caused by hepatitis C virus in cell cultures. Bull Exp Biol Med 151:612–614 Sillapachaiyaporn C, Chuchawankul S (2019) HIV-1 protease and reverse transcriptase inhibition by tiger milk mushroom (Lignosus rhinocerus) sclerotium extracts: in vitro and in silico studies. J Tradit Complement Med 10(4):396–404 Sillapachaiyaporn C, Nilkhet S, Ung AT, Chuchawankul S (2019) Anti-HIV-1 protease activity of the crude extracts and isolated compounds from Auricularia polytricha. BMC Complement Altern Med 19(1):351 Souilmi Y, Lauterbur ME, Tobler R, Huber CD, Johar AS, Enard D (2021) An ancient viral epidemic involving host coronavirus interacting genes more than 20,000 years ago in East Asia. bioRxiv Sun X, Feng X, Zheng D et al (2019) Ergosterol attenuates cigarette smoke extract induced COPD by modulating inflammation, oxidative stress and apoptosis in vitro and in vivo. Clin Sci 133(13):1523–1536 Suwannarach N, Kumla J, Sujarit K, Pattananandecha T, Saenjum C, Lumyong S (2020) Natural bioactive compounds from fungi as potential candidates for protease inhibitors and

2 Therapeutic Potential of Medicinal Mushrooms: Insights into Its Use. . .

45

immunomodulators to apply for coronaviruses. Molecules 25(8):1800. https://doi.org/10.3390/ molecules25081800 Szychowski KA, Bartosz S, Tadeusz P, Jan G (2020) Inonotus obliquus–from folk medicine to clinical use. J Tradit Complement Med 11:293–302 Teplyakova TV, Psurtseva NV, Kosogova TA, Mazurkova NA (2012) Antiviral activity of polyporoid mushrooms (higher Basidiomycetes) from Altai Mountains (Russia). Int J Med Mushrooms 14:37–45. https://doi.org/10.1615/IntJMedMushr.v14.i1.40 Thota SM, Balan V, Sivaramakrishnan V (2020) Natural products as home-based prophylactic and symptom management agents in the setting of COVID-19. Phytother Res 34(12):3148–3167. https://doi.org/10.1002/ptr.6794 Tong S, Zhong H, Yi C et al (2014) Simultaneous HPLC determination of ergosterol and 22,23dihydroergosterol in Flammulina velutipes sterol-loaded microemulsion. Biomed Chromatogr 28(2):247–254 Van Q, Nayak B, Reimer M, Jones P, Fulcher R, Rempel CB (2009) Anti-inflammatory effect of Inonotus obliquus, Polygala senega L., and Viburnum trilobum in a cell screening assay. J Ethnopharmacol 125:487–493 Velavan TP, Meyer CG (2020) The COVID-19 epidemic. Tropical Med Int Health 25:278–280 Vilček J, Le J (1998) Interferon γ. In: Delves PJ (ed) Encyclopedia of immunology, 2nd edn. Elsevier, Oxford Wang J, Wang H, Ng T (2007) A peptide with HIV-1 reverse transcriptase inhibitory activity from the medicinal mushroom Russulapaludosa. Peptides 28:560–565 Wang N, Li J, Huang X, Chen W, Chen Y (2016) Herbal medicine Cordycepssinensis improves health-related quality of life in moderate-to-severe asthma. Evid Based Complement Alternat Med 2016:6134593. https://doi.org/10.1155/2016/6134593 Wang M, Cao R, Zhang L, Yang X, Liu J (2020a) Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res 30(3):269–271 Wang T, Du Z, Zhu F (2020b) Comorbidities and multi-organ injuries in the treatment of COVID-19. Lancet 395(10228):e52 Wang H, Yang X, Xiaohong Y, Yang L et al (2020c) Retrospective study of clinical features of COVID-19 in inpatients and their association with disease severity. Med Sci Monit 26:e927674 Wasser SP (2017) Medicinal mushrooms in human clinical studies. Part I. anticancer, oncoimmunological, and immunomodulatory activities: a review. Int J Med Mushrooms 19 (4):279–317. https://doi.org/10.1615/IntJMedMushrooms.v19.i4.10 WHO (2020) World Health Organization. Novel coronavirus (2019-nCoV). Situation report 13. 2020. https://apps.who.int/iris/handle/10665/330778 WHO (2021) World Health Organization. 15 June 2021. Retrieved 2021-08-16. Lambda has been associated with substantive rates of community transmission in multiple countries, with rising prevalence over time concurrent with increased COVID-19 incidence. The earliest sequenced samples were reported from Peru in August 2020 Winkler D (2009) Caterpillar fungus (Ophiocordycepssinensis) production and sustainability on the Tibetan Plateau and in the Himalayas. Asian Med 5(2):291–316 Wold CW, Gerwick WH, Wangensteen H, Inngjerdingen KT (2020) Bioactive triterpenoids and water-soluble melanin from Inonotus obliquus (chaga) with immunomodulatory activity. J Funct Foods 71:104025 Worldometer (2021) COVID-19 coronavirus pandemic. Worldometer, New York Xia Q et al (2014) A comprehensive review of the structure elucidation and biological activity of triterpenoids from Ganoderma spp. Molecules 19(11):17478–17535 Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C et al (2020) Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med 8(4):420–422 Yahaya NF, Rahman MA, Abdullah N (2014) Therapeutic potential of mushrooms in preventing and ameliorating hypertension. Trend Food Sci Technol 39(2):104–115

46

K. K. Hapuarachchi and T. C. Wen

Yang Z, Zhou D, Li H et al (2020) The genome-wide risk alleles for psychiatric disorders at 3p21.1 show convergent effects on mRNA expression, cognitive function, and mushroom dendritic spine. Mol Psychiatry 25:48–66. https://doi.org/10.1038/s41380-019-0592 Yanuck SF, Pizzorno J, Messier H, Fitzgerald KN (2020) Evidence supporting a phased immunophysiological approach to COVID-19 from prevention through recovery. Integr Med (Encinitas) 19(suppl 1):8–35 Yuen WMJ, Gohel MDI (2005) Anti-cancer effects of Ganoderma lucidum: a review of scientific evidence. Nutr Cancer 53(1):11–17 Zhao JK, Wang HX, Ng TB (2009) Purification and characterization of a novel lectin from the toxic wild mushroom Inocybe umbrinella. Toxicon 53:360–366. https://doi.org/10.1016/j.toxicon. 2008.12.009 Zhu Q et al (2015) Inhibition of neuraminidase by Ganoderma triterpenoids and implications for neuraminidase inhibitor design. Sci Rep 26:13194 Zhu YG, Deng ZW, Liu LH et al (2020) Compilation of drug information for the diagnosis and treatment of COVID-19 (version 1). Cent South Pharm 2020:31–14

Chapter 3

Recent Advances in the Discovery of Bioactive Metabolites from Xylaria Hill ex Schrank Sunil K. Deshmukh, Kandikere R. Sridhar, Sanjai Saxena, and Manish Kumar Gupta

Abstract Xylaria is the largest genus of the family Xylariaceae (Xylariales, Sordariomycetes) and presently consists of ca. 300 accepted species of stromatic pyrenomycetes. They are popularly known as dead man’s finger, have common distribution in soil, leaf litter, woody litter, and termite mounds. In addition, they also have mutualistic association as endophytes in tropical and temperate plant species. The xylarial stromata constitutes one of the important raw biomaterials in traditional Chinese and other ethnic medicinal systems. The genus Xylaria is a major source of a wide range of bioactive compounds (sesquiterpenoids, terpenoids, cytochalasins, mellein, alkaloids, polyketides, and aromatic compounds). Some of the metabolites of Xylaria deploy antibacterial, antifungal, anticancer, antimalarial, anti-inflammatory, and α-glucosidase inhibitory activities. The metabolites of Xylaria are also known for potential herbicidal, fungicidal, and insecticidal activities. Xylaria is known for the production of many volatile and non-volatile compounds and their volatiles are functional in various pharmaceutical and agricultural applications. This review covers the bioactive metabolites reported from different species of Xylaria and along with their source of origin and biological properties.

S. K. Deshmukh (*) TERI–Deakin Nano Biotechnology Centre, The Energy and Resources Institute, New Delhi, India K. R. Sridhar Department of Biosciences, Mangalore University, Mangalagangotri, Mangalore, Karnataka, India Centre for Environmental Studies, Yenepoya (Deemed to be University), Mangalore, Karnataka, India S. Saxena Department of Biotechnology, Thapar Institute of Engineering & Technology (Deemed to be a University), Patiala, Punjab, India AGPharm Bio-Innovations LLP, STEP-TIET, Patiala, Punjab, India M. K. Gupta SGT College of Pharmacy, SGT University, Gurugram, Haryana, India © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_3

47

48

S. K. Deshmukh et al.

Keywords Xylaria · Wood rot fungi · Endophytic fungi · Bioactive metabolites · VOC

3.1

Introduction

Xylaria Hill ex Schrank is the largest genus (Xylariaceae Tul. & C. Tul., Xylariales, Sordariomycetes) consists up to 300 accepted species of stromatic pyrenomycetes (Kirk et al. 2008). Besides their occurrence in soil, wood, leaf litter, and termite mounds, they have mutualistic association with plant species as endophytes in tropical and temperate regions. Several Xylaria spp. associated with termites and termite mounds possess valuable medicinal value (Ko et al. 2011; Song et al. 2011; Zhao et al. 2014; Nagam et al. 2020; Deshmukh et al. 2021). Perithecia of Xylaria has been considered as one of the potential components in traditional Chinese medicine. Xylaria produces a large number of non-volatile and volatile compounds in addition to a wide range of bioactive metabolites such as sesquiterpenoids (eremophilanes, eudesmanolides, presilphiperfolanes, guaianes, brasilanes, thujopsanes, bisabolanes, other sesquiterpenes) diterpenoids and diterpene glycosides, triterpene glycosides, steroids, n-containing compounds (cytochalasins, cyclopeptides, miscellaneous compounds), aromatic compounds (xanthones, benzofuran derivatives, benzoquinones, coumarins and isocoumarins, chroman derivatives, naphthalene derivatives, anthracenone derivatives, miscellaneous phenolic derivatives), pyranone derivatives, and polyketides (Song et al. 2014, MacíasRubalcavaand Sánchez-Fernández 2017). Some of these metabolites serve as potential antimicrobial, anticancer, antimalarial, α-glucosidase inhibitory, and antiinflammatory activities. Their volatiles compounds can be used in various pharmaceutical and agriculture applications. This review evaluates the diversity of bioactive metabolites of the genus Xylaria reported in the recent past. A comprehensive list of bioactive metabolites reported from different species of Xylaria and their site of collections are depicted in Table 3.1 and their chemical structures are given in Figs. 3.2, 3.3, 3.4, 3.5, 3.6, 3.7, 3.8, 3.9, 3.10, 3.11, 3.12, 3.13 and 3.14. Stromata of some of the Xylaria spp. dealt in this review have been presented in Fig. 3.1.

3.2 3.2.1

Bioactive Metabolites Antibacterial Metabolites

Ellisiiamide A (1) (Fig. 3.2) was isolated from Xylaria ellisii J.B. Tanney, Seifert & Y.M. Ju from blueberry (Vaccinium angustifolium). Its structure was elucidated based on 1D and 2D NMR, HRMS/MS data analysis. It showed modest inhibitory activity against Escherichia coli (MIC, 100 μg/ml) (Ibrahim et al. 2020). Eremophilane sesquiterpene, xylareremophil (2) along with eremophilanes and mairetolides B (3) and G (4) (Fig. 3.2) were purified from Xylaria sp. (GDG-102)

Source

Xylaria sp. (GDG-102)

Xylaria sp. (GDG-102)

3.

Locality

Sophora tonkinensis –

Acadian forest region of Nova Scotia, Canada Sophora tonkinensis Hechi, Guangxi province, China

Antibacterial metabolites Xylaria ellisii Vaccinium angustifolium

Fungal strain

2.

1.

Sr. No.

Ampicillin

(
)-5-Methylmellein (7)

(
)-5-Carboxylmellein (6)

Ampicillin G Xylarphthalide A (5)

Xylareremophil (2), mairetolides B (3), G (4) Ampicillin G Compounds (2 and 4)

Ellisiiamide A (1)

Compounds Isolated

Table 3.1 Novel bioactive compounds reported from the genus Xylaria

B. anthracis, B. megaterium, B. subtilis, S. aureus, E. coli, S. dysenteriae and S. paratyphi, Against B. anthracis, B. megaterium, B. subtilis, S. aureus, E. coli, S. dysenteriae and S. paratyphi B. megaterium, B. subtilis, S. aureus, E. coli, S. dysenteriae and S. paratyphi B. anthracis, B. megaterium, B. subtilis, S. aureus, E. coli, S. dysenteriae and S. paratyphi

Proteus vulgaris

Micrococcus luteus

Escherichia coli

Biological target

MICs, 6.25, 6.25, 6.25, 6.25, 3.125, 3.125, and 6.25 μg/ml

MICs, 25, 12.5, 12.5, 25, 25, and 50 μg/ml

MICs, 25, 25, 12.5, 25, 25, 25, and 25 μg/ml

Modest activity against (MIC, 100 μg/ml) MIC, 25 50 and 50 μg/ml MIC, 6.25 μg/ml MIC, 25 μg/ml each MIC, 3.125 μg/ml MICs, 50, 25, 12.5, 25, 12.5, 25, and 25 μg/ml

Biological active value (IC50/ED50)

(continued)

Zheng et al. (2018a)

Liang et al. (2019)

Ibrahim et al. (2020)

References

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 49

Xylaria sp. (YUA-026)

8.

Twigs and petioles

Anoectochilus setaceus

Dead hardwood branch

Antifungal metabolites X. longipes (A 19Wood 91)

Xylaria sp.

7.

9.

Xylaria sp.

Bark unidentified plant

X. curta (92092022)

6.

Leaves, Sophora tonkinensis

Xylaria sp. GDG-102

5.

Lescun, France

Kanneliya forest reserve, Galle, Sri Lanka Mt. Takadate, Yamagata, Japan

Kailua-Kona, Hawaii Co., Hawaii

Ailao Moutain, Yunnan Province of China He Chi, Guangxi Province, China Taiwan

–

X. longipes

4.

Locality

Source

Fungal strain

Sr. No.

Table 3.1 (continued)

Xylaramide (17)

12 and 13 mm at a concentration of 100 μg/disk

Nematospora coryli and S. cerevisiae

MIC, 1 and 5 μg/ ml

12.5 and 25 μg/ml 6.25 and 12.5 μg/ ml

Schneider et al. (1996)

Shiono and Murayama 2005

Ratnaweera et al. (2014)

Deyrup et al. (2007)

Tchoukoua et al. (2017a)

Zheng et al. (2018b)

MIC, 50 μg/ml

References Li et al. (2019)

MIC, 128 μg/ml MIC, 93 μg/ml

Biological active value (IC50/ED50)

13 and 13 mm at a concentration of 100 μg/disk B. subtilis and S. aureus 16 and 12 mm, at 200 μg/disk, after 48 h (agar disk diffusion assays) B. subtilis (UBC 344), MIC, 2 and 4 μg/ MRSA, ATCC 33591 ml

Staphylococcus aureus NBRC 13276

Pseudomonas aeruginosa ATCC 15442

E. coli and S. aureus

P. aeruginosa Salmonella enterica

Biological target

Eremoxylarins A (15), B (16) S. aureus, Eremoxylarins A (15), B (16) P. aeruginosa

Helvolic acid (14)

Kolokosides A (13)

(3aS,6aR)-4,5-dimethyl3,3a,6,6a-tetrahydro-2Hcyclopenta[b]furan-2-one (11) Myrotheciumone A (12)

6-Heptanoyl-4-methoxy-2Hpyran-2-one (10)

Xylaridines A (8) Xylaridines B (9)

Compounds Isolated

50 S. K. Deshmukh et al.

X. cf. curta

X. curta (E10)

X. polymorpha

X. multiplex BCC 1111

Xylaria spp.

Xylaria sp. (YM311647)

10.

11.

12.

13.

14.

15.

Azadirachta indica

Leaves of Paullinia cupana

Fruit bodies

Fruit bodies

Stem Solanum tuberosum

Ko Charng National Park, Than Mayom Waterfall, Trat Province, Thailand Federal University of Amazonas Fazenda SantaHelena Yuanjiang County, Yunnan Province, China

Gwangneung forest in Gyeonggi province, Korea

Dali, Yunnan, China

Positive control Captan and difenoconazole (1S,2S,4S,5S,7R,10R)guaiane-2,10,11,12-tetraol (28), (1S,2S,4R,5R,7R,10R)guaiane-2,4,10,11,12-pentaol (29), (1S,4R,5S,7R,10R)guaiane-4,5,10,11,12-pentaol

Piliformic acid (26), Cytochalasin D (27)

Multiplolides A (24) and B (25)

Xylarinic acids A (22) and B (23)

Curtachalasins A (20) and B (21)

Curtachalasins C and E (18,19)

P. oryzae and H. compactum

C. gloeosporioides

P. capsici, A. mali, A. porri, B. cinerea, R. solani, F. fulva and C. destructans Candida albicans

A. niger, A. panax, and F. oxysporium

P. ultinum, M. grisea

C. albicans strain with resistant genes Cdr1, Cdr2, and Mdr1 Microsporum gypseum

Jang et al. (2007)

Wang et al. (2018a)

Wang et al. (2019a)

MIC, 16.63 and 0.02 μM/ml MIC range, 32–256 μg/ml

MIC, 2.92 and 2.46 μM/ml

(continued)

Huang et al. (2015)

Elias et al. (2018)

IC50, 7 and 2 μg/ml Boonphong et al. (2001)

Fluconazole resistance reversal activity 70.3 and 68.4% inhibitory activity at 200 μM concentration Zone diameter, 16–20 mm Moderate activity with zone diameter, 11–15 mm Marginal activity

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 51

X. multiplex (MSX48662)

Xylaria sp. (F0010)

17.

Fungal strain

16.

Sr. No.

Table 3.1 (continued)

Abies holophylla

Cedar wood

Source

–

Little Rock, Arkansas, USA

Locality

Dechlorogriseofulvin (34)

Dechlorogriseofulvin (34) Griseofulvin (33)

Griseofulvin (33)

Positive control nystatin

(30), (1R,4S,5R,7R,10R)guaiane-1,5,10,11,12-pentaol (31), (1R,4R,5R,7R, 10R)11- methoxyguaiane-4,10,12triol (32) Compound (31) Compounds (30, 31) Compounds (31, 32) Compound (30)

Compounds Isolated

References

MIC, 8 μg/ml against each fungus Zone of inhibition Paguigan et al. of 35 mm at 25 μg/ (2017) disk

MIC, 32 μg/ml MIC, 64 μg/ml MIC, 32 μg/ml MIC, 64 μg/ml

Biological active value (IC50/ED50)

Effectively conPark et al. (2005) trolled the development of at doses of 50–150 μg/ml, depending on the disease Botritis cinerea Active in vivo against on tomato plants Rice sheath blight and Inhibited only the barley powdery mildew development

Rice blast, rice sheath blight, wheat leaf rust, and barley powdery mildew

P. oryzae H. compactum C. albicans C. albicans, A. niger, and H. compactum C. albicans, A. niger, P. oryzae, and H. compactum M. gypseum

Biological target

52 S. K. Deshmukh et al.

X. feejeensis (E6912B) Xylaria sp.

19.

Xylaria sp. (YM 311647)

23.

Azadirachta indica

Xylaria sp. (A19-91) Wood-inhabiting

22.

Leaves Garcinia dulcis

Xylaria sp. (PSUD14)

Leptogium saturninum

Casearia sylvestris leaves

21.

20.

Xylaria sp.

18.

Yuanjiang County, Yunnan Province, China.

–

Songkhla Province, Thailand

Zixi Mountain, Yunnan, China

São Paulo State, Brazil

(1S,4S,5R,7R,10R,11R)Guaiane-5,10,11,12-tetraol (40), (1S,4S,5S,7R,10R,11S)Guaiane-1,10,11,12-tetraol (41), (1S,4S,5R,7R,10R,11S)Guaiane-5,10,11,12-tetraol (42), (1S,4S,5S,7R,10R,11R)Guaiane-1,10,11,12-tetraol (43), (1R,3S,4R,5S,7R,10R,11S)guaiane-3,10,11,12-tetraol (44), (1R,3R,4R,5S,7R,10R,11R)-

Sordaricin (38) Positive control amphotericin B Xylarin (39)

Cyclo-(-NMePhe-Pro-LeuIle-Val) (37)

5-Carboxy6-hydroxy-3methyl-3,4dihydroisocoumarin (35) Xyolide (36)

N. fulvescens, N. coryli, S. cerevisiae S-288c, S. cerevisiae, M. miehei, and U. nuda C. albicans and H. compactum

C. albicans ATCC90028

C. albicans S C5314

Pythium ultimum

C. cladosporioides and C. sphaerospermum

MIC range, 32–256 μg/ml (positive control nystatin MIC, 8.0 μg/ml)

MIC, 50 s, 0.5, 20 s, 5, 25 s, and 25 s μg/ml

Synergistic antifungal activity with 0.004 μg/ml ketoconazole MIC, 32 μg/ml MIC, 0.25 μg/ml

Active at 10 μg using the TLC diffusion method MIC, 425 μM

(continued)

Wu et al. (2014)

Schneider et al. (1995)

Pongcharoen et al. (2008)

Baraban et al. (2013) Wu et al. (2011)

Chapla et al. (2018)

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 53

24.

Sr. No.

Xylaria sp. (Acra L38)

Fungal strain

Table 3.1 (continued)

Aquilaria crassna

Source

Thailand

Locality

Zofimarin (52)

Compound (51)

Guaiane-3,10,11,12-tetraol (45), (1R,4S,5S,7S,9R,10S,11R)guaiane-9,10,11,12-tetraol (46), (1R,4S,5S,7R,10R,11S)Guaiane-10,11,12-triol (47), (1R,4S,5S,7R,10R,11R)Guaiane-10,11,12-triol (48), 14a,16-Epoxy-18norisopimar-7-en-4a-ol (49), 16-O-Sulfo-18-norisopimar7-en-4 a,16-diol (50), 9-deoxy-hymatoxin A (51) Compounds (41) and (46) Compounds (41) and (43) Compound (50) Compounds (40–48)

Compounds Isolated

C. albicans A. niger P. oryzae A. niger, P. oryzae, and H. compactum C. albicans, P. oryzae, and A. niger C. albicans C316, C. albicans ATCC 10231 C. albicans 2402E, Candida pseudotropicales 2371E and C. neoformans ATCC 32045

Biological target

MIC, 32 μg/ml MIC, 64 μg/ml MIC, 32 μg/ml Moderate or weak antifungal activity MIC, 16, 16, and (MIC, 32 μg/ml MIC value of 1,1, 2, 0.25, and 16 microg/ml

Biological active value (IC50/ED50)

Chaichanan et al. (2014), Kennedy et al. (1998)

References

54 S. K. Deshmukh et al.

X.intracolorata

Xylaria sp. (YX-28)

28.

Ginkgo biloba

Jiangsu and Shandong provinces, China

NinhBinh, Vietnam

7-amino-4-methylcoumarin (57)

Positive control nystatin

Positive control gentamicin

Coloratin A (56)

Antimicrobial metabolites X. escharoidea Gut and comb of Guangdong (
)-Regiolone (53) Macrotermes Province, Chin barneyi Xylaria sp. Sophora tonkinensis Hechi, Xylapeptide A (54) Guangxi Province, China Xylapeptide B (55)

27.

26.

25. S. aureus, B. subtilis, P. aeruginosa, and C. albicans Bacillus subtilis and B. cereus B. subtilis, B. cereus, B. megaterium, Micrococcus luteus, S. aureus, Shigella castellani, Canidia albicans S. aureus, P. aeruginosa, Klebsiella pneumoniae, Salmonella enteritidis, E. coli, A. niger, C. albicans S. aureus, P. aeruginosa, K. pneumoniae, S. enteritidis, E. coli A. niger and C. albicans S. aureus, E. coli, S. typhi, S. typhimurium, S. enteritidis, A. hydrophila, Yersinia sp., V. anguillarum, Shigella sp., V. parahaemolyticus, C. albicans, Xu et al. (2017)

MIC, 12.5 μg/ml

18 and 17 mm zone of inhibition MIC, 16, 10, 20, 15,8.5, 4.0, 12.5, 25,6.3, 12.5, 15, 40, and 25 μg/ mL, respectively)

(continued)

Liu et al. (2008)

Quang et al. 15, 16, 22, (2006) 16, 16,15, and 17 mm zone of inhibition (including the diameter of disc 6 mm) 15,16, 14, 16 and 18 mm zone of inhibition

MIC, 12.5, 6.25, 6.25, 12.5, 12.5, and 12.5 and 12.5 μg/ml

Nagam et al. (2020)

MIC of 6.25 μg

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 55

31.

Ficus pumila

Source

Locality

Xylaria sp. (SWUF09-62)

–

–

Cytotoxic metabolites Xylaria Wood-decaying PhuKhieo sp. (SWUF08-37) Stromatal specimens Wildlife Sanctuary, Chaiyaphum Province, Northeast of Thailand

X. psidii FPL-52(S)

29.

30.

Fungal strain

Sr. No.

Table 3.1 (continued)

HeLa, HT29, HCT116, cells HeLa, HT29, HCT116, MCF-7 and Vero cells

Xylochalasin (60)

4S,5S,6S-4-Hydroxy-3methoxy-5-methyl-5,6epoxycyclohex-2-en-1-one (61) Positive control cisplatin

HT29 cells

Vero, HeLa, HT29, HCT116, MCF-7 cells

Vero, HeLa, HT29, HCT116, MCF-7 cells

6-Ethyl-7,8-dihydroxy-4Hchromen-4-one, (62), (3S)3,4-dihydro-5,7,8-trihydroxy3-methylisocoumarin (63)

Biological active value (IC50/ED50)

IC50, 67.89, 44.98, 31.92, 37.98, and 14.62 μg/ml IC50, 56.94, 90.44, and 92.52 μg/ml IC50, 9.60,17.31,14.28, 15.38, and 24.97 μg/ml IC50, 12.86, 5.12, 5.79, 6.29, and 8.75 μg/ml IC50, 16.46, and 97.78 μg/ml

P. expansum, and A. niger Gram-positive and MIC in the range Gram-negative bacteof 0.39–25 μg/ml ria, dermatophytes, and phytopathogenic fungi

Biological target

Pentaminolarin (59)

3-O-Methylmellein (58)

Compounds Isolated

Patjana et al. (2019)

Noppawan et al. (2020)

Rakshith et al. (2016)

References

56 S. K. Deshmukh et al.

X. cf. curta

X. cf. curta

X. cf. curta

X. longipes

32.

33.

34.

35.

Solanum tuberosum

Solanum tuberosum

Solanum tuberosum

–

–

– HL-60 cells

SMMC-7721 cells

(continued)

Wang et al. (2019d) Wang et al. (2019e)

Wang et al. (2019c)

IC50, 13.31, 37.16, Wang et al. 25.83, 1.11, and (2019b) 10.04 μM

IC50, 26.64, and 34.03 μM Positive control cisplatin HL-60 and SMMCIC50, 4.86 and 7721 cells 23.59 μM Xylarichalasin A (69) HL-60, A-549, SMMC- IC50, 17.3, 11.8, 7721, MCF-7, SW480, 8.6, 6.3, and 13.2 μM cell lines Positive control cisplatin IC50, 2.0, 13.2, 12.7, 23.3, and 18.0 μM Cytochalasins D1 (70), and HL-60 IC50, 12.7 and 22.3 μM C1 (71) Cytochalasin P (72), cytocha- HL-60, cell lines IC50, 26.74, 4.17,6.43, lasin D (27), zygosporin D 26.02,12.05 μM (73), 6,7-dihydro-7-oxo-cytochalasin C (74) and 6,7-dihydro-7-oxodeacetylcytochalasin C (75) Cytochalasin P (72) SMMC-7721, MCF-7, IC50, 37.18, 28.05, 35.35 μM SW480 cell lines Compound (27) SMMC-7721 cell line IC50, 22.69 μM Compounds (74) and (75) MCF-7 cell lines IC50, 36.44, 27.24 μM

19-Epi-cytochalasin P1 (64), 7-O-acetyl-6-epi-19,20epoxycytochalasin P (65), 7-O-acetyl-19,20epoxycytochalasin D (66), and known 19,20epoxycytochalasin C (67), 5,6-dihydro-7-oxo-19,20epoxycytochalasin C (68) Compounds (65) and (66)

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 57

Xylaria sp. (SOF11)

Xylaria sp. C-2

39.

40.

38

37.

X. striata

36.

Source

Locality

Unidentified gorgonian (XS-2009-03)

Marine-derived

Xisha Islands, South China Sea

South China Sea

Stumps of Sophora Sichuan Provjaponica ince, China X. allantoidea (SWU Stromatal specimens Phukhieo F76) Wildlife Sanctuary, Chaiyaphum Province, north-east of Thailand X. allantoidea (BCC Wood decaying Hot-spring 23163) park, Nakhon Si Thammarat province, Thailand

Fungal strain

Sr. No.

Table 3.1 (continued)

NCI-H187 cells Plasmodium falciparum K1 SF-268 cell line

NCI-H460 cell lines SF-268, MCF-7, and NCI-H460 cell line HeLa, Hep-2, and RD cell lines

Eremoxylarin C (80)

Compound (83) Positive control cisplatin Ergosta-5,7,22-trien-3β-ol (85)

Cytochalasin P1 (81), cytochalasin P (72), 19, 20-epoxycytochalasin N (82), 20-epoxycytochalasin D MCF-7 cell line (83), and zygosporin G (84)

NCI-H187 cells Vero

HEPG2, B16 and A549 cell lines Hela, and Vero cell lines Hela, HT29, HCT116, MCF-7 and Vero cell lines

Biological target

Xylallantin A (79)

Chaxine C (78)

Demethylincisterol A3 (77)

Xylastriasan A (76)

Compounds Isolated

McCloskey et al. (2017)

Lei et al. (2018)

References

IC50, 1.37, 4.17, 1.57, 0.33, and 1.38 μM IC50, 0.71, 3.28, 2.67, 0.53, and 4.11 μM IC50, 49.38 μM IC50, 1.93, 5.87, and 1.32 μM IC50, 20.1, 37.0, and 40.2 M

Sun et al. (2017)

Chen et al. (2017)

IC50, 17 and 33 μg/ Isaka et al. (2014) ml IC50 ¼ 6.7 μg/ml IC50 ¼ 3.1 μg/ml

IC50, 93.61, 85.61 and 91.58 μM IC50, 76.57 and 50.17 μg/ml IC50, 2.24, 2.51, 3.50, 3.77, and 3.65 μg/ml

Biological active value (IC50/ED50)

58 S. K. Deshmukh et al.

X. psidii

X. nigripes

X. cf. cubensis (PK108)

41.

42.

43.

Yamuna Nagar, Haryana, India

Deqing County in Zhejiang Province, China

PhuKhieo Wildlife Sanctuary, Thailand

Aegle marmelos

–

–

MCF-7, MIA-Pa-Ca-2, NCI-H226, HepG2, and DU145 cell line Decrease NO production

Xylarione A (86), (
) 5-methylmellein (7)

Chevalone C (93), helvolic acid (14) Positive control Dihydroartemisinine

Positive control ellipticine

Ergosterol peroxide (94) Positive control doxorubicin

IC50, 27.6 mm (positive control, L-NMMA, IC50, 14.4 μm) (IC50, 0.93, 6.0, and 13.2 μm

IC50, 16.0 and 19.0 μM IC50, 79.0 and 76.0 μM IC50 range, 16–37 μM

(IC50, 11.9 μm) IC50, 0.01 and 0.003 μm IC50, 33.63 and 21.01 μg/ml IC50, 5.95 and 5.81 μg/ml IC50, 3.25 and 0.36 μg/ml Vero cell line IC50, 47.95 μg/ml KB, NCI-H187 MCF-7 IC50, 0.779, cell lines 0.110, 9.61 μg/ml KB, NCI-H187 MCF-7 IC50, 0.779, 0.110, 9.61 μg/ml cell lines P. falciparum K1 IC50, 25 and 6.25 μg/ml P. falciparum K1 IC50, 0.00215 μg/ ml

Ergosterol D (88), (3 β,5 α, U2OS cell lines 6 β,22Ε)-6-methoxyergosta7,22-diene-3,5-diol (89), (3 β,5 α,6 β)-stigmastane3,5,6-triol (90) Compound (89) A549 cell line Positive control Staurosporine U2OS and A549 cell lines Tryptoquivaline L (91), MCF-7 fiscalin C (92) Cytochalasin D (27), ErgosNCI-H187 terol peroxide (94) Cytochalasin D (27) KB and Vero cell lines

(3β,5α,8α,22Ε)-ergosta-6,22diene-3,5,8-triol (87)

MIA-Pa-Ca-2 cancer cell line Normal cells (fR2)

Xylarione A (86), (
) 5-methylmellein (7)

(continued)

Sawadsitang et al. (2015)

Xiong et al. (2016)

Arora et al. (2016)

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 59

Fungal strain

X. schweinitzii

Xylaria sp. (NC1214)

Xylaria sp. (BM9)

Sr. No.

44.

45.

46.

Table 3.1 (continued)

Saccharum arundinaceum

Moss Hypnum sp.

Fruit bodies

Source

Yichang, Hubei Province, China

–

Cuc Phuong national park, NinhBinh province, Vietnam

Locality

Biological target

Biological active value (IC50/ED50)

Schweinitzins A (95)

KB, Hep-G2, SK-Lu-1, IC50, 0.72, 2.13, 2.32, and 4.09 μg/ and MCF-7 cell lines ml (S)-torosachrysone-8-O-Me KB, Hep-G2, SK-Lu-1, IC50, 0.66, 3.26, 2.51, and 2.24 μg/ ether (96) andMCF-7 cell lines ml Positive control ellipticin KB, Hep-G2, SK-Lu-1, IC50, 0.31, 0.35, 0.45, and 0.53 μg/ and MCF-7 cell lines ml Cytochalasin C (97) PC-3M, NCI-H460, IC50, 1.65, 1.06, 0.96, >5, 1.72 μM SF-268, MCF-7 andMDA-MB-231cell lines Cytochalasin D (27) PC-3M, NCI-H460, IC50, 1.03, 0.22, 0.43, 1.44, and SF-268, MCF-7 and 1.01 μM MDA-MB-231cell lines Cytochalasin Q (98) PC-3M, NCI-H460, (IC50, 1.53, 1.51, 1.31, >5, and SF-268, MCF-7 and 1.32 μM MDA-MB-231cell lines Positive control doxorubicin PC-3M, NCI-H460, 0.25, 0.05, 0.45, SF-268, MCF-7 and 0.32, 0.67 μM MDA-MB-231cell lines Cytochalasin E (99), cytocha- HepG2 and Caski cell IC50, 25, 59 45 and 29, 63 and 53 μM lasin K (100), cytochalasin lines Z16 (101)

Compounds Isolated

Zhang et al. (2015)

Wei et al. (2015)

Linh et al. (2014)

References

60 S. K. Deshmukh et al.

X. humosa

X. cubensis (SNB-GCI02)

Xylaria sp. (A23)

Xylaria sp. (BL321)

Xylaria sp. (BCC 4297)

X. carpophila

Xylaria sp.

47.

48.

49.

50.

51.

52.

53.

–

Gaoligong Mountains in Yunnan Province, China

–

–

Sicun Province, China

–

–

Termite nest

Xiamen University, Fujian, China

Annona squamosa

Angiospermic plant

IC50, 5.8, 21.4 and 17.7 μg/ml

NCI-H187 cell lines

IC50, 1.3, 17.3, 15.8; 24.4 μM IC50, 124 and 147 μM IC50, 127 and 117 μM

IC50, 0.27 and 0.11 μg/ml KB, and MRC-5 cells IC50, 10 μM each IC50, 0.0002 and 0.0005 μM HeLa and 293T cells 25.04 and 32.8% inhibition at 1.0 μg/ml concentration MCF-7 and MDA-MB- IC50, 22.5, 33.0, 26.3 and 13.6; 7.1, 435 cell lines 9.3, 11.1, and 6.9 μM KB, MCF-7, IC50, 1.0, 13, 65, and 41 μM NCI-H187 and CV-1 line HL-60, A-549, MCF-7, IC50, 7 23.1, 35.7, 28.5; 29.0 μM SW480 cell line

NCI-H187 cell lines

Chlorine heptelidic acid (108) A549 and S GC7901 cell lines 16-(α-D glucopyranosyloxy) isopimar
7-en-19-oic acid (109)

(4S,5S,6S)-5,6-epoxy4hydroxy-3-methoxy-5methyl-cyclohex-2-en-1-one (107) Positive control cisplatin

07H239-A (105), cytochalasins C–D (98, 27), and 19, 20-epoxycytochalasin C (69) Xylopimarane (106)

Cytochalasin H2 (104)

Ergosterol peroxide (94), chevalone B (102) and C (103) Positive control ellipticine and doxorubicin French Guiana Griseofulvin (39) Positive control docetaxel

PhuKhieo Wildlife Sanctuary, Thailand

(continued)

Yan et al. (2011)

Yin et al. (2011)

Isaka et al. (2011)

Li et al. (2012)

Casella et al. (2013)

Sodngam et al. (2014)

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 61

Xylaria sp. (SCSIO156)

Xylaria sp.

X. polymorpha

55.

56.

Fungal strain

54.

Sr. No.

Table 3.1 (continued)

Fruit bodies

Leaves Piper aduncum

Marine sediment

Source

Sao Paulo, Brazil

South China Sea

Locality

IC50, 132, 71, 75 and 112 μM IC50, 0.02, 0.10, 0.90 and 0.07 μM Induces apoptosis along with typical DNA fragmentation HL60, K562, HeLa, and LNCaP cell lines HL60 cells

Compounds (115) and (117)

HL60, K562, HeLa, and LNCaP cell lines

16-α-Dmannopyranosyloxyisopimar7-en-19-oic acid (115) 15-hydroxy-16-α-Dmannopyranosyloxyisopimar7-en-19-oic acid (116) 16-α-Dglucopyranosyloxyisopimar7-en-19-oic acid (117) Positive control camptothecin

HL60, K562, HeLa, and LNCaP cell lines

C. cladosporioides, C. sphaerospermum

Phomenone (114)

IC50, 327, 390, 288 and 607 μM

CHO cell line

HL60, K562, HeLa, and LNCaP cell lines

IC50 range, of 14.4–96.4 μM

Biological active value (IC50/ED50)

IC50, 2.9, 5.3; 0.55 μM 20 and 50%, of cytotoxicity at 20 mM and 200 mM Activate at 10 μg using the TLC diffusion method IC50, 165, 143, 235, 215 μM

MCF-7, SF-268, and NCI-H460 cell lines

Biological target

Phaseolinone (113)

21-O-deacetylcytochalasin Q (110), 19,20epoxycytochalasin Q (111), 21-O-deacetyl-19,20epoxycytochalasin Q (112), cytochalasin Q (98), and cytochalasin D (27) Positive control cisplatin

Compounds Isolated

References

Shiono et al. (2009)

Silva et al. (2010a)

Chen et al. (2011)

62 S. K. Deshmukh et al.

X. obovata

Xylaria sp. (BCC 9653)

Xylaria sp.

59.

60.

61.

63.

62.

X. hypoxylon strain (A27–94)

58.

Unidentified wood

Wood inhabiting

Fresh stems of Ligustrum lucidum

Outer bark, Glochidion ferdinandi Xylaria sp. Xylaria Stems of sp. (M71) Camptotheca acuminate Antimicrobial and cytotoxic metabolites Xylaria sp. (NCY2) Torreya jackii

X. hypoxylon (AT-028)

57.

Jiangshi Nature Reserve Zone of Fujian Province, China

Hep G2 cells

Methyl aminobenzoate (123), cytochalasin D (27), desacetylcytochalasin D (124) Cytochalasin D (27), 5-carboxymellein (125), and 4-quinolinecarboxaldehyde oxime (126) (
)-xylariamide A (127)

HepG2 and HeLa cell

E. coli, B. subtilis, S. aureus, Saccharomyces cerevisiae, and C. albicans

Xylarenones A (129) and B (130), and xylarenic acid (131) Xylarenones A (129)

Cytotoxic, produced via the MVA pathway

Brine shrimp (Artemia salina) lethality assay

Mycobacterium tuberculosis

Vero cells

Positive control 5-fluorouracil Xylarone (120) Colo320; L1210 cells 8,9-dehydroxylarone (121) Colo-320, L1210 and HL-60cells 19,20-epoxycytochalasin Q Lethal to brine shrimp (111), and its new deacetyl HL-60 cells analog (122) Vero monkey cell

Xylariol A (118), B (119)

Toohey Forest, Queensland, Australia Qinba moun10-hydroxycamptothecin tains, China. (128)

Bala-Hala Wildlife Sanctuary, Naratiwat Province, Thailand

Munsea forest in Arsi Province Ethopia

Vicinity of Vancouver, Canada

Suburb of Nanjing, China

Liu et al. (2010), Ding et al. (2017)

Davis (2005)

Pongcharoen et al. (2007)

Dagne et al. (1994)

Schüffler et al. (2007)

Gu and Ding (2008)

(continued)

Hu et al. (2008) (IC50, 8.7, 23.8, 2.63, and 27.8, 21.1, and 19.9 mg/ ml 13.5, 21.6, 21.6, 1.13, and 2.61% inhibition at 50 μg/ml concentration

0% and 71% lethality at 20 and 200 μg/ml –

MICs, 394.3, 900.7, and 581.2 μM

IC50, 22.3 and 21.2 μg/ml (IC50, 6.4 μg/ml) IC50, 40; 50 μg/ml IC50, 25, 25 and 50 μg/ml LC50, 2.5 μg/ml Cytotoxic to at 1 μg/ml IC50, 0.46; 1.9 μg/ ml IC50, 26.13, 0.19, and 16.61 μM

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 63

Fungal strain

Xylaria sp.

Sr. No.

64.

Table 3.1 (continued)

Taxus mairei

Source

Tonglu county, Zhejiang Province, China

Locality

References

Nalgiovensin (133)

Nalgiovensin (133)

3,7-dimethyl-9-(
2,2,5,5tetramethyl-1,3-dioxolan-4yl)nona-1,6-dien-3-ol (132)

Xylarenic acid (131)

E. coli, B. subtilis, 14.9, 36.3, 36.3, S. aureus, S. cerevisiae, 2.56, and 1.75% C. albicans inhibition at 50 μg/ml concentration E. coli, B. subtilis, 20.1, 20.1, 23.5, S. aureus, S. cerevisiae, 0.39, and 1.28% C. albicans inhibition at 50 μg/ml concentration B. subtilis ATCC 9372 48.1, 31.6, and Lin et al. (2016) B. pumilus 7061 and 47.1% inhibition at S. aureus ATCC 25923 concentration of 50 μg/ml 46.0, 40.0, 42.1, C. albicans As 2.538, 36.8, 47.1, and A. niger 16888, 41.2%, at concenS. aureus ATCC tration of 50 μg/ 25923, B. subtilis ml ATCC 9372, B. pumilus ATCC 7061 and E. coli ATCC 25922 HeLa cell 94.1% inhibition at concentration of 10 μg/ml

Xylarenones B (130)

Biological active value (IC50/ED50)

Biological target

Compounds Isolated

64 S. K. Deshmukh et al.

Xylaria sp. (NCY2)

X. cubensis (PSU-MA34)

Xylaria sp. (XC-16)

65.

66.

67.

Toona sinensis

Bruguiera parviflora

Torreyajackii Chun

Yangling, Shaanxi province, China

Suratthani province, Thailand

Jiangshi Nature Reserve Zone of Fujian Province, China

Cytochalasin E (99)

Cytochalasin Z28 (144)

Another positive control hymexazol

2-chloro-5-methoxy-3methylcyclohexa-2,5-diene1,4-dione (142) Cytochalasin D (27) Cytochalasin Z27 (143), Cytochalasin Z28 (144), Seco-cytochalasin E (145), Cytochalasin Z18, (146), Cytochalasin E (99) Positive control carbendazim

1-(xylarenone A)xylariate A (134), xylarioic acid B (135), xylariolide A (136), xylariolide B (137), xylariolide C (138), Me xylariate C (139), xylariolide D (140), taiwapyrone (141) MIC, above 10 mg/ml

Positive control toosendanin

Brine shrimp,

A. solani, B. cinerea, F. solani, and G. saubinetti A. solani, B. cinereal, F. solani, and G. saubinetti G. saubinetii

The fungicidal effect better than hymexazol With LC50 value of 2.79 μM LC50 value of 4.03 μM

MIC, 12.5, 50, 50, and 25 μM

MIC, 3.13, 6.25, 6.25, and 3.13 μM

Weak activities at 10 μg/ml, the inhibitory rates were less than 30% S. aureus ATCC 25923 MIC, 128 μg/ml and methicillineach resistant S. aureus KB cell lines IC50, 3.99 μg/ml As Alternaria solani, MIC, range B. cinerea, Fusarium 12.5–100 μM solani, and Gibberella saubinetti

E. coli ATCC 25922, B. subtilis ATCC 9372 and S. aureus ATCC 25923 HepG2 and HeLa cells

(continued)

Zhang et al. (2014)

Klaiklay et al. (2012)

Hu et al. (2010)

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 65

Xylaria sp. (BCC 21097)

70.

Licuala spinosa

Leaf Ficus carica

Xylaria sp. (ZJWCF255)

69.

Source

Xylaria Bisboecklera sp. (SNB-GTC2501) microcephala

Fungal strain

68.

Sr. No.

Table 3.1 (continued)

Trang Province, Thailand

Locality

Compound (152)

C. albicans

IC50 6.3 μM IC50, 8.1 and 13 μM IC50 7.8 μM

IC50 0.40, 1.8, and 0.066 μM

IC50, 10 10 5.8; 9.4 μM

IC50, 21 15 3.8 and 3.9 μM

(IC50, 17.24, 7.75 and 10.30 μg/ml IC50, 5.0, 15, 7.2; 8.5 μM

IC50, 1.9 μM EC50, 0.04, 6.24, 6.72, 7.96, 10.27, 11.56, 12.34,33.8, 50.46, and 73.44 μg/ml

Xylabisboein A (147) and B (148), melle (149), (
)-5methylmellein (7) ergosterol peroxide (94) Ergosterol peroxide (94) Cytochalasin Q (98) MRC5 cells D. bryoniae, R. solani, P. diospyri, S. sclerotiorum, B. cinerea, C. orbiculare, V. nigrescens, V. dahliae, F. oxysporum, and P. ultimum SMMC-772, MCF-7, MGC80-3 cell lines 1b,7a,10aKB, MCF-7, Trihydroxyeremophil-11(13)- NCI-H187, Vero cell en-12,8b-olide (150) 7a,10a-Dihydroxy-1bKB, MCF-7, methoxyeremophil-11(13)NCI-H187, Vero cell en-12,8b-olide (151) 1a,10a-Epoxy-7aKB, MCF-7, hydroxyeremophil-11(13)-en- NCI-H187, Vero cell 12,8b-olide (152) Positive control doxorubicin KB, MCF-7, and hydrochloride NCI-H187 cancer celllines Positive control ellipticine Vero cell-lines Compounds (151 and 152) P. falciparum K1

Biological active value (IC50/ED50) MIC, >128 μg/ml

Biological target S. aureus, Trichophyton rubrum and C. albicans

Compounds Isolated

References

Isaka et al. (2010)

Wang et al. (2014)

Sorres et al. (2015)

66 S. K. Deshmukh et al.

Xylaria sp.

X. ianthinovelutina

X. mellisii

Xylaria sp. (BCC 1067)

71.

72.

73.

74.

Wood-decaying

Unidentified seed

Piper aduncum

Nam Nao National Park Northeastern, Thailand

Kaeng Krachan National Park, Phetchaburi, Thailand

Hala-Bala Wildlife Sanctuary, Narathiwat province, southern Thailand

(
)-Depudecin (161), (+)phaseolinone (113), (+)phomenone (114), 19,20epoxycytochalasin Q (111)

Compound (157) Positive control Dihydroartemisinin Mellisol (159), 1,8-dihydroxynaphthol 1-O-α-glucopyranoside (160)

Positive control cisplatin 19,20-epoxycytochalasin Q (111) 12,8-eudesmanolides namely 3α,4α,7β-Trihydroxy-11(13)eudesmen-12,8-olide (155) 4α,7β-Dihydroxy-3α-methoxy-11(13)eudesmen-12,8-olide (156) 7β-Hydroxy-3,11(13)eudesmadien-12,8-olide (157) 13-Hydroxy-3,7(11)eudesmadien-12,8-olide (158) Positive control doxorubicin

19,20-epoxycytochalasin C (67), Q (111), R (153) and D (154)

KB cells

HSV- type 1

(continued)

IC50 39.4 and Pittayakhajonwut 45.8 μg/ml et al. (2005) IC50, 10.50; 8.40 μg/ml, respectively IC50, 2.8, 0.68, 1.2; Isaka et al. (2000) 0.72 μg/ml

IC50, 10.25, 6.28, and 1.48 μg/ml IC50, 4 0.65, 4.14 μg/ml IC50, 0.13, 0.89; 0.04 μg/ml IC50, 2.271 μg/ml IC50, 1.14 μg/ml

KB, MCF-7, NCI-H187 cell lines KB, NCI-H187 cell lines KB, NCI-H187 cell lines P. falciparum P. falciparum Vero cells

IC50, 18.21, 9.94; 0.78 μg/ml

KB, MCF-7, NCI-H187 cell lines

Silva et al. (2010b)

IC50, 19.15, 22.82; Pittayakhajonwut 2.61 μg/ml et al. (2009)

(IC50, 120.0, 125.0, 4.00 and 90.0 μM respectively) IC50, 20 μM Weakly active

C. cladosporioides and C. sphaerospermum KB, MCF-7, NCI-H187 cell lines

HeLA cell lines

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 67

Source

X. nigripes (YMJ653)

X. cubensis

X. papulis

Xylaria sp.

X. fimbriata (YMJ491)

77.

78.

79.

80.

Termite nestderived

Leaves of Litsea akoensis Stem of Taiwanese Lepidagathis stenophylla

Termite nest-

Anti-inflammatory metabolites Xylaria sp. (SWUF09-62)

Fungal strain

76.

75.

Sr. No.

Table 3.1 (continued)

Hengchun Peninsula of southern Taiwan Vietnam

Locality

Inhibition of NO production iNOS inhibitory activity iNOS inhibitory activity

Positive control aminoguanidine and Nu-nitro-L-arginine

Inhibition on NO production

Inhibition on NO production IL-6 inhibitory activity

Inhibition on NO production and iNOS and COX-2 expression

Inhibition of NO production in LPS-stimulated RAW264.7 cells

Ergosta-4,6,8(14),22-tetraen3-one (166) Fimbriethers A-G (167–173)

(
)-(R)-7-hydroxymellein (164) Xylapapuside A (165)

Positive control curcumin

Fomannoxin alcohol (163)

6-Ethyl-7,8-dihydroxy-4Hchromen-4-one (62), and (3S)-3,4-dihydro-5,7,8-trihydroxy-3-methylisocoumarin (63) Nigriterpene C (162)

BC1 cells

Compounds (161,113, 114, 111) Compounds (161,113, 114, 111) P. falciparum

Biological target

Compounds Isolated

Patjana et al. (2019)

References

Ngoc and Dinh (2008) Chen et al. (2019)

IC50, 28.96 μM Emax, 4.6, 31.3, 7.7, 7.3, 38.9, 6.0, and 49.7% Emax, 83.7 and 42.1%

Chen et al. (2016)

Fan et al. (2014) Emax value of 34.3 μM

IC50, 9.4 μM

IC50, 21.7, 8.1, and Chang et al. 16.6 μM (2017) IC50, 33.8, 11.6 and 12.7 μM IC50, 4.5 μM

IC50 ¼ 1.57, and 3.02 μg/ml

IC50, 1.6, 0.36, 0.51; 20 μg/ml EC50, 1.0, 0.5, 0.32, 0.59 μg/ml

Biological active value (IC50/ED50)

68 S. K. Deshmukh et al.

Xylaria sp.

84.

Mangrove plant

Fruit bodies

X. nigripes

83.

Qurcus sp.

Acetylcholinesterase (AChE) inhibitors X. polymorpha

Xylaria sp. (MF 5809)

82.

81.

South China Sea coast

Chuxiong County, Yunnan Province, China

Valley of Yinggeling, Hainan province of China

Congree swamp, Columbia, South Carolina Inhibition of AChE

Inhibitor of IL-1 beta converting enzyme Inhibitor of ICE activity

Inhibition of AChE

Inhibition of AChE

Positive control tacrine

Xyloketal A-D (182–185)

Inhibition of AChE

Agroclavine (179)

Xylanigripones A (177), Inhibition of CEPT agroclavine (179), 8,9-didehydro-10-hydroxy6,8-dimethylergolin (180), and (6S)-agroclavine N-oxide (181) Xylanigripones C (178) Inhibition of AChE

Positive control Tacrine

Xylariaines A-B (175–176)

Xylaric acid (174)

38.1%, at the concentration of 50 μM 11.9% at the concentration of 50 μM 45.4% at the concentration of 50 μM IC50, 29.9, 137.4, 109.3 and 425.6 μM/L

Inhibitory rate 12.4% and 18.0%, at a concentration of 50 μg/ml Inhibitory rate, 56.7% 49, 73, 36.50 and 58.50%

IC50, 33 μM

Ki of 8 μM

(continued)

Jinghui et al. (2004)

Hu and Li (2017)

Yang et al. (2017)

Salvatore et al. (1994)

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 69

87.

X. longipes (HFG1018)

Wood-rotting basidiomycete Fomitopsis betulinus

Immunosuppressive metabolites X. cf. curta Solanum tuberosum

Piper aduncum

Xylaria sp.

86.

Mangrove plant

Xylaria sp. (2508)

85.

Source

Fungal strain

Sr. No.

Table 3.1 (continued)

Changbaishan National Nature Reserve, Jilin Province, China

Dali, Yunnan, China

South China Sea Sao Paulo, Brazil

Locality

Curtachalasins F (187), H (189), I (190), J (191), L (192), M (193), N (194), O (195), P (196), curtachalasin A-B (20, 21), E (19) Curtachalasins F (188), H (189), I (190), P (196) curtachalasin B (21), E (19) Positive control dextromethorphan Curtachalasins G (188), Compounds (192), and (18) Xylarinorditerpenes B-E, I, N, (197, 198, 199, 200, 201,202), 14α,16-epoxy-18norisopimar-7-en-4α-ol (203), agatadiol (204)

Detection limit of 3.0 μg Detection limit of 1 μg in each case Detection limit of 1.0 μg

1.5  10–6 mol/L ( p < 0.01) Detection limit of 10.0 and 25.0 μg

Biological active value (IC50/ED50)

(IC50, 70.9,28.5, 13.3, 21.0, 31.1, 62.5, 12.6, 16.5, 29.0, 39.7 and 22.4 μM Inhibition on B-cell IC50, 2.4, 28.5, 19.5, 72.3, 35.4 proliferation and 88.0 μM Inhibition on T-cell and IC50, 1.6 and 0.8 μM B-cell proliferation Cytotoxic, the viabil45.1, 60.7 and ities of treated cells 10.0% Cell proliferation by IC50, ranging from Con A-induced T lym- 1.0 to 27.2 μM and phocytes and from 16.1 to lipopolysaccharide51.8 μM, induced B lymphocytes respectively Inhibition on T-cell proliferation

C. cladosporioides and C. sphaerospermum Inhibition of AChE

Positive control nystatin Positive control galantamine

Cladosporium cladosporioides and C. sphaerospermum Inhibition of AChE

Inhibition of AChE

Biological target

(3R,4R)-3,4-dihydro-4,6dihydroxy-3-methyl-1-oxo1H-isochromene-5-carboxylic acid (186)

Xyloketal A (182)

Compounds Isolated

References

Chen et al. (2020a)

Wang et al. (2019f)

Oliveira et al. (2011)

Lin et al. (2001)

70 S. K. Deshmukh et al.

X. nigripes

90.

Other bioactive metabolites X. striata Trunk base and stumps Sophora japonica

X. nigripes

89.

91.

Metabolites with Antioxidant activities Xylaria sp. Casearia sylvestris leaves

88.

Sichuan Province, China

São Paulo State, Brazil

Ergosterol (211)

Xylapyrrosides A (207), B (208), pollenopyrrosides A (209) and B (210)

Prolonging sleeping time and reducing sleep latency at a dosage of 5 mg/kg

Moderate antioxidant effects by preventing the oxidative stressinduced cytotoxicity of A7r5 rat VSMCs

DPPH assay

AChE inhibition

Compounds (205, 95)

5,8-dihydroxy-3-methyl-3,4dihydroisocoumarin (206)

Antioxidant activity

Griseofulvin (33), Cytochalasin B (205), D (27), C (95)

Yellow spots against the purple background on TLC bioautography at 1 mg/ml TLC bioautography at 60 μg Antioxidant activity was as 1.67 times as that of vitamin C or 2.10 times as that of vitamin E at the concentration of 20 μM/l

(continued)

Lei et al. (2018)

Li et al. (2015)

Wu (2001)

Chapla et al. (2018)

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 71

Xylaria sp. (SYPF 8246)

Xylaria sp. (HNWSW-2)

93.

Fungal strain

92.

Sr. No.

Table 3.1 (continued)

Stem, Xylocarpus granatum

Root of Panax notoginseng

Source

Dong Zhai Gang Mangrove Reserve in Hainan province, China

Wenshan, Yunnan, China

Locality

Biological target

AChE inhibition

α-Glycosidase inhibition

α-Glycosidase inhibition

Positive control tacrine

Astropyrone (219)

Acarbose

hCE 2 inhibition Xylarianin A (212), 6-methoxycarbonyl-20 -methyl-3,5,40 ,60 -tetramethoxy-diphenyl ether (213), 2-chlor-6methoxycarbonyl-20 -rnethyl3,5,40 ,60 -tetramethoxydiphenyl ether (214), 2-chlor40 -hydroxy-6-methoxy carbonyl-20 -methyl-3,5,60 -trimethoxy-diphenyl ether (215), grisephenone A (216), 5,9,11-trimethoxy-3,13dihydroxy benzophenone (217), 2-hexylidene-3-methyl succinic acid 4-methyl ester (218) Astropyrone (219), guaidiol AChE inhibition (220)

Compounds Isolated

Inhibition rates of 10.4 and 12.9% at a concentration of 50 μg/ml Inhibition rate of 77.4% at a concentration of 50 μg/ml Inhibition rate of 77.0% at a concentration of 0.25 mg/ml Inhibition rate of 59.7% at a concentration of 0.25 mg/ml

IC50, 10.43, 6.69, 12.36,18.25, 29.78, 18.86, and 20.72 μM

Biological active value (IC50/ED50)

Wang et al. (2018b)

Zhang et al. (2018)

References

72 S. K. Deshmukh et al.

Xylaria sp. (#2508)

X. polymorpha

X. persicaria

X. feejeensis

Xylaria sp. (BL321)

95.

96.

97.

98.

99.

100. Xylaria sp.

X. feejeensis

94.

Siparuna sp.

Hintonia latiflora

Fallen fruits L. styraciflua

Avicennia marina

Sponge Stylissa massa

Altos Campanas National Park, Panama.

North Edison, Middlesex County, New Jersey USA

Hong Kong, China

Beijiao of Dongsha, South China Sea

(+) Phomalactone (230), 5-hydroxymellein (231)

3S,4R-(+)-4-hydroxymellein (228), 3S,4S-(+)-4hydroxymellein (229) Acarbose positive control 07H239-A (105)

Xylarenals A (226) and B (227)

Spiropolin A (225)

Xyloketal F (224), xyloketals A (182), B (183)

Macrolide (221), scirpyrone D (222), (6S,1’S)-LL-P880β (223) Scirpyrone D (222), (6S,1’S)LL-P880β (223)

α-Glucosidase inhibition Chloroquine-resistant strain of P. falciparum

Restored the growth inhibition caused by the hyperactivated Ca-signaling in mutant yeast Cloned mouse NPY Y5 receptors Y1, Y2, Y4, and y6 receptors Saccharomyces cerevisiae α-glucosidase (αGHY)

Reduced the numbers of osteoblast cells at 1 μM L-calcium channel blocking activity

Reduced the areas of the osteoclasts

Rivera-Chávez et al. (2015)

Smith et al. (2002)

Shiono et al. (2013)

Wu et al. (2005)

Wang et al. (2018c)

(continued)

Song et al. (2012b) IC50, 13 and 19 μg/ Jiménez-Romero ml, respectively et al. (2008)

IC50 ¼ 545 μM IC50, 6.54 μM

IC50, 441 and 549 μM

IC50, 1.5 and 0.3 μM Low affinities

Inhibiting rates were 21.47%, 12.05%, and 50.33%, respectively, at 0.03 μmol/L concentration

At 0.5 and 1 μM

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 73

Fungal strain

Puerto Rico

Fruit body

103. Xylaria sp. (MF6837) 104. X. polymorpha

Locality

South China Sea coast

Dead branch

Source

102. Xylaria sp. (2508)

101. Xylaria sp. (V-27)

Sr. No.

Table 3.1 (continued)

19,20-epoxycytochalasin Q (111) Xylarinic acid A (22)

Xylopyridine A (234)

13,13-dimethoxyintegric acid (232), integric acid (233)

Compounds Isolated

Biological active value (IC50/ED50)

Promoted growth restoring activity against the mutant yeast strain and inhibited degranulation of rat basophilic leukemia RBL-2H3 cells stimulated by IgE + DNPBSA, thapsigargin and A23187 Strong DNA-binding affinity toward calf thymus (CT) DNA presumably via an intercalation mechanism, thus it is exploitable as a strong DNA-binders Poor inhibition binding IC50, 60 μM activity Inhibited NO production and m RNA expressions of iNOS, COX-2, IL-1β, and IL-6 in a concentrationdependent pattern without cytotoxicity effect.

Biological target

References

Jayasuriya et al. (2004) Kim et al. (2010)

Xu et al. (2009)

Tchoukoua et al. (2017b)

74 S. K. Deshmukh et al.

Leaves of Prachinburi Sandoricumkoetjape Province, Thailand Mai Po, Hong Kong, China

Hainan, China

Seed of an angiosperm tree

106. Xylaria sp.

107. Xylaria sp. (2508)

108. Co-culture - Penicil- Root of Sonneratia caseolaris lium crustosum (PRB-2) Xylaria sp. (HDN13-249)

Changbaishan National Nature Reserve, Jilin Province, China

Fomitopsis betulinus

105. X. longipes (HFG1018)

Positive control Ciprofloxacin

Compounds (240 and 243)

Penixylarins A-D (238–241), 1,3-dihydroxy-5(12-hydroxyheptadecyl)benzene (242) and 1,3-dihydroxy-5(12-sulfoxyheptadecyl) benzene (243) Compounds (240, 242, 243)

Tansuwan et al. (2007)

IC50, 1.84 and 6.68 μM IC50, 1.35 and >184 μM Induces angiogenesis in zebra fish embryos and in human endothelial cells

(continued)

Yu et al. (2019)

Lu et al. (2012)

Chen et al. (2020b)

IC50, 13.6 and 22.4 μM

MIC, 6.25, 25.0, and 12.5 μM Vibrio parahemolyticus MIC, 12.5 and 25.0 μM Mycobacterium phlei MIC, 1.56 and and V. parahemolyticus 12.5 μM

Mycobacterium phlei

Inhibitory activity against the cell proliferation of Con A-induced T lymphocytes and lipopolysaccharideinduced B lymphocytes Xylaria quinone A (236), and Plasmodium falciparum, K1 strain 2-chloro-5-methoxy-3Vero cells methylcyclohexa-2,5-diene1,4-dione (142) Xyloallenoide A (237) Inhibition of PI3K/Akt/ eNOS by LY294002

Xylarilongipins A (235)

3 Recent Advances in the Discovery of Bioactive Metabolites from. . . 75

Fungal strain

Xylaria psidii

109. Co-culture - Aspergillus fischeri (NRRL 181) and X. flabelliformis (G536)

Sr. No.

Table 3.1 (continued)

Vitis vinifera

Source

Locality

Resveratrol (245)

Positive control taxol

Wheldone (244)

Compounds Isolated MDA-MB-231, OVCAR-3, MDA-MB435 cell lines MDA-MB-231, OVCAR-3, MDA-MB435 cell lines Antioxidant

Biological target

Dwibedi et al. (2019)

Knowles et al. (2020)

IC50, 1 7.6, 3.8, and 2.4 μM IC50, 0.17, 0.0051, and 0.00043 μM

References

Biological active value (IC50/ED50)

76 S. K. Deshmukh et al.

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

77

Fig. 3.1 Xylaria spp. from the scrub jungles of Southwest India: (a) Xylaria escharoidea grown on termite mound, (b) X. hypoxylon grown on humus, (c) X. longipes grown on wood log, (d) X. multiplex grown on wood log, (e) X. nigripes grown on termite mound, (f) X. obovata grown on wood log, and (g) X. polymorpha grown on wood log

associated with the leaves of Sophora tonkinensis. Compounds (2–4) displayed antibacterial activities against Micrococcus luteus (MIC, 25 50 and 50 μg/ml, respectively), while positive control ampicillin G displayed antibacterial activity

78

S. K. Deshmukh et al.

Fig. 3.2 Structures of metabolites isolated from Xylaria sp. (1–19)

(MIC, 6.25 μg/ml). Compounds (2) and (4) displayed antibacterial activities against Proteus vulgaris (MIC, 25 μg/ml each), while ampicillin G as positive control displayed antibacterial activity (MIC, 3.125 μg/ml) (Liang et al. 2019). Phthalide derivative xylarphthalide A (5) and two previously reported compounds (
)-5-carboxylmellein (6) and (
)-5-methylmellein (7) (Fig. 3.2) were purified from Xylaria sp. (GDG-102) associated with Sophora tonkinensis. Compound (5) displayed antibacterial activity with MIC of value of 50, 25, 12.5, 25, 12.5, 25, and 25 μg/ml against Bacillus anthracis, B. megaterium, B. subtilis, Staphylococcus aureus, Escherichia coli, Shigella dysenteriae, and Salmonella paratyphi, respectively. Compound (6) showed antibacterial activity with MIC of value of 25, 25, 12.5, 25, 25, 25, and 25 μg/ml against B. anthracis, B. megaterium, B. subtilis, S. aureus, E. coli, S. dysenteriae, and S. paratyphi, respectively. Compound (7) was antibacterial with MIC of value of 25, 12.5, 12.5, 25, 25, and 50 μg/ml against B. megaterium, B. subtilis, S. aureus, E. coli,

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

79

S. dysenteriae, and S. paratyphi, respectively. Positive control ampicillin showed antibacterial activity against B. anthracis, B. megaterium, B. subtilis, S. aureus, E. coli, S. dysenteriae, and S. paratyphi (MIC value of 6.25, 6.25, 6. 25, 6.25, 3.125, 3.125, and 6.25 μg/ml, respectively) (Zheng et al. 2018a). Alkaloids xylaridines A (8) and B (9) (Fig. 3.2) were purified racemic mixture from the Xylaria longipes Nitschke. Compound (8) showed weak antibacterial activity against Pseudomonas aeruginosa (MIC, 128 μg/ml), while the compound (9) displayed poor activity against Salmonella enterica (MIC, 93 μg/ml) (Li et al. 2019). A new compound, 6-heptanoyl-4-methoxy-2H-pyran-2-one (10) (Fig. 3.2), was purified from Xylaria sp. (GDG-102) residing inside the leaves of S. tonkinensis and displayed antibacterial activity against E. coli as well as S. aureus (MIC, 50 μg/ ml) (Zheng et al. 2018b). A new compound (3aS,6aR)-4,5-dimethyl-3,3a,6,6a-tetrahydro-2H-cyclopenta [b]furan-2-one (11) and known metabolites myrotheciumone A (12) (Fig. 3.2) were purified from the Xylaria (fungal strain 92092022). Compounds (12) showed average antibacterial activity against Pseudomonas aeruginosa and S. aureus with zone of inhibition of 13 mm and 12 mm, respectively, at a concentration of 100 μg/ disk. Compounds (11) displayed moderate activity against P. aeruginosa and S. aureus with zone of inhibition of 13 mm each at a concentration of 100 μg/disk (Tchoukoua et al. 2017a). Triterpenoid glycoside kolokosides A (13) (Fig. 3.2) from Xylaria sp. obtained from dead hardwood and displayed activity against B. subtilis and S. aureus with clear zones of 16 and 12 mm, respectively, after 48 h in agar diskdiffusion assays at 200 μg/disk (Deyrup et al. 2007). An endophytic Xylaria sp. isolated from Anoectochilus setaceus was the source of helvolic acid (14) (Fig. 3.2), which was active against Bacillus subtilis (UBC 344) as well as methicillin-resistant Staphylococcus aureus (MRSA, ATCC 33591) (MIC, 2 and 4 μg/ml) (Ratnaweera et al. 2014). Eremophilane, sesquiterpenes, and eremoxylarins A (15) and B (16) (Fig. 3.2) were purified from the Xylaria sp. (YUA-026)an endophytic fungus isolated from twigs and petioles of Mt. Takadate, Yamagata, Japan. Eremoxylarins A (15) and B (16) displayed activity against S. aureus (MIC, 12.5 and 25 μg/ml, respectively) and against P. aeruginosa (MIC, 6.25 and 12.5 μg/ml, respectively) (Shiono and Murayama 2005).

3.2.2

Antifungal Metabolites

Xylaramide (17) (Fig. 3.2) was isolated from the wood inhabiting X. longipes A 19-91, collected in Lescun, France, which was found to be active against Nematospora coryli and S. cerevisiae (MIC, 1 and 5 μg/ml, respectively) (Schneider et al. 1996). Curtachalasins C (18) and E (19) (Fig. 3.2) were extracted from Xylaria cf. curta Fr.. In the resistance reversal assay for (18) and (19), Candida albicans strain with resistant genes Cdr1, Cdr2, and Mdr1, against which the MIC50 value of fluconazole is higher than 500 μg/ml were used. When this resistant strain was treated by compound (18) combined with 10 μg/ml of fluconazole, compound (18) showed

80

S. K. Deshmukh et al.

Fig. 3.3 Structures of metabolites isolated from Xylaria sp. (20–38)

dose-dependent resistant reversal activity. Upon treatment with 16 μg/ml of (18) combined with 10 μg/ml of fluconazole, the inhibitory ratio against this strain was close to 50%, which was a significant improvement compared to fluconazole alone. Markedly, compound (18) alone showed no inhibitory activity even at a concentration of 128 μg/ml (inhibitory ratio of
4.188%), implying that compound (18) may be non-toxic to eukaryotes (Wang et al. 2019a). Curtachalasins A (20) and B (21) (Fig. 3.3) were extracted from Xylaria curta (E10) residing inside the stem of Solanum tuberosum. Compounds (20 and 21) were found poorly active against Microsporum gypseum (70.3 and 68.4%, respectively, at concentration of 200 μM)(Wang et al. 2018a). Xylarinic acids A (22) and B (23) (Fig. 3.3) were purified from the fruit body of Xylaria polymorpha (Pers.) Grev. Compounds, (22 and 23) displayed good antifungal activity with clear inhibition zone, 16–20 mm diameter against Pythium ultinum and Magnaporthe grisea. Both the compounds showed average activity with clear inhibition zone, against Alternaria panax, Aspergillus niger, and Fusarium oxysporium and poor activity against Alternaria mali, A. porri, Botrytis cinerea, Cylindrocarpon destructans, Fulvia fulva, Phytophthora capsica, and Rhizoctonia

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

81

solani (Jang et al. 2007). Xylaria multiplex (BCC 1111) was the source of new lactones, multiplolides A (24) and B (25) (Fig. 3.3). Compounds (24 and 25) displayed activity against C. albicans (IC50, 7 and 2 μg/ml, respectively) (Boonphong et al. 2001). Compounds piliformic acid (26) and cytochalasin D (27) (Fig. 3.3) were extracted from two Xylaria species from the leaves of Paullinia cupana. Compounds (26) and (27) displayed antifungal activity against Colletotrichum gloeosporioides (MIC, 2.92 and 2.46 μM/ml, respectively). Captan and difenoconazole were used as positive controls (MIC, 16.63 and 0.02 μM/ml, respectively) (Elias et al. 2018). New guaiane sesquiterpenes (28–32) (Fig. 3.3) were purified from Xylaria sp. (YM311647) residing inside the plant Azadirachta indica. Compounds (28–32) displayed moderate or poor activities against Pyricularia oryzae and Hormodendrum compactum (MIC range, 32–256 μg/ml). Compound (31) showed potent activity to P. oryzae (MIC, 32 μg/ml). Compounds (30, 31) exhibited average antifungal activity against H. compactum (MIC, 64 μg/ml). In addition, (31, 32) displayed potent activity against C. albicans (MIC, 32 μg/ml). Compound (30) displayed moderate inhibition against C. albicans, A. niger, and H. compactum (MIC, 64 μg/ml). Positive control nystatin active against C. albicans, A. niger, P. oryzae, and H. compactum (MIC, 8 μg/ml on each fungus) (Huang et al. 2015). Griseofulvin (33) and dechlorogriseofulvin (34) (Fig. 3.3) were isolated from Xylaria cubensis (Mont.) Fr. (MSX48662) obtained from cedar wood. Compound (33) displayed antifungal activity against M. gypseum (zone of inhibition, 35 mmat 25 μg/disk) (Paguigan et al. 2017). Both the compounds were previously purified from endophytic Xylaria sp. (F0010) from Abies holophylla. Griseofulvin (33) was found to be effective in controlling the rice blast, rice sheath blight wheat leaf rust, and barley powdery mildew caused by M. grisea, Corticium sasakii, Puccinia recondite, and Blumeria graminis f. sp. Hordei at doses of 50–150 μg/ml. It was also active in vivo against Botritis cinerea on tomato plants. On the other hand, compound (34) inhibited only the development of rice sheath blight and barley powdery mildew (Park et al. 2005). Compound 5-carboxy6-hydroxy-3-methyl-3,4-dihydroisocoumarin (35) (Fig. 3.3) was purified from Xylaria sp. associated the Casearia sylvestris leaves and displayed potent antifungal activity against C. cladosporioides and C. sphaerospermum at 10 μg by the TLC diffusion method. (Chapla et al. 2018). A new nonenolide, xyolide (36) (Fig. 3.3), was isolated from Xylaria feejeensis (Berk.) Fr. (E6912B) displayed inhibition against plant pathogen Pythium ultimum (MIC, 425 μM) (Baraban et al. 2013). Cyclic pentapeptides cyclo-(-NMePhe-Pro-Leu-Ile-Val) (37) (Fig. 3.3) was purified from Xylaria sp. associated with the lichen Leptogium saturninum collected from Zixi mountain, Yunnan, Chinadis played synergistic antifungal activity against C. albicans (S C5314) with 0.004 μg/ml ketoconazole (Wu et al. 2011). Sordaricin (38) (Fig. 3.3), the diterpene aglycone was purified from Xylaria sp. (PSUD14) isolated from Garcinia dulcis and exhibited average antifungal activity against C. albicans (ATCC90028) (MIC, 32 μg/ml), while the amphotericin

82

S. K. Deshmukh et al.

Fig. 3.4 Structures of metabolites isolated from Xylaria Sp. (39–56)

B as positive control displayed higher antifungal activity (MIC, 0.25 μg/ml) (Pongcharoen et al. 2008). Sordaricin derivative xylarin (39) (Fig. 3.4), was purified from a wood-inhabiting Xylaria sp. (A19-91), which displayed antimicrobial activity against Nadsonia fulvescens, Nematospora coryli, Saccharomyces cerevisiae (S-288c), S. cerevisiae, Mucor miehei, and Ustilago nuda (MIC, 50s, 0.5, 20s, 5, 25 s, and 25 s μg/ml, respectively) (Schneider et al. 1995). Oxygenated guaiane-type sesquiterpenes (40–48) new isopimarane diterpenes (49–51) (Fig. 3.4) were purified from Xylaria sp. (YM 311647) residing inside the stem of A. indica. Compounds (40–51) displayed antifungal activity against C. albicans and H. compactum with (MIC range, 32–256 μg/ml), while nystatin as a positive control displayed higher inhibition against both the pathogens (MIC, 8.0 μg/ml). Compounds (41 and 46) displayed the considerable activity against C. albicans (MIC, 32 μg/ml) while compounds (41) and (43) displayed the potent activity against A. niger (MIC,

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

83

64 μg/ml). Compound (50) displayed moderate activity against P. oryzae (MIC, 32 μg/ml). In addition, compounds (40–48) displayed average or poor activities against A. niger, P. oryzae, and H. compactum. Compound (51) exhibited the most potent inhibitory activity against C. albicans, P. oryzae (MIC, 16 μg/ml), and A. niger (MIC, 32 μg/ml) (Wu et al. 2014). Compound zofimarin (52) (Fig. 3.4) was purified from Xylaria sp. (Acra L38) associated with Aquilaria crassna, from Thailand (Chaichanan et al. 2014). This metabolite exhibited selective activity against C. albicans C316, C. albicans ATCC 10231 C. albicans 2402E, C. pseudotropicales 2371E, and Cryptococcus neoformans ATCC 32045. The MIC was 1,1, 2, 0.25 and 16 μg/ml, respectively (Kennedy et al. 1998).

3.2.3

Antimicrobial Metabolites

Compound (
)-regiolone (53) (Fig. 3.4) was isolated from Xylaria escharoidea (Berk.) Sacc. from the gut as well as comb of termite Macrotermes barneyi and found active against S. aureus, B. subtilis, P. aeruginosa, and C. albicans (MIC of 6.25 μg). In addition, molecular docking study reveals that compound (53) is a prominent antibacterial agent with a marked interaction with key residues on protein A (agrA) that regulates the accessory gene (Nagam et al. 2020). Two new cyclopentapeptides, xylapeptide A (54), and xylapeptide B (55) (Fig. 3.4) were purified from Xylaria sp. isolated from S. tonkinensis. Compound (54) displayed potential bacterial activity against B. subtilis and B. cereus (MIC, 12.5 μg/ml). Compound (55) also displayed potent antibacterial against B. subtilis, B. cereus, B. megaterium, M. luteus, S. aureus, and Shigella castellani (MIC, 12.5, 6.25, 6.25, 12.5, 12.5, and 12.5 μg/ml, respectively). Compound (55) also displayed potent antifungal activity against C. albicans (MIC, 12.5 μg/ml) (Xu et al. 2017). A new coloratin A (56) (Fig. 3.4) was purified from Xylaria intracolorata (J.D. Rogers, Callan & Samuels) J.D. Rogers & Y.M. Ju which displayed activity against S. aureus, P. aeruginosa, Klebsiella pneumoniae, Salmonella enteritidis, E. coli, A. niger, and C. albicans (including the diameter of disc 6 mm, 15, 16, 22, 16, 16, 15 and 17 mm inhibition, respectively). As positive control, gentamicin showed activity against S. aureus, P. aeruginosa, K. pneumoniae, S. enteritidis, and E. coli (zone of inhibition, 15, 16, 14, 16 and 18 mm, respectively). Another positive control nystatin exhibited activity against A. niger and C. albicans with 18 and 17 mm zone of inhibition, respectively (Quang et al. 2006). An endophytic Xylaria (YX-28), isolated and characterized from Ginkgo biloba, was the source of 7-amino-4-methylcoumarin (57) (Fig. 3.5). This compound showed strong antimicrobial activities against S. aureus, E. coli, Salmonella typhi, S. typhimurium, S. enteritidis, Aeromonas hydrophila, Yersinia sp., Vibrio anguillarum, V. parahaemolyticus, Shigella sp., C. albicans, Penicillium expansum, and A. niger (MIC, 16, 10, 20, 15, 8.5, 4.0, 12.5, 25, 12.5, 6.3, 15, 40, and 25 μg/ml, respectively) (Liu et al. 2008).

84

S. K. Deshmukh et al.

Fig. 3.5 Structures of metabolites isolated from Xylaria sp. (57–75)

A ploychitide 3-O-Methylmellein (58) (Fig. 3.5) was purified from endophytic Xylaria psidii J.D. Rogers & Hemmes FPL-52(S) residing inside the leaves of Ficus pumila. The compound (58) exhibited antimicrobial activity against both Gram-positive and -negative bacteria, dermatophytes as well as phytopathogenic fungi (MIC range, 0.39–25 μg/ml) (Rakshith et al. 2016).

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

3.2.4

85

Cytotoxic Metabolites

Compounds pentaminolarin (59), xylochalasin (60), and 4S,5S,6S-4-hydroxy-3methoxy-5-methyl-5,6-epoxycyclohex-2-en-1-one (61) (Fig. 3.5) were purified from the fruit bodies of Xylaria sp. (SWUF08-37). Compound (61) showed moderate cytotoxicity against HeLa, HT29, HCT116, MCF-7, and Vero cell lines (IC50, 19.60, 17.31, 14.28, 15.38, and 24.97 μg/ml, respectively). Compound (59) was cytotoxic against Vero, HeLa, HT29, HCT116, MCF-7 cell lines (IC50, 67.89, 44.98, 31.92, 37.98, and14.62 μg/ml, respectively). According to Noppawan et al. (2020) compound (60) possesses cytotoxicity against HeLa, HT29, HCT116 cell lines (IC50, 56.94, 90.44, and 92.52 μg/ml, respectively). Cisplatin as positive control cytotoxic against Vero, HeLa, HT29, HCT116, MCF-7 cell lines (IC50, 12.86, 5.12, 5.79, 6.29, and 8.75 μg/ml, respectively). New compounds 6-ethyl-7,8-dihydroxy-4H-chromen-4-one (62) and (3S)-3,4dihydro-5,7,8-trihydroxy-3-methylisocoumarin (63) (Fig. 3.5), were purified from Xylaria sp. (SWUF09-62). Compounds (62, 63) were cytotoxic against HT29 cells (IC50 ¼ 16.46 and 97.78 μg/ml) (Patjana et al. 2019). New 19,20epoxycytochalasans, namely 19-epi-cytochalasin P1 (64), 7-O-acetyl-6-epi-19,20epoxycytochalasin P (65), 7-O-acetyl-19,20-epoxycytochalasin D (66), known 19,20-epoxycytochalasin C (67), and 5,6-dihydro-7-oxo-19,20-epoxycytochalasin C (68) (Fig. 3.4) were isolated from the endophytic Xylaria cf. curta obtained from the stem tissues of potato (S. tuberosum). Compounds (64–68) displayed cytotoxicity against HL-60 cell line (IC50, 13.31, 37.16, 25.83, 1.11, and 10.04 μM, respectively). Compounds (65, 66) were cytotoxic against SMMC-7721 cell line(IC50, 26.64, and 34.03 μM, respectively). As positive control cisplatin displayed cytotoxic activity against HL-60 and SMMC-7721 cell lines (IC50, 4.86, and 23.59 μM, respectively) (Wang et al. 2019b). In another study, xylarichalasin A (69) (Fig. 3.5) obtained from the same fungus. This metabolite was cytotoxic against HL-60, A-549, SMMC-7721, MCF-7, SW480 cell lines (IC50, 17.3, 11.8, 8.6, 6.3, and 13.2 μM, respectively). The positive control cisplatin displayed cytotoxicity against HL-60, A-549, SMMC-7721, MCF-7, SW480 cell lines (IC50, 2.0, 13.2, 12.7, 23.3, and 18.0 μM, respectively) (Wang et al. 2019c). Cytochalasins D1 (70), and C1 (71) (Fig. 3.5), were purified from Xylaria cf. curta. Cytochalasins D1 (70), and C1 (71), displayed moderate cytotoxic activity against HL-60 cell lines (IC50, 12.7 and 22.3 μM, respectively) (Wang et al. 2019d). Cytochalasin D (27) (Fig. 3.2), cytochalasin P (72), zygosporin D (73), 6,7-dihydro-7-oxo-cytochalasin C (74), and 6,7-dihydro-7-oxodeacetylcytochalasin C (75) (Fig. 3.5) were isolated from X. longipes, Compounds (27, 72–75) displayed cytotoxicity against HL-60, cell lines (IC50, 4.17, 26.74, 6.43, 26.02, and 12.05 μM, respectively). Compounds (72) exhibited cytotoxic activity against SMMC-7721, MCF-7, SW480 cell lines (IC50, 37.18, 28.05, 35.35 μM, respectively), while compound (27) was active against only SMMC-7721 cell line (IC50, 22.69 μM). Compounds (74,75) were found active against MCF-7 cell lines (IC50, 36.44, 27.24 μM, respectively) (Wang et al. 2019e).

86

S. K. Deshmukh et al.

Fig. 3.6 Structures of metabolites isolated from Xylaria sp. (76–92)

Xylastriasan A (76) (Fig. 3.6), a new cytochalasan alkaloid was isolated from the fruit bodies of Xylaria striata Pat. collected from Sophora japonica. This compound showed poor cytotoxicity against HEPG2, B16 and A549 cell lines (IC50, 93.61, 85.61 and 91.58 μM, respectively) (Lei et al. 2018). Known steroid derivative demethylincisterol A3 (77) and chaxine C (78) (Fig. 3.6) were isolated from stromatal specimens of Xylaria allantoidea (SWU F76). Compound (78) displayed potent cytotoxicity against Hela, HT29, HCT116, MCF-7, and Vero cell lines (IC50,

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

87

2.24, 2.51, 3.50, 3.77, and 3.65 μg/ml, respectively). Compound (77) showed poor cytotoxicity against Hela and Vero cell lines (IC50, 76.57 and 50.17 μg/ml, respectively) (McCloskey et al. 2017). Isopimarane diterpenes, xylallantin A (79) a new eremophilane sesquiterpene, eremoxylarin C (80) (Fig. 3.6), were isolated from the wood-decaying Xylaria allantoidea (Berk.) Fr. (BCC 23163). Compound (79) displayed cytotoxic activity against NCI-H187 (IC50, 17 μg/ml) and Vero cell line(IC50 ¼ 33 μg/ml). Compound (80) displayed activity against Plasmodium falciparum K1 (IC50, 3.1 μg/ml) and cytotoxicity to NCI-H187 cell line (IC50, 6.7 μg/ml) (Isaka et al. 2014). Cytochalasin namely cytochalasin P1 (81), along with four previously reported compounds cytochalasin P (72) 19, 20-epoxycytochalasin N (82), 20-epoxycytochalasin D (83), and zygosporin G (84) (Fig. 3.6) were purified from marine-derived Xylaria sp. (SOF11). Compounds (72, 81–84) exhibited cytotoxicity against SF-268 cell line (IC50, 1.37, 4.17, 1.57, 0.33, and 1.38 μM, respectively). These compounds also exhibited cytotoxicity against MCF-7 cell line. Compound (83) also showed cytotoxicity against NCI-H460 cell lines (IC50, 49.38 μM). As positive control cisplatin exhibited cytotoxic activity against SF-268,MCF-7and NCI-H460 cell line (IC50, 1.93, 5.87, and 1.32 μM, respectively) (Chen et al. 2017). Ergosta-5,7,22-trien-3β-ol (85) (Fig. 3.6) was isolated from Xylaria sp. (C-2), purified from the unidentified gorgonian (XS-2009-03) and exhibited poor cytotoxicity against the HeLa, Hep-2, and RD cell lines (IC50, 20.1, 37.0, and 40.2 M, respectively) (Sun et al. 2017). A new compound Xylarione A (86) (Fig. 3.6), and known molecule (
) 5-methylmellein (7) (Fig. 3.2), were purified from Xylaria psidii associated with the leaves of Aegle marmelos. Both the compounds displayed activity against MIA-Pa-Ca-2 cancer cell line (IC50, 16.0 and 19.0 μM, respectively). Compounds (86 and 7) displayed activity against normal cells (fR2) (IC50, 79.0 and 76.0 μM, respectively). Compounds (86) and (7) also displayed cytotoxicity against MCF-7, MIA-Pa-Ca-2, NCI-H226, HepG2, and DU145 cell line (IC50 range, 16–37 μM). The cell cycle distribution in MIA-Pa-Ca-2 cells, confirmed a cell cycle arrest at the sub-G1 phase. Compounds (86) and (7) induced apoptosis and displayed substantial decrease in membrane potential of mitochondria in concentration-dependent manner (Arora et al. 2016). Steroids (3β,5α,8α,22Ε)-ergosta-6,22-diene-3,5,8-triol (87), ergosterol D (88), (3β,5α,6β,22Ε)-6-methoxyergosta-7,22-diene-3,5-diol (89), (3β,5α,6β)stigmastane-3,5,6-triol (90) (Fig. 3.6) were purified from Xylaria nigripes (Klotzsch) Cooke. Compound (87) could significantly decrease NO production (IC50, 27.6 mm). Positive control, NG-monomethyl-L-arginine displayed inhibition of NO production (IC50 ¼ 14.4 μm). Steroids (88, 89, and 90) displayed potent cytotoxicity against U2OS cell lines (IC50, 0.93, 6.0, and 13.2 μm, respectively). Additionally, compound (89) also displayed cytotoxicity against A549 cell line (IC50, 11.9 μm). Staurosporine was used as a positive control (IC50, 0.01 and 0.003 μm, U2OS and A549 cell lines, respectively) (Xiong et al. 2016). Xylaria cf. cubensis PK108 was the source of tryptoquivaline L (91), fiscalin C (92) (Fig. 3.6), chevalone C (93), ergosterol peroxide (94) (Fig.3.7) cytochalasin D

88

S. K. Deshmukh et al.

Fig. 3.7 Structures of metabolites isolated from Xylaria Sp. (93–110)

(27) (Fig. 3.3), and helvolic acid (14) (Fig. 3.2). Compounds (27 and 94) displayed good cytotoxicity against NCI-H187 cell line (IC50, 5.95 and 5.81 μg/ml, respectively). In addition, cytochalasin D (27) displayed potent cytotoxicity against KB and Vero cell lines (IC50, 3.25 and 0.36 μg/ml). Compound (94) displayed poor cytotoxicity against Vero cell line (IC50, 47.95 μg/ml). Compounds (91 and 92) showed poor cytotoxicity against MCF-7 cell lines (IC50, 33.63 and 21.01 μg/ml,

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

89

respectively). The positive control doxorubicin exhibited cytotoxicity against KB, NCI-H187 MCF-7 cell lines (IC50, 0.779, 0.110, 9.61 μg/ml). Another positive control, ellipticine displayed cytotoxicity against KB, NCI-H187 MCF-7 cell lines (IC50, 0.779, 0.110, 9.61 μg/ml). Compounds (93 and 14) displayed activity against P. falciparum (K1, multidrug resistant strain) (IC50, 25 and 6.25 μg/ml, respectively). Dihydroartemisinine a positive control displayed antimalarial activity with IC50 value of 0.00215 μg/ml) (Sawadsitang et al. 2015). A novel fungal pigment schweinitzins A (95), and (S)-torosachrysone-8-O-Me ether (96) (Fig. 3.7), were purified from Xylaria schweinitzii Berk. & M.A. Curtis. Compound (95) exhibited cytotoxicity against KB, Hep-G2, SK-Lu-1, andMCF-7 cell lines (IC50, 0.72, 2.13, 2.32, and 4.09 μg/ml, respectively). Compound (96) exhibited cytotoxicity against KB, Hep-G2, SK-Lu-1, and MCF-7 cell lines (IC50, 0.66, 3.26, 2.51, and 2.24 μg/ml, respectively). Positive control ellipticin was active against KB, Hep-G2, SK-Lu-1, and MCF-7 cell lines (IC50, 0.31, 0.35, 0.45, and 0.53 μg/ml, respectively) (Linh et al. 2014). Cytochalasins C (97), D (27), and Q (98) (Fig. 3.7), were isolated from Xylaria sp. (NC1214) associated with moss Hypnum sp. Compound (97) exhibited cytotoxicity against PC-3M, NCI-H460, SF-268, MCF-7, and MDA-MB-231cell lines (IC50, 1.65,1.06, 0.96, >5, 1.72 μM, respectively). Compound (27) exhibited cytotoxicity against PC-3M, NCI-H460, SF-268, MCF-7, and MDA-MB-231cell lines (IC50, 1.03, 0.22, 0.43, 1.44, and1.01 μM, respectively). Compound (98) displayed cytotoxic activity against PC-3M, NCI-H460, SF-268, MCF-7, and MDA-MB231cell lines (IC50, 1.53, 1.51, 1.31, >5, and 1.32 μM, respectively). The positive control doxorubicin active against PC-3M, NCI-H460, SF-268, MCF-7, and MDA-MB-231cell lines (IC50, doxorubicin 0.25, 0.05, 0.45, 0.32, 0.67 μM, respectively) (Wei et al. 2015). Compounds cytochalasin E (99), cytochalasin K (100), cytochalasin Z16 (101) (Fig. 3.7) were purified from Xylaria sp. (BM9) residing inside the leaves of Saccharum arundinaceum. Compounds (99–101) exhibited cytotoxicity against HepG2 and Caski cell lines (IC50, 25, 59, 45 and 29, 63, and 53 μM, respectively) (Zhang et al. 2015). Compounds ergosterol peroxide (94), two meroterpenoids, chevalone B (102) and C (103) (Fig. 3.7), were isolated from Xylaria humosa Lloyd. Compounds (94, 102,103) exhibited cytotoxic activity against NCI-H187 cell lines (IC50, 5.8, 21.4, and 17.7 μg/ml, respectively), while the positive control sellipticine and doxorubicin were active with IC50, 0.27 and 0.11 μg/ml, respectively (Sodngam et al. 2014). Compound griseofulvin (33) (Fig. 3.2) was purified from Xylaria cubensis SNB-GCI02 and found active against KB and MRC-5 cells (IC50, 10 μM each), whereas the positive control docetaxel displayed cytotoxicity with IC50, 0.0002 and 0.0005 μM, respectively (Casella et al. 2013). A new natural product, cytochalasin H2 (104) (Fig. 3.7), was purified from the strain Xylaria sp. (A23), which was isolated from Annona squamosa. This compound exhibited week cytotoxicity against HeLa and 293T cell lines (25.04 and

90

S. K. Deshmukh et al.

32.8% inhibition with the concentration of 1.0 μg/ml, respectively) and induced cell contraction in both cell lines (Li et al. 2012). Known compounds 07H239-A (105) (Fig. 3.7), cytochalasins C–D (97, 27), and 19,20-epoxycytochalasin C (67) were isolated from the mangrove Xylaria sp. (BL321). Compounds (27, 67, 97, and 105) were cytotoxic against MCF-7 and MDA-MB-435 cell lines,(IC50, 33.0, 13.6, 26.3, 22.5; 9.3, 6.9, 11.1, 7.1 μM, respectively) (Song et al. 2012a). A novel 20-norpimarane glucoside, xylopimarane (106) (Fig. 3.7), was purified from the Xylaria sp. (BCC 4297). This compound displayed cytotoxic effect against KB, MCF-7, and NCI-H187 cell lines (IC50, 1.0, 13, and 65 μM, respectively). It also showed cytotoxicity against CV-1 cell line (IC50, 41 μM) (Isaka et al. 2011). A known compound (4S,5S,6S)-5,6-epoxy4-hydroxy-3-methoxy-5-methylcyclohex-2-en-1-one (107) (Fig. 3.7), was isolated from Xylaria carpophila (Pers.) Fr. This compound displayed poorly cytotoxic against HL-60, A-549, MCF-7, SW480 cell line (IC50, 23.1, 35.7, 28.5; 29.0 μM, respectively), whereas the positive control cisplatin displayed cytotoxicity (IC50, 1.3, 17.3, 15.8, 24.4 μM, respectively) (Yin et al. 2011). Known compounds chlorine heptelidic acid (108), 16-(α-D-glucopyranosyloxy) isopimar-7-en-19-oic acid (109) (Fig. 3.7), were purified from Xylaria sp. isolated from the termite nest. Compounds (108) displayed cytotoxic activity against A549 and S GC7901 cell lines (IC50, 124 and 147 μM). Compounds (109) displayed toxicity against A549 and SGC7901 cell lines (IC50, 127 and 117 μM) (Yan et al. 2011). A new cytochalasins 21-O-deacetylcytochalasin Q (110) (Fig. 3.7) along with known compounds 19,20-epoxycytochalasin Q (111), 21-O-deacetyl-19,20epoxycytochalasin Q (112) (Fig. 3.8), cytochalasin Q (98) (Fig. 3.7), and cytochalasin D (27) (Fig. 3.3), were purified from the Xylaria sp. (SCSIO156). Compounds (27, 98, 110–112) were toxic against MCF-7, SF-268, and NCI-H460 cell lines (IC50 range, of 14.4–96.4 μM), while the positive control cisplatin displayed cytotoxic activity against MCF-7, SF-268, and NCI-H460 cell lines (IC50, 2.9, 5.3, 0.55 μM, respectively) (Chen et al. 2011). Two known eremophilane sesquiterpenes, phaseolinone (113), and phomenone (114) (Fig. 3.8), were purified from Xylaria sp., associated with the leaves of Piper aduncum. At 20 mM and 200 mM concentration compound (113) displayed 20 and 50%, cytotoxicity, respectively, against CHO cell line, compared to the DMSOtreated cells. Compound (114) found active against C. cladosporioides and C. sphaerospermum with a detection limit of 10.0 μg comparable with the same amount of the standard nystatin (Silva et al. 2010a). Compounds 16-α-D-mannopyranosyloxyisopimar-7-en-19-oic acid (115), 15-hydroxy-16-α-D-mannopyranosyloxyisopimar-7-en-19-oic acid (116), and 16-α-D-glucopyranosyloxyisopimar-7-en-19-oic acid (117) (Fig. 3.8) were purified from the fruit bodies of the Xylaria polymorpha. Compound (115) exhibited cytotoxicity against HL60, K562, HeLa, and LNCaP cell lines (IC50, 165, 143, 235; 215 μM, respectively). Compound (116) exhibited cytotoxicity against HL60, K562, HeLa, and LNCaP 327, 390, 288, and 607 μM, respectively. Compound (117)

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

91

Fig. 3.8 Structures of metabolites isolated from Xylaria sp. (111–131)

exhibited cytotoxicity against HL60, K562, HeLa, and LNCaP cell lines (132, 71, 75, and 112 μM respectively). The positive control camptothecin displayed cytotoxicity against HL60, K562, HeLa, and LNCaP (0.02, 0.10, 0.90, and 0.07 μM respectively). Compounds (115) and (117) induce apoptosis along with typical DNA fragmentation in HL60 cells (Shiono et al. 2009). Two new tetralone derivatives named xylariol A (118) and B (119) (Fig. 3.8) were extracted from the Xylaria hypoxylon (L.) Grev. (AT-028) associated with the stems of Ligustrum lucidum. Compounds (118 and 119) showed moderate cytotoxicity against Hep G2 cell line (IC50, 22.3 and 21.2 μg/ml, respectively), while the positive control 5-fluorouracil displayed cytotoxicity at lower concentration (IC50, 6.4 μg/ml) (Gu and Ding 2008). Two new alpha-pyrone derivatives, xylarone (120), and 8,9-dehydroxylarone (121) (Fig. 3.8), were purified from Xylaria hypoxylon, strain A27-94. Compound (121) displayed anti-proliferative activity (IC50, 25, 25,

92

S. K. Deshmukh et al.

and 50 μg/ml against Colo-320, L1210, and HL-60 cell lines, respectively). Compound (120) also displayed anti-proliferative activity (IC50, 40; 50 μg/ml against Colo320; L1210 cell lines, respectively) (Schüffler et al. 2007). Cytotoxic cytochalasins, 19,20-epoxycytochalasin Q (111), and its new deacetyl analog (122) (Fig. 3.8) were isolated from the wood inhabiting Xylaria obovate (Berk.) Fr. Compounds (112 and 122) displayed toxicity towards brine shrimp (LC50, 2.5 μg/ml) and cytotoxic to HL-60 cell line at 1 μg/ml. Both the compounds displayed cytotoxicity against Vero monkey cell (IC50, 0.46; 1.9 μg/ml, respectively) (Dagne et al. 1994). A new methyl aminobenzoate (123) along with known compounds desacetylcytochalasin D (124), 5-carboxymellein (125), and 4-quinolinecarboxaldehyde oxime (126) (Fig. 3.8), and cytochalasin D (27), were purified from Xylaria sp. (BCC 9653) from an unidentified wood. Compounds (123, 27 and 124) showed cytotoxic activity against Vero cells (IC50, 26.13, 0.19, and 16.61 μM, respectively). Furthermore, cytochalasin D (27) showed better activity than the standard drug ellipticine. Compounds (27, 125, and 126), possessed weak activity against Mycobacterium tuberculosis with respective MIC values of 394.3, 900.7, and 581.2 μM (Pongcharoen et al. 2007). Later, cytochalasin D (27) was also purified from Xylaria sp. (BCC 9653) associated with Brazilian marine seaweed Bostrychia tenella (Ceramiales, Rhodophyta) collected in rocky shores of Praia Dura, Ubatubacity, São Paulo state, Brazil (de Felício et al. 2015). More recently, it is extracted from endophytic Xylaria sp. (DAP KRI-5) isolated from the plant Albertisia papuana. The site of collection was Bogor Botanical Garden, West Java. The bio-production capacity of cytochalasin D (27), by this strain was 0.05763 g/l (Fathoni and Agusta 2019). The (
)-xylariamide A (127) (Fig. 3.8) was purified from Xylaria sp. isolated from the outer bark of Glochidion ferdinandi and displayed toxicity against brine shrimp (Artemia salina) with 0% and 71% lethality at 20 and 200 μg/ml, respectively (Davis 2005). A new 10-hydroxycamptothecin (128) (Fig. 3.8) was purified from Xylaria sp. endophytic fungi in the stems of Camptotheca acuminate. The yield of 5.4 mg 10-hydroxycamptothecin/l (128) on addition of salicylic acid (0.1 mM) to the submersed culture medium (Liu et al. 2010). Ding et al. (2017) identified genes that were putatively involved in the production of compound (128) via transcriptome sequencing and characterization of the Xylaria sp. (M71) treated with salicylic acid suggesting that it is produced via the MVA pathway.

3.2.5

Antimicrobial and Cytotoxic Metabolites

Sesquiterpene, xylarenones A (129) and B (130), and xylarenic acid (131) (Fig. 3.8) were extracted from Xylaria sp. (NCY2), isolated from Torreya jackii. Compounds (129–131) displayed cytotoxicity against HepG2 and HeLa cell lines (IC50, 8.7, 23.8, 2.63;27.8, 21.1, and 19.9 μg/ml, respectively). Compound (129) exhibited

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

93

Fig. 3.9 Structures of metabolites isolated from Xylaria sp. (132–155)

antimicrobial activity against E. coli, B. subtilis, S. aureus, Saccharomyces cerevisiae, and C. albicans, with 13.5, 21.6, 21.6, 1.13, and 2.61% inhibition at 50 μg/ml concentration, respectively. Compound (130) exhibited antimicrobial activity against E. coli, B. subtilis, S. aureus, S. cerevisiae, C. albicans, with 14.9, 36.3, 36.3, 2.56, and 1.75% inhibition at 50 μg/ml concentration. The compound (131), exhibited antimicrobial activity against E. coli, B. subtilis, S. aureus, S. cerevisiae, C. albicans, with 20.1, 20.1, 23.5, 0.39, and 1.28% inhibition at 50 μg/ml concentration, respectively (Hu et al. 2008). Compound 3,7-dimethyl-9-(-2,2,5,5-tetramethyl-1,3-dioxolan-4-yl)nona-1,6dien-3-ol (132) and nalgiovensin (133) (Fig. 3.9) were purified from Xylaria sp. isolated from Taxus mairei. Compound (132) displayed good antibacterial activity against B. subtilis ATCC 9372 B. pumilus 7061 and S. aureus ATCC 25923 with 48.1, 31.6, and 47.1% inhibition, respectively, at the 50 μg/ml concentration. Compound (133) exhibited antimicrobial activity against C. albicans As 2.538, A. niger 16,888, S. aureus ATCC 25923, B. subtilis ATCC 9372, B. pumilus

94

S. K. Deshmukh et al.

ATCC 7061, and E. coli ATCC 25922 with 46.0, 40.0, 42.1, 36.8, 47.1, and 41.2%, respectively, at the 50 μg/ml concentration. Compound (133) also displayed potent cytotoxicity against HeLa cell with 94.1% inhibition at concentration 10 μg/ml (Lin et al. 2016). Polyketides, namely, 1-(xylarenone A)xylariate A (134), xylarioic acid B (135), xylariolide A (136), xylariolide B (137), xylariolide C (138), Me xylariate C (139), and xylariolide D (140), along with previously isolated compound taiwapyrone (141) (Fig. 3.9), were purified from Xylaria sp. (NCY2) associated with the plant Torreya jackii. Compounds (134–141) found active against E. coli ATCC 25922, B. subtilis ATCC 9372, and S. aureus ATCC 25923 (MIC, above 10 μg/ml). Compounds (134–141) showed poor activity against HepG2 and HeLa cell lines at 10 μg/ml. The inhibitory rates were 128 μg/ml). Compound (95) displayed cytotoxicity against MRC5 cell line (IC50, 1.9 μM) and is known to exhibit μM inhibitory concentrations for various human tumor cell lines (Sorres et al. 2015). An endophytic Xylaria sp. (ZJWCF255) associated with a leaves of Ficus carica was the source of cytochalasin Q (98) (Fig. 3.6). Compound (98) exhibited antifungal activity against Didymella bryoniae, Rhizoctonia solani, Pestalotia diospyri, Sclerotinia sclerotiorum, B. cinerea, Colletotrichum orbiculare, Verticillium

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

95

nigrescens, Verticillium dahliae, F. oxysporum, and P. ultimum (EC50, 0.04, 6.24, 6.72, 7.96, 10.27, 11.56, 12.34, 33.8, 50.46, and 73.44 μg/ml, respectively). Compound (98) exhibited strong cytotoxic activity against SMMC-772, MCF-7, MGC80-3 cell lines (IC50, 17.24, 7.75, and 10.30 μg/ml, respectively) (Wang et al. 2014). New eremophilane-type sesquiterpenoids 1b,7a,10a-Trihydroxyeremophil-11 (13)-en-12,8b-olide (150) 7a,10a-Dihydroxy-1b-methoxyeremophil-11(13)-en12,8b-olide) (151), and 1a,10a-Epoxy-7a-hydroxyeremophil-11(13)-en-12,8b-olide (152) (Fig. 3.9), were purified from Xylaria sp. (BCC 21097) associated with the palm Licuala spinose. Compound (150) exhibited cytotoxicity against KB, MCF-7, NCI-H187, Vero cell (IC50, 5, 15, 7.2; 8.5 μM, respectively). Compound (151) showed cytotoxic activity against KB, MCF-7, NCI-H187, and Vero cell lines (IC50, 21, 15, 3.8, and 3.9 μM respectively). Compound (152) displayed cytotoxic activity against KB, MCF-7, NCI-H187, and Vero cell lines (IC50, 10, 10, 5.8; 9.4 μM, respectively). The standard compound, doxorubicin hydrochloride, displayed cytotoxicity against KB, MCF-7 and NCI-H187 cell-lines (IC50, 0.40, 1.8, and 0.066 μM, respectively). Another standard compound, ellipticine displayed cytotoxicity with IC50 value of 6.3 μM against Vero cell-lines. Compounds (151, 152) also exhibited anti-malarial activity against P. falciparum K1 (respective IC50, 8.1 and 13 μM). Only (152) was active against C. albicans (IC50 7.8 μM) (Isaka et al. 2010). Known cytochalasin compounds 19,20-epoxycytochalasin C (67) (Fig. 3.5), Q (111), R (153), and D (154) (Fig. 3.9), were purified from an endophytic Xylaria sp. grown on Piper aduncum. The compounds (67, 111, 153, and 154) exhibited cytotoxicity against HeLA cell lines, while the positive control cisplatin displayed the activity at IC50, 20 μM. Compound (111) showed weak activity against C. cladosporioides and C. sphaerospermum (Silva et al. 2010b). Four new 12,8-eudesmanolides, namely 3α,4α,7β-Trihydroxy-11(13)-eudesmen12,8-olide (155) (Fig. 3.9), 4α,7β-Dihydroxy-3α-methoxy-11(13)-eudesmen-12,8olide (156), 7β-Hydroxy-3,11(13)-eudesmadien-12,8-olide (157), and 13-Hydroxy3,7(11)-eudesmadien-12,8-olide (158) (Fig. 3.10), were purified from Xylaria ianthinovelutina (Mont.) Mont. associated with unidentified seed. Compound (157) was also active against KB, MCF-7, NCI-H187 cell lines (IC50, 10.25, 6.28, and 1.48 μg/ml, respectively). Compound (155) was active against KB, MCF-7, NCI-H187 cell lines (IC50, 19.15, 22.82; 2.61 μg/ml, respectively). The compound (156) displayed cytotoxicity against KB, MCF-7, NCI-H187 cell lines (IC50, 18.21, 9.94; 0.78, μg/ml, respectively); Compound (158) was active against KB, MCF-7, NCI-H187 cell lines (IC50, 4, 0.65, 4.14 μg/ml, respectively). The positive control doxorubicin displayed cytotoxicity (IC50, 0.13, 0.89; 0.04 μg/ml, respectively). Compound (157) was active against P. falciparum (IC50, 2.27 μg/ml), whereas positive control dihydroartemisinin displayed antimalarial activity (IC50, 1.14 μg/ ml) (Pittayakhajonwut et al. 2009). A unique polyketide, mellisol (159), and 1,8-dihydroxynaphthol 1-O-α-glucopyranoside (160) (Fig. 3.10) were purified from the Xylaria mellisii

96

S. K. Deshmukh et al.

Fig. 3.10 Structures of metabolites isolated from Xylaria sp. (156–181)

(Berk.) Cooke. Compounds (159, 160) were cytotoxic against Vero cells (IC50, 39.4 and 45.8 μg/ml, respectively). Compounds (159, 160) also exhibited antiviral activity against HSV type 1 (IC50, 10.50; 8.40 μg/ml, respectively) (Pittayakhajonwut et al. 2005). Compounds, (
)-depudecin (161) (Fig. 3.10), 19,20-epoxycytochalasin Q (111), (+)-phaseolinone (113), and (+)-phomenone (114), (Fig. 3.8), were purified from the

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

97

wood-decaying Xylaria sp. (BCC 1067). Compounds (109, 114, 115, and 161) displayed cytotoxicity against KB cells (IC50, 2.8, 0.68, 1.2; 0.72 μg/ml, respectively) and compounds (111,113, 114, and 161) also displayed cytotoxicity against BC1 cells (IC50, 1.6, 0.36, 0.51; 20 μg/ml, respectively). Compounds (161, 113, 114 and 111) exhibited antiplasmodial activity against P. falciparum (EC50, 1.0, 0.5, 0.32, 0.59; 19 μg/ml, respectively) (Isaka et al. 2000).

3.2.6

Anti-inflammatory Metabolites

New compounds 6-ethyl-7,8-dihydroxy-4H-chromen-4-one (62), and (3S)-3,4dihydro-5,7,8-trihydroxy-3-methylisocoumarin (63) (Fig. 3.5) were purified from Xylaria sp. (SWUF09-62). Compounds (62 and 63) displayed anti-inflammatory activity by reducing NO production in LPS-stimulated RAW264.7 cells (IC50 ¼ 1.57 and 3.02 μg/ml) (Patjana et al. 2019). A new eremophilane-type sesquiterpenes, namely, nigriterpene C (162) along with fomannoxin alcohol(163) (Fig. 3.10), were isolated from the termite nestderived X. nigripes YMJ653. Compound (162) exhibited inhibition on NO production and iNOS and COX-2 expression (IC50, 21.7, 8.1, and 16.6 μM, respectively). The compound (163) also inhibited NO production and iNOS and COX-2 expression (IC50, 33.8, 11.6, and 12.7 μM, respectively). The positive control curcumin showed inhibition of NO production (IC50, 4.5 μM) (Chang et al. 2017). The (
)(R)-7-hydroxymellein (164) (Fig. 3.10), was purified from X. cubensis, isolated from the leaves of Litsea akoensis, which showed IL-6 inhibitory activity (IC50, 9.4 μM) (Fan et al. 2014). A new isopimarane-type diterpene glycoside xylapapuside A (165) (Fig. 3.10), was extracted from Xylaria papulis Lloyd associated with the stem of Taiwanese Lepidagathis stenophylla. This compound displayed potent NO inhibition in lipopolysaccharide-activated RAW 264.7 murine macrophages with Emax value of 34.3 μM (Chen et al. 2016). Ergosta-4,6,8(14),22-tetraen-3-one (166) (Fig. 3.10) a fluorescent constituent was extracted from Xylaria sp. and displayed potential inhibitory activity of NO production in RAW 264.7 cells stimulated by lipopolysaccharide (IC50, 28.96 μM) (Ngoc and Dinh 2008). Isoprenyl phenolic ethers, namely fimbriethers A-G (167–173) (Fig. 3.10), were isolated from Xylaria fimbriata Lloyd (YMJ491) associated with termite nest. Compounds (167–173) showed moderate iNOS inhibitory activity (Emax, 4.6, 31.3, 7.7, 7.3, 38.9, 6.0, and 49.7%, respectively) in lipopolysaccharide (LPS)induced murine macrophage RAW 264.7 cells without significant cytotoxicity. Positive control aminoguanidine and Nu-nitro-L-arginine displayed iNOS inhibitory activity (Emax, 83.7 and 42.1%, respectively) (Chen et al. 2019). Xylaric acid (174) (Fig. 3.10) was purified from Xylaria sp. (MF 5809) residing inside the bark of oak (Quercus sp.). Compound (175) is a competitive irreversible

98

S. K. Deshmukh et al.

inhibitor of IL-1 beta converting enzyme with a Ki of 8 μM and inhibits ICE activity with IC50, 33 μM. Compound (174) is a competitive irreversible inhibitor exhibiting a Ki of 8 μM (Salvatore et al. 1994).

3.2.7

Acetylcholinesterase (AChE) Inhibitors

Sesquiterpenoids namely, xylariaines A-B (175–176) (Fig. 3.10), were purified from Xylaria polymorpha. Compounds (175, 176) displayed weakly inhibitory AChE activities with inhibition ratios of 12.4 and 18.0%, respectively, at a concentration of 50 μg/ml (Tacrine as positive control with inhibitory rate, 56.7%) (Yang et al. 2017). Compounds xylanigripones A (177) and C (178), agroclavine (179), 8,9-didehydro-10-hydroxy-6,8-dimethylergolin (180), and (6S)-agroclavine N-oxide (181) (Fig. 3.10), were purified from the Xylaria nigripes. Compound (179) displayed inhibitory activity against AChE activity at the concentration of 50 μM by 11.9%, and compound (178), displayed inhibitory activity against AChE activity at the concentration of 50 μM by up to 38.1%, compared with 45.4% inhibition rate of the positive control tacrine. The compounds (177, 179–181) exhibited different levels inhibition of Cholesteryl Ester Transfer Protein activity with inhibition rates of 49, 73, 36.50, and 58.50%, respectively, compared with the blank control (Hu and Li 2017). Xyloketal A-D (182–185) (Fig. 3.11) were purified from the mangrove Xylaria sp. Compounds (182–185) displayed AChE inhibition activity (IC50, 29.9, 137.4, 109.3, and 425.6 μM/l, respectively) in comparison to the positive control velnacrine. All the four compounds along with velnacrine showed inhibitory effects on BuChE in different degrees, and the inhibitory activity of xyloketals on AChE was found to be reversible and noncompetitive. These compounds can be considered as drug candidates against Alzheimer’s disease (AD) (Jinghui et al. 2004). Xyloketal A (182) (Fig. 3.10), was previously extracted from mangrove Xylaria sp. (2508), obtained from the South China sea. Xyloketal A (183) displayed the activity of inhibiting AchE at 1.5  10
6 mol/l ( p < 0.01) (Lin et al. 2001). More recently Xyloketal B has been implicated in the treatment for hypoxic-ischemic brain injury (Xiao et al. 2015). It has also exhibited potential for treating glioblastoma, which is one of the aggressive types of brain tumors (Chen et al. 2015). The dihydroisocoumarin (3R,4R)-3,4-dihydro-4,6-dihydroxy-3-methyl-1-oxo1H-isochromene-5-carboxylic acid (186) (Fig. 3.11), was purified from Xylaria sp. residing inside the plant Piper aduncum. It exhibited moderate toxicity against C. cladosporioides and C. sphaerospermum showing a detection limit of 10.0 and 25.0 μg, respectively. Compound (186) exhibited average AChE inhibitory activity, with a detection limit of 3.0 μg. Positive control nystatin displayed antifungal

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

99

Δ6,12, Δ8,13 Δ5, Δ13

Fig. 3.11 Structures of metabolites isolated from Xylaria sp. (182–196)

activity against C. cladosporioides and C. sphaerospermum, showing a detection limit of 1 μg in each. Another positive control, galantamine displayed AChE inhibitory activity, exhibiting a detection limit of 1.0 μg (Oliveira et al. 2011).

100

3.2.8

S. K. Deshmukh et al.

Immunosuppressive Metabolites

New cytochalasins, curtachalasins F (187), G (188), H (189) I (190), J (191), L (192), M (193), N (194), O (195), P (196) (Fig. 3.11), and known chemicals cytochalasins, curtachalasin A–C (20, 21, 18) and E (19), were extracted from Xylaria cf. curta associated with the stem of potato (Solanum tuberosum). In the immunosuppressive assay against Con A-induced T lymphocyte cell proliferation compounds (19–21,187, 189–191, 193–196), exhibited inhibition of T-cell proliferation (IC50, 70.9, 28.5, 13.3, 21.0, 31.1, 62.5, 12.6, 16.5, 22.4, 29.0, and 39.7 μM, respectively). Lipopolysaccharide (LPS)-induced B lymphocyte cell proliferation showed that compounds (187, 189, 190, 196, 19, and 21) exhibited inhibition on B-cell proliferation (IC50, 2.4, 28.5, 19.5, 72.3, 88.0, and 35.4 μM, respectively). Positive control dextromethorphan exhibited inhibition on the proliferation of T-cell and B-cell (IC50, 1.6 and 0.8 μM, respectively). Compounds (188, 192, and 18) were cytotoxic, and the viabilities of treated cells were 45.1, 60.7, and 10.0%, respectively (Wang et al. 2019f). New nor-isopimarane diterpenes, xylarinorditerpenes B-E, I, N (197–202), and known compounds, 14α,16-epoxy-18-norisopimar-7-en-4α-ol (203) and the labdane-type diterpene agatadiol (204) (Fig. 3.12), were extracted from X. longipes (HFG1018) isolated from the wood-rotting basidiomycete Fomitopsis betulinus. Compounds (197–204) showed immunosuppressive activity but were devoid of cytotoxicity against the cell proliferation by Con A-induced T lymphocytes and lipopolysaccharide-induced B lymphocytes (IC50 ranging from 1.0 to 27.2 μM and from 16.1 to 51.8 μM, respectively) (Chen et al. 2020a).

3.2.9

Metabolites with Antioxidant Activities

Compound cytochalasin D (27), griseofulvin (33) (Fig. 3.4), cytochalasin C (97) (Fig. 3.7), cytochalasinB (205) (Fig. 3.12) were purified from Xylaria sp. associated the leaves of Casearia sylvestris. The TLC bioautography profile of compounds (33, 205, and 27) showed yellow spots against the purple background indicating antioxidant capacity of these compounds at 1 μg/ml. These results demonstrated that the radical scavenging activities were due to direct reduction via electron transfer and/or radical quenching stabilizing the radical DPPH. The compounds (205, 97) showed potent AChE inhibition at 60 μg using TLC bioautography (Chapla et al. 2018).The compound 5,8-dihydroxy-3-methyl-3,4-dihydroisocoumarin (206) (Fig. 3.12) was isolated from Chinese medicine called “Wulingshen” (Xylaria nigripes), which displayed antioxidant activity 1.67-times as that of vitamin C or 2.10-times as that of vitamin E at the concentration of 20 μM/l, its DPPH free radical-scavenging assay (Wu 2001). Two new natural spirocyclic pyrrole alkaloids namely xylapyrrosides A (207, 208) and previously reported compounds pollenopyrrosides A (209) and B

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

101

Fig. 3.12 Structures of metabolites isolated from Xylaria sp. (197–222)

(210) (Fig. 3.12), were isolated from the edible and medicinal Xylaria nigripes. Compounds (207–210) displayed average antioxidant effects by preventing the oxidative stress-induced cytotoxicity of A7r5 rat vascular smooth muscle cells (VSMCs) (Li et al. 2015).

3.3

Other Bioactive Metabolites

Ergosterol (211) (Fig. 3.12) was isolated from the fruit bodies of Xylaria striata collected from trunk base and stumps of S. japonica. This compound potentiated pentobarbital-induced sleep by not only increasing the number of falling asleep and

102

S. K. Deshmukh et al.

prolonging sleeping time but also reducing sleep latency at a dosage of 5 mg/kg (Lei et al. 2018). A new xylarianin A (212), 6-methoxycarbonyl-20 -methyl-3,5,40 ,60 -tetramethoxydiphenyl ether (213), 2-chlor-6-methoxycarbonyl-20 -rnethyl-3,5,40 ,60 -tetramethoxydiphenyl ether (214), and 2-chlor-40 -hydroxy-6-methoxy carbonyl-20 -methyl-3,5,60 -trimethoxy-diphenyl ether (215), along with known compounds grisephenone A (216) 5,9,11-trimethoxy-3,13-dihydroxy benzophenone (217), and 2-hexylidene-3methyl succinic acid 4-methyl ester (218) (Fig. 3.12) were purified from an endophytic Xylaria sp. (SYPF 8246), associated with the root of Panax notoginseng. Compounds (212–218) exhibited potent inhibitory activities against hCE 2 (IC50, 10.43, 6.69, 12.36,18.25, 29.78, 18.86, and 20.72 μM, respectively) (Zhang et al. 2018). Astropyrone (219), guaidiol (220) (Fig. 3.12) were purified from Xylaria sp. (HNWSW-2) was associated with the stem of Xylocarpus granatum. Compounds (219 and 220) at a concentration of 50 μg/ml showed poor inhibitory activity against AChE with inhibition rates of 10.4 and 12.9% (tacrine was used to be positive control with inhibition rate of 77.4%), respectively. In addition, compound (219) also exhibited inhibitory activity against α-glycosidase with inhibition rate of 77.0% at a concentration of 0.25 μg/ml acarbose was used to be positive control with inhibition rate of 59.7%) (Wang et al. 2018b). A ten-membered macrolide (221) and known compounds scirpyrone D (222) (Fig. 3.12), and (6S,1’S)-LL-P880β (223) (Fig. 3.13) were isolated from the Xylaria feejeensis isolated from the South China Sea sponge Stylissa massa. Compounds (221–223) significantly reduced the areas of the osteoclasts at 0.5 and 1 μM, while compounds (222, 223) reduced the numbers of osteoblast cells at 1 μM, as compared to the blank control group (Wang et al. 2018c). Xyloketal F (I) (224) (Fig. 3.13), along with xyloketals A (182) (Fig. 3.9), B (183) (Fig. 3.10),were purified from Xylaria sp. (2508) isolated from seeds of Avicennia marina. Compound (182, 183 and 224) displayed L-calcium channel blocking activities with inhibiting rates were 21.47, 12.05, and 50.33%, respectively, at the same concentration (0.03 μM) (Wu et al. 2005). A new isopimarane-type diterpene, spiropolin A (225) (Fig. 3.13) was purified from the fruit bodies of X. polymorpha. This compound restored the growth inhibition caused by the hyperactivated Ca-signaling in mutant yeast (Shiono et al. 2013). Two novel eremophilane sesquiterpenoids xylarenals A (226) and B (227) (Fig. 3.13), were purified from Xylaria persicaria collected on fallen fruits of Liquidambar styraciflua. Compounds (226, 227) showed affinity against cloned mouse NPY Y5 receptors (IC50, 1.5 and 0.3 μM, respectively). They showed low affinities for the Y1, Y2, Y4, and y6 receptors (Smith et al. 2002). A new compound, 3S,4R-(+)-4-hydroxymellein (228), and the known compounds 3S,4S-(+)-4-hydroxymellein (229) (Fig. 3.13), were purified from Xylaria feejeensis (Schwein.) Berk. & M.A. Curtis, associated with the plant Hintonia latiflora. Compounds (228 and 229) inhibited Saccharomyces cerevisiae α-glucosidase (αGHY) (IC50, 441 and 549 μM, respectively). The inhibitory action

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

103

Fig. 3.13 Structures of metabolites isolated from Xylaria sp. (223–237)

of these compounds was similar to that of acarbose (IC50 ¼ 545 μM) used as positive control (Rivera-Chávez et al. 2015). Known compounds 07H239-A (105) (Fig. 3.7) was purified from the mangrove Xylaria sp. (BL321). This compound exhibited inhibitory activity against on α-glucosidase with increasing concentration (IC50, 6.54 μM) (Song et al. 2012b). Two lactones (+) phomalactone (230) and 5-hydroxymellein (231) (Fig. 3.13) were purified from an endophytic Xylaria sp. associated with the leaves of Siparuna sp. (Siparunaceae). Compounds (230–231) showed weak anti-plasmodial activity against a chloroquine-resistant strain of P. falciparum (IC50, 13 and 19 μg/ml, respectively) (Jiménez-Romero et al. 2008). A new eremophilane sesquiterpene, 13,13-dimethoxyintegric acid (232), along with known compound integric acid (233) (Fig. 3.13), were purified from Xylaria sp. (V-27) isolated from a dead branch. Compounds (232, 233) promoted growth restoring activity against the mutant yeast strain (Saccharomyces cerevisiae zds1Δ erg3Δ pdr1Δ pdr3Δ) and inhibited degranulation of rat basophilic leukemia RBL-2H3 cells stimulated by IgE + 2,4-dinitrophenylated-bovine serum albumin (IgE + DNP-BSA), thapsigargin, and A23187 (Tchoukoua et al. 2017b).

104

S. K. Deshmukh et al.

A novel metabolite xylopyridine A (234) (Fig. 3.13) was purified from mangrove endophytic Xylaria sp. (2508). Compound (234) showed a strong DNA-binding affinity toward calf thymus (CT) DNA presumably via an intercalation mechanism, thus it is exploitable as a strong DNA-binders (Xu et al. 2009). Compound 19,20-epoxycytochalasin Q (111) (Fig. 3.7) was purified from Xylaria sp. (MF6837) collected in Puerto Rico. The compound (111) effectively competed with 125I-gp120 for the binding with human CCR5 receptor and exhibited an IC50 value of 60 μM (Jayasuriya et al. 2004). Xylarinic acid A (22) isolated from X. polymorpha inhibited NO production and m RNA expressions of iNOS, COX-2, IL-1β, and IL-6 in a concentration-dependent pattern without cytotoxicity effect (Kim et al. 2010). Xylarilongipin A (235) (Fig. 3.13) a diterpenes was isolated from the X. longipes (HFG1018) inhabiting in the medicinal fungus Fomitopsis betulina. This compound exhibited average inhibitory activity against the cell proliferation of Con A-induced T lymphocytes and lipopolysaccharide-induced B lymphocytes (IC50, 13.6 and 22.4 μM, respectively) (Chen et al. 2020b). Two novel benzoquinone metabolites, xylaria quinone A (236) (Fig. 3.13) and 2-chloro-5-methoxy-3-methylcyclohexa-2,5-diene-1,4-dione (142) (Fig. 3.9) were isolated from an endophytic Xylaria sp. of leaves of Sandoricum koetjape. Compounds (142 and 236) showed in vitro activity against P. falciparum, K1 strain (IC50, 1.84 and 6.68 μM, respectively) and cytotoxicity against Vero cells (IC50, 1.35 and >184 μM, respectively) (Tansuwan et al. 2007). Xyloallenoide A (237) (Fig. 3.13), was purified from Xylaria sp. (2508) residing inside the seeds of an angiosperm tree. This compound induced angiogenesis in zebrafish embryos and in human endothelial cells, which was accompanied by increased phosphorylation of eNOS and Akt and NO release. Inhibition of PI3K/ Akt/eNOS by LY294002 or L-NAME suppressed X-13-induced angiogenesis (Lu et al. 2012).

3.4

Cultivation Strategies of Xylaria

Traditionally, monocultures technique was used for screening of metabolites and the absence of biotic and abiotic interactions generally observed in nature still limit the chemical diversity and leads to “poorer” chemical diversity. In recent years, several methods have been developed to determine the conditions under which cryptic genes are activated to induce these silenced biosynthetic pathways. Among those, Chemical Epigenetic Manipulation and co-culture strategies are frequently applied to enhance metabolic production. Here, we report some of the examples of these strategies. Four new alkyl aromatics, penixylarins A–D (238–241), along with the known biogenetically related 1,3-dihydroxy-5-(12-hydroxyheptadecyl)benzene (242) and 1,3-dihydroxy-5-(12-sulfoxyheptadecyl) benzene (243) (Fig. 3.14) were purified from a mixed culture of the Antarctic deep-sea-derived Penicillium crustosum

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

105

Fig. 3.14 Structures of metabolites isolated from Xylaria sp. (238–245)

(PRB-2) and the mangrove-derived Xylaria sp. (HDN13-249) isolated from the root of Sonneratia caseolaris. Compounds (238) and (239) were produced by combination of the two fungi, while compounds (240–243) could be produced by Xylaria sp. (HDN13-249) alone, but in noticeably increased quantities by co-cultivation. The compounds (240, 242, 243) displayed antibacterial activity against Mycobacterium phlei (MIC, 6.25, 25.0, and 12.5 μM, respectively). Compounds (240 and 243) showed antibacterial activity against Vibrio parahemolyticus (MIC, 12.5 and 25.0 μM, respectively). The positive control ciprofloxacin exhibited antibacterial activity against M. phlei and V. parahemolyticus (MIC, 1.56 and 12.5 μM, respectively) (Yu et al. 2019). Wheldone (244) (Fig. 3.14) isolated from a co-culture of Aspergillus fischeri (NRRL 181) and Xylaria flabelliformis (Schwein.) Berk. & M.A. Curtis (G536), where biosynthesis of this compound was stimulated by antagonism between fungi which was monitored by droplet probe. Compound (240) displayed cytotoxic activity against MDA-MB-231, OVCAR-3, MDA-MB-435 cell lines (IC50, 1 7.6, 3.8, and 2.4 μM, respectively). Taxol as positive control displayed cytotoxic activity against MDA-MB-231, OVCAR-3, MDA-MB-435 cell lines (IC50 0.17, 0.0051, and 0.00043 μM, respectively) (Knowles et al. 2020). Compound resveratrol (245) (Fig. 3.14) was characterized from the endophytic Xylaria psidii residing in the leaves of Vitis vinifera. Resveratrol concentration was maximum and enhanced by treatment with 5 μm SAHA (52.32 μg/ml) and by 10 μm AZA (48.94 μg/ml) in comparison to untreated once (35.43 μg/ml) and a significant increase in antioxidant potential was obtained (Dwibedi et al. 2019).

106

3.5

S. K. Deshmukh et al.

VOC’s Produced by Xylaria

Fungi apart from secondary metabolites have been found to produce a host of volatile secondary metabolites or signals which modulate the ecological niche in which they thrive (Hung et al. 2015). Today the term “Volatilome” is being used analogous to “Metabolome” to denote the ensemble of the volatile organic compounds produced by a living system (Morath et al. 2012; Farbo et al. 2018). The understanding of volatile organic compounds (VOC’s) produced by living organisms such as bacteria, fungi, plants, and humans was enhanced beyond the smell perception through powerful analytical techniques like GC-MS/MS (Zhang and Li, 2010). Fungi have been a producer of volatile compounds in the form of odors and malodors. From the characteristic odors of mushroom and truffles to malodors of sick building syndrome, the VOC’s exhibit an impressive diversity of different chemical moieties which may broadly be classified as aldehydes, ketones, terpenes, sesquiterpenoids, aromatics, and thiols. Focus on exploration and exploitation of VOCs for different sectors such as agriculture, medicine, and environment came into limelight with the discovery of Muscodor albus, an endophytic member of Xylariaceae family (Strobel 2011). The battery of volatiles produced by different types of species and isolates of the genus Muscodor have been exploited for development of a variety of products with applications in different industrial sectors (Strobel 2012). Over 30 patents already exist on the direct and indirect uses of volatiles produced by the members of Muscodor genus having relevant scientific, societal, and environmental applications. Other members of Xylariaceae, the genus Hypoxylon/Nodulisporium and Daldinia complex were found to produce VOCs which could have potential applications in agriculture, pharma, and other industrial sectors. However, volatiles reported from Xylaria species are very rare despite the fact that both Muscodor and Xylaria belong to the Xylarioid group. One report for Xylaria sp. strain PB3f3 existing as an endophyte in Haematoxylon brasiletto has been found to elaborate a gaseous mixture of 40 volatile organic compounds of which,3-methyl-1-butanol and Thujopsene, 2-methyl-1-butanol and 2-methyl-1-propanol were major volatiles. The volatiles of Xylaria sp. PB3f3 strain exhibited a potential anti-fungal activity and anti-oomycete activity (Sánchez-Ortiz et al. 2016). Hence exploring and understanding the VOC produced by endophytic Xylaria species opens up further avenues for their exploration in pharmaceutical as well as agricultural settings.

3.6

Conclusions

The current review reveals that the species of Xylaria possess a large chemical diversity and prolific producers of several bioactive metabolites of biotechnological potential. Among the 245 compounds reported, 118 are new compounds. The major classes of compounds include cytochalasan, carbohydrate and glycosides, cyclic peptides, terpene and terpenoids, sesquiterpene, isocoumarin, and steroids (Table 3.2). Due to their

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

107

Table 3.2 Chemical class of various metabolites identified from Xylaria sp. Species Xylaria sp. (GDG-102) Xylaria sp. (GDG-102)

Class or derivative Sesquiterpene Phthalide

Metabolite 2–4 5

Xylaria sp. (GDG-102)

Phenolic

6,7

Xylaria longipes Xylaria sp. (GDG-102)

Pyridine Pyran

8,9 10

Xylaria curta (92092022)

Furan

11

Xylaria sp.

Glycoside

13

Xylaria sp. (YUA-026)

Sesquiterpenes

15, 16

X. curta (E10)

Curtachalasin

20, 21

Xylaria multiplex (BCC 1111)

Lactones

24, 25

Xylaria sp. (YM311647)

28–32

Xylaria sp.

Guaiane sesquiterpene Isocoumarin

Xylaria sp.

Nonenolide

36

Xylaria sp.

37

Xylaria sp. (PSUD14)

Cyclic pentapeptides Diterpene aglycone

Xylaria sp. (A19-91)

Sordaricin

39

Xylaria sp. (YM 311647)

40–48

Xylaria escharoidea

Guaianesesquiterpenes Naphthalen

Xylaria sp. Xylaria (YX-28) Xylaria sp. (SWUF08-37)

Cyclopentapeptides Coumarin Epoxycyclohexen

54, 55 57 61

Xylaria sp. (SWUF09-62)

Chromen

62

Xylaria sp. (SWUF09-62)

Isocoumarin

63

Xylaria cf. curta

Cytochalasan

64–68

X. cf. curta.

Cytochalasan

70, 71

35

38

53

References Liang et al. (2019) Zheng et al. (2018a, b) Zheng et al. (2018a, b) Li et al. (2019) Zheng et al. (2018a, b) Tchoukoua et al. (2017a) Deyrup et al. (2007) Shiono and Murayama 2005 Wang et al. (2018a) Boonphong et al. (2001) Huang et al. (2015) Baraban et al. (2013) Baraban et al. (2013) Wu et al. (2011) Pongcharoen et al. (2008) Schneider et al. (1995) Wu et al. (2014) Nagam et al. (2020) Xu et al. (2017) Liu et al. (2008) Noppawan et al. (2020) Patjana et al. (2019) Patjana et al. (2019) Wang et al. (2019a) Wang et al. (2019c) (continued)

108

S. K. Deshmukh et al.

Table 3.2 (continued) Species X. longipes

Class or derivative Cytochalasan

Metabolite 72, 74, 75

Xylaria striata Xylaria allantoidea (SWU F76)

Cytochalasan Steroid derivative

76 77, 78

X. allantoidea (BCC 23163) X. allantoidea (BCC 23163) Xylaria sp. (SOF11) Xylaria sp. (C-2) Xylaria nigripes Xylaria cf. cubensis (PK108)

Diterpene Sesquiterpene Cytochalasin Steroid Steroid Steroid

79 80 81–83 85 87–90 93, 94

Xylaria sp. (NC1214) Xylaria humosa

Cytochalasins Steroid

97–101 102, 103

Xylaria sp. (A23) Xylaria sp. (BCC 4297) Xylaria carpophila Xylaria sp. (SCSIO156) Xylaria sp. Xylaria polymorpha

104 106 107 110–112 113, 114 115–117

Xylaria hypoxylon (AT-028)

Cytochalasin Glycoside Cyclohexane der. Cytochalasins Sesquiterpenes Carbohydrative der. Tetralone der.

X. hypoxylon, strain (A27-94)

Pyrone der.

120, 121

Xylaria obovate

Cytochalasins

122

Xylaria sp. (BCC 9653)

Aminobenzoate

123

Xylaria sp. (BCC 9653)

Quinoline

126

Xylaria sp. (M71) Xylaria sp. (NCY2), Xylaria sp. (XC-16)

Camptothecin Sesquiterpene Cytochalasin

128 129, 130 143–146

Xylaria sp. (SNB-GTC2501) Xylaria sp.

Diterpenoids Cytochalasin

147, 148 153, 154

Xylaria ianthinovelutina

Eudesmanolide

155–158

Xylaria mellisii

Polyketide

159

X. mellisii

Naphthol

160

Xylaria sp. (BCC 1067)

Cytochalasin

111

118, 119

References Wang et al. (2019d) Lei et al. (2018) McCloskey et al. (2017) Isaka et al. (2014) Isaka et al. (2014) Chen et al. (2017) Sun et al. (2017) Xiong et al. (2016) Sawadsitang et al. (2015) Wei et al. (2015) Sodngam et al. (2014) Li, et al. (2012) Isaka et al. (2011) Yin et al. (2011) Chen et al. (2011) Silva et al. (2010a) Shiono et al. (2009) Gu and Ding (2008) Schüffler et al. (2007) Dagne et al. (1994) Pongcharoen et al. (2007) Pongcharoen et al. (2007) Ding et al. (2017) Hu et al. (2008) Zhang et al. (2014) Sorres et al. (2015) Silva et al. (2010b) Pittayakhajonwut et al. (2009) Pittayakhajonwut et al. (2005) Pittayakhajonwut et al. (2005) Isaka et al. (2000) (continued)

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

109

Table 3.2 (continued) Species Xylaria sp. (SWUF09-62)

Class or derivative Chromenone

Metabolite 62

Xylaria sp. (SWUF09-62)

Isocoumarin

63

X. nigripes (YMJ653)

Sesquiterpenes

162

Xylaria papulis Xylaria sp.

Glycoside Steroid

165 166

Xylaria fimbriata YMJ491 X. polymorpha Xylaria sp. Xylaria sp.

Phenolic ether Sesquiterpenoid Xyloketal Isocoumarin

167–173 175, 176 182–185 186

Xylaria cf. curta

Cytochalasins

187–196

X. longipes (HFG1018)

Diterpene

197–202

Xylaria sp.

Cytochalasin

205

X. nigripes X. nigripes Xylaria striata Xylaria sp. (SYPF 8246)

Isocoumarin Pyrrole Ergosterol Diphenyl-ether

206 207, 208 211 213–215

Xylaria feejeensis

Macrolide

221

Xylaria sp. (2508) X. polymorpha.

Xyloketal Diterpene

224 225

Xylaria persicaria Xylaria sp.

Sesquiterpenoid Lactone

226, 227 230

Xylaria sp. (V-27)

Sesquiterpene

232

Xylaria sp. (2508) X. longipes (HFG1018)

Xylopyridine Diterpene

234 235

Xylaria sp.

Benzoquinone

236

Penicillium crustosum (PRB-2) and Xylaria sp. (HDN13-249)

Phenolic der.

238–241

References Patjana et al. (2019) Patjana et al. (2019) Chang et al. (2017) Chen et al. (2016) Ngoc and Dinh (2008) Chen et al. (2019) Yang et al. (2017) Lin et al. (2001) Oliveira et al. (2011) Wang et al. (2019f) Chen et al. (2020a) Chapla et al. (2018) Wu (2001) Li et al. (2015) Lei et al. (2018) Zhang et al. (2018) Wang et al. (2018a, b) Wu et al. (2005) Shiono et al. (2013) Smith et al. (2002) Jiménez-Romero et al. (2008) Tchoukoua et al. (2017b) Xu et al. (2009) Fomitopsis betulinus Tansuwan et al. (2007) Yu et al. (2019)

110

S. K. Deshmukh et al.

structural diversity, the compounds from these classes have shown a wide range of useful biological activities. Some of these metabolites possess antibacterial, antifungal, anticancer, antimalarial, anti-inflammatory, and α-glucosidase inhibitory activities. Many of these compounds exhibit a strong potential to be expanded as novel drugs. Selected compounds need further evaluation of mode of their action along with toxicity studies. There is ample scope for chemical modification of some compounds to improve their activities as well as their drug-like properties. Owing to the production of some of the bioactive metabolites in small quantities or below detectable levels need media optimization using the one strain many compounds (OSMAC) technique, co-cultivation, and application of epigenetic modifier. The whole-genome sequencing is required for assessment of their potential for producing new and novel compounds. Molecular approaches like the transfer of biosynthetic gene clusters to a vector suitable for large-scale fermentation could be targeted. Another avenue to produce novel compounds from Xylaria is employing precursors of biosynthetic pathways in the culture medium that may short-track the biosynthetic pathways of secondary metabolites (Ramm et al. 2017). Bioactive secondary metabolites from endophytic Xylaria open the opportunities to explore new compounds and new chemical skeletons those could serve as structural prototypes to develop targeted therapeutic agents. Apart from the non-volatile secondary metabolites, huge scope exists in exploring the volatile organic compounds of this genus to have prospective applications in the pharmaceutical as well as agricultural sectors.

References Arora D, Sharma N, Singamaneni V, Sharma V et al (2016) Isolation and characterization of bioactive metabolites from Xylaria psidii, an endophytic fungus of the medicinal plant Aegle marmelos and their role in mitochondrial dependent apoptosis against pancreatic cancer cells. Phytomedicine 23(12):1312–1320 Baraban EG, Morin JB, Phillips GM, Phillips AJ et al (2013) Xyolide, a bioactive nonenolide from an Amazonian endophytic fungus, Xylaria feejeensis. Tetrahedron Lett 54(31):4058–4060 Boonphong S, Kittakoop P, Isaka M, Pittayakhajonwut D et al (2001) Multiplolides A and B, new antifungal 10-membered lactones from Xylaria multiplex. J Nat Prod 64(7):965–967 Casella TM, Eparvier V, Mandavid H, Bendelac A et al (2013) Antimicrobial and cytotoxic secondary metabolites from tropicalleaf endophytes: isolation of antibacterial agent pyrrocidine C from Lewia infectoria SNB-GTC2402. Phytochemistry 96:370–377 Chaichanan J, Wiyakrutta S, Pongtharangkul T, Isarangkul D et al (2014) Optimization of zofimarin production by an endophytic fungus, Xylaria sp. Acra L38. Braz J Microbiol 45(1):287–293 Chang JC, Hsiao G, Lin RK, Ku YH, Ju YM et al (2017) Bioactive constituents from the termite nest-derived medicinal fungus Xylaria nigripes. J Nat Prod 80(1):38–44 Chapla VM, Zeraik ML, Cafeu MC, Silva GH et al (2018) Griseofulvin, Diketopiperazines and Cytochalasins from endophytic fungi Colletotrichum crassipes and Xylaria sp., and their antifungal, antioxidant and anticholinesterase activities. J Braz Chem Soc 29(8):1707–1713 Chen HP, Li J, Zhao ZZ, Li X, Liu SL et al (2020a) Diterpenes with bicyclo [2.2.2] octane moieties from the fungicolous fungus Xylaria longipes HFG1018. Org Biomol Chem 18(13):2410–2415

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

111

Chen HP, Zhao ZZ, Cheng GG, Hanet ZK et al (2020b) Immunosuppressive nor-isopimarane diterpenes from cultures of the fungicolous fungus Xylaria longipes HFG1018. J Nat Prod 83 (2):401–412 Chen MC, Wang GJ, Kuo YH, Chiang YR, Cho TY et al (2019) Isoprenyl phenolic ethers from the termite nest-derived medicinal fungus Xylaria fimbriata. J Food Drug Anal 27(1):111–117 Chen Z, Chen Y, Huang H, Yang H, Zhang W et al (2017) Cytochalasin P1, a new cytochalasin from the marine-derived fungus Xylaria sp. SOF11. Z Naturforsch C 72(3–4):129–132 Chen YS, Chang HS, Cheng MJ, Chan HY et al (2016) New chemical constituents from the endophytic fungus Xylaria papulis cultivated on Taiwanese Lepidagathis stenophylla. Records Nat Prod 10(6):735–743 Chen WL, Turlova E, Sun CL, Kim JS et al (2015) Xyloketal B suppresses glioblastoma cell proliferation and migration in vitro through inhibiting TRPM7-regulated PI3K/Akt and MEK/ERK signaling pathways. Mar Drugs 13(4):2505–2525. https://doi.org/10.3390/ md13042505 Chen Z, Huang H, Chen Y, Wang Z et al (2011) New cytochalasins from the marine-derived fungus Xylaria sp. SCSIO 156. Helv Chim Acta 94(9):1671–1676 Dagne E, Gunatilaka AL, Asmellash S, Abate D et al (1994) Two new cytotoxic cytochalasins from Xylaria obovata. Tetrahedron 50(19):5615–5620 Davis RA (2005) Isolation and structure elucidation of the new fungal metabolite (
)-xylariamide A. J Nat Prod 68(5):769–772 de Felício R, Pavão GB, de Oliveira ALL, Erbert C et al (2015) Antibacterial, antifungal and cytotoxic activities exhibited by endophytic fungi from the Brazilian marine red alga Bostrychia tenella (Ceramiales). Rev Bras Farmacogn 25(6):641–650 Deshmukh SK, Sridhar KR, Gupta MK (2021) Application of selected species of the genus Xylaria in traditional medicine. In Sridhar KR, Deshmukh SK (eds) Advances in macrofungi: pharmaceuticals and cosmeceuticals. CRC Press, pp 122–136. Deyrup ST, Gloer JB, O’Donnell K, Wicklow DT (2007) Kolokosides A
D: triterpenoid glycosides from a Hawaiian isolate of Xylaria sp. J Nat Prod 70(3):378–382 Ding X, Liu K, Zhang Y, Liu F (2017) De novo transcriptome assembly and characterization of the 10-hydroxycamptothecin-producing Xylaria sp. M71 following salicylic acid treatment. J Microbiol 55(11):871–876 Dwibedi V, Kalia S, Saxena S (2019) Isolation and enhancement of resveratrol production in Xylaria psidii by exploring the phenomenon of epigenetics: using DNA methyltransferases and histone deacetylase as epigenetic modifiers. Mol Biol Rep 46(4):4123–4137 Elias LM, Fortkamp D, Sartori SB, Ferreira MC et al (2018) The potential of compounds isolated from Xylaria spp. as antifungal agents against anthracnose. Braz J Microbiol 49(4):840–847 Fan NW, Chang HS, Cheng MJ, Hsieh SY et al (2014) Secondary metabolites from the endophytic fungus Xylaria cubensis. Helv Chim Acta 97(12):1689–1699 Farbo MG, Urgeghe PP, Fiori S, Marcello A, Oggiano S et al (2018) Effect of yeast volatile organic compounds on ochratoxin A-producing Aspergillus carbonarius and A. ochraceus. Int J Food Microbiol 284:1–10 Fathoni A, Agusta A (2019) Bioproduction of cytochalasin D by endophytic fungus Xylaria sp. DAP KRI-5. J Appl Pharm Science 9(3):105–110 Gu W, Ding H (2008) Two new tetralone derivatives from the culture of Xylaria hypoxylon AT-028. Chin Chem Lett 19(11):1323–1326 Hu D, Li M (2017) Three new ergot alkaloids from the fruiting bodies of Xylaria nigripes (Kl.) Sacc. Chem Biodivers 14(1):e1600173 Hu ZY, Li YY, Lu CH, Lin T et al (2010) Seven novel linear polyketides from Xylaria sp. NCY2. Helv Chim Acta 93(5):925–933 Hu ZY, Li YY, Huang YJ, Su WJ et al (2008) Three new sesquiterpenoids from Xylaria sp. NCY2. Helv Chim Acta 91(1):46–52

112

S. K. Deshmukh et al.

Huang R, Xie XS, Fang XW, Ma KX, Wu SH (2015) Five new guaiane sesquiterpenes from the endophytic fungus Xylaria sp. YM 311647 of Azadirachta indica. Chem Biodivers 12(8):1281– 1286 Hung R, Lee S, Bennett JW (2015) Fungal volatile organic compounds and their role in ecosystems. Appl Microbiol Biotechnol 99:3395–3405 Ibrahim A, Tanney JB, Fei F, Seifert KA et al (2020) Metabolomic-guided discovery of cyclic nonribosomal peptides from Xylaria ellisii sp. nov., a leaf and stem endophyte of Vaccinium angustifolium. Sci Rep 10(1):1–17 Isaka M, Yangchum A, Supothina S, Chanthaket R, Srikitikulchai P (2014) Isopimaranes and eremophilanes from the wood-decay fungus Xylaria allantoidea BCC 23163. Phytochem Lett 8: 59–64 Isaka M, Yangchum A, Auncharoen P, Srichomthong K, Srikitikulchai P (2011) Ring B aromatic norpimarane glucoside from a Xylaria sp. J Nat Prod 74(2):300–302 Isaka M, Chinthanom P, Boonruangprapa T, Rungjindamai N, Pinruan U (2010) Eremophilanetype sesquiterpenes from the fungus Xylaria sp. BCC 21097. J Nat Prod 73(4):683–687 Isaka M, Jaturapat A, Kladwang W, Punya J, Lertwerawat Y et al (2000) Antiplasmodial compounds from the wood-decayed fungus Xylaria sp. BCC 1067. Planta Med 66(05):473–475 Jang YW, Lee IK, Kim YS, Lee S, Lee HJ et al (2007) Xylarinic acids A and B, new antifungal polypropionates from the fruiting body of Xylaria polymorpha. J Antibiot 60(11):696–699 Jayasuriya H, Herath KB, Ondeyka JG, Polishook JD et al (2004) Isolation and structure of antagonists of chemokine receptor (CCR5). J Nat Prod 67(6):1036–1038 Jiménez-Romero C, Ortega-Barría E, Arnold AE, Cubilla-Rios L (2008) Activity against Plasmodium falciparum of lactones isolated from the endophytic fungus Xylaria sp. Pharm Biol 46(10–11):700–703 Jinghui L, Yingbao Y, Yongcheng L, Zhiliang C, Xiongyu W (2004) Effects of metabolites of mangrove fungus Xylaria sp. from South China Sea Coast on the activity of acetyl cholin esterase in vitro. J Chin Med Mater 27(4):261–264 Kennedy TC, Webb G, Cannell RJ, Kinsman OS, Middleton RF, Sidebottom PJ, Taylor NL, Dawson MJ, Buss AD (1998) Novel inhibitors of fungal protein synthesis produced by a strain of Graphium putredinis. J Antibiot 51(11):1012–1018 Kim CG, Kim TW, Endale M, Yayeh T et al (2010) Inhibition of nitric oxide production and mRNA expressions of proinflammatory mediators by xylarinic acid A in RAW 264.7 cells. J Med Plants Res 4(22):2370–2378 Kirk PM, Cannon PF, Minter DW, Stalpers JA (2008) Ainsworth & Bisby’s dictionary of the fungi, 10th edn. CABI Publishing, Wallingford Klaiklay S, Rukachaisirikul V, Sukpondma Y, Phongpaichit S, Buatong J et al (2012) Metabolites from the mangrove-derived fungus Xylaria cubensis PSU-MA34. Arch Pharm Res 35(7): 1127–1131 Knowles SL, Raja HA, Isawi IH, Flores-Bocanegra L et al (2020) Wheldone: characterization of a unique scaffold from the Coculture of Aspergillus fischeri and Xylaria flabelliformis. Org Lett 22(5):1878–1882 Ko HJ, Song A, Lai MN, Ng LT (2011) Immunomodulatory properties of Xylaria nigripes in peritoneal macrophage cells of Balb/c mice. J Ethnopharmacol 138:762–768 Lei CW, Yang ZQ, Zeng YP, Zhou Y et al (2018) Xylastriasan A, a new cytochalasan from the fungus Xylaria striata. Nat Prod Res 32(1):7–13 Li J, Wang WX, Chen HP, Li ZH, He J et al (2019) ()-Xylaridines A and B, highly conjugated alkaloids from the fungus Xylaria longipes. Org Lett 21(5):1511–1514 Li M, Xiong J, Huang Y, Wang LJ, Tang Y et al (2015) Xylapyrrosides A and B, two rare sugarmorpholine spiroketal pyrrolederived alkaloids from Xylaria nigripes: isolation, complete structure elucidation, and total syntheses. Tetrahedron 71(33):5285–5295 Li Y, Lu C, Huang Y, Li Y, Shen Y (2012) Cytochalasin H2, a new cytochalasin, isolated from the endophytic fungus Xylaria sp. A23. Rec Nat Prod 6(2):121–126

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

113

Liang Y, Xu W, Liu C, Zhou D, Liu X et al (2019) Eremophilane sesquiterpenes from the endophytic fungus Xylaria sp. GDG-102. Nat Prod Res 33(9):1304–1309 Lin X, Yu M, Lin T, Zhang L (2016) Secondary metabolites of Xylaria sp., an endophytic fungus from Taxus mairei. Nat Prod Res 30(21):2442–2447 Lin Y, Wu X, Feng S, Jiang G, Luo J et al (2001) Five unique compounds: xyloketals from mangrove fungus Xylaria sp. from the South China Sea coast. J Org Chem 66(19):6252–6256 Linh DTP, Hien BTT, Que DD, Lam DM et al (2014) Cytotoxic constituents from the Vietnamese fungus Xylaria schweinitzii. Nat Prod Commun 9(5):659–660 Liu K, Ding X, Deng B, Chen W (2010) 10-Hydroxycamptothecin produced by a new endophytic Xylaria sp., M20, from Camptotheca acuminata. Biotechnol Lett 32(5):689–693 Liu X, Dong M, Chen X, Jiang M, Lv X, Zhou J (2008) Antimicrobial activity of an endophytic Xylaria sp. YX-28 and identification of its antimicrobial compound 7-amino-4-methylcoumarin. Appl Microbiol Biotechnol 78(2):241–247 Lu XL, Xu ZL, Yao XL, Su FJ, Ye CH et al (2012) Marine cyclotripeptide X-13 promotes angiogenesis in zebrafish and human endothelial cells via PI3K/Akt/eNOS signaling pathways. Mar Drugs 10(6):1307–1320 Macías-Rubalcava ML, Sánchez-Fernández RE (2017) Secondary metabolites of endophytic Xylaria species with potential applications in medicine and agriculture. World J Microbiol Biotechnol 33(1):15 McCloskey S, Noppawan S, Mongkolthanaruk W, Suwannasai N et al (2017) A new cerebroside and the cytotoxic constituents isolated from Xylaria allantoidea SWUF76. Nat Prod Res 31(12): 1422–1430 Morath SU, Hung R, Bennett JW (2012) Fungal volatile organic compounds: a review with emphasis on their biotechnological potential. Fungal Biol Rev 26:73–83 Nagam V, Aluru R, Shoaib M, Dong GR, Li Z et al (2020) Diversity of fungal isolates from fungusgrowing termite Macrotermes barneyi and characterization of bioactive compound from Xylaria escharoidea. Insect Sci. https://doi.org/10.1111/1744-7917.12799 Ngoc QD, Dinh BD (2008) Ergosta-4, 6, 8 (14), 22-tetraen-3-one from Vietnamese Xylaria sp. possessing inhibitory activity of nitric oxide production. Nat Prod Res 22(10):901–906 Noppawan S, Mongkolthanaruk W, Suwannasai N, Senawong T, Moontragoon P et al (2020) Chemical constituents and cytotoxic activity from the wood-decaying fungus Xylaria sp. SWUF08-37. Nat Prod Res 34(4):464–473 Oliveira CM, Regasini LO, Silva GH, Pfenning LH (2011) Dihydroisocoumarins produced by Xylaria sp. and Penicillium sp.,endophytic fungi associated with Piper aduncum and Alibertia macrophylla. Phytochem Lett 4(2):93–96 Paguigan ND, Al-Huniti MH, Raja HA, Czarnecki A et al (2017) Chemoselective fluorination and chemoinformatic analysis of griseofulvin: natural vs fluorinated fungal metabolites. Bioorg Med Chem 25(20):5238–5246 Park JH, Choi GJ, Lee HB, Kim KM et al (2005) Griseofulvin from Xylaria sp. strain F0010, an endophytic fungus of Abies holophylla and its antifungal activity against plant pathogenic fungi. J Microbiol Biotechnol 15(1):112–117 Patjana T, Jantaharn P, Katrun P, Mongkolthanaruk W et al (2019) Anti-inflammatory and cytotoxic agents from Xylaria sp. SWUF09-62 fungus. Nat Prod Res 35:2010–2019 Pittayakhajonwut P, Usuwan A, Intaraudom C, Veeranondha S, Srikitikulchai P (2009) Sesquiterpene lactone 12, 8-eudesmanolides from the fungus Xylaria ianthinovelutina. Planta Med 75 (13):1431–1435 Pittayakhajonwut P, Suvannakad R, Thienhirun S, Prabpai S, Kongsaeree P, Tanticharoen M (2005) An anti-herpes simplex virustype 1 agent from Xylaria mellisii (BCC 1005). Tetrahedron Lett 46(8):1341–1344 Pongcharoen W, Rukachaisirikul V, Phongpaichit S, Kühn T, Pelzing M, Sakayaroj J, Taylor WC (2008) Metabolites from the endophytic fungus Xylaria sp. PSU-D14. Phytochemistry 69(9): 1900–1902

114

S. K. Deshmukh et al.

Pongcharoen W, Rukachaisirikul V, Isaka M, Sriklung K (2007) Cytotoxic metabolites from the wood-decayed fungus Xylaria sp. BCC 9653. Chem Pharm Bull 55(11):1647–1648 Quang DN, Bach DD, Hashimoto T, Asakawa Y (2006) Chemical constituents of the Vietnamese inedible mushroom Xylaria intracolorata. Nat Prod Res 20(04):317–321 Rakshith D, Santosh P, Pradeep TP, Gurudatt DM, Baker et al (2016) Application of bioassayguided fractionation coupled with a molecular approach for the dereplication of antimicrobial metabolites. Chromatographia 79(23–24):1625–1642 Ramm S, Krawczyk B, Mühlenweg A, Poch A, Mösker E, Süssmuth RD (2017) A self-sacrificing n-methyltransferase is the precursor of the fungal natural product omphalotin. Angew Chem Int Ed 56:9994–9997 Ratnaweera PB, Williams DE, de Silva ED, Wijesundera RL, Dalisay DS, Andersen RJ (2014) Helvolic acid, an antibacterial nortriterpenoid from a fungal endophyte, Xylaria sp. of orchid Anoectochilus setaceus endemic to Sri Lanka. Mycology 5(1):23–28 Rivera-Chávez J, Figueroa M, González MDC, Glenn AE, Mata R (2015) α-Glucosidase inhibitors from a Xylaria feejeensis associated with Hintonia latiflora. J Nat Prod 78(4):730–735 Salvatore MJ, Hensens OD, Zink DL, Liesch J et al (1994) L-741,494, a fungal metabolite that is an inhibitor of interleukin-1β converting enzyme. J Nat Prod 57(6):755–760 Sánchez-Ortiz BL, Sánchez-Fernández RE, Duarte G, Lappe-Oliveras P, Macías-Rubalcava ML (2016) Antifungal, anti-oomycete and phytotoxic effects of volatile organic compounds from the endophytic fungus Xylaria sp. strain PB 3f3 isolated from Haematoxylon brasiletto. J Appl Microbiol 120(5):1313–1325 Sawadsitang S, Mongkolthanaruk W, Suwannasai N, Sodngam S (2015) Antimalarial and cytotoxic constituents of Xylaria cf. cubensis PK108. Nat Prod Res 29(21):2033–2036 Schüffler A, Sterner O, Anke H (2007) Cytotoxic alpha-pyrones from Xylaria hypoxylon. Z Naturforsch C J Biosci 62(3–4):169–172 Schneider G, Anke H, Sterner O (1996) Xylaramide, a new antifungal compound, and other secondary metabolites from Xylaria longipes. Z Naturforsch C 51(11–12):802–806 Schneider G, Anke H, Sterner O (1995) Xylarin, an antifungal Xylaria metabolite with an unusual tricyclic uronic acid moiety. Nat Prod Lett 7(4):309–316 Shiono Y, Matsui N, Imaizumi T, Koseki T et al (2013) An unusual spirocyclic isopimarane diterpenoid and other isopimarane diterpenoids from fruiting bodies of Xylaria polymorpha. Phytochem Lett 6(3):439–443 Shiono Y, Motoki S, Koseki T, Murayama T et al (2009) Isopimarane diterpene glycosides, apoptosis inducers, obtained from fruiting bodies of the ascomycete Xylaria polymorpha. Phytochemistry 70(7):935–939 Shiono Y, Murayama T (2005) New eremophilane-type sesquiterpenoids, eremoxylarins A and B from xylariaceous endophytic fungus YUA-026. Z Naturforsch B 60(8):885–890 Silva GH, de Oliveira CM, Teles HL, Pauletti PM et al (2010a) Sesquiterpenes from Xylaria sp., an endophytic fungus associated with Piper aduncum (Piperaceae). Phytochem Lett 3(3):164–167 Silva GH, De Oliveira CM, Teles HL, Araujo AR, Pfenning LH et al (2010b) Cytochalasins produced by Xylaria Sp., an endophytic fungus from Piper aduncum. Quim Nova 33 (10):2038–2041 Smith CJ, Morin NR, Bills GF, Dombrowski AW, Salituro GM et al (2002) Novel sesquiterpenoids from the fermentation of Xylaria persicariaare selective ligands for the NPY Y5 receptor. J Org Chem 67(14):5001–5004 Sodngam S, Sawadsitang S, Suwannasai N, Mongkolthanaruk W (2014) Chemical constituents, and their cytotoxicity, of the rare wood decaying fungus Xylaria humosa. Nat Prod Commun 9(2):157–158 Song A, Ko HJ, Lai MN, Ng LT (2011) Protective effects of Wu-Ling-Shen (Xylaria nigripes) on carbon tetrachloride-induced hepatotoxicity in mice. Immunopharmacol Immunotoxicol 33:454–460 Song F, Wu SH, Zhai YZ, Xuan QC, Wang T (2014) Secondary metabolites from the genus Xylaria and their bioactivities. Chem Biodivers 11(5):673–694

3 Recent Advances in the Discovery of Bioactive Metabolites from. . .

115

Song YX, Wang J, Li SW, Cheng B, Li L et al (2012a) Metabolites of the mangrove fungus Xylaria sp. BL321 from the South China Sea. Planta Med 78(02):172–176 Song Y, Wang J, Huang H, Ma L, Wang J et al (2012b) Four eremophilane sesquiterpenes from the mangrove endophytic fungus Xylaria sp. BL321. Mar Drugs 10(2):340–348 Sorres J, Nirma C, Touré S, Eparvier V, Stien D (2015) Two new isopimarane diterpenoids from the endophytic fungus Xylaria sp. SNB-GTC2501. Tetrahedron Lett 56(31):4596–4598 Strobel G (2011) Muscodor albus and its biological promise. Phytochem Rev 10:165–172 Strobel G (2012) Muscodor albus–the anatomy of an important biological discovery. Microbiol Today 39:108–111 Sun DW, Cao F, Liu M, Guan FF, Wang CY (2017) New fatty acid from a Gorgonian-derived Xylaria sp. Fungus. Chem Nat Compd 53(2):227–230 Tansuwan S, Pornpakakul S, Roengsumran S, Petsom A, Muangsin N et al (2007) Antimalarial benzoquinones from an endophytic fungus, Xylaria sp. J Nat Prod 70(10):1620–1623 Tchoukoua A, Ota T, Akanuma R, Ju YM, Supratman U et al (2017a) A phytotoxic bicyclic lactone and other compounds from endophyte Xylaria curta. Nat Prod Res 31(18):2113–2118 Tchoukoua A, Suzuki T, Ariefta NR, Koseki T, Okawa Y et al (2017b) A new eremophilane sesquiterpene from the fungus Xylaria sp. V-27 and inhibition activity against degranulation in RBL-2H3 cells. J Antibiot 70(12):1129–1132 Wang WX, Lei X, Ai HL, Bai X, Li J et al (2019a) Cytochalasans from the endophytic fungus Xylaria cf. curta with resistance reversal activity against fluconazole-resistant Candida albicans. Org Lett 21(4):1108–1111 Wang WX, Li ZH, Ai HL, Li J, He J et al (2019b) Cytotoxic 19, 20-epoxycytochalasans from endophytic fungus Xylaria cf. curta. Fitoterapia 137:104253 Wang WX, Lei X, Yang YL, Li ZH, Ai HL et al (2019c) Xylarichalasin A, a halogenated hexacyclic cytochalasan from the fungus Xylaria cf. curta. Org Lett 21(17):6957–6960 Wang WX, Feng T, Li ZH, Li J et al (2019d) Cytochalasins D1 and C1, unique cytochalasans from endophytic fungus Xylaria cf. curta. Tetrahedron Lett 60(34):150952 Wang WX, Li ZH, He J, Feng T, Li J, Liu JK (2019e) Cytotoxic cytochalasans from fungus Xylaria longipes. Fitoterapia 137:104278 Wang WX, Cheng GG, Li ZH, Ai HL, He J et al (2019f) Curtachalasins, immunosuppressive agents from the endophytic fungus Xylaria cf. curta. Org Biomol Chem 17(34):7985–7994 Wang WX, Li ZH, Feng T, Li J et al (2018a) Curtachalasins A and B, two cytochalasans with a tetracyclic skeleton from the endophytic fungus Xylaria curta E10. Org Lett 20(24):7758–7761 Wang P, Cui Y, Cai CH, Kong FD, Chen HQ, Zhou LM et al (2018b) A new cytochalasin derivative from the mangrove-derived endophytic fungus Xylaria sp. HNWSW-2. J Asian Nat Prod Res 20(10):1002–1007 Wang J, Xu CC, Tang H, Su L, Chou Y, Soong K et al (2018c) Osteoclastogenesis inhibitory polyketides from the spongeassociated fungus Xylaria feejeensis. Chem Biodivers 15(12):– e1800358 Wang LW, Wang GP, Tang T, Xing WX, Zheng W et al (2014) An endophytic fungus in Ficus carica and its secondary metabolites. Mycosystema 5:19 Wei H, Xu YM, Espinosa-Artiles P, Liu MX et al (2015) Sesquiterpenes and other constituents of Xylaria sp. NC1214, a fungal endophyte of the moss Hypnum sp. Phytochemistry 118:102–108 Wu SH, He J, Li XN, Huang R, Song F et al (2014) Guaiane sesquiterpenes and isopimarane diterpenes from an endophytic fungus Xylaria sp. Phytochemistry 105:197–204 Wu W, Dai H, Bao L, Ren B, Lu J, Luo Y et al (2011) Isolation and structural elucidation of prolinecontaining cyclopentapeptides from an endolichenic Xylaria sp. J Nat Prod 74(5):1303–1308 Wu XY, Liu XH, Lin YC, Luo JH, She ZG et al (2005) Xyloketal F: a strong L-calcium channel blocker from the mangrove fungus Xylaria sp. (# 2508) from the South China Sea Coast. Eur J Org Chem 2005(19):4061–4064 Wu G (2001) A study on DPPH free-radical scavengers from Xylaria nigripes. Acta Microbiol Sin 41(3):363–366

116

S. K. Deshmukh et al.

Xiao AJ, Chen W, Xu B, Liu R, Turlova et al (2015) Marine compound xyloketal B reduces neonatal hypoxic-ischemic brain injury. Mar Drugs 13(1):29–47 Xiong J, Huang Y, Wu XY, Liu XH, Fan H et al (2016) Chemical constituents from the fermented mycelia of the medicinal fungus Xylaria nigripes. Helv Chim Acta 99(1):83–89 Xu WF, Hou XM, Yao FH, Zheng N, Li J et al (2017) Xylapeptide A, an antibacterial cyclopentapeptide with an uncommon L-pipecolinic acid moiety from the associated fungus Xylaria sp.(GDG-102). Sci Rep 7(1):1–8 Xu F, Pang J, Lu B, Wang J, Zhang Y et al (2009) Two metabolites with DNA-binding affinity from the mangrove fungus Xylaria sp.(# 2508) from the South China Sea Coast. Chin J Chem 27(2): 365–368 Yan S, Li S, Wu W, Zhao F, Bao L et al (2011) Terpenoid and phenolic metabolites from the fungus Xylaria sp. associated with termite nests. Chem Biodivers 8(9):1689–1700 Yang NN, Kong FD, Ma QY, Huang SZ et al (2017) Drimane-type sesquiterpenoids from cultures of the fungus Xylaria polymorpha. Phytochem Lett 20:13–16 Yin X, Feng T, Li ZH, Su J, Li Y et al (2011) Chemical investigation on the cultures of the fungus Xylaria carpophila. Nat Prod Bioprospect 1(2):75–80 Yu G, Sun Z, Peng J, Zhu M, Che Q, Zhang G et al (2019) Secondary metabolites produced by combined culture of Penicillium crustosum and a Xylaria sp. J Nat Prod 82(7):2013–2017 Zhang J, Liang JH, Zhao JC, Wang YL, Dong PP et al (2018) Xylarianins AD from the endophytic fungus Xylaria sp. SYPF 8246 as natural inhibitors of human carboxylesterase 2. Bioorg Chem 81:350–355 Zhang H, Deng Z, Guo Z, Peng Y, Huang N et al (2015) Effect of culture conditions on metabolite production of Xylaria sp. Molecules 20(5):7940–7950 Zhang Q, Xiao J, Sun QQ, Qin JC, Pescitelli G, Gao JM (2014) Characterization of cytochalasins from the endophytic Xylaria sp. and their biological functions. J Agric Food Chem 62(45): 10962–10969 Zhang Z, Li G (2010) A review of advances and new developments in the analysis of biological volatile organic compounds. Microchem J 95:127–139 Zheng N, Liu Q, He DL, Liang Y, Li J, Yang RY (2018a) A new compound from the endophytic fungus Xylaria sp. from Sophora tonkinensis. Chem Nat Compd 54(3):447–449 Zheng N, Yao F, Liang X, Liu Q, Xu W et al (2018b) A new phthalide from the endophytic fungus Xylaria sp. GDG-102. Nat Prod Res 32(7):755–760 Zhao Z, Li Y, Chen H, Huang L, Zhao F et al (2014) Xylaria nigripes mitigates spatial memory impairment induced by rapid eye movement sleep deprivation. Int J Clin Exp Med 7:356–362

Chapter 4

Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology, and Uses Gordana Kasom and Sead Hadžiablahović

Abstract The large number of macrofungus that belongs to divisions Basidiomycota and Ascomycota possesses various medical properties there is a total more than 130 medicinal functions produced by medical mushrooms and fungi. They offer important health benefits and exhibit a broad spectrum of pharmacological activities including immunological, antitumor, antibacterial, antifungal, antiviral, cytotoxic, immunomodulating, anti-inflammatory, anti-oxidative, antiallergic, anti-depressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, hypotensive, and hypotensive activities. Compared to other countries in the world, Montenegro, although rich in macrofungi, has no tradition in their medical use. In order to draw attention to the importance of these species and point out their richness in Montenegro, this paper includes a checklist of all macrofungi identified so far, which, based on available scientific literature, have been found to have appropriate medicinal properties It was found that 268 species of macrofungi from Montenegro (14 species from the division of Ascomycota and 254 species from the division of Basidiomycota) have certain medicinal properties. In relation to the number of macrofungal species found so far in Montenegro 1200 species, the 22.4% of these have certain medicinal properties. Based on the medical functions, it can be concluded that the most common medicinal functions of the macrofungi from Montenegro are antitumor or anticancer, and then follow antioxidant and antimicrobial. The paper also presents the distribution of medicinal macrofungi in different habitats in the territory of Montenegro according to the Eunis Habitat Classification. Certainly, it is necessary in Montenegro to conduct extensive researches on medical macrofungi by applying global trends and practices so that certain other species could find application for medical purposes.

G. Kasom (*) · S. Hadžiablahović Environmental Protection Agency of Montenegro, Podgorica, Montenegro e-mail: [email protected]; [email protected] © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_4

117

118

G. Kasom and S. Hadžiablahović

Keywords Distribution · Diversity · Ecology · EUNIS classification · Medicinal uses · Medical macrofungi · Montenegro

4.1

Introduction

Wild macrofungi (macromycetes or mushrooms) growing worldwide in the nature and produce visible fruiting bodies that have a role of the distribution of their spores. A large number of macrofungi belong to division Basidiomycota, while the smaller number is from division Ascomycota. Some numbers of these possesses various immunological and anticancer properties (Gargano et al. 2017). According to them there are a total of more than 130 medicinal functions produced by medical mushrooms and fungi. They offer important health benefits and exhibit a broad spectrum of pharmacological activities including antibacterial, antifungal, antiviral, cytotoxic, immunomodulating, anti-inflammatory, anti-oxidative, anti-allergic, anti-depressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities (Gargano et al. 2017). Some mushrooms have now been declared “medicinal mushrooms,” and dedicated journals, associations, and conferences have been formed to explore their medicinal properties (Gründemann et al. 2020). Also, interest in the cultivation, consumption, and medicinal use of mushrooms has recently increased across the globe (Wu et al. 2019). Macrofungi have been used as an important kind of foods and medications in some ancient civilizations worldwide for thousands of years (Wu et al. 2019). For example, the use of macrofungi for health purposes has a long tradition and is very present in Asian countries. The latest archaeological evidence indicated that the earliest use of species of Ganoderma for medical use could date back 6800 years ago in Neolithic China (Wu et al. 2019). Also, in Asian countries, medical macrofungi have become subjects of numerous scientific studies. Thus, Wu et al. (2019), based on the published scientific papers on the medicinal properties of different types of fungi, gave a check list of fungi where they presented edible, poisonous, and fungal species with medicinal properties; from 1662 listed fungal species 1020, 692, and 480 are considered edible, medicinal, or poisonous mushrooms, respectively. Wu et al. (2019) presented medicinal species with their known medicinal functions with a source of scientific article on the given medical function of the fungus. They concluded that the most common medicinal functions that Chinese macrofungi have are antitumor or anticancer, followed by antioxidant and antimicrobial. In Europe, the situation is different when it comes to the application of medicinal species of macrofungi and the study of their medicinal properties. Gründemann et al. (2020) mentioned that traditional experiences and modern studies demonstrate that mushrooms from the European ethno medicine possess promising pharmacological potential, but in opposite to herbal drugs and to fungal drugs from Traditional Chinese Medicine (TCM), Europe is far away from exploration of this potential. In most cases the traditional use was interrupted for some centuries and/or limited to some countries: the number of modern chemical, biological, and pharmacological

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . .

119

studies is relatively low; for some mushroom species actually no studies exist; most investigations have been done on a cell culture level; also, unfortunately, nearly no clinical studies can be found (Gründemann et al. 2020). Furthermore, they mentioned that critical points are the missing of clear declaration and standardization of test samples, the lack of positive controls, the focus on very common activities like anti-oxidative activities and the use of unspecific test methods; most of the published studies have a lack of information about the endotoxin content and its contribution to the observed immune-stimulatory effects of the mushroom extracts. Gründemann et al. (2020) concluded that mushrooms of traditional European medicine have potential in modern medicine. To explore this potential, not only in the form of dietary supplements but also in the form of regular drugs a lot of research, interdisciplinary collaboration, inclusion of pharmaceutical industry, time, and money are necessary. About 2000 species of fungi have been identified in Montenegro so far, of which about 1200 are macrofungi (Lazarević and Bojović 2017); but due to the rather unexplored nature of this group of organisms for the territory of Montenegro, it is expected that in future research, a significantly large number of new macrofungi will be discovered. Although, Montenegro has rich diversity of fungi, there is no tradition of using medicinal macrofungi. In Montenegro, there is only a tradition of using medicinal plants in traditional medicine. Macrofungi are used only in diet and the general public is aware of their nutritional value, so certain species of macrofungi have a commercial significance. Based on the regulations “Rule book on the detailed manner and conditions of collection, use and trade of unprotected wild species of animals, plants and fungi used for commercial purposes” (Off. Gaz. No 62/2010) it is possible to use a significant number of macrofungal species for commercial purposes as: Armillaria mellea, A. ostoyae, Boletus aestivalis, B. edulis, B. pinophilus, Cantharellus cibarius, Craterellus cornucopioides, Hydnum repandum, H. rufescens, Lactarius deliciosus, L. deterrimus, L. salmonicolor, L. sanguifluus, L. semisanguifluus, Morchella conica, M. esculenta, Marasmius oreades, and Tuber spp. The research papers have been published on medicinal macrofungi growing in Montenegro. Lazarević and Bojović (2017) and Perić and Perić (2000a) provided a list with a number of species that have medicinal properties. Perić and Perić (2000a) presented some frequently used edible and medicinal mushrooms that grow in Montenegro. In this paper they list 43 edible and 11 medicinal species and one variety with their findings. In this paper Lazarević and Bojović (2017) had stated that more than 50 species of fungi, which were recorded in Montenegro, mainly on the roots of trees, have medicinal properties. They list several well-known mushrooms that are characterized by medicinal properties: Armillaria mellea, Auricularia auricula-judea, Bovistella utriformis (as Calvatia utriformis), Cantarelus cibarius, Fomes fomentarius, Ganoderma lucidum, Laetiphorus sulphureus, Lactarius deliciosus, Morchella elata, Pleurotus ostreatus, Schizophyllum commune, and Trametes versicolor. So far, there are no studies that have examined the medicinal properties of macrofungi that grow in territory of Montenegro. Lazarević and Bojović (2017) mentioned that in order to study the fungi from Montenegro for any treatment, it is

120

G. Kasom and S. Hadžiablahović

necessary to first conduct extensive researches on their medicinal properties because it is known that the content and quality of active substances even within the same species can vary depending on habitat type and climatic conditions. Also, due to the simultaneous presence of toxic substances, one should be very careful when using mushrooms in treatment. The aim of our paper is to present rich diversity and distribution of macrofungi with medical properties in the territory of Montenegro. This checklist of medical macrofungi in Montenegro will be useful for planning future studies on the examination of medicinal properties of macrofungi associated with different plant communities and their possible applications for medical purposes.

4.2

The Characteristics of Vegetation of Montenegro

According to Biogeographic map of Europe (Rivas-Martínez et al. 2004) territory of Montenegro belongs to Holarctic kingdom which is represented by Mediterranean and Eurosiberian region. The Mediterranean region is presented by the Eastern Mediterranean subregion, the Adriatic province, and the Epiro-Dalmatian sector, while the Eurosiberian subregion is presented by Alpino-Caucasian subregion, the Apennino-Balkan province, and the Ilyrian sector. An overview of vegetation (with emphasis on forest, scrub, grasslands, herblands—zonal, intrazonal, and azonal) of Montenegro is given on the basis of the literature data (Blečić and Lakušić 1976; Jovanović et al. 1986; Šilc et al. 2016; Hadžiablahović 2018; Karadžić et al. 2020; Stešević et al. 2020) and harmonized with Mucina et al. (2016). The narrow coastal area of Montenegro is dominated by zonal evergreen Mediterranean vegetation (class Quercetea ilicis Br.-Bl. ex A. Bolós et O. de Bolòs in A. Bolòs y Vayreda 1950) which is represented by evergreen and semi-deciduous holm oak forests, Aleppo pine forests, macchia vegetation, relict Mediterranean laurel forests and the garrigue. Intrazonal Mediterranean vegetation in coastal part of Montenegro is presented by scrub of the class Nerio-Tamaricetea Br.-Bl. et O. de Bolòs 1958 while intrazonal grasslands and herblands dominate in the South and are presented by the Lygeo sparti-Stipetea tenacissimae Rivas-Mart. 1978 nom. conserv. propos. and Helianthemetea guttati Rivas Goday et Rivas-Mart. 1963. Azonal halophytic vegetation of the coastal dunes as very specific type of habitat for fungi is presented by the classis Cakiletea maritimae Tx. et Preising in Tx. ex Oberd. 1952, Ammophiletea Br.-Bl. et Tx. ex Westhoff et al. 1946 and HelichrysoCrucianelletea maritimae Géhu et al. in Sissingh 1974 with their pioneer vegetation and tallgrass perennial swards on mobile white and embryonic coastal sand dunes. This vegetation includes the coastal cliffs (Cakiletea maritimae Tx. et Preising in Tx. ex Oberd. 1952) and saline and brackish swamps and marshes (Spartinetea maritimae Beeftink 1962, Thero-Salicornietea Tx. in Tx. et Oberd. 1958. Juncetea maritimi Br.-Bl. in Br.-Bl. et al. 1952).

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . .

121

Azonal forests and scrubs of Montenegro dominate along to the Montenegrin rivers as riparian and wetland vegetation of the classes Alno glutinosae-Populetea albae P. Fukarek et Fabijanić 1968, Salicetea purpureae Moor 1958 and Alnetea glutinosae Br.-Bl. et Tx. ex Westhoff et al. 1946. Steppe grasslands, pastures of the class Festuco-Brometea Br.-Bl. et Tx. ex Soó 1947 have “Zonal” character and belongs (Festucetalia valesiacae Soó 1947 and Brachypodietalia pinnati Korneck 1974 nom. conserv. propos.) to the subcontinental—Northern region (Pljevlja, Berane, Durmitor mt.) rocky grassland vegetation on calcareous substrates (Scorzoneretalia villosae Kovačević 1959) sub- and oromediterranean vegetation of Dinarides (Orjen, Lovćen and Rumija Mountains). Vegetation of the nemoral forest zone is presented by zonal temperate broadleaved forests. Thermophylous deciduous oak forests (class Quercetea pubescentis Doing-Kraft ex Scamoni et Passarge 1959) are mostly presented with Carpinion orientalis Horvat 1958, Fraxino orni-Ostryion Tomažič 1940 and occupy warm, south-exposed, slopes of numerous canyons. Acidophilous oak and oak-birch forests (class Quercetea robori-petraeae Br.-Bl. et Tx. ex Oberd. 1957) are presented by Castaneo-Quercion petraeae Soó 1964 with interesting Balkan chestnut forests (South of Montenegro). Mesic deciduous and mixed forests (class Carpino-Fagetea sylvaticae Jakucs ex Passarge 1968) cover the continental mountain regions (regions between 600 and 1100 m) that are characterized by moderate and moist climate includes refugial basiphilous beech and mixed fir-beech forests (Aremonio-Fagion (Horvat 1950) Borhidi in Török et al. 1989 and Fagion sylvaticae Luquet 1926) and the scree and ravine maple-lime forests of Fraxino excelsioris-Acerion pseudoplatani P. Fukarek 1969. Intrazonal scrub of the nemoral zone of Montenegro presented by the class Crataego-Prunetea Tx. 1962 nom. conserv. propos. while intrazonal boreotemperate grasslands and heath includes different vegetation classes (CallunoUlicetea Br.-Bl. et Tx. ex Klika et Hadač 1944, Nardetea strictae Rivas Goday et Borja Carbonell in Rivas Goday et Mayor López 1966 nom. conserv. propos., SedoScleranthetea Br.-Bl. 1955, Trifolio-Geranietea sanguinei T. Müller 1962). The anthropogenic managed pastures, meadows, and tall-herb meadow fringes of the class Molinio-Arrhenatheretea Tx. 1937 involve mown meadows and pastures of Arrhenatheretalia elatioris Tx. 1931 with mesic mown meadows of the lowland to submontane belts, Poo alpinae-Trisetetalia Ellmauer et Mucina 1993 with the mesic montane meadows, Molinietalia caeruleae Koch 1926 with the mown meadows on temporarily wet soils at low altitudes, Trifolio-Hordeetalia Horvatić 1963 with Amphiadriatic wet meadows on gleyic soils of the river floodplains and karstic poljes and Holoschoenetalia Br.-Bl. ex Tchou 1948 with humid grass-rush meadows of the Mediterranean. The chasmophytic vegetation of the canyons and high mountains is represented by communities of the classes Asplenietea trichomanis (Br.-Bl. in Meier et Br.-Bl. 1934) Oberd. 1977, Adiantetea Br.-Bl. et al. 1952 and Thlaspietea rotundifolii Br.Bl. 1948.

122

G. Kasom and S. Hadžiablahović

Vegetation of the boreal zone of Montenegro of acidophilous conifer forests (Vaccinio-Piceetea Br.-Bl. in Br.-Bl. et al. 1939) dominate in continental mountains (Durmitor, Bjelasica, Ljubišnja) and is presented by the boreo-montane spruce forests (Piceion excelsae Pawłowski et al. 1928), acidophilous Macedonian-pine forests (Pinion peucis Horvat 1950), mesophilous fir forests (Abieti-Piceion (Br.-Bl. in Br.-Bl. et al. 1939) Soó 1964), and hemiboreal zone is presented by Brachypodio pinnati-Betuletea pendulae Ermakov et al. 1991. Vegetation of the nemoral orosystems presented by the vegetation of the class Erico-Pinetea is presented by the relict Pinus sylvestris forests, the relict Pinus nigra forests on calcareous substrates, the relict Pinus nigra forests on dolomite and ultramafic substrates, and the relict Pinus heldreichii forests on calcareous and ultramafic substrates. Acidophilous grasslands in the alpine belt of the nemoral zone (Juncetea trifidi Hadač in Klika et Hadač 1944) includes the oligotrophic vegetation of mountain ranges and Alpine and subalpine grasslands while Alpine and subalpine calcicolous swards of the nemoral mountain ranges of Elyno-Seslerietea Br.-Bl. 1948 while the cryophilic vegetation of Montenegro, include Arctic-Alpine vegetation of snow-rich habitats (class Salicetea herbaceae Br.-Bl. 1948), graminoid tundra (class Carici rupestris-Kobresietea bellardii Ohba 1974), and dwarf heath mountain tundra (class Loiseleurio procumbentis-Vaccinietea Eggler ex Schubert 1960).

4.3

Materials and Methods

This paper contains check list of wild species of macrofungi that have been recorded in Montenegro so far, and which have certain medicinal properties. Data on these species in Montenegro is based on available literature and our unpublished data. Data on the findings of these macfungi in Montenegro are used from the following scientific papers: Beck and Szyszylowicz (1888); Bubák (1906, 1915); Černjavski et al. (1949); Ćetković et al. (2011); Hadžiablahović and Kasom (2005); Hadžić (1995, 2018); Hadžić and Vukojević (1999); Jaap (1916); Karadžić (1995, 2000); Karadžić and Anđelić (1997, 2002); Karadžić and Vujanović (1994, 1996); Karadžić et al. (1999); Kasom (2003, 2004, 2013); Kasom and Karadelev (2011, 2012a, b); Kellner et al. (2005); Kotlaba and Pouzar (1978); Lazarević and Bojović (2017); Lazarević et al. (2006, 2011); Matočec and Focht (2000); Mijušković (1953); Perić (1999, 2011); Perić and Perić (1995a, b, 1996a, b, c, 1997a, b, c, d, 1998a, b, c, d, e, 1999a, b, 2000a, b, 2002, 2003, 2004, 2005, 2006, 2008); Perić and Raspopović (2011); Perić et al. (2000, 2001); Přihoda (1985); Reid (1975); Tortić (1974, 1985, 1988); Tortić and Kotlaba (1976). All taxon names and authorities are rechecked according to the records updated by May 1, 2021 in the authentic mycological databases, namely Index Fungorum (http://www.indexfungorum.org/) and MycoBank Database (http://www.mycobank.org/). As a basic article to show the medicinal properties of fungi, we used the comprehensive articles by Wu et al. (2019). For species that have been recorded in

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . .

123

Montenegro, and thay have not been treated in paper Wu et al. (2019) such as: Morchella crassipes, Auricularia auricula-judae, A. mesenterica, Boletus aereus, B. edulis, Butyriboletus regius, Fistulina hepatica, Flammulina velutipes, Guepinia helvelloides, Hemileccinum impolitum, Hymenopellis radicata, Laccaria amethystina, Megacollybia platyphylla, Mucidula mucida, Panellus stipticus, and Phylloporia ribis we used the following articles for presentation of their medicinal properties: Dai et al. (2009, 2010); Gregori (2013) and Gründemann et al. (2020). Known distribution of the cited fungal species for the territory of Montenegro is done for the parts of Montenegro as follows: N—North, NE—North-East, W— West, C—Central, W—West, S—South, and SW—South-West. Habitat types in which these medicinal species of macro fungi occur in Montenegro are given according to the Eunis Habitat Classification - EUNIS2020 code (Chytrý et al. 2020) (Table 4.1).

4.4

The Review of Taxa of Wild Medical Macrofungi in Montenegro with Their Distribution and Ecology

According to the data from the literature and our unpublished data, it was determined that for 268 species of macrofungi occurring in the territory of Montenegro are stated in the literature to have certain medicinal properties. These include 14 species from the Ascomycota division and 254 species from the Basidiomycota division (Table 4.2). In relation to the number of macrofungal species found so far in Montenegro—total of 1200 species, 22.4% of the species has certain medicinal properties. This indicates that there is a great potential in Montenegro when it comes to macrofungi with medicinal properties. Also, based on the medical functions of macrofungi in Table 4.2, it can be concluded that the most common medicinal functions of the macrofungi from Montenegro are antitumor or anticancer, and then follow antioxidant and antimicrobial. In addition to the most common medical functions, they also offer a broad spectrum of pharmacological activities such as: antifungal, antiviral, immunomodulating, anti-inflammatory, anti-allergic, anti-depressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities (Table 4.2). Also, it can be seen from Table 4.2 that a large number of species have several different medicinal properties. In order for macrofungal species from Montenegro to be used in treatment, it is necessary to first conduct detailed tests of their medicinal properties from different habitat type and climatic conditions. They are recommended for research of species that are widespread and common in the territory of Montenegro, such as: Armillaria mellea, A. ostoyae, Auricularia auricula-judea, Boletus edulis, Bovistella utriformis, Cantharellus cibarius, Craterellus cornucopioides, Fomes fomentarius, Ganoderma applanatum, G. resinaceum, Hydnum repandum, Lactarius deliciosus, Laetiphorus sulphureus, Morchella esculenta, Marasmius oreades, Pleurotus ostreatus,

124

G. Kasom and S. Hadžiablahović

Table 4.1 Overview of the EUNIS2020 habitat types (Chytrý et al. 2020) in which medicinal macrofungi of Montenegro were recorded EUNIS2020 code R R1 R1A R1D R1K R2 R21 R23 S S2 S26 S3 S37 S5 S52 S54 S9 S93 T T1 T11 T12 T14 T17 T19 T1B T1D T2 T21 T24 T3 T31 T32 T34a T36 T37 T39 T3A T3Db a

EUNIS2020 habitat name Grasslands and lands dominated by forbs, mosses or lichens Dry grasslands Semi-dry perennial calcareous grassland (meadow steppe) Mediterranean closely grazed dry grassland Balkan and Anatolian oro-mediterranean dry grassland Mesic grasslands Mesic permanent pasture of low lands and mountains Mountain hay meadow Heathlands, scrub, and tundra Arctic, alpine, and subalpine scrub Subalpine Pinus mugo scrub Temperate and Mediterranean montane scrub Corylus avellana scrub Maquis, arborescent matorral, and thermo-Mediterranean scrub Submediterranean pseudomaquis Thermo-mediterranean arid scrub Riverine and fen scrub Mediterranean riparian scrub Forests and other wooded land Broad-leaved deciduous forests Temperate Salix and Populus riparian forest Alnus glutinosa–Alnus incana forest on riparian and mineral soils Mediterranean and Macaronesian riparian forest Fagus forest on non-acid soils Temperate and submediterranean thermophilous deciduous forest Acidophilous Quercus forest Southern European mountain Betula and Populus tremula forest on mineral soils Broad-leaved evergreen forests Mediterranean evergreen Quercus forest Olea europaea-Ceratonia siliqua forest Coniferous forests Temperate mountain Picea forest Temperate mountain Abies forest Temperate subalpine Larix, Pinus cembra, and Pinus uncinata forest Temperate and submediterranean montane Pinus sylvestris–Pinus nigra forest Mediterranean montane Pinus sylvestris–Pinus nigra forest Mediterranean and Balkan subalpine Pinus heldreichii–Pinus peuce forest Mediterranean lowland to submontane Pinus forest Mediterranean Cupressaceae forest

Planted stands of Larix decidua on Durmitor mt Naturalized Cupressus sempervirens planted together with Pinus halepensis

b

Neobulgaria pura (Pers.) Petr. Sarcosphaera coronaria (Jacq.) J. Schröt. Verpa bohemica (Krombh.) J. Schröt. Xylaria carpophila (Pers.) Fr. X. longipes Nitschke Basidiomycota Abortiporus biennis (Bull.) Singer

Morchella crassipes (Vent.) Pers. M. elata Fr. M. esculenta (L.) Pers.

Daldinia concentrica (Bolton) Ces. & De Not. Dissingia leucomelaena (Pers.) K. Hansen & X.H. Wang Helvella lacunosa Afzel. Hypoxylon fragiforme (Pers.) J. Kickx f.

Species name Ascomycota Aleuria aurantia (Pers.) Fuckel Bulgaria inquinans (Pers.) Fr.

E, SW N, E, S C, E, S N N W

Antitumor, immunomodulation

N, NE, SW N, NE, C, SW NE, SW N, NE N, NE

N, S S

N N, NE

Improving digestion, dissipating phlegm Antioxidant Tonifying intestines, dissipating phlegm, invigorating kidney, Antitumor, antimicrobial, antioxidant, immunomodulation Antibiotics Antioxidant Antimicrobial, antioxidant Antitumor Antifungus

Antioxidant Anti-HIV

Immunomodulation Reducing blood viscosity, antitumor, anticancer, antimicrobial, antioxidant, antimalarial, eliminating blood stasis, immunomodulation, relieving itching Treating infantile convulsion, antioxidant Antioxidant

Medical function(s)

Known distribution

T19

T17 T17, T3A, T3D T17, T19 T17 T17

R1K, R23 T17, T31, T39 T17, T37

R1K, T17, T19 T17

T17 T3A

T17 T17, T19

(continued)

EUNIS2020 code (overview of EUNIS2020 habitat types with EUNIS2020 code are given in Table 4.1)

Table 4.2 Medical macrofungi in Montenegro with their medical functions, known distribution in Montenegro and EUNIS2020 code of habitats

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . . 125

Antitumor, antibacteria Antitumor Lowering cholesterol, antitumor

Agrocybe dura (Bolton) Singer

A. pediades (Fr.) Fayod A. praecox (Pers.) Fayod Albatrellus confluens (Alb. & Schwein.) Kotl. & Pouzar A. ovinus (Schaeff.) Kotl. & Pouzar

Aleurodiscus amorphus (Pers.) J. Schröt. Amanita muscaria (L.) Lam.

Reducing effects of Alzheimer, antioxidant, relief of heat pain on hyperalgesic skin Antitumor Antitumor, treating insomnia, antioxidant

Antibacteria, antifungus

A. urinascens (Jul. Schäff. & F.H. Møller) Singer A. xanthodermus Genev.

A. dulcidulus Schulzer A. sylvaticus Schaeff.

A. bresadolanus Bohus A. campestris L.

A. bitorquis (Quél.) Sacc.

Medical function(s) Treating lumbago and skelalgia, and limb numbness, antioxidant, antitumor Promoting digestion, lowering blood pressure, antibacteria, antitumor; antioxidant, immunomodulation Antioxidant Treating anemia, dermatophytosis and hypopepsia, antibacteria, antitumor Antitumor, promoting digestion Antibacteria, anticancer, anticomplement, antioxidant, antivirus, decreasing parasitaemia, immunostimulant, reducing oxidativestress Antioxidant Antimicrobial

Species name Agaricus arvensis Schaeff.

Table 4.2 (continued)

N N, NE, E

N, NE

N, NE, E, S N, NE, S, SW N, NE, S, SW S NE, S N, NE

E N, NE, E, S, SW NE N, NE, S

E

Known distribution E, NE, S

T17, T32 R23, T17, T31, T32, T1D

T31, T32

R1K T17, T31, T3A T17, T31

R1K, R23

R1K, R23 R23, T31, T32, T37, T3A, T3D

T17 T31, T3A, T3D

T19 R1K, R1D, R23

EUNIS2020 code (overview of EUNIS2020 habitat types with EUNIS2020 code are given in Table 4.1) R23, T17, T3A

126 G. Kasom and S. Hadžiablahović

Bovista nigrescens Pers.

B. edulis Bull.

B. fumosa (Pers.) P. Karst. Boletus aereus Bull.

A. mesenterica (Dicks.) Pers. Bjerkandera adusta (Willd.) P. Karst.

Auricularia auricula-judae (Bull.) Quél.

Astraeus hygrometricus (Pers.) Morgan

Antitumor, antioxidant, immunomodulation Invigorating spleen and resolving food stagnation, invigorating the kidney Treating lumbago and skelalgia, deadlimb, antitumor Hemostasis, antimicrobial

Improving immunity, treating insomnia, antitumor, anticancer, antiedema, antimicrobial, antioxidant, anti-inflammation, antineuroinflammation Tranquilizing, improving immunity, treating neurasthenia, insomnia and limb numbness Hemostasis, treating chilblain, antifungus, antioxidant, antitumor, anti-inflammation, hepatoprotection Antiulcer, replenishing the blood, moistening the lug, hemostasis, lowering blood glucose, treatment of sore throats, sore eyes, and jaundice, astringent, physically and mentally invigorating, to reduce alleviate pain, treatment of gastrointestinal pain, and toothaches Antitumor Antitumor N, SW, S N, E, S, SW N NE, E, S, SW N, NE, E, S, SW N, NE, S

W, S, SW

N, NE, W, S

N, NE

N, NE, W, S, SW

Antimicrobial Antitumor

A. virosa Bertill. 1866 Ampulloclitocybe clavipes (Pers.) Redhead, Lutzoni, Moncalvo & Vilgalys Armillaria mellea (Vahl) P. Kumm.

A. ostoyae (Romagn.) Herink

N, NE, E, S, SW NE N, NE, S

Antimicrobial, antioxidant

A. vaginata (Bull.) Lam.

R23

T17, T19, T31, T39

T17 T17, T19, T1B

T17, T19 T17, T19, T32

T19

S52, T17, T19, T3A, T3D

T31

T12, T17, T19, T1B

T31 T31, T3A

(continued)

R23, T17, T19, T31, T32, T39, T3A, T3D

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . . 127

Anti-inflammatory, hemostasis, antibacteria, detoxification, prevention of diabetes type II and Alzheimer’s disease, antioxidant Treating lumbago and skelalgia, and limb numbness, antimicrobial, antioxidant, antiradical activity Antitumor Antioxidant Invigorating qi, thermolysis, antifungus, antitumor, immunomudulation Detumescence, anagesic, clearing the lung, detoxification, treating dermatomycosis, antitumor, analgesic, antibacteria, antioxidant, anti-inflammation, hepatoprotection Improving eyesight, promoting digestion, treating the respiratory and gastrointestinal tract infection, antitumor, antimicrobial, antioxidant, antihyperlipidemic activity, anti-inflammation, neuroprotective Antibacteria, antioxidant Improving immunity, antitumor, antimicrobial, antioxidant Dispelling wind-evil, tonifying meridians and collaterals

Bovistella utriformis (Bull.) Demoulin & Rebriev

C. varius (Pers.) Zmitr. & Kovalenko

C. tubaeformis Fr. Cerioporus squamosus (Huds.) Quél.

Cantharellus cibarius Fr.

Calvatia gigantea (Batsch) Lloyd

B. regius (Krombh.) D. Arora & J.L. Frank Calocera viscosa (Pers.) Fr. Calocybe gambosa (Fr.) Donk

Butyriboletus appendiculatus (Schaeff.) D. Arora & J.L. Frank

Medical function(s) Hemostasis, detumescence, detoxification

Species name B. plumbea Pers.

Table 4.2 (continued)

N, NE, E, S, SW

NE N, S, SW

N, NE, C, E, W, SW

T17, T19

T31, T32 T14, T17, T19

T17, T19, T1B, T31, T32

R1K, R23, T19

R1A, R1K, R23, T17, T37

N, NE, SW N, NE, C, E, SW

T17, T19

T17, T37

R1K, R23, T16 T39

EUNIS2020 code (overview of EUNIS2020 habitat types with EUNIS2020 code are given in Table 4.1) R1K, R23, T17, T31, T32, T37, T3A, T3D

N, E

N, E, SW

Known distribution N, NE, E, C, S, SW N, NE, E, C, S, SW

128 G. Kasom and S. Hadžiablahović

Antibacteria Antitumor, antimicrobial, antioxidant, antidiabetic activity, antiacetylcholinesterase, anti-inflammation, anti-tyrosinase, a-glucosidase inhibitory Antitumor

C. sinopica (Fr.) P. Kumm. Coprinellus micaceus (Bull.) Vilgalys, Hopple & Jacq. Johnson

Cortinarius caperatus (Pers.) Fr.

C. lagopus (Fr.) Redhead, Vilgalys & Moncalvo Coprinus comatus (O.F. Müll.) Pers.

Promoting digestion, eliminating phlegm, detoxification, detumescence, antitumor, antibacteria, antifungus Antitumor Promoting digestion, treating hemorrhoids and diabetes, antitumor, antifungus, antioxidant, antiproliferation, HIV-1 reverse transcriptase inhibitor, antidiabetic activities Antitumor, antivirus

Antitumor, antifungus, antioxidant

C. odora (Bull.) P. Kumm.

C. radians (Desm.) Vilgalys, Hopple & Jacq. Johnson Coprinopsis atramentaria (Bull.) Redhead, Vilgalys & Moncalvo

Antibacteria, antitumor, antiproliferation

Treating chronic bronchitis, antitumor, anticancer, antimicrobial, antivirus, antioxidant, immunomodulation Treating neurodermatitis, antioxidant, antitumor, hypoglycemic and hypolipidemic activities, prevention and treatment of Parkinson’s disease Antibacteria Antitumor, antioxidant

C. nebularis (Batsch) P. Kumm.

Clavariadelphus truncatus (Quél.) Donk Clitocybe geotropa (Bull.) Quél.

Chroogomphus rutilus (Schaeff.) O.K. Mill.

Cerrena unicolor (Bull.) Murrill

N, NE

S, SW N, NE, S, SW

N, NE, S, SW

NE

N, NE, SW NE, C, S, SW N, NE, E, S, SW N, NE, E, S, SW N N, E, S, SW

N, NE, C, E, S

N, NE, ES, W, S

T17, T31

T19 R23, T17, T19, T31

T17, T19

T17

T32 T17, T19

T17, T19, T31, T3A

T17, T31, T37, T39, T3A, T3D

T17, T31, T32 T17, T19, T31, T32, T3A, T3D

S26, T36, T37, T39, T3A

T17, T19

(continued)

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . . 129

Fomes fomentarius (L.) Fr.

Flammulina velutipes (Curtis) Singer

Daedaleopsis tricolor (Bull.) Bondartsev & Singer Desarmillaria tabescens (Scop.) R.A. Koch & Aime Entoloma clypeatum (L.) P. Kumm. E. sinuatum (Bull.) P. Kumm. Fistulina hepatica (Schaeff.) With.

Cyathus stercoreus (Schwein.) De Toni C. striatus (Huds.) Willd. Cyclocybe cylindracea (DC.) Vizzini & Angelini

Species name C. cinnamomeus (L.) Gray C. collinitus (Sowerby) Gray C. sanguineus (Wulfen) Gray C. torvus (Fr.) Fr. C. violaceus (L.) Gray Craterellus cornucopioides (L.) Pers.

Table 4.2 (continued)

S, SW N E, S N, S, SW

Treating hepatopathy, antitumor Antitumor Antitumor Antitumor and treating gastrointestinal diseases Lowering blood pressure, lowering cholesterol, antitumor Eliminating blood stasis, antitumor, antibacteria, antiinfection, immunomodulation

N, NE, S, SW N, NE, E, C, W, S, SW

C

Medical function(s) Antitumor Antitumor Antitumor Antitumor Antitumor, antioxidant Anticomplement, antitumor, antiinflammation Treating gastropathy Antibacteria, treating gastropathy Inducing diuresis, invigorating the spleen, improving immunity, antitumor, antidiarrheal, antifungus, antioxidant, antinematode Antitumor, antioxidant

Known distribution NE NE NE NE NE N, NE, E, SW S N, SW S

T12, T17, T19, T31

T17, T19

R23 T17, T19 T19, T1B

T14, T19

T19

T19 T17, T19 T12

EUNIS2020 code (overview of EUNIS2020 habitat types with EUNIS2020 code are given in Table 4.1) T31 T31 T31 T17, T31 T17 T17, T19, T1B, T31

130 G. Kasom and S. Hadžiablahović

Gloeophyllum sepiarium (Wulfen) P. Karst. G. trabeum (Pers.) Murrill Guepinia helvelloides (DC.) Fr.

G. rufescens Pers. G. triplex Jungh.

Geastrum fimbriatum Fr.

G. resinaceum Boud.

G. lucidum (Curtis) P. Karst.

Fuscoporia torulosa (Pers.) T. Wagner & M. Fisch. Ganoderma applanatum (Pers.) Pat.

F. robusta (P. Karst.) Fiasson & Niemelä Fomitopsis pinicola (Sw.) P. Karst.

Fomitiporia punctata (P. Karst.) Murrill

Anti-inflammation, hemostasis, detoxification, antibacteria, antioxidant, antitumor Hemostasis Hemostasis, disinfecting, clearing the lung, relieving sore throat, detoxification, antibacteria Antitumor Antitumor Antitumor

Treating coronary artery diseases, antioxidant, antitumor, antivirus Antitumor, antibacteria, antioxidant Dispelling wind-evil, eliminating dampness, antitumor, antifungus, antioxidant, immunomodulation, neuroprotective activities Detoxification, treating anemia, antibacteria, antioxidant Antitumor, antiviral, lowering blood glucose, improving immunity, antibacterial, antimicrobial, antioxidant Antitumor, lowering blood pressure, improving immunity, antithrombotic, antioxidant, biofortified with essential elements (Se, Cu, and Zn), immunomodulation, preventing radiation-induced DNA damage and apoptosis Antitumor

N, NE, E, S SW N, NE

NE, W, S, SW N, NE, E, C, S N, NE, W N, NE, E, W, S

T17, T31, T32, T3A, T3D T3D T31

T31, T32, T37 T17, T19, T31, T32, T39, T3A

T17, T31, T32, T37, T39, T3A

T11, T12, T19, T31

T11, T12, T17, T19, T31

T17, T19

N, NE, E, C, W, SW N, NE, S, SW

S54, T1B, T24, T19, T3D

T19, T24 T12, T17, T31, T32, T39

S54, T19, T1B, T24,

W, NW

N, W N, E

W, S, SW

(continued)

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . . 131

Antivirus Antibacteria, antimicrobial, antitumor Antitumor Antioxidant Antioxidant, antiproliferation Lowering blood pressure, antitumor Antioxidant Antitumor

Hygrocybe conica (Schaeff.) P. Kumm.

Hygrophoropsis aurantiaca (Wulfen) Maire Hymenopellis radicata (Relhan) R.H. Petersen

Hypholoma capnoides (Fr.) P. Kumm. H. fasciculare (Huds.) P. Kumm.

Medical function(s) Treating arthritis, antitumor, analgesic effect on neuropathic pain Anticancer, antioxidant Treating hepatopathy and diabetes, antihypertensive, antitumor, antidiabetic activity, antioxidant, antivirus, hypolipidemic, immunomodulation Antitumor Treating limb numbness, antitumor Treating gastric ulcer and neurasthenia, promoting digestion Antitumor

Hortiboletus rubellus (Krombh.) Simonini, Vizzini & Gelardi Hydnellum concrescens (Pers.) Banker H. scabrosum (Fr.) E. Larss. Hydnum repandum L.

Gyroporus castaneus (Bull.) Quél. Hemileccinum impolitum (Fr.) Šutara Hericium coralloides (Scop.) Pers.

Species name Gymnopus androsaceus (L.) Della Magg. & Trassin. Gomphus clavatus (Pers.) Gray Grifola frondosa (Dicks.) Gray

Table 4.2 (continued)

NE W N, NE, E, SW N, NE, E, W, S, SW N, NE N, NE, E, SW N, NE, S N, NE, E, W, S, SW

N, W, S

T31, T39, T3A T17, T19, T31

T17, T31 T17, T19

R23, T17, T19, T31, T32, T39, T3A

T31 T3A, T3D T17, T31, T37

T17, T19

T17, T1B S37, T17, T19 T17

T31 T17

N, NE N

N, W N, W N

EUNIS2020 code (overview of EUNIS2020 habitat types with EUNIS2020 code are given in Table 4.1) T31

Known distribution N, NE

132 G. Kasom and S. Hadžiablahović

Anti-inflammation Antitumor Hemostasis, analgesic, treating hemorrhoids Hemostasis, anagesic, treating hemorrhoids Antitumor, antieczematic Hemostasis, antitumor Improving digestion, hemostasis, antitumor, activating the circulation to remove blood stasis, antibacteria, antioxidant, antihyperglycemic activity, immunomodulation, treatment of candidiasis Improving immunity, lowering blood glucose, antitumor, anticancer, antimicrobial, antioxidant, antiproliferation, antiinflammation Treating oliguria, edema and lumbago, lowering blood pressure, antiproliferation, anti-inflammation, immunomodulation, prevention and treatment of chronic glomerulonephritis Antitumor Antitumor, antioxidant Antitumor Anticancer, antibiotic, antimicrobial, antioxidant

Imleria badia (Fr.) Vizzini Infundibulicybe gibba (Pers.) Harmaja

Inocutis rheades (Pers.) Fiasson & Niemelä I. tamaricis (Pat.) Fiasson & Niemelä Inocybe rimosa (Bull.) P. Kumm. Inonotus cuticularis (Bull.) P. Karst. I. hispidus (Bull.) P. Karst.

L. amethystina Cooke

Lactarius controversus Pers.

Ischnoderma resinosum (Schrad.) P. Karst. Laccaria laccata (Scop.) Cooke

Irpex lacteus (Fr.) Fr.

I. obliquus (Ach. Ex Pers.) Pilát

Antitumor

H. lateritium (Schaeff.) P. Kumm.

N, NE N, NE, E, W, S, SW N, NE, S, SW N, NE, C, S

W, NW

NE

N, NE, E, W, S, SW E NE, W, SW N S, SW N, NE, S N W, S, SW

T1B, T1D, T3D

T17, T19, T31, T39

T17, T31 T17, T19, T31, T37, T3A

T19

T1D

T1D S93 T14, T17, T3A T17 T17, T19

T31 T17, T19, T31, T32, T3A, T3D

T12, T17, T19

(continued)

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . . 133

Leccinum aurantiacum (Bull.) Gray Lentinellus cochleatus (Pers.) P. Karst. L. micheneri (Berk. & M.A. Curtis) Pegler Lentinus arcularius (Batsch) Zmitr.

Laetiporus sulphureus (Bull.) Murrill

Lactifluus piperatus (L.) Kuntze

L. volemus (Fr.) Fr. L. zonarius (Bull.) Fr.

L. pubescens Fr. L. rufus (Scop.) Fr. L. salmonicolor R. Heim & Leclair L. sanguifluus (Paulet) Fr. L. vellereus (Fr.) Fr.

L. lignyotus Fr. L. pallidus Pers. L. picinus Fr.

Species name L. deliciosus (L.) Gray

Table 4.2 (continued)

Medical function(s) Antitumor, anticancer, antimicrobial, antioxidant, immunostimulant Antitumor Antitumor Treating lumbago and skelalgia, limb numbness Antioxidant Antinociceptive, anti-inflammation Antioxidant Antibacteria, antioxidant, antivirus Treating lumbago and skelalgia, limb numbness, antitumor, antifungus, antimicrobial, antioxidant immunosuppressive Antitumor, antioxidant Treating lumbago and skelalgia, limb numbness Treating lumbago and skelalgia, limb numbness, antitumor Invigorating qi and replenishing blood, antitumor, antimicrobial, antioxidant Antioxidant Antitumor Antibacteria Antitumor, antimicrobial N, NE, W, S N, E, S, SW N, NE, E N, NE NE N, E, W, S, SW

N, E, W S, SW

N, NE NE, SW N N, E, W, S N, W, SW

Known distribution N, NE, C, S, SW NE N, NE, SW N, NE

T1D T17, T31 T31 T17, T19, T37

T12, T17, T19

T17, T19, T1B

T17, T19, T31 T19

T1D T31, T37 T17, T31, T32 T19, T37, T39, T3A, T3D T17, T19, T1B

T31 T17 T17, T31, T32, T39

EUNIS2020 code (overview of EUNIS2020 habitat types with EUNIS2020 code are given in Table 4.1) T31, T32, T36, T37, T39, T3A

134 G. Kasom and S. Hadžiablahović

Marasmiellus ramealis (Bull.) Singer M. confluens (Pers.) J.S. Oliveira

M. procera (Scop.) Singer

Macrolepiota excoriata (Schaeff.) Wasser

L. umbrinum Pers. Lyophyllum decastes (Fr.) Singer

L. pyriforme Schaeff.

L. mammiforme Pers L. perlatum Pers.

Leucoagaricus leucothites (Vittad.) Wasser Lycoperdon excipuliforme (Scop.) Pers.

L. sordida (Schumach.) Singer

Lepista irina (Fr.) H.E. Bigelow L. nuda (Bull.: Fr.) Cooke

Lenzites betulinus (L.) Fr.

L. tigrinus (Bull.) Fr.

Promoting digestion, anticancer, antimicrobial, antioxidant Antibacteria, antitumor Antibacteria, antifungus

Hemostasis, antibacteria Detumescence, hemostasis, antibacteria, clearing the lung, relieving sore throat, detoxification, antimicrobial, antioxidant Antitumor, antibacteria, hemostasis, clearing the lung, relieving sore throat, detoxification Anti-inflammatory, hemostasis, antibacteria Antitumor, antimicrobial, lowering blood glucose Antioxidant

Calming the nervousness, invigorating the liver, antibacteria, antioxidant, antitumor, immunomodulation, treatinglaryngeal cancer Antimicrobial, antioxidant Antioxidant

Lowering blood glucose, antimicribial, antioxidant Dispelling cold, relaxing tendons, anticancer, antimicrobial, antioxidant Antitumor, antioxidant Antibacteria, antitumor, antioxidant

N, NE, W, S N, NE, E, W, S N, W N, NE, E

N, NE, SW N

N, NE, E, C, W, SW

NE, S N, NE, E, W, S, SW E, SW N, NE, E, W, S, SW

NE N, NE, W, S NE, W, S

S, SW

N, C, W, S

T17, T19 T17 (continued)

R1A, R1K, R23, T17, T3A, T3D

R1K, R23, T3A

T17, T31, T32 R23

T17, T31, T32, T37

R21, R23 R1K, R23, T17, T19, T21, T31, T36, T37, T3A T19, T1B R1D, T17, T19, T31, T32, T37, T39, T3A, T3D

T17, T19, T3A

T17 T17, T31, T39, T3A

T19

T11, T14, T17, T19, T1D, T3A

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . . 135

P. neostrigosus Drechsler-Santos & Wartchow Paxillus involutus (Batsch) Fr.

Panus conchatus (Bull.) Fr.

W, C, S N, NE, E, S, SW N, NE, E, W N, E, S N, NE, E, W

Treating lumbago and skelalgia, limb numbness, antitumor Treating scabs, antitumor Treating lumbago and skelalgia, limb numbness, antioxidant

Antitumor Antitumor Antibiotics, antioxidant Hemostasis, antitumor

Mycetinis scorodonius (Fr.) A.W. Wilson & Desjardin Neoboletus erythropus (Pers.) C. Hahn

Neofavolus alveolaris (DC.) Sotome & T. Hatt. Neolentinus adhaerens (Alb. & Schwein.) Redhead & Ginns Omphalotus olearius (DC.) Singer Panellus stipticus (Bull.) P. Karst.

Antibacteria, antifungal

Mycena galericulata (Scop.) Gray M. haematopus (Pers.) P. Kumm. M. pura (Pers.) P. Kumm.

N, NE, E, W, S, SW N N

Antitumor Antitumor Antitumor

Megacollybia platyphylla (Pers.) Kotl. & Pouzar Mensularia radiata (Sowerby) Lázaro Ibiza Meripilus giganteus (Pers.) P. Karst. Mucidula mucida (Schrad.) Pat.

Known distribution N, NE, E, W, S, SW N, NE N N, E N, NE, E, W, SW N N, W N, NE, E, W, S, SW N, NE

Antitumor

Medical function(s) Treating lumbago and skelalgia, limb numbness, antitumor Antitumor Antitumor Antibacteria, antioxidant Antifungal, antitumor

Species name Marasmius oreades (Bolton) Fr.

Table 4.2 (continued)

T14, T17, T19 T19, T1B, T1D

T17, T19, T32

S54, T24, T19, T1B T17, T19

T17 T17, T31, T32

T17, T19, T31, T32,

T17, T31

T17 T17, T1B T17, T31, T32, T37, T39, T3A, T3D

T17, T31 T12 T17 T17

EUNIS2020 code (overview of EUNIS2020 habitat types with EUNIS2020 code are given in Table 4.1) R1K, R23

136 G. Kasom and S. Hadžiablahović

P. eryngii (DC.) Quél.

P. aurivella (Batsch) P. Kumm. P. highlandensis (Peck) Quadr. & Lunghini P. populnea (Pers.) Kuyper & Tjall.-Beuk. P. squarrosa (Weigel) P. Kumm. Phylloporia ribis (Schumach.) Ryvarden 1978 Pisolithus arhizus (Scop.) Rauschert Pleurotus cornucopiae (Paulet) Rolland

P. tremulae (Bondartsev) Bondartsev & P.N. Borisov Phlebia tremellosa (Schrad.) Nakasone & Burds. Pholiota adiposa (Batsch) P. Kumm.

P. rimosus (Berk.) Pilát

Phellinus hartigii (Allesch. & Schnabl) Pat. P. igniarius (L.) Quél.

Phaeolepiota aurea (Matt.) Maire ex Konrad & Maubl. Phaeolus schweinitzii (Fr.) Pat. Phaeotremella foliacea (Pers.) Wedin Phallus impudicus L.

Antitumor, antibacteria Antibacteria, improving immunity, antioxidant, antiproliferation, antitumor Antimicrobial Antitumor Antitumor Antitumor, immunomodulation Antitumor Antifungus, antioxidant Antitumor, antioxidant, hepatoprotection, HIV-1 reverse transcriptase inhibitor Antioxidant, antitumor, hepatoprotection, hypolipidemic activities, immunomodulation

N, NE NE, SW N, NE, E, W, SW N N, E

Antitumor, antimicrobial, antioxidant Treating gynecopathy Anagesic, promoting blood circulation, treating rheumatism, clearing the lung Antitumor Hemostasis, antitumor, antibacteria, antioxidant, anti-fatigue, anti-inflammatory, immunomodulation, hepatoprotection, lowering blood glucose Invigorating qi, replenishing the blood, improving immunity, antitumor, antioxidant Antitumor, improving immunity

W, S

N E C N, NE, SW S W E, C

NE, W N, SW

N, NE

W

N, NE, E

Antitumor

R1A, R1D

T17 T17 T1D T17, T31, T32 T11 T19, T1B T17

T31, T39 T17, T31

T12, T1D

T19

T32 T12, T17, T19

T36, T37, T39 T17 T17, T19

T17, T31, T1D

(continued)

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . . 137

Ramaria aurea (Schaeff.) Quél. R. botrytis (Pers.) Ricken R. flava (Schaeff.) Quél. R. formosa (Pers.) Quél. Rhizopogon roseolus (Corda) Th. Fr. Rigidoporus ulmarius (Sowerby) Imazeki Rubroboletus satanas (Lenz) Kuan Zhao & Zhu L. Yang

Pseudoclitocybe cyathiformis (Bull.) Singer Pseudohydnum gelatinosum (Scop.) P. Karst. Pycnoporus cinnabarinus (Jacq.) P. Karst.

Psathyrella candolleana (Fr.) Maire

Polyporus umbellatus (Pers.) Fr.

P. pulmonarius (Fr.) Quél.

Species name P. ostreatus (Jacq.) P. Kumm.

Table 4.2 (continued)

Antitumor, antifungus Antitumor, antioxidant Relieving fever, anti-inflammatory, antitumor Antitumor Antibacteria, antioxidant, antitumor Antitumor, antibacteria, antioxidant Antitumor, neutrophil elastase inhibitor Antitumor, antioxidant Antitumor Antitumor, antioxidant

Medical function(s) Treating lumbago and skelalgia, limb numbness, improving the system of meridians and collaterals, antitumor, antioxidant Antitumor, anticholinesterase, anticoagulant, antidiabeticactivity, antimicrobial, antinociception, antioxidant, antiinflammation, immunomodulation Inducing diuresis, treating hepatopathy, antitumor, antimicrobial, immunostimulant, prevention of early renal injury, reducing hepatitis B infection Antibacteria NE, E, W, S, SW N, NE N, NE N, NE, E, C W, SW N, NE, E N, NE N, NE, W NE, E N, E, S W, SW N, NE, C, SW

N

N, NE, S

Known distribution N, NE, E, C, SW

T17, T19, T31, T32 T19 T17 T17, T19 T37, T39, T3A T19 T17, T19

T17, T31, T32 T31, T32 T17, T19, T31

R1A, T17, T19

S37, T17

T17

EUNIS2020 code (overview of EUNIS2020 habitat types with EUNIS2020 code are given in Table 4.1) S54, T17, T24

138 G. Kasom and S. Hadžiablahović

Antitumor, antimicrobial, antioxidant, HIV-1 reverse transcriptase inhibitor Antitumor, antioxidant, anti-tyrosinase, hyperglycemic inhibitor Treating lumbago and skelalgia, limb numbness, antitumor Antitumor, antimicrobial, antioxidant Treating lumbago and skelalgia, limb numbness Antibacteria Treating lumbago and skelalgia, limb numbness, antitumor Antitumor Antitumor

R. delica Fr.

S. leucopus (Pers.) Maas Geest. & Nannf. Schizophyllum commune Fr.

R. virescens (Schaeff.) Fr. Sarcodon imbricatus (L.) P. Karst.

R. sororia (Fr.) Romell R. vesca Fr.

R. rosea Pers. R. sanguinea (Bull.) Fr.

R. queletii Fr. R. nigricans Fr.

R. grata Britzelm. R. integra (L.) Fr.

R. foetens Pers.

R. emetica (Schaeff.) Pers.

Antitumor Promoting digestion, antitumor, antimicrobial, antioxidant Improving eyesight, antitumor, antioxidant Lowering cholesterol, antioxidant, antitumor, immune enhancement Antioxidant, a-glucosidase inhibitor Treating neurasthenia, anti-inflammatory, antitumor, antimicrobial, antioxidant, antiaging

Antitumor, antimicrobial, antioxidant

R. cyanoxantha (Schaeff.) Fr.

R. aurea Pers.

Tonifying meridians and collaterals, antitumor, antioxidant Antitumor, antioxidant

Russula alutacea (Pers.) Fr.

N N, NE, E, C, W, S, SW

N, E, W N, E

N, W, SW N, NE, S, SW NE N, NE, E

N, NE, S N, NE

N, E N, NE, E

N, NE, SW

N, NE, W, SW N, NE, E, C, W N, NE, W, SW NE, W

N, NE

T19, T31 T11, T14, T17, T19

T17, T19, T1B, T31 T17, T31, T32, T39

T31 T17

T17, T19, T37 T17, T31, T37, T3A

T31, T37, T3A T17, T31

T17 T19, T31

T17, T19

T17, T19

T17, T19, T31, T32, T3A

T17, T19, T31, T32

R23, T17, T19

T31

(continued)

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . . 139

Anti-inflammation, hemostasis Anti-inflammation Detumescence, hemostasis, antiinflammation Hemostasis Antitumor Antitumor, antimicrobial, immunosuppressant Antitumor Antihyperglycemic activity, antioxidant Antitumor, antioxidant Antioxidant, antitumor Treating Kaschin-Beck’s disease, antitumor, antioxidant Treating lumbago and skelalgia, limb numbness, antitumor, antioxidant Treating Kaschin-Beck’s disease, antitumor, antidiabetic and antioxidant activities Antibacteria

S. bovista Fr. S. citrinum Pers.

S. polyrhizum (J.F. Gmel.) Pers.

Strobilomyces strobilaceus (Scop.) Berk. Suillellus luridus (Schaeff.) Murrill

Suillus bovinus (L.) Roussel S. collinitus (Fr.) Kuntze

S. granulatus (L.) Roussel

S. grevillei (Klotzsch) Singer

Tapinella atrotomentosa (Batsch) Šutara

S. luteus (L.) Roussel

S. verrucosum (Bull.) Pers. Serpula lacrymans (Wulfen) P. Karst. Stereum hirsutum (Willd.) Pers.

Medical function(s) Anti-inflammation, hemostasis, antioxidant

Species name Scleroderma areolatum Ehrenb.

Table 4.2 (continued)

N, NE, E, W, SW N, NE, E, C, W, SW

W, S NE N, NE, E, W, S, SW N, NE N, NE, E, W, S, SW N, NE NE, E, W, S, SW N, NE, E, C, W, S, SW N

Known distribution N, NE, W, S W, S N, W, S, SW W, S

T31, T32, T37, T39

S26, T36, T37, T39

T34

T17, T31, T32, T37, T39, T3A

T31, T36, T37 T37, T39, T3A

T17 S37, S52, T17, T19, T1B, T32, T3A

R1D, T19, T1B T31 T17, T19

S52, T19

T19, T39 T19, T31, T37, T3A, T3D

EUNIS2020 code (overview of EUNIS2020 habitat types with EUNIS2020 code are given in Table 4.1) R1K, T19, T37

140 G. Kasom and S. Hadžiablahović

Anti-hypoxia, relieving cough and sputum Anticancer, antioxidant, antitumor Relieving fever, treating hepatopathy, antiinflammatory, antitumor, antioxidant, antivirus Treating neurasthenia and breathless, antihypertensive, antioxidant, treating asthma Antitumor

T. suaveolens (L.) Fr. T. trogii Berk. T. versicolor (L.) Lloyd

Antitumor, antibacteria, antioxidant Antitumor, antioxidant Antitumor Antimicrobial, antioxidant Antitumor Antioxidant, cholinesterase inhibitor Antitumor, antimicrobial Antitumor Antitumor, antimicrobial, antioxidant Antitumor, antioxidant Antitumor Antitumor

Trichaptum abietinum (Pers. ex J.F. Gmel.) Ryvarden T. fuscoviolaceum (Ehrenb.) Ryvarden Tricholoma acerbum (Bull.) Quél. T. albobrunneum (Pers.) P. Kumm. T. caligatum (Viv.) Ricken T. equestre (L.) P. Kumm.

T. imbricatum (Fr.) P. Kumm. T. portentosum (Fr.) Quél. T. sejunctum (Sowerby) Quél. T. sulphureum (Bull.) P. Kumm. T. ustale (Fr.) P. Kumm. T. vaccinum (Schaeff.) P. Kumm. T. virgatum (Fr.) P. Kumm.

Tremella mesenterica Retz.

T. pubescens (Schumach.) Pilát

T. hirsuta (Wulfen) Lloyd

Antitumor Antitumor, antimicrobial, antioxidant, antivirus, hypoglycemic activity Treating rheumatism, relieving cough, antitumor, antimicrobial Antitumor

Tephrocybe anthracophila (Lasch) P.D. Orton Trametes gibbosa (Pers.) Fr.

S E, C S S N, NE, S, SW E, W N, NE W N, NE, SW NE, E N, NE, SW NE

N, W, S, SW NE, E

NE, E N, NE, E, SW N, NE, E, SW N, NE, E, S, SW NE, E W, S N, NE, E, W, S, SW

T39 T31 T19 T17, T19, T31, T37 T19 T31, T32, T39, T3A T31

T3A T19 T3A, T3D T3A, T3D T17, T31, T3A, T3D

T32

T17, T19

T12 T14 T17, T19, T3A

T14, T17

T17, T19

T39 T17, T19, T3D

(continued)

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . . 141

Antitumor

Xeromphalina campanella (Batsch) Kühner & Maire Xylobolus frustulatus (Pers.) P. Karst. E, SW

Known distribution W, SW, S N, NE S N, NE, SW N, NE, S, SW N, NE T19

T31, T32

EUNIS2020 code (overview of EUNIS2020 habitat types with EUNIS2020 code are given in Table 4.1) R1K, S52, T14, T3A, T3D T31 T1B T17, T19 T17, T19, T1B, T31, T32, T39,

Known distribution in the part of Montenegro (N—North, NE—North-East, W—West, C—Central, W—West, S—South, SW—South-West)

Antitumor

Medical function(s) Hemostasis Anti-inflammation, treating hepatopathy Antitumor Antioxidant Antioxidant

Species name Tulostoma brumale Pers. Tylopilus felleus (Bull.) P. Karst. Vanderbylia fraxinea (Bull.) D.A. Reid Volvariella bombycina (Schaeff.) Singer Xerocomus subtomentosus (L.) Quél.

Table 4.2 (continued)

142 G. Kasom and S. Hadžiablahović

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . .

143

Fig. 4.1 Some widespread and common medical macrofungi in Montenegro. (Photographs by author): (a) Bovistella utriformis (Bull.) Demoulin & Rebriev, (b) Ganoderma resinaceum Boud., (c) Fomes fomentarius (L.) Fr., (d) Laetiporus sulphureus (Bull.) Murrill, (e) Meripilus giganteus (Pers.) P. Karst., (f) Pleurotus ostreatus (Jacq.) P. Kumm., Photos by G. Kaso

Schizophylom commune, Trametes versicolor, and other common species. It is also necessary to examine the possible presence of toxic substances in these fungi because it is known that they may accumulate heavy metals and other toxic substances in their fruiting bodies, which can negatively affect human health. The largest number of species of medicinal macrofungi that grow in forest ecosystems was found in the following forest habitat types: Fagus forest on non-acid soils (T17); Temperate and submediterranean thermophilous deciduous forest (T19), Temperate mountain Picea forest (T31) as well as Temperate mountain Abies forest (T32) (Fig. 4.1, Table 4.2).

144

G. Kasom and S. Hadžiablahović

Medicinal macrofungi related to grassland habitats are registered in the largest number in the vegetation of Balkan and Anatolian oromediterranean dry grassland (R23) as well as in the vegetation of Mountain hay meadow (R23) (Table 4.2). From the aspect of rare types of habitats to which certain species of medical macrofungi are exclusively related, the following significant habitats can be recognized: Temperate Salix and Populus riparian forest (T11), Alnus glutinosa–Alnus incana forest on riparian and mineral soils (T12), Acidophilous Quercus forest (T1B), Southern European mountain Betula and Populus tremula forest on mineral soils (T1D), Temperate subalpine Larix, Pinus cembra and Pinus uncinata forest (T34), Mediterranean and Balkan subalpine Pinus heldreichii–Pinus peuce forest (T39) (Table 4.2).

4.5

Conclusion

Montenegro has a rich diversity of fungi. About 2000 species of fungi have been identified so far, of which about 1200 are macrofungi. Until now, in Montenegro, there is not a tradition of using macrofungi in traditional medicine as well as in pharmacy. Macrofungi are used only in diet and the general public is aware of their nutritional value. Certain species of macrofungi have a commercial significance. This chapter presents a comprehensive overview of fungal species that have been registered in Montenegro so far, and which, based on available scientific papers, have been found to have certain medicinal properties. It was found that 268 species of macrofungi from Montenegro (14 species from the division of Ascomycota and 254 species from the division of Basidiomycota) have certain medicinal properties. In relation to the number of macrofungal species found so far in Montenegro, 22.4% of species has certain medicinal properties. Based on the medical functions of macrofungi, it can be concluded that the most common medicinal functions of the macrofungi from Montenegro are antitumor or anticancer, and then follow antioxidant and antimicrobial. But, they also offer a broad spectrum of pharmacological activities such as antifungal, antiviral, immunomodulating, anti-inflammatory, antiallergic, anti-depressive, antihyperlipidemic, antidiabetic, digestive, hepatoprotective, neuroprotective, nephroprotective, osteoprotective, and hypotensive activities. It is necessary to first conduct detailed tests of their medicinal properties from different habitat types and climatic conditions. There are a large number of species that are widespread and common in the territory of Montenegro, whose medicinal importance is well known. It is also necessary to examine the possible presence of toxic substances with negative health effects in these fungi. The largest number of species of medicinal macrofungi that grows in forest ecosystems was found in the following forest habitat types: Fagus forest on non-acid soils (T17), Temperate and submediterranean thermophilousdeciduous forest (T19), Temperate mountain Picea forest (T31) as well as temperate mountain with Abies forest (T32) (Table 4.1). Medicinal macrofungi related to grassland

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . .

145

habitats were registered in the largest number in the vegetation of Balkan and Anatolian oromediterranean dry grassland (R23) as well as in the vegetation of Mountain hay meadow (R23) (Table 4.2). From the aspect of rare types of habitats to which certain species of medical macrofungi are exclusively related, the following significant habitats can be recognized: Temperate Salix and Populus riparian forest (T11), Alnus glutinosa–Alnus incana forest on riparian and mineral soils (T12), Acidophilous Quercus forest (T1B), Southern European mountain Betula and Populus tremula forest on mineral soils (T1D), Temperate subalpine Larix, Pinus cembra and Pinus uncinata forest (T34), and Mediterranean and Balkan subalpine Pinus heldreichii–Pinus peuce forest (T39) (Table 4.2). Certainly, in Montenegro it is necessary to conduct extensive researches on medical macrofungi by applying global trends and practices in the area so that certain new species could be found for applications for medical purposes. Acknowledgement We express our gratitude to Prof. Dr. Ulrike Lindequist (Freiburg, Germany) for sending us on her scientific articles on medicinal species of macrofungi for the territory of Europe.

References Beck G, Szyszylowicz I (1888) Plantae a Dre Ign. Syzszylowicz in itinere per Cernagoram et in Albania adjecente anno 1886 lactae. Cracoviae, p 166 Blečić V, Lakušić R (1976) Prodromus biljnih zajednica Crne Gore. Glas Rep Zavoda Zašt Prir – Prir Muz 9:57–98 Bubák F (1906) Zweiter Beitrag zur Pilzflora von Monteneüo. Bulletin de l’Herbier Boissietr 6(2): 393–408, 473–488 Bubák F (1915) Dritter Beitrag zur Pilzflora von Montenegro. Botanikai Közlemenyek 14:39–83 Černjavski P, Grebenščikov O, Pavlović Z (1949) O vegetaciji i flori Skadarskog jezera. Glasnik Prirodnjačkog Muzeja Srpske Zemlje, Serija B, Biološke nauke 1–2:5–91 Ćetković I, Kasom G, Malidžan S (2011) Collection of fungi at the Natural History Museum of Montenegro. Natura Montenegrina 10(4):359–376 Chytrý M, Tichý L, Hennekens SM et al (2020) EUNIS habitat classification: expert system, characteristic species combinations and distribution maps of European habitats. Appl Veg Sci 23:648–675. https://doi.org/10.1111/avsc.12519 Dai YC, Yang ZL, Cui BK, Yu CJ, Zhou LW (2009) Species diversity and utilization of medicinal mushrooms and fungi in China (Review). Int J Med Mushrooms 11:287–302 Dai YC, Zhou LW, Yang ZL, Wen HA, Bau T, Li TH (2010) A revised checklist of edible fungi in China. Mycosystema 29:1–21 Gargano ML, van Griensven LJLD, Isikhuemhen OS, Lindequist U, Venturella G, Wasser SP, Zervakis GI (2017) Medicinal mushrooms: valuable biological resources of high exploitation potential. Plant Biosyst 151(3):548–565. https://doi.org/10.1080/11263504.2017.1301590 Gregori A (2013) Medicinal mushrooms native to Slovenia. Acta Biol Slov 56(2):9–22 Gründemann C, Reinhardt JK, Lindequist U (2020) European medicinal mushrooms: do they have potencial for modern medicine? An update. Phytomedicine 66:1–12

146

G. Kasom and S. Hadžiablahović

Hadžiablahović S (2018) The diversity of the flora and vegetation of Lake Skadar/Shkodra. In: Pešić V, Karaman G, Kostianoy A (eds) The Skadar/Shkodra Lake environment. The handbook of environmental chemistry, vol 80. Springer, Cham, pp 203–238 Hadžiablahović S, Kasom G. (2005) Ljekovito bilje i samonikle jestive gljive u Srbiji i Crnoj Gori. Monografija za sakupljače po principima organske proizvodnje. Njemačko društvo za tehničku saradnju (GTZ). Podgorica, p 148 Hadžić I (1995) Prilog izučavanju mikoflore rožajskog kraja. Rožajski zbornik 7:11–34 Hadžić I (2018) Gljive Crne Gore- Katalog gljiva rožajskog kraja. Agencija za zaštitu prirode i životne sredine Crne Gore, Javno preduzeće za nacionalne parkove Crne Gore. Podgorica, p 230 Hadžić I, Vukojević J (1999) 10 Gasteromycetes sa terena Srbije i Crne Gore. Mycol Monten 2(1): 15–32 Jaap O (1916) Beitrag zur Kenntnis der Pilze Dalmatiens. Annales Mycologici 14:1–44 Jovanović B, Lakušić R, Rizovski R, Trinajstić I, Zupančić M (1986) Prodromus Phytocenosum Jugoslaviae ad mappam vegetationis Bribir-Ilok. Naučno veće vegetacijske karte Jugoslavije Karadžić D (1995) Gljive Nacionalnog parka Durmitor, najčešće vrste. Nacionalni park Durmitor. Žabljak, Šumarski fakultet - Beograd, p 270 Karadžić D (2000) Najčešće Phellinus vrste u Crnoj Gori. Mycol Monten 3(1):127–137 Karadžić D, Anđelić M (1997) Uticaj patogene mikoflore na sušenje stabala alepskog bora (Pinus halepensis Mill.) u kulturama u okolini Skadarskog jezera. Prirodne vrijednosti i zaštita Skadarskog jezera, Crnogorska Akademija Nauka i Umjetnosti 44:290–298 Karadžić D, Anđelić M (2002) Najčešće gljive prouzrokovači truleži drveta u šumama i šumskim stovarištima. Centar za zaštitu i unapređenje šuma Crne Gore, Podgorica, p 154 Karadžić D, Vujanović V (1994) Bolesti bukovih sastojina na području nacionalnog parka ‘Lovćen’. Nacionalni park ‘Lovćen’ - prirodna i kulturna dobra, Crnogorska Akademija Nauka i Umjetnosti 34:175–183 Karadžić D, Vujanović V (1996) Najčešće patogene gljive u šumama nacionalnog parka Durmitor. Priroda nacionalnog parka Durmitor, Geografski fakultet, Beograd 8:270–279 Karadžić D, Knežević M, Anđelić M, Zarubica B (1999) Najčešće parazitske i saprofitske gljive na stablima sive jove (Alnus incana Mnch.) u NP ‘Biogradska gora’. Mycol Monten 2(1):69–77 Karadžić B, Bulić Z, Jarić S, Mitrović M, Pavlović P (2020) Vegetation in ravine habitats of Montenegro. In: Pešić V, Paunović M, Kostianoy A (eds) The rivers of Montenegro. The handbook of environmental chemistry. Springer, Berlin Kasom G (2003) Prvi prilog pročavanju makromiceta Lovćena (Crna Gora). Doclea 4:247–271 Kasom G (2004) The contribution to the study of macromycetes of Montenegro. Glasnik Republičkog zavoda za zaštitu prirode u Podgorici 27–28:19–32 Kasom G (2013) Basidiomycota macrofungi of Montenegro. PhD thesis, University of Montenegro, Faculty of Science and Mathematics, Podgorica. (in Montenegrin). https://fedora.ucg.ac. me/fedora/get/o:334/bdef:Content/get. Accessed 1 May 2021 Kasom G, Karadelev M (2011) Preliminary checklist of the genus Boletus L. in Crna Gora (Montenegro). Natura Montenegrina 10(3):187–199 Kasom G, Karadelev M (2012a) Survey of the family Russulaceae (Agaricomycetes, fungi) in Montenegro. Acta Bot Croat 71(2):285–298 Kasom G, Karadelev M (2012b) The family Boletaceae s.l. (excluding Boletus) in Montenegro. Turk J Bot 36(5):566–579 Kellner H, Renker C, Buscot F (2005) Species diversity within the Morchella esculenta group (Ascomycota: Morchellaceae) in Germany and France. Org Divers Evol 5:101–107 Kotlaba F, Pouzar Z (1978) Notes on Phellinus rimosus complex (Hymenochaetaceae). Acta Bot Croat 37:171–182 Lazarević J, Bojović D (2017) Hrana i ljekovi iz prirode, priručnik o jestivim gljivama i ljekovitom bilju planinskih područja. Univerzitet Crne Gore, Biotehnički fakultet, p 171 Lazarević J, Perić O, Perić B (2006) Phellinus torulosus as decay fungus on evergreen broadleaves in Montenegro. Mycol Monten 9:25–33

4 Wild Medical Macrofungi in Montenegro: Diversity, Distribution, Ecology,. . .

147

Lazarević J, Perić O, Perić B (2011) Ektomikorizne gljive u Crnoj Gori-diverzitet i distribucija. Mycol Monten 14:85–115 Matočec N, Focht I (2000) On some autumnal Discomycetes collected from Mt. Orjen, Montenegro 1982-1984. Mycol Monten 3(1):149–165 Mijušković M (1953) Bolesti i štetočine suptropskih voćaka. Univerzitet Crne Gore, Biotehnički institut, Podgorica, p 228 Mucina L, Bültmann H, Dierßen K, Theurillat JP, Raus T, Čarni A, Šumberová K, Willner W, Dengler J, García RG, Chytrý M, Hájek M, Di Pietro R, Iakushenko D, Pallas J, Daniëls FJA, Bergmeier E, Guerra AS, Ermakov N, Valachovič M, Schaminée JHJ, Lysenko T, Didukh YP, Pignatti S, Rodwell JS, Capelo J, Weber HE, Solomeshch A, Dimopoulos P, Aguiar C, Hennekens SM, Tichý L (2016) Vegetation of Europe: hierarchical floristic classification systemof vascular plant, bryophyte, lichen, and algal communities. Appl Veg Sci 19(suppl 1): 3–264 Perić B (1999) 12 espèces de la subdivision des Ascomycotina, nouvelles pour le Monténégro. Mycol Monten 2(1):33–60 Perić B (2011) Gljive i cvjetnice Crne Gore. Prilog estetici prirodno lijepog. Odjeljenje prirodnih nauka 34. Crnogorska Akademija Nauka i Ujetnosti, Podgorica, p 391 Perić B, Perić O (1995a) Gljivarske staze-ljeto. Mala mikološka edicija. Dizajn studio, Beograd, p 86 Perić B, Perić O (1995b) Prilog proučavanju gljiva Crne Gore. Agric For Poljoprivreda i šumarstvo 41(1–4):61–69 Perić B, Perić O (1996a) Gljivarske staze- jesen. Mala mikološka edicija. CID, Podgorica, p 104 Perić B, Perić O (1996b) Makromicete Crne Gore (8. prilog proučavanju makromiceta Crne Gore). Agric For Poljoprivreda i šumarstvo 42(1–4):69–84 Perić B, Perić O (1996c) Nacionalni park Biogratska gora. Prilog proučavanju mikodiverziteta. Balkan coference: ‘National parks and their role in biodiversity protection on Balkan peninsula’. Organized by: Macedonian Ecological Society and Republic of Macedonia National Parks Union, Ohrid, 25–28 June. Republic of Macedonia, pp 151–161 Perić B, Perić O (1997a) Diverzitet makromiceta u Crnoj Gori. Glasnik Odjeljenja prirodnih nauka, Crnogorka akademija nauka i umjetnosti 11:45–142 Perić B, Perić O (1997b) Makromicete šumskih kultura na području urbane zone Podgorice. Prirodne vrijednosti i zaštita Skadarskog jezera.Glasnik Odjeljenja prirodnih nauka, Crnogorka akademija nauka i umjetnosti 44:279–290 Perić B, Perić O (1997c) Petit étude de la Mycologie du Monténégro. Flora Mediterranea 7:11–20 Perić B, Perić O (1997d) Jestive gljive iz porodice Boletaceae u Crnoj Gori. Agric For Poljoprivreda i šumarstvo 43(1–2):57–71 Perić B, Perić O (1998a) Champignons rares et intéressants récoltés au Parc National ‘Durmitor’ au Monténégro. Schweiz Z Pilzkd 76(5):252–259 Perić B, Perić O (1998b) Gljivarske staze - proljeće. Mala mikološka edicija. Mikološko društvo Crne Gore, Podgorica, p 100 Perić B, Perić O (1998c) Gljivarske staze- zima. Mala mikološka edicija. Mikološko društvo Crne Gore, Podgorica, p 104 Perić B, Perić O (1998d) Les macromycètes du Monténégro (Cinq espèces nouvelles dans le région du Monténégro). Mycol Monten 1(1):37–47 Perić B, Perić O (1998e) Prilog proučavanju makromiceta NP ‘Durmitor’. Glasnik Odeljenja prirodnih nauka, Crnogorka Akademija Nauka i Umjetnosti 12:71–94 Perić B, Perić O (1999a) Makromicete Crne Gore (18. prilog proučavanju makromiceta Crne Gore). Agric For Poljoprivreda i šumarstvo 45(1–2):47–67 Perić B, Perić O (1999b) Prilog proučavanju makromiceta Crne Gore. Mycol Monten 2(1):83–98 Perić O, Perić B (2000a) Neke najčešće jestive i ljekovite samonikle gljive Crne Gore. Agric For Poljoprivreda i šumarstvo 46(3–4):97–119

148

G. Kasom and S. Hadžiablahović

Perić B, Perić O (2000b) Pet rijetkih i zanimljivih makromiceta (Prilog proučavanju gljiva Crne Gore). Glasnik Odeljenja prirodnih nauka, Crnogorka Akademija Nauka i Umjetnosti 13:259– 272 Perić B, Perić O (2002) Makromicete Crne Gore (Prilog proučavanju 33). Mycol Monten 5:131– 146 Perić B, Perić O (2003) Makromicete Crne Gore 36 prilog proučavanju. Mycol Monten 6:73–95 Perić B, Perić O (2004) Preliminarna Crvena lista makromiceta Crne Gore - 2 . Mycol Monten 7:7– 33 Perić B, Perić O (2005) Makromicete Crne Gore, 46 prilog proučavanju. Mycol Monten 8:85–102 Perić B, Perić O (2006) Contribution to the study of the genus Boletus s.l. in Montenegro (Contribution to the study of macromycetes of Montenegro 51 ). Mycol Monten 9:35–54 Perić B, Perić O (2008) Agaricus xanthodermus var. lepiotoides nouvelle espèce de la flora mycologique du Monténégro. Butelletí del L’Associació Micològica Font et Quer 6:56–61 Perić B, Raspopović D (2011) Dva taksona iz roda Verpa (Morchellaceae, Pezizales), nova za Crnu Goru: V. digitaliformis i V. bohemiva var. bohemica. Mycol Monten 14:69–84 Perić B, Perić O, Perić I (2000) Prilog proučavanju makromicete Crne Gore. Mycol Monten 3(1): 149–165 Perić B, Karadelev M, Tkalčec Z (2001) Ugroženost i zaštita gljiva u Crnoj Gori, Makedoniji i Hrvatskoj. Crnogorski mikološki centar, Podgorica, p 105 Přihoda A (1985) From the ecology of Pinus halepensis Miller. Folia Dendrol 12:303323 Reid DA (1975) Notes on some Jugoslav fungi. Acta Bot Croat 34:133–137 Rivas-Martínez S, Penas A, Díaz TE (2004) Biogeographic map of Europe. Scale 1:16.000.000. Cartographic Service, University of León, Spain. ISBN 84-9773-276-6 Šilc U, Mullaj A, Alegro A, Ibraliu A, Dajić-Stevanović Z, Luković M, Stešević D (2016) Sand dune vegetation along the eastern Adriatic coast. Phytocoenologia 46(4):339–355 Službeni list Crne Gore (2010) Pravilnik o bližem načinu i uslovima sakupljanja, korišćenja i prometa nezaštićenih divljih vrsta životinja, biljaka i gljiva koje se koriste u komercijalne svrhe. Br 62/2010 (Rule book on the detailed manner and conditions of collection, use and trade of unprotected wild species of animals, plants and fungi used for commercial purposes Official Gazette of Montenegro, number 62/2010) Stešević D, Küzmič F, Milanović Đ, Stanišić-Vujačić M, Šilc U (2020) Coastal sand dune vegetation of Velika plaža (Montenegro). Acta Bot Croat 79(1):43–54 Tortić M (1974) Mali prilog ljetnoj flori makromiceta Crne Gore. Zbornik radova sa simpozijuma o flori i vegetaciji jugoistočnih Dinarida, Andrijevica, VII 1973. Tokovi 9:207–214 Tortić M (1985) Distribution of Polyporales in Yugoslavia. II Ganoderma. Rasprostranjenost poliporoidnih gljiva u Jugoslaviji. II Ganoderma. Acta Bot Croat 44:59–71 Tortić M (1988) Macromycetes of Crna Gora (Montenegro). Glasnik Odeljenja prirodnih nauka, Crnogorska Akademija Nauka i Umjetnosti 6:113–138 Tortić M, Kotlaba F (1976) A handful of polypores, rare or not previously published from Jugoslavija. Acta Bot Croat 35:217–231 Wu F, Zhou LW, Yang ZL, Bau T, Li TH, Dai YC (2019) Resource diversity of Chinese macrofungi: edible, medicinal and poisonous species. Fungal Divers 98:1–76

Chapter 5

Health Promoting and Pharmacological Compounds from Mushrooms K. Madhusudhanan, N. K. Shahina, and Angel Mathew

Abstract The consumption of foods with immune-modulating activities is an efficient way to prevent or to mitigate the severity of various diseases and pathogenic attacks. Variety of biological compounds are necessary for the proper functioning immunity in human beings. Mushrooms contain various health-promoting biological compounds that are immune boosters and having the ability to control various diseases, and can prevent the multiplication viruses. This paper summarizes the effectiveness of mushroom as a functional food and recommends people to include these body shielding and immune-modulating food in their regular diet as a defensive measure in association with other health solutions to ensure protection against the fast spreading enveloped viruses. Keywords Mushrooms · Functional food · Pharmacological compounds · Immunomodulatory · Antioxidant · Antiviral activity

5.1

Introduction

Proper and balanced food is necessary for the best immunological outcomes, it supports the functions of immune cells allowing them to initiate effective responses against various pathogens. Various micronutrients and dietary components have specific roles in the development and maintenance of an effective immune system and reducing chronic inflammations. The beneficial microbes that live in the gut also have role in enhancing immunity, which also protect the human body from various diseases. When the body immune response is low, weak, or damaged, it opens up the possibility for various microbial infections or other diseases such as increase of cholesterol, diabetes, heart disease, or cancer (Arshad et al. 2020).

K. Madhusudhanan · N. K. Shahina (*) Department of Botany and Research Centre, St. Albert’s College (Autonomous), Ernakulam, Kerala, India A. Mathew Department of Statistics, Maharaja’s College, Ernakulam, Kerala, India © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_5

149

150

K. Madhusudhanan et al.

Mushrooms possess significant pharmacological effects and physiological properties and help in cure of diseases. They are also found to have substances that act as antifungal, anti-inflammatory, antitumor, antiviral, antibacterial, hepatoprotective, antidiabetic, hypolipedemic, antithrombotic, and hypotensive activities. The various bioactive substances present in mushrooms are contributing these properties (Thatoi and Singdevsachan 2014). Proteins, polysaccharides, and secondary metabolites such as terpenoids, polyphenols, sesquiterpenes, alkaloids, lactones, sterols, metal chelating agents, and nucleotide analogs extracted from mushrooms were studied for their medicinal properties. Glycoproteins, polysaccharides, and some amino acids are also attributed with therapeutic properties (Barros et al. 2008). Various myconanoparticles extracted from mushrooms are good potential candidates and can be used in pharmacological and food industries (Elkhateeb et al. 2019). This chapter overviewed the various health promoting and therapeutic compounds present in the mushrooms.

5.2

Traditional Usage of Mushrooms as Protective and Health Boosting Food

The perception of mushrooms and its related cultural use has been different among various cultures according to the traditional knowledge of each community and region. The early history regarding the use of mushrooms among different countries has been reviewed by workers (Boa 2004), and recorded the mushrooms usage as food and medicine in back to several 100 years BC in China. Ancient Egyptians believed that mushroom would bring immortality, while Romans served it on special occasions and treated it as “food of Gods.” According to Greeks eating mushrooms will provide strength. Mexican Indians were used mushrooms as hallucinogens and also they were aware about its therapeutic strength. Varied ethnomycological works from Asia, South America, Canada, and Africa also represent the diverse usage of wild mushrooms and their perception as health boosting, protective food (Wasser 2010; Osemwegie et al. 2014; Teke et al. 2018). A quantitative ethnomedicinal study among six tribal communities of Kerala documented the usage of edible mushrooms for eight categories of ailment including skin diseases, gynecological problems, cancer, and respiratory diseases (Shahina 2019). The nutritional, biochemical profiling and in vitro cytotoxicity studies against Dalton’s Lymphoma Ascites (DLA) of these ethnomedicinal mushrooms is reported by Shahina and Madhusudhanan (2018). Studies of Ajith and Janardhanan (2007) have proved antioxidant and anticancer properties of many South Indian traditional mushrooms. Mushroom are source of nutrients, bioactive, and flavor compounds as well as functionality as traditional medicine effectors.

5 Health Promoting and Pharmacological Compounds from Mushrooms

5.3 5.3.1

151

Nutritional and Bioactive Components of Mushrooms Proteins and Amino Acids

On dry weight basis, mushrooms normally contain 19–35% protein which was much higher than other vegetarian protein sources (Wang et al. 2014). Even though the palatability of mushroom determines the various amino acids present in it, essential amino acids are the reliable indicator of nutritive value and some amino acids show functional properties. Mushrooms usually contain all the essential amino acids in varied amounts, especially glutamic acid, aspartic acid, and arginine are found in higher amounts (Wani et al. 2010). The presence of amino acids such as leucine, isoleucine, tyrosine, and phenylalanine has found to be influenced the antiinflammatory activity of Pleurotus ostreatus (Jedinak et al. 2011). It is observed that the antioxidative effect of Agaricus bisporus is linked to the presence of histidine derivative (Asahi et al. 2016). Ergothioneine, an antioxidant isolated from Coprinus comatus, is an essential amino acid for humans was reduced the number of DNA lesions and inhibited inflammation caused by UV-B radiation (Chen et al. 2012). Various bio-active proteins and peptides from mushrooms (Ma et al. 2018) including lectins, fungal immunomodulatory proteins (FIP), ribosome inactivating proteins (RIP), antimicrobial proteins, ribonucleases, and laccases have shown to possess antiproliferative, antitumor, and immunomodulatory activities (Xu et al. 2011). Lectins are extensively investigated mushroom proteins which can bind specifically to cell surface carbohydrates, with ability in cell agglutination, antiproliferation, antitumor effect, and immune-modulation. Laccases purified from Pleurotus eryngii (DC.) Quel., and Tricholoma mongolicum S. Imai are displayed an inhibitory activity on HIV-1 reverse transcriptase (Wang and Ng 2006; Li et al. 2010a, b).

5.3.2

Carbohydrates and Fiber

Carbohydrates are found in high proportions in edible mushrooms accounts 50–60% on dry weight basis (Singdevsachan et al. 2013). It comprises of sugars, their derivatives, and oligosaccharides. Main components of mushroom carbohydrates are found to be non-starchy materials such as polysaccharides as well as glycoproteins. Polysaccharides from mushrooms showing a β-linkage are most interested bioactive compounds which boost the human immune system and are commonly termed biological response modifiers (BRM). As a result of the activation of the host’s immune system, these polysaccharides show therapeutic action such as antitumor, antiviral, and antimicrobial activity. The individual therapeutic potential of β glucan and its potential application is determined by the molecular weight, chemical composition, and number of branches of side chains as well as spatial configuration (Villares et al. 2012). The sugar alcohol, such as trehalose, is known to

152

K. Madhusudhanan et al.

synthesize stress-responsive factors in human cells when exposed to environmental stresses such as heat, cold, oxidation, desiccation, etc. by retaining cellular integrity. Glucan is produced by different mushrooms with various terms, such as lentinan (Lentinula edodes (Berk.) Pegler), ganoderan (Ganoderma lucidum (Curtis)P. Karst.), grifolan (Grifola frondosa (Dicks.) Gray), and schizophyllan (Schizophyllum commune Fr.). These polysaccharides show antitumor action mainly via activation of the immune response of the host organism instead of directly killing tumor cells. Mushroom polysaccharides exhibit various biological activities such as anti-tumor, neuro protective, anti-diabetic, hypolipidaemic, hypoglycaemic, and anti-alzheimer’s and antioxidant effects (Ma et al. 2018). The polysaccharides commonly functions by activating dendritic cells, monocytes, neutrophils, natural killer cells, cytotoxic macrophages, and cytokines. More than that mushroom polysaccharides have found to influence on gut microbiota as well as the gastrointestinal function. Crude fiber is a group of indigestible carbohydrates which can improve the function of the alimentary tract and also lower blood glucose, cholesterol levels and prevent type 2 diabetes as well as cardiovascular risk. Mushrooms constitute the dietary fibers in good amount which is sufficient for the daily requirement of a person (Ghosh 2016) and the hypocholesterolemic effects of many edible mushrooms are attributed due to the dietary fiber supply.

5.3.3

Lipids

Fatty acids play a major role in the functioning of the immune system and the maintenance of all hormonal functions. Lipid content of mushroom species is generally found low and in different species, it ranges between 1.75 and 15.5% in dried fruit bodies (Wani et al. 2010). Mushrooms contain essential fatty acids such as linoleic, oleic, and linolenic in their lipid profiles, usually as the major constituents and when comparing, unsaturated fatty acid levels are generally greater than those of saturated ones (Sande et al. 2019). Linoleic acid can reduce cardiovascular diseases, triglyceride levels, blood pressure, arthritis, whereas mushroom ergosterol shows antioxidant properties. Palmitic, linoleic, and α-linolenic acids present in A. bisporus are found to have a protective effect against hormone-dependent breast cancer by inhibiting the aromatase activity (Chen et al. 2006). Tocopherols are a cluster of volatile unsaturated hydrocarbons and act as natural antioxidants. Various sesquiterpenes, diterpenes, and triterpenes from mushrooms are associated with multiple health benefits, including antiviral, anticancer, anti-inflammatory, antimalarial, and anticholinesterase activities (Lee et al. 2011; Heleno et al. 2012).

5 Health Promoting and Pharmacological Compounds from Mushrooms

5.3.4

153

Minerals

Minerals are essential for various metabolic reactions such as transmission of nerve impulses, rigid bone formation, and regulation of water salt balance. Mushrooms show ability to assimilate various bio-elements from the soil. Many such elements are with antioxidant and anti-inflammatory properties. The levels of essential elements potassium, phosphorus, magnesium, manganese, zinc, iron, and calcium in mushroom species are reported to be high. More than that mushrooms are one of the richest, natural sources of selenium which are hardly found in many vegetables (Gençcelep et al. 2009). According to the National Heart Lung and Blood Institute (NHLI), healthy foods usually have low amount of sodium ( T. versicolor > Suillus granulatus with higher TPC in the aq extract, compared to the EtOH extract (Stojanova et al. 2020). Out of the total number of seven species from genus Ganoderma known in Europe, within the researches in the Republic of Macedonia, the following six species have been recorded: Ganoderma adspersum, G. applanatum, G. carnosum, G. lucidum, G. pfeifferi, and G. resinaceum (Karadelev et al. 2008). Antimicrobial potential of MeOH extracts of six wild species (Boletus lupinus, F. velutipes, Phellinus igniarius, Sarcodon imbricatus, Tricholoma aurantium, Xerocomus ichnusanus) was evaluated (Nikolovska Nedelkoska et al. 2013) exhibiting more potent

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

215

inhibitory effects on the growth of bacteria than on fungi. The highest antibacterial and antifungal activity was observed in MeOH extract of P. igniarius. Recent study reveals that knowledge of useful mushrooms differs between two ethnic groups where the Macedonian ethnic group has much higher ethnomycological expertise compared to Aromanian, which is expressed in their extensive cultural and practical use of fungi (Rexhepi and Reka 2020). It was demonstrated that Macedonians use different ways of preparations compared to Aromanians for the treatment of various health issues (Fig. 8.1). For Bosnia and Herzegovina data about MMs are scarce and can be found from the period before 2015 although regionally this area is the richest area in terms of forest diversity of mushroom species. AO activity of dry boletus mushroom, white and brown champignon, oyster mushroom, and shiitake from bosnian markets was determined in terms of TPC and total anthocyanin content pointing to the Oyster and Boletus mushroom (Alispahić et al. 2015). In a recent study (Salihović et al. 2020) antimicrobial activity of wild mushrooms, traditionally used in the diet, from different areas of Bosnia proved that activity mostly depends on the locality on which mushrooms grow. The broader spectrum of antibacterial activity was observed for C. cibarius against S. aureus (18.11  0.20 mm) and B. subtilis, while B. edulis exhibited higher effect against MRSA (20.03  0.08 mm). The wild mushrooms: L. piperatus, L. deliciosus, Amanita caesarea, Lycoperdon pyriforme, Macrolepiota procera, and cultivated mushrooms: Agaricus bisporus, Boletus aestivalis, C. cibarius, P. ostreatus, and A. bisporus var. avellaneus were investigated for the evaluation of AAs composition and AO activity in order to promote the consumption of food rich in BAM, especially the species P. ostreatus where the highest content of Ala, Gly, Phe, Lys, Val, and Leu was found (Salihović et al. 2019). In Croatia biodiversity of mushroom species is the best investigated field in mycological research which led to the establishment of the Red List of Croatian Fungi where 314 species were defined as strictly protected in 2006. The Red Book of Croatian Fungi based on that list was published by Tkalčec et al. (2008). On the contrary, bioactive properties of medicinal mushrooms are less studied and have been presented just in the last decade in a few papers (Zeković et al. 2010; PiljacŽegarac et al. 2011). Among the three tested wild species, A. auricula-judae, Sarcoscypha austriaca, and Strobilurus esculentus water extract of S. esculentus possessed the highest concentration of TP, and expressed the highest reducing power, and the best RSC (DPPH) (Piljac-Žegarac et al. 2011). Two species A. mellea and Lycoperdon saccatum originated from the mountain Nature Park Učka (Istria in Croatia) expressed reductive capabilities and thus were capable of reducing iron (III) (Zeković et al. 2010). A few papers presented the cytotoxic, antitumor, immunomodulatory properties of differently prepared extracts and the mixture of several species in a preparation of AGARIKON tested on colorectal tumor (HCT-116, SW620) cell lines in vitro and colorectal mice model in vivo. This was based on M1 macrophage polarization enhancement, inhibition of M2, and tumor-associated macrophage (TAM) polarization, effects on T helper cell Th1/Th2/ Th17 cytokine profiles, direct inhibition of CT26.WT tumor growth, inhibition of

216

M. Karaman et al.

vascular endothelial growth factors (VEGF), and metalloproteinases 2 and 9 (MMP-2 and MMP-9) modulation (Jakopović et al. 2020). Determination of cytotoxic effects on human lung cancer cells, lung adenocarcinoma, colon cancer, and brain astrocytoma cancer cells revealed that polyphenolic AO and soluble PSH are very important, and the use of these mushrooms is beneficial in maintaining good health. Blended mushroom extracts exhibit significantly stronger cytotoxic effects on human tumor cell lines than commercial mushroom products derived from single mushroom species or single mushroom compounds (Durgo et al. 2013). In Montenegro the diversity of mushrooms and other fungal species is very well investigated, especially after the establishment of the journal Mycologia Montenegrina in 1997, which covers the diversity of fungal species throughout the region. Peric and Peric (1997) have displayed the paper which encompasses edible mushrooms from the Boletaceae family up to date of publishing in Montenegro and summarizes nutritional values and their distribution with protection measures proposed for the mycorrhizal mushrooms since they have been found to be most endangered. Data on medicinal properties of local species is scarce except for few papers from foreign researchers for Ganoderma AO and antimicrobial agents from fermentation broth and ability to produce PSH (Vukojević et al. 2006; Ćilerdžić et al. 2016). In a recent study (Naimushina et al. 2020) Boletus species were analyzed with respect to the influence of geographical position (Montenegro and Serbia) on demonstrated activities showing that the growth of ceps in a certain climatic zone can affect the value of antiradical activity, but practically do not affect the manifestation of antibacterial properties by B. edulis. In the future, scientists should take more attention on controlling mushroom cultivation processes in bio fermenters to obtain optimal environmental factors for significantly enhanced production of BAM (Gründemann et al. 2019). For that purpose, fed-batch cultivation or multi-stage cultivation strategies could be used to achieve a highly productive process on a large scale. Fundamental factors affecting the synthesis of AO and lectins in submerged and solid-state fermentation of lignocellulose are still missing.

8.3

Taxonomy of Genera Ganoderma, Coprinus, Pleurotus, Schizophyllum, Trametes, and Hericium

The genus Ganoderma (gr. ganos—brightness, derma—skin) was named by Petter Adolf Karsten in 1881 (Wang et al. 2020). Ganoderma is widely distributed in tropical and subtropical regions of Africa, America, Asia, and Oceania, and it is also distributed in Europe (Wang et al. 2020). The main Ganoderma species are G. lucidum, G. sinensis, G. applanatum, G. tsugae, G. atrum, and G. formosanum. G. lucidum and G. sinensis which are recorded in ChP 2015 (Pharmacopeia of the People’s Republic of China) while G. lucidum is recorded in USP40-NF35 (U.S. Pharmacopeia/National Formulary)

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

217

(Cao et al. 2018). The species G. carnosum, G. lucidum, and G. resinaceum have annual FB with lateral stipe, while G. applanatum, G. adspersum, G. pfeifferi, and G. abietinus have perennial FB without stipe. Ganoderma species are among the most important destructors (causing white wood rot) in the forests of Serbia and Montenegro. Of the total number of seven species of this genus known in Europe, during the research in the Republic of Macedonia, six Ganoderma species have been recorded (Karadelev et al. 2008), while seven species were found in the forests of Serbia and Montenegro (Karadžić et al. 2014). Laccate species (mushrooms with shining surface with lacquered appearance) of Ganoderma, i.e., G. lucidum complex, have been used as medicinal fungi in traditional Chinese medicine for over two millennia and gained much interest in western medicine in the last few decades. However, the taxonomy of the G. lucidum species complex is problematic and species concepts in this group lack consensus in morphology. For example, the evidence has emerged that one of the most widely used medicinal species G. lucidum is, in fact, a different species and was recently described as G. lingzhi (Cao et al. 2012). In the study of Zhou et al. (2015) 32 collections belonging to the G. lucidum complex from Asia, Europe, and North America were examined in terms of their morphology and phylogeny based on four molecular markers (ITS, tef1a, rpb1, and rpb2) (Fig. 8.2). Thirteen well-delineated species were recognized—G. boninense, G. curtisii, G. flexipes, G. lingzhi, G. lucidum, G. multipileum, G. oregonense,

Fig. 8.2 Overview of the mostly used molecular markers in phylogenetic analyses of G. lucidum complex, P. ostreatus complex, C. comatus, S. commune, T. versicolor, and H. erinaceus

218

M. Karaman et al.

G. resinaceum, G. sessile, G. sichuanense, G. tropicum, G. tsugae, and G. zonatum. Although they are all morphologically very similar, phylogenetic analysis showed that they all form at least three lineages which are not in accordance with their geographic distribution. Previously, Chinese species G. lingzhi, G. multipileum, and G. sichuanense had all been misidentified as G. lucidum. Also, G. tsugae has been treated as synonym of G. lucidum, but molecular phylogeny supports G. tsugae as separate species. Beside this, G. tsugae grows exclusively on conifers, while G. lucidum inhabits mostly angiosperm trees. In the same study, a dichotomous key to the 13 phylogenetic species is provided together with informative morphological comparison of the species of G. lucidum complex. Since there are a lot of morphological ambiguities in the G. ludicum species complex, it could be expected that identification of these species using internal transcribed spacer (ITS) as DNA barcode (Schoch et al. 2012) would help resolve these issues. But, identification of Ganoderma species only by comparison of ITS sequences through BLAST is often not helpful and can be misleading. Fryssouli et al. (2020) addressed this problem in their work by performing a thorough metadata analysis of a global dataset of Ganoderma ITS sequences. Also, they evaluated the accuracy of specimen identifications to species and determined partially assessed or erroneously labeled sequences in databases. The results of their work showed that even the recently uploaded sequences are associated with an exceptionally high number of misidentifications or errors. There are a lot of reasons for such unreliability of Ganoderma sequences—very high variability/plasticity in morphological characters, incorrect use of terms describing anatomical features, using of ambiguous synonyms or misapplied names, the non-uniformity of taxonomic criteria adopted by researchers, and the growing number of non-experts working on Ganoderma material. Phylogenetic analysis using more than one molecular marker should be used to identify new material. There are several species which are often misidentified as G. lucidum. Hennicke et al. (2016) showed that chemotaxonomy can be helpful in distinguishing G. lucidum with. G. lingzhi which is one of the most frequently used MMs in China and East Asia. Analysis of commercially available strains using a combined approach including morphological characteristics of the basidiocarps, molecular phylogenetic analyses, and triterpenic acid profiling determined that G. lingzhi strain contained a higher diversity and higher amounts of GAs (GA) than the G. lucidum strain. These acids are responsible for the strong bitter taste that was evident only for the ethanol extract of G. lingzhi strain. This opens the question if other authors who published chemical analyses of “G. lucidum” strains which showed high diversity of TRIs were actually dealing with G. lingzhi. GA profiling of different Ganoderma species is needed to resolve whether GA profiles can be used as chemotaxonomic traits and help in their identification. Coprinus comatus (O.F. Müll.) Pers. 1797 also known as chicken drumstick mushroom, the shaggy ink cap, lawyer’s wig or shaggy mane is a fungal species with cosmopolitan distribution. It is edible, but only while young due to the certain processes that happen with maturity and can be cultivated (Li et al. 2010).

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

219

Genus Coprinus contains morphologically divergent species with global distribution. All species are saprotrophic and inhabit a great number of different substrates (Hopple and Vilgalys 1999). To date there have been several phylogenetic studies of this genus (Hopple and Vilgalys 1999; Moncalvo et al. 2000) and all results showed that Coprinus is polyphyletic with type C. comatus and its close ally C. sterquilinus separated from all other “Coprini.” Segregation of the species of Genus Coprinus into Coprinopsis, Parasola, Coprinellus, and some species not placed in any of the former genera, was generally accepted among taxonomists but infrageneric relationships within these groups are still to be elucidated (Nagy et al. 2012, 2013). Pleurotus ostreatus (Jacq.) P. Kumm. 1871, the oyster mushroom, is a common edible mushroom with the bitter sweet aroma of benzaldehyde. The genus Pleurotus comprises of 40 different species that are commonly referred to as “oyster mushrooms” (Jayakumar et al. 2011) while there are two major ecotypes: brown forms from North America and blue/brown forms from Europe (Ogidi et al. 2020). P. ostreatus occurs in Europe and it is widely distributed throughout most of Asia, and is present in some parts of North America. It contains at least five species complexes (Bao et al. 2004), with P. ostreatus species complex being economically the most important group. This group accommodates most of the species from the sect. Pleurotus as defined by Singer (1986) which all possess a monomitic hyphal system (P. ostreatus, P. pulmonarius, P. placentodes and their allies) (Li et al. 2020). Exact definition of the species within the Pleurotus genus has long been problematic because of phenotypic plasticity, especially in species complexes. Also, morphology of the FB of Pleurotus species also shows vast variability under different cultivation conditions (Shnyreva and Shnyreva 2015). Up to day there were several phylogenetic and mating studies (Bao et al. 2004, 2005; Avin et al. 2014; Shnyreva and Shnyreva 2015; Li et al. 2020) performed in order to determine species delimitations within the P. ostreatus species complex. Study of Li et al. (2020) was the most comprehensive presenting robust phylogeny of the P. ostreatus species complex based on 40 nuclear single-copy orthologous genes and extensive sampling of species from East Asia, Europe, North and South America, and Africa. In this study P. ostreatus species complex was strongly supported as monophyletic, and 20 phylogenetic species could be distinguished within this clade with seven putatively new species. Also, it was confirmed that the North American population of P. pulmonarius differs from the European population in morphological traits and mating behavior. Besides that, four phylogenetic species were recognized (specimens from East Asia, Europe, North America, and Africa), but they were poorly differentiated morphologically. These results may suggest that these taxa might be relatively young so morphological differences were not yet accumulated. S. commune is one of the most common fungal species and can be found on all continents, except for Antarctica. It usually grows as a pathogen of many different species of trees causing a white rot, but also, it has been reported to be a pathogen of immunocompromised humans (Alam et al. 2010; Ohm et al. 2010). S. commune is very well recognized and identification of this species can be problematic only in clinical samples (Siqueira et al. 2016). The genus Schizophyllum contains nearly

220

M. Karaman et al.

20 species (http://www.mycobank.org), and to our knowledge there are no comprehensive studies concerning phylogenetic relationships among them. Trametes versicolor (L.) Lloyd 1921 commonly called “Yun Zhi” in China or turkey tail is one of the most well-known medicinal mushrooms in the world. T. versicolor is a saprotroph; grows usually on dead, diseased, and damaged deciduous (Oak, Prunus) trees, occasionally on conifers (Fir and Pine trees) causing white rot. It is a well distributed species and inhabits a significant part of the world’s forests of Europe, America, and Asia (China) (Hobbs 2005). Species of the genus Trametes are found frequently on various genera of hardwood with 18 species reported from North America, nine from Europe, and ca. 20 species in the Neotropics (Justo and Hibbett 2011). Although it is one of the most recognizable genera of polyporoid fungi, taxonomy on the species level is still uncertain. There were several studies dealing with molecular phylogeny of Trametes and related genera (Tomšovský et al. 2006; Welti et al. 2012) but studies of Justo and Hibbett (2011) and Carlson et al. (2017) were the most comprehensive. T. versicolor, the most investigated medicinal species of this genus, belongs to the T. versicolor species complex which includes the following species: T. versicolor sensu stricto, T. ochracea, T. pubescens, and T. ectypa (Carlson et al. 2017). Morphological delimitation of these taxa is difficult given the variability of their morphological characters. In the study of Justo and Hibbett (2011) it was determined that this group form a strongly supported clade in the phylogenetic tree based on ITS marker, but the internal topology of the clade was poorly resolved. This may be due to the very low variability (1–2%) between ITS sequences within this group which was determined by Carlson et al. (2017). In the same study three protein coding genes (RPB1, RPB2, and TEF1) were included in phylogenetic analysis and it was concluded that individual or combined analyses of these genes gives better separation of the taxa in this species complex which all appeared as strongly supported lineages. Hericium erinaceus (Bull.) Pers. 1797, also known as Yamabushi take (Japanese), Bear’s Head, Hog’s Head Fungus, Old Man’s Beard, Pom Pom, and Bearded Tooth, is one of the mostly used edible species around the world, primarily in Asian countries (Thongbai et al. 2015). Hericium is a white-rot basidiomycota genus characterized by a dentate and coralloid FB. All currently accepted species of Hericium are documented from temperate North and South America, Asia, Europe, Australia, and Africa (Jumbam et al. 2019). In the genus Hericium, species are distinguished by macro morphological traits of their basidiomes, while microscopic features are very similar. As a result, species barriers are not always clear. To address this problem, Hallenberg et al. (2013) performed a study to clarify species delimitations based on a phylogenetic analysis of ITS sequences, critical analysis of morphological characters, geographical distribution, and substrate preferences. They found that H. coralloides clade is well supported and seems to be composed of at least three species. H. abietis clade is another well-supported clade. H. alpestre–H. americanum–H. erinaceus complex is more difficult to distinguish because of the great variation exposed by different developmental stages and the limited resolution in ITS phylogeny. For the species H. americanum and H. alpestre differences in

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

221

geographical distribution and substrate preferences seem to be distinct enough to allow their recognition as two separate species. In the study of Singh and Das (2019) results of phylogenetic analysis showed similar branching as in Hallenberg et al. (2013) even though the ITS sequences from more Hericium species were used. H. alpestre–H. americanum–H. erinaceus clade was not fully resolved, as shown in the study of Hallenberg et al. (2013). Although the taxonomy of the present Hericium species is not fully resolved new species have been described recently— H. rajendrae from India (Singh and Das 2019) and H. bembedjaense collected from Cameroon (Jumbam et al. 2019). It is evident that comprehensive analysis including more molecular markers is needed to help fully resolve taxonomic issues in these genera.

8.4 8.4.1

Chemical Characterization and Biological Activity (Antioxidative, Antidiabetic, Ache Inhibitory) Ganoderma lucidum

Fresh G. lucidum contains about 90% moisture and 8–10% ash, which contains protein (10–40%), fat (28%), carbohydrate (3–28%), fiber (3–32%), and minerals (Rašeta et al. 2016; Cör et al. 2018). Modern studies have revealed that G. lucidum contains a variety of bioactive ingredients (Fig. 8.3), including TRI, PSH, sterols, FAs, nucleosides, alkaloids, and small amounts AA and proteins (Paterson 2006; Baby et al. 2015; Obodai et al. 2017; Taofiq et al. 2017; Liang et al. 2019), and possess comprehensive biological activities, such as antitumor, antimicrobial, AO, neuroprotective, antidiabetic, and anti-tyrosinase among other effects (Karaman et al. 2005, 2010; Paterson 2006; Kozarski et al. 2012, 2019; Villares et al. 2012; Zhou et al. 2012; Stojković et al. 2014; Rašeta et al. 2016, 2020a; Obodai et al. 2017; Veljović et al. 2017; Cör et al. 2018). PSH as the main primary metabolites from mushrooms have attracted a great deal of attention due to the many health benefits they have demonstrated, such as AO (Kozarski et al. 2012, 2019; Villares et al. 2012), immunomodulation, anticancer activity (Veljović et al. 2017), antimicrobial, antidiabetic, and cardioprotective effects among others (Vetter 2019). Actually, the effects of PSH are closely related to their chemical characteristics, such as monosaccharide composition, molecular mass, configuration, and position of the glycosidic linkages (Xie et al. 2012). Over 200 different PSH have been examined from spores, FB, and M (Boh et al. 2007; Villares et al. 2012; Xie et al. 2012; Obodai et al. 2017; Veljović et al. 2017; Ahmad 2018; Kozarski et al. 2019). Beside soluble PSH, G. lucidum also contains a matrix of the chitin PSH, which is largely indigestible and it is partly responsible for the physical hardness of the mushroom (Bishop et al. 2015).

Fig. 8.3 Overview of the selected Ganoderma species based on the BAM related to their medicinal properties

222 M. Karaman et al.

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

223

Some bioactive proteins have been isolated from G. lucidum spores and FB (Ahmad 2018), including 18 AAs, and the most abundant AA was leucine, which showed strong hypoglycemic and AO activities (Yang et al. 2019b) (Fig. 8.3). Beside proteins, several G. lucidum enzymes have also been isolated (Ahmad 2018) (Fig. 8.3). Furthermore, it also contains nucleosides as well as nucleotides (Ahmad 2018; Yang et al. 2019a, b), various vitamins (Yang et al. 2019a, b) (Fig. 8.3) and they play an important role in normal physiological body functions (Rašeta et al. 2016). As secondary metabolites, more than 200 compounds belonged to G. lucidum TRIs, GLTs which were regarded as the main medicinal components with LMW and various health benefits: antioxidative (Stojković et al. 2014), neuroprotective, and antiproliferative activities on different cancer cell lines, with direct inhibition of cell proliferation through cancer-specific cell cycle arrest and apoptosis (Bishop et al. 2015; Ahmad 2018; Yang et al. 2019b) (Fig. 8.3). Based on Boh et al. (2000), the highest concentration of TRIs is present in the tubes (pores), then the dark layers of the pileus, while the older segments of the FB have the lowest content of terpenoid acids. There has been significant progress in TRIs research in the recent decades. The current preclinical or clinical studies of GLTs indicate that these compounds have now become recognized as alternative adjuvants for the treatment of leukemia, carcinomas, hepatitis, and diabetes (Liang et al. 2019). Based on the investigation of Liang et al. (2019), seven GAs are currently at different stages of clinical trials (GAs A, C2, D, F, DM, X, and Y). Several sterols, FAs and their esters, and some volatile compounds with significant biological functions were also separated or identified from G. lucidum (Fig. 8.3) (Stojković et al. 2014; Taofiq et al. 2017; Obodai et al. 2017). The PCs composition of G. lucidum has also been widely studied and phenolic acids represent the most prominent compounds from this class, followed by flavonoids (Karaman et al. 2010; Rašeta et al. 2016, 2020a; Obodai et al. 2017; Taofiq et al. 2017) (Fig. 8.3). These molecules have been identified as contributors to its AO, antimicrobial, anti-tyrosinase, and anti-inflammatory properties (Stojković et al. 2014; Rašeta et al. 2016, 2020a). Beside PCs, from G. lucidum some organic acids have been identified (Stojković et al. 2014; Obodai et al. 2017). A major barrier to the application of natural products as pharmaceuticals and cosmeceuticals is their complexity (Kozarski et al. 2019). However, this could be an advantage for application of these products. For example, certain components of natural products can reduce the cytotoxicity of the whole product, and interactions between different BAM can be responsible for their effects. Based on the available research data, G. lucidum PSH extracts could represent promising alternative raw ingredients for the use in cosmeceutical products (Kozarski et al. 2019). The use of G. lucidum bioactive extracts in the design of cosmeceutical formulations for topical application is supported by reports on their power as tyrosinase inhibitors, inflammatory mediator suppressors, and as photoprotective agents, which makes them multifunctional ingredients that can be used to control hyperpigmentation, suppressing skin inflammatory diseases, and preventing skin photo-aging (Taofiq et al. 2017).

224

8.4.2

M. Karaman et al.

Ganoderma applanatum

To date, various BAM (Fig. 8.2) have been isolated and identified from G. applanatum, such as: steroids, FAs, PCs, saponins, cardiac glycosides, and highly oxidized lanostane-type triterpenoids (Paterson 2006; Manasseh et al. 2012) (Fig. 8.2). The chemical composition of G. applanatum species varies within the same species due to different growth conditions in the habitats (Jeong et al. 2008). Recently, G. applanatum is well explored and express a wide spectrum of biological activities including: AO (Karaman et al. 2010; Kozarski et al. 2012; Rašeta et al. 2016, 2020a) related to their PCs as the major AO (Karaman et al. 2010; Rašeta et al. 2016, 2020a), antibacterial (Karaman et al. 2010), Karaman et al. (2012a) antiproliferative (Sun et al. 2015; Rašeta et al. 2016), and antidiabetic effect through the inhibition of aldose reductase (Jung et al. 2005) among others. AO, antiproliferative, antidiabetic, anti-tyrosinase, and neuroprotective biopotentials of G. applanatum are under high impact of PCs (Fig. 8.3) (Rašeta et al. 2016, 2020a). Some authors suggest that also PSH and PSH-protein complexes (Fig. 8.2) acts as important AO (Jeong et al. 2008; Kozarski et al. 2012, 2019; Sun et al. 2015; Deveci et al. 2019) and may also present important neuroprotective biomolecules (Deveci et al. 2019). Proteins from G. applanatum are mostly present as protein-bound PSH (Kozarski et al. 2012), while publication of free proteins are rare, with the exception of FIP-gap1 and gap-2 with their potential application in cosmetic preparations (Li et al. 2019a). G. applanatum contains a series of secondary metabolites (Fig. 8.3) (Paterson 2006; Manasseh et al. 2012; Karaman et al. (2012c); Baby et al. 2015; Sun et al. 2015). Luo and co-workers worked on the identification of meroterpenoids and alkaloids from this mushroom (Fig. 8.2) (Luo et al. 2015, 2016), while Hakkim et al. (2016) identified some other secondary metabolites (Fig. 8.3) with significant antitumor potential.

8.4.3

Ganoderma pfeifferi

In contrast to G. lucidum and G. applanatum, from which a number of biologically and pharmacologically active triterpenes and PSH have been isolated, G. pfeifferi is one of the phytochemically less examined species from the family Ganodermataceae. In screening investigations with a broad spectrum of different Ganoderma species, G. pfeifferi attracted attention with its strong antimicrobial, AO, antidiabetic, and anti-tyrosinase activities (Mothana et al. 2000; Niedermeyer et al. 2005; Lindequist et al. 2015; Al-Fatimi et al. 2016; Kuo et al. 2016; Rašeta et al. 2020a, b). All below determined compounds (Fig. 8.3) were isolated from the M and FB (Lindequist et al. 2015). One of the first reports about chemical composition of G. pfeifferi is based on determination of meroterpenoids, ganomycin A and B with antimicrobial activities

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

225

(Mothana et al. 2000). Few years later, the same scientists worked on isolation of antiviral TRIs from G. pfeifferi (Mothana et al. 2003). Niedermeyer et al. (2005, 2013) isolated TRIs and sterols from FB of G. pfeifferi (Fig. 8.2). To 2016, from G. pfeifferi were determined sterols, including ergosterol (Niedermeyer et al. 2005, 2013; Kuo et al. 2016), sesquiterpenoids (Mothana et al. 2000; Niedermeyer et al. 2013), TRIs (Mothana et al. 2003; Niedermeyer et al. 2005; Kuo et al. 2016), some volatile compounds (Al-Fatimi et al. 2016), and other secondary metabolites (Al-Fatimi 2001) (Fig. 8.3). Most TRIs exert antimicrobial activity, especially against influenza A virus and herpes simplex virus type I (HSV), while volatile compounds have significant antimicrobial and AO activities. Yalcin et al. (2020) and Rašeta et al. (2020a, b) worked on the determination of the PCs as the most important AO.

8.4.4

Ganoderma resinaceum

G. resinaceum has long been used for enhancing health and treating liver diseases (Peng et al. 2013; Rašeta et al. 2020b), hyperglycemia, and immune-regulation in Traditional Chinese Medicine (Chen et al. 2017a, 2018a, b; Shi et al. 2020) but also exhibited antimicrobial, antiproliferative, anti-obesity, AO, anti-AChE, antihypertensive, anti-tyrosinase, α-amylase, and α-glucosidase activity (Zengin et al. 2015; Chen et al. 2018a, b; Huang et al. 2020b; Kozarski et al. 2020; Rašeta et al. 2020a, b). PSH, FAs, lanostane-type TRIs, nor TRIs, meroterpenoids, steroids, and PCs had been reported from the FB and cultured M of G. resinaceum (Fig. 8.3) (Paterson 2006; Peng et al. 2013; Zengin et al. 2015; Chen et al. 2017a, b, 2018a; Yang et al. 2018; Shi et al. 2019; Rašeta et al. 2020a, b). PSH from G. resinaceum express significant antiproliferative and AO activity (Kozarski et al. 2020). Ganoderma TRIs (GTs) are one of the major BAM in Ganoderma species, and are deemed to be the main functional constituents in G. resinaceum (Peng et al. 2013; Li et al. 2016; Chen et al. 2018a, b; Yang et al. 2019a; Huang et al. 2020a) (Fig. 8.2). Resinacein S, as one of the major lanostane-type TRIs from G. resinaceum, with increased intake provides a potential method for enhancing the activity of brown and beige adipocyte, thus providing a therapeutic strategy for preventing and treating obesity and related diseases (Huang et al. 2020b), while some others showed antidiabetic and hepatoprotective effects (Chen et al. 2018a; Shi et al. 2020). Although substantial TRIs have been reported from Ganoderma, norTRIs are rare deriving from lanostane-type TRIs, and possess C-24 or C-27 skeleton in Ganoderma (Chen et al. 2017a), while some of them contain an unusual fourmembered ring skeleton produced by a bond across C-1 to C-11 (Wang et al. 2010) (Fig. 8.3). There are over 50 meroterpenoids that have been isolated from Ganoderma since the discovery of ganomycins A and B (Fig. 8.3) (Mothana et al. 2000; Chen et al. 2017b; Yang et al. 2018). In the G. resinaceum polar extracts were

226

M. Karaman et al.

determined the PCs including flavonoids (Fig. 8.3), and they have attracted considerable interest due to their biological properties including AO, anti-AChE, antidiabetic among others (Zengin et al. 2015; Rašeta et al. 2020a, b).

8.4.5

Coprinus comatus

This fungus contains high percent of minerals (Stilinović et al. 2014, 2020), vitamins (Li et al. 2010; Stojković et al. 2013), up to 25% of proteins in the early growth stages but also PSH, triglycerides, essential AAs, and dietary fibers (Stilinović et al. 2020) and could be a valuable source of PCs (Fig. 8.3). The first isolated compound from C. comatus was ergothioneine (ESH), a thiol compound with AO properties (Li et al. 2010) while the selenium-PSH isolated from M caused a significant decrease in the level of malondialdehyde (MDA), a significant increase in the activities of enzymatic AO and levels of non-enzymatic AO in liver and kidney of diabetic mice related to their AO and antidiabetic potential (Yu et al. 2009). Additionally, fat content of C. comatus is low, consisting mainly of polyunsaturated and omega-3 FAs (Stilinović et al. 2020) among others (Yilmaz et al. 2006). In fermentation broth, among other metabolites, comatin was isolated from C. comatus, which activity was associated with the hypoglycemic effect on both normal and alloxan-induced-diabetic rats (Ding et al. 2010). Recently, in Serbia, it has been thoroughly investigated for its wide range of biological activities (Stojković et al. 2013; Stilinović et al. 2014, 2020; Pejin et al. 2017; Tešanović et al. 2017; Karaman et al. 2018a, 2019a, b). Related to this, various bioactive properties of C. comatus have been reported in recent years beside abovementioned AO, antidiabetic, antimicrobial, hypoglycemic, hepatoprotective, and neuroprotective (Ding et al. 2010; Li et al. 2010; Stojković et al. 2013; Stilinović et al. 2014, 2020; Pejin et al. 2017; Tešanović et al. 2017; Karaman et al. 2018a, b, 2019a, b). C. comatus also expresses antitumor and immunomodulatory activities which are primarily related to their PSH content (Jiang et al. 2013). Many studies have shown that natural AO in mushrooms are closely related to their bioactivities such as the reduction of chronic diseases and inhibition of pathogenic bacteria growth, which are often associated with the termination of free radical propagation in biological systems (Li et al. 2010). Typical PCs with AO and neuroprotective activity have been characterized as phenolic acids and flavonoids whose content was determined in the extracts of this mushroom species (Stilinović et al. 2014, 2020; Tešanović et al. 2017).

8.4.6

Pleurotus ostreatus

The biodiversity of mushrooms Pleurotus spp. is impressive due to its complexity and diversity related to their HMW BAM such as PSH, peptides, glycoproteins, and

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

227

also low MW compounds (alkaloids, TRIs, FA esters, polyphenols, flavonoids, and betalains) (Fig. 8.3) (Golak-Siwulska et al. 2018). This is probably one of the best known edible mushroom genuses in the world due to P. ostreatus gastronomic, nutritional importance (Gomes Correa et al. 2016; Acosta-Urdapilleta et al. 2020) and also wide spectrum of biological activities, such as AO, hepatoprotective, antidiabetic, immunomodulatory, and antitumor activities among others (Jayakumar et al. 2011; Gomes Correa et al. 2016; Golak-Siwulska et al. 2018; AcostaUrdapilleta et al. 2020; Venturella et al. 2021). P. ostreatus possess higher nutritional value, mainly due to the high protein (30.50%) and carbohydrate content (51.90%), whereas fat (1.50%), minerals, and vitamins are determined in lower amounts (Gomes Correa et al. 2016; AcostaUrdapilleta et al. 2020; Gallotti et al. 2020). Mushrooms represent highly valued and delicious food, due to low calories, low fat composition, and high essential FA levels (Fig. 8.3) (Ergönül et al. 2013). The major biological role of α-tocopherol is to protect PUFAs and other components of mushroom cell wall membranes from oxidation caused by free radicals (Gallotti et al. 2020). P. ostreatus is an interesting source of PSH. Pleuran is the best known β-D-glucan isolated from FB of P. ostreatus, which promoted beside antibacterial also AO activity (Jayakumar et al. 2011; Villares et al. 2012; Golak-Siwulska et al. 2018; Ogidi et al. 2020). A group of PSH which has not been well investigated is α-Dglucans, they can be found in the deepest layer of the mushroom cell wall and also exhibit AO potential (Golak-Siwulska et al. 2018). Proteins, peptides, and lectins are other HMW substances acquired from P. ostreatus which exhibit important medicinal properties (Golak-Siwulska et al. 2018; Landi et al. 2020). Oyster mushroom proteins contain all nine essential AAs required by humans (Gomes Correa et al. 2016) with higher concentrations of methionine and aspartic acid than other edible mushrooms (Jayakumar et al. 2011). P. ostreatus and its ligninolytic enzymes also have important application values in the field of treatment of environmental pollutants and bioremediation (Liu et al. 2021). Focusing on mushrooms’ secondary metabolites, ESH and lovastatin are important metabolites of mushroom growth, and ESH has beneficial effects against autoimmune disorders (rheumatoid arthritis and Crohn’s disease), that are strongly related to ESH’s AO properties (Tsiantas et al. 2021). Several comparative studies report that P. ostreatus contain higher concentrations of ESH compared to other edible mushrooms, which is possibly associated with differences or changes in the biosynthetic pathways, which are responsible for the formation of ESH, among mushroom species, while lovastatin is present in lower concentration compared to ESH (Tsiantas et al. 2021) and similar to ESH exhibit AO properties (GolakSiwulska et al. 2018). PCs profile was determined according to Gąsecka et al. (2016a), and beside lectins and PSH, PCs are the most important AO compounds from this mushroom species (Jayakumar et al. 2011; Gąsecka et al. 2016a, b; Gomes Correa et al. 2016; Golak-Siwulska et al. 2018). The use of oyster mushrooms in cosmetology and dermatology is due to the presence of AO, anti-aging, anti-wrinkle, whitening, and moisturizing components from its extracts (Golak-Siwulska et al. 2018). Application of a pleuran-based cream

228

M. Karaman et al.

as an adjunctive therapeutic to patients with atopic dermatitis has produced good results (Taofiq et al. 2016; Wu et al. 2016).

8.4.7

Schizophyllum commune

Recently, various functional ingredients have been found in S. commune, such as PSH, alkaloids, PCs, terpenoids, ergosterol, iminolactones, vitamins, etc. (Chen et al. 2020b) and express a wide spectra of biological activities, such as AO, antiinflammatory, antimicrobial, anti-AChE, and anti-tyrosinase among others (Fig. 8.4) (Debnath et al. 2017; Razak et al. 2018; Mišković et al. 2021). The nutritional components of S. commune were crude fat (9.0%), fiber (30.0%), ash (3.5%), protein (15.55%), lipid (0.4%), and total carbohydrates (42.0%) (Debnath et al. 2017). Du et al. (2016) concluded that LMW compounds (chitosans) exhibited stronger biological activities compared to HMW compounds. Related to this, the application of PSH from S. commune as pharmaceuticals and cosmeceuticals have been limited for its HMW and viscosity and scientists are looking for LMW PSH. One of the useful methods for preparation of LMW PSH could be ultrasonication, and it was proved to be an effective and favorable tool to improve the bioactivities of these PSH (Zhong et al. 2015; Du et al. 2016). S. commune produces exo-PSH (MW of 2900 kDa) (Du et al. 2016, 2017), whereas the total carbohydrate content was determined to be 89.0%, the protein content was 2.2%, thus this exo-PSH could be proved to be protein-PSH bound compounds. It was confirmed that, this hetero-PSH belongs to a kind of β-(1 ! 3)-Dglucans consisting of a backbone of β-(1 ! 3)-linked glucose residues substituted with (1 ! 4) and (1 ! 6)-β-D-glucopyranosyl residues on main-chain residues (Du et al. 2017). Based on the literature data, the isolated exo-PSH could significantly decrease iNOS mRNA expression in a dose-dependent manner and NO and 5-LOX production from RAW 264.7 macrophages in vitro showing AO and antiinflammatory potential (Du et al. 2017). Schizophyllan (SPG) (MW of 450 kDa) is an exo-PSH isolated from S. commune and valued as a multipurpose compound applicable in many fields, including food industry and pharmacy (Zhang et al. 2013). Since its first discovery in the late 1960s, SPG has been one of the most important PSH produced by mushrooms (Zhang et al. 2013). It is water-soluble homoglucan which possesses a β-(1 ! 3)-linked backbone with single β-(1 ! 6)-linked glucose side chains at approximately every third residue (Zhang et al. 2013). It has been reported that the functional properties of SPG depend on its total PSH content, monosaccharide compositions, MW, and water solubility; furthermore, these physicochemical characteristics are greatly influenced by extraction methods (Chen et al. 2020b). SPGs composition is made mostly of PSH (about 70%) and in some of them uronic acid was found (Du et al. 2017; Chen et al. 2020b), while the presence of PCs in SPG are very rare (Klaus et al. 2011; Mišković et al. 2021). SPG had great biological potential such as: cosmetic

Fig. 8.4 Overview of the BAM related to medicinal properties of C. comatus, P. ostreatus, S. commune, T. versicolor, and H. erinaceus

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . . 229

230

M. Karaman et al.

ingredient (wound healing effects, a thickener for cosmetic lotions), oxygenimpermeable films for food preservation, and wide spectrum of biological activities such as bioactive cosmetics ingredient in the drugs and functional foods (Zhong et al. 2015), antitumor, anti-inflammation, antimicrobial, hypoglycemic, AO, and antityrosinase among others (Klaus et al. 2011; Zhang et al. 2013; Razak et al. 2018; Chen et al. 2020b; Mišković et al. 2021). Some PCs are identified from S. commune (Fig. 8.4) (Tripathi and Tiwary 2013; Mišković et al. 2021), phenolic esters (Liu et al. 2015), vitamins (ascorbic acid) (Tripathi and Tiwary 2013), and others. PCs profile could indicate that in addition to PSH (Yim et al. 2013), the PCs are primarily responsible for AO properties (Mišković et al. 2021). The formation of iminolactones is unprecedented among other natural products and related mostly to inhibition of the growth of cancer cells, and schizines A and B, are the first naturally occurring iminolactones that have been isolated from the FB of S. commune (Liu et al. 2015).

8.4.8

Trametes versicolor

Many in vitro and in vivo studies have shown that T. versicolor possesses important medicinal properties, such as AO, antidiabetic, antitumor, neuroprotective, and hepatoprotective potentials among others (Fig. 8.4) (Kozarski et al. 2012; Kamiyama et al. 2013; Cruz et al. 2016; Jhan et al. 2016; Janjušević et al. 2017, 2018; Pop et al. 2018; Habtemariam 2020; Rašeta et al. 2020c). BAM detected in this species mostly belong to a group of proteins and PSH, while the PSH krestin (PSK) and polysaccharopeptide (PSP) being the most studied ones. Related to this, T. versicolor may be used in the extract or biomass forms. Extract forms, PSK and PSP were extensively studied in past years, while the biomass is more resistant to proteolytic degradation and contains not only β-glucans but also other compounds with large clinical interest, such as relevant enzymes with different activities (Fig. 8.4) (Cruz et al. 2016). Recently, most of the previous studies on T. versicolor have been focused on its main compounds, the PSP extracted from the strains of “COV-1” and the PSK derived from the strain CM101 and it is used most widely in China and Japan, where both products have been approved as medicines primarily as adjuvants in cancer therapy (Cruz et al. 2016; Habtemariam 2020). PSP with PSH-peptide balance of 90–10% has antidiabetic, immunomodulating, antitumor, anti-inflammatory, and antiviral effects, as well some of physiological effects (liver-protecting, systembalancing, anti-aging, and memory-enhancing properties) and potential for application as cosmeceutical in skin care industry (Cruz et al. 2016; Jhan et al. 2016; Ogidi et al. 2020). PSK is with a PSH-peptide balance of 40–60%, and it is also composed mainly of β-D-glucans, and has antitumor potential, improve insulin resistance and hyperlipidemia by regulating the expression of inflammatory cytokines, a reduction in plasma triglycerides (TGs) and FFAs, and increase the levels of glutathione

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

231

peroxidase (GPx) in macrophages (Kozarski et al. 2012). However, up to date, few data has been reported comprehensively on further screening and comparing of AO activities of PSH from T. versicolor to discover the basic laws of their structure and function relationship (Kozarski et al. 2012; Sun et al. 2014; Cruz et al. 2016; Jhan et al. 2016). One of the proposed mechanisms of AO effects can be explained in the following manner: the sample combines with radicals or radical ions by supplying hydrogen from its structure, which forms a stable radical to terminate the radical chain reaction (Sun et al. 2014). Beside PSP and PSK, in T. versicolor other PSH are also determined (MW about 400 kDa), mostly (1 ! 3)-β-D-glucans with short (1 ! 6)-β-linked branches (Kozarski et al. 2012; Su et al. 2016). Sun et al. (2014) isolated and purified six PSH-protein complexes with the similar monosaccharide composition (MW in the range of 568–1840 kDa). Among the six fractions, fractions with lower MW, higher protein content, and larger uronic acid amount, basically exhibited higher radical scavenging effects at the same concentration and appeared to be significant for the improvement of bioactivities (Sun et al. 2014). In addition to PSH, the PSH extract contained a mixture of protein and PCs compounds covalently linked to mushroom β-glucan in varying degrees (Kozarski et al. 2012; Janjušević et al. 2017). These phenolics could improve their AO potential (Kozarski et al. 2012). Scientists found a relationship between MW of PSH and AO potential, where low MW PSH exhibit stronger AO activities based on their poor penetration capability on cell membranes, thereby enhancing their activities (Jhan et al. 2016). Lipid fractions of this mushroom contain some triterpenoid sterols (Fig. 8.4) (Hobbs 2005). In addition to the major macromolecules (proteins, PSH, and lipids) and minerals, this mushroom is known to contain potential pharmacologically active secondary metabolites belonging to small MW compounds. Kamiyama et al. (2013) worked on chemical characterization of T. versicolor extracts and determined 76 compounds (Fig. 8.3), 16 alkyl esters, and the compounds with the AO activity are mainly heterocyclic and aromatic compounds including lactones which also have hepatoprotective effects (Kamiyama et al. 2013). Wang et al. (2015) reported the isolation of some new spiroaxane sesquiterpenes from non-polar fractions. Scientists that worked on PCs determination of the selected polar extracts of T. versicolor, resulted in identification of 38 PCs (Janjušević et al. 2017; Pop et al. 2018; Rašeta et al. 2020c). The AO activities of the water extracts are probably a consequence of the cumulative effects of the PCs, while less polar EtOH and MeOH contained higher content of them and expressed better potential (Janjušević et al. 2017). Janjušević et al. (2018) concluded that there is a significant positive correlation between AO and antitumor activities, suggesting that oxidative mechanisms lay in the basis of proliferation of tumor cells. Quercetin and kaempferol together with some other flavonoids (catechin and amentoflavone) have shown to express anti-AChE activity (Choi et al. 2012). The highest AO potential was also determined for MeOH which is in good correlation with phenolic profile (Janjušević et al. 2017; Pop et al. 2018). Phenolic profile and determined AO

232

M. Karaman et al.

potential are in correlation with Janjušević et al. (2018) and Pop et al. (2018) where better sources of AO compounds were less polar extracts, in this case EtOH.

8.4.9

Hericium erinaceus

Over the past decades, the chemical constituents of H. erinaceus (Fig. 8.3) have been explored, which range from macromolecules such as glycoproteins and PSH to about 70 different small molecules, subdivided into five classes of structurally different and potentially BAM (alkaloids, aromatic compounds, erinacines, lactones, and steroids) (Friedman 2015; Wang et al. 2016; He et al. 2017; Chen et al. 2020a). Dried powder of FB of H. erinaceus are composed of protein (20%), carbohydrate (61%), fat (5%), ash (7%), AAs, and water (6%) content, whereas M consist of protein (42%), carbohydrate (42%), fat (6%), ash (4%), AAs, and water content (4%) (Chaiyasut and Sivamaruthi 2017). The content of H. erinaceus PSH is higher in the FB than in M and up to date, and a total of more than 35 PSH have been isolated from H. erinaceus and represent the main BAM with important gastroprotective and AO potential (Fig. 8.3) (Villares et al. 2012; He et al. 2017; Wu et al. 2018; Chen et al. 2020a; Liao et al. 2020). H. erinaceus residue (HER) was left after the extraction of H. erinaceus PSH, is composed of chitin (β-(1,4)-linked homopolymer of N-acetylglucosamine), minerals, protein, and pigment, whereas chitin, is one of the most abundant biopolymer from H. erinaceus (Liao and Huang 2019). H. erinaceus PSH have attracted much attention due to its various healthpromoting effects, including neuroprotective, antidiabetic, AO, and antitumor properties (Villares et al. 2012; Zhang et al. 2012; Chaiyasut and Sivamaruthi 2017; He et al. 2017; Chen et al. 2020a; Hetland et al. 2020; Liao et al. 2020). Antitumor properties are related to regulation of oxidative stress through inflammation-related signaling pathways (Hetland et al. 2020). Besides PSH, glycoproteins are important H. erinaceus compounds (Fig. 8.3), with protein/polysaccharide ratio of 10:1 (%), and inhibition of the growth of human gastric carcinoma cells (Cui et al. 2014) an downregulation of the expression of inducible nitric oxide synthase, involved in nitrosative stress (Diling et al. 2017). Numerous low MW secondary metabolites have recently been isolated from FB and cultured mycelia of H. erinaceus (Fig. 8.3). Most interestingly secondary metabolites from H. erinaceus are two classes of terpenoid compounds, hericenones and erinacines with significant neurotrophic and neuroprotective effects (Thongbai et al. 2015). From a chloroform extract of the FB of H. erinaceus were isolated some hericerins (Li et al. 2014, 2015), and resorcinols, erinacerins, and hericenols, also from the FB of H. erinaceus (Friedman 2015) (Fig. 8.3). Most of these compounds can easily pass through the blood–brain barrier and have demonstrated neurotrophic and neuroprotective effects in pathologies in Alzheimer’s and Parkinson’s disease (Venturella et al. 2021). For H. erinaceus are also determined lactones (Wang et al.

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

233

2015, 2016), ergosterol (Avtonomova et al. 2012) and erinarols G-J (Chaiyasut and Sivamaruthi 2017). Heleno et al. (2015) determined FAs composition, whereas saturated FAs predominated over polyunsaturated (PUFA) and monounsaturated (MUFA) FAs. Short-chain FAs (SCFAs) were also determined after fermentation for H. erinaceus (He et al. 2017). Kim (2020) detected 18 putative AO substances and categorized them into tyrosinase inhibitors, AO, and polyamines (Fig. 8.3). In addition to the mentioned compounds, in this species were also determined some PCs (Heleno et al. 2015). Mainly, the AO activity of the H. erinaceus species is due to the presence of PSH (β-glucans), diterpenoids (hericenons, erinacines), and PCs (Heleno et al. 2015; Kim 2020). Due to the high AO potential and many BAM, this mushroom has been used for diabetic treatments via anti-hyperglycemic properties of methanol as well as aqueous extracts applied in streptozotocin induced diabetes (Liang et al. 2013). In conclusion, this medicinal mushroom has antioxidative, anti-inflammatory, anticancer, immunostimulatory, antidiabetic, antimicrobial, hypolipidemic, and antihyperglycemic properties, although its most frequent use is for the treatment of neurodegenerative diseases and cognitive impairment (Zhang et al. 2012, 2015, 2017; Liang et al. 2013; Li et al. 2014; Friedman 2015; Heleno et al. 2015; Wang et al. 2016; Chaiyasut and Sivamaruthi 2017; Diling et al. 2017; Chen et al. 2020a, b; Hetland et al. 2020; Kim 2020; Venturella et al. 2021).

8.4.10 Cosmeceuticals Cosmeceuticals are products applied topically, while nutricosmetics are known to have similar perceived benefits but are ingested orally. The term “cosmeceutical” was introduced by Albert Kligman, in 1984 and defined as a term between cosmetics and pharmaceuticals since they are products formulated with bioactive ingredients, topically applied on the skin to produce a medical drug-like benefit, while improving skin structure and function as well (Taofiq et al. 2017). Numerous mushrooms have recently been exploited as potential components in the cosmetic industry (Wu et al. 2016) while some of important compounds are: PCs (phenolic acids and flavonoids) Karaman et al. (2014), terpenoids (monoterpenes and sesquiterpenes), selenium, PSH (β-glucans, lentinan, schizophyllan), vitamins (carotenoids), sterols (ergosterol), Fas, and volatile organic compounds (Wu et al. 2016). They have multifunctional benefits on skin such as AO, anti-aging, antibacterial, anti-wrinkle, anti-tyrosinase, skin whitening, and moisturizing effects, which make them ideal candidates for cosmetic products (Taofiq et al. 2016; Wu et al. 2016). Based on these properties, several mushroom extracts and their BAM are either presently used (G. lucidum, L. edodes, Agaricus subrufescens, Cordyceps sinensis, Inonotus obliquus, S. commune, Tremella fuciformis, P. ostreatus) or patented (L. edodes extract as a hair care cosmetic composition) to be used for

234

M. Karaman et al.

topical administration and nutricosmetics for oral administration (Wu et al. 2016). Two other patents for using mushrooms as cosmeceuticals have been issued as: US Patent 6843995 uses the common truffles (Ascomycota, Tuberales), Choiromyces maeandriformis, Tuber uncinatum, T. melanosporum, T. magnatum, T. aestivum, and T. brumale and mixtures thereof in cosmetics formulations and US Patent 6,645,502 B2: Revlon Consumer Products Corp. is for an anhydrous cosmetic composition, comprising a water-insoluble Polyporus extract (Hyde et al. 2010). There are many requirements for cosmetics products of natural origin, but most importantly they should be safe to use, with no side effects, and have positive effects on the skin (Wu et al. 2016). Nowadays, they are preferred by consumers compared to synthetic ingredients (Abd Razak et al. 2020). Related to this, of all abovementioned mushroom species, G. lucidum and their extracts, alone or in combination with other natural ingredients have been mostly used in anti-aging skincare products since the 1980s, starting with Japanese brand Menard in product Menard Embellir Refresh Massage cream, and other products such as: Body repair lotion, Dr. Andrew Weil for Origins™ Mega-Mushroom Skin Relief Face Mask, etc. (Wu et al. 2016; Taofiq et al. 2017). Beside G. lucidum, P. ostreatus (Hankook Sansim Firming Cream (Tan Ryuk SANG), Korea) and S. commune (Alqvimia Eternal Youth Cream Facial Máxima Regeneración and Sulwhasoo Hydroaid, Korea) also have been used in the form of the cosmeceuticals around the world (Wu et al. 2016). In the early 2000s, mushrooms hit the Western market for skincare applications. These products have all been used to suppress the severity of hyperpigmentation, to brighten skin appearance and prevent aging effects, and to protect skin against UV radiation (Taofiq et al. 2016). On the other hand, nutricosmetics are usually based on combinations of these BAM: carotenoids, PCs, vitamins, mushroom extracts, micronutrients, glycopolyglycans, AAs, other mushroom-based elements, and PUFAs (Wu et al. 2016). Some of the most important cosmeceutical ingredients related to their AO and anti-tyrosinase activity are from the large group of BAM, PSH, and phenolic acids (ferulic, p-coumaric and caffeic acid) (Abd Razak et al. 2020). Mushroom ingredients for skin care are becoming popular due to their strong AO protective and defensive role against generation of free radicals and reduced production of oxidative enzymes, inducible nitric oxide synthase (iNOS) associated with inflammation, collagenase, and elastase which cause degradation of the extracellular matrix of the skin, and tyrosinase, key enzyme included in melanin biosynthesis (Taofiq et al. 2016; Abd Razak et al. 2020). Also, further in vivo and clinical studies are necessary in order to develop and validate novel cosmeceuticals, nutraceuticals, and pharmacological formulations (Taofiq et al. 2017).

8.5 8.5.1

Environmental Contamination Trace Element Accumulation

It is well documented that immense number of macrofungi, including medicinal species, with different nutritional modes, have the ability to concentrate and

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

235

accumulate TE in their FB, in amounts that often exceed those in agricultural crop plants, vegetables, fruits or animal tissue (Karaman et al. 2012b; Falandysz and Borovička 2012; Kalač 2016). In mushrooms, higher concentrations were recorded in the cap, predominantly in the part of hymenophore, than in the stipe (Alonso et al. 2003; Li et al. 2019a, b). Major differences in the concentrations of different TE observed among different species within the same habitat, but also in the concentrations of the same element among the same species within different habitat/location indicating that the accumulating abilities are mostly species specific (Niedzielski et al. 2017; Kalač 2019; Siwulski et al. 2019). Fungi that inhabit sites exposed to different sources of pollution (fossil fuel combustion, industrial plants, mines, etc.) generally show higher concentrations of toxic metals (Petkovšek and Pokorny 2013; Murati et al. 2019). Unfortunately, even species collected from seemingly unpolluted areas, such as deep forests and mountain habitats, may show relatively high concentrations of toxic elements (Cocchi et al. 2006; Rakić 2019). Also, the content of elements in cultivated mushrooms may be higher if the substrates on which they grow are enriched with different elements (Rzymski et al. 2016; Mleczek et al. 2020). Hazardous elements that occur in substrates decomposed by fungi are stored in fungal mycelia and FB. The following elements are often investigated from the aspect of potential toxicity in humans: Cd, Pb, Hg, Ni, Cr, Cu, As, Zn, Se. The content of Cd and Pb in edible mushrooms is regulated within the European Union (EU). The established maximum concentration limits for Cd and Pb are 0.2 mg/kg and 0.3 mg/kg of fresh weight (fw), respectively, for cultivated fungi (corresponding to 2 mg/kg and 3 mg/kg of dry weight—dw, according to consensus that the dry weight of mushrooms is 10% of their fresh weight (Kalač 2019)) and 1.0 mg/kg and 2.0 mg/kg fw, respectively, for other fungi (approximately 10 mg/kg and 20 mg/kg dw) (Commission Regulation (EC) 2006a, b, 2008, 2014). The EU has not mandated any regulations for Hg levels in mushrooms so far, while the Czech statutory limit (former Czech Regulation 53, 2002) for Hg content in wild growing edible mushrooms is 5.0 mg/kg dw. Maximum permitted levels for Pb, Cd, and Hg in food supplements in the EU are: 3, 1, and 0.1 mg/kg fw (EC No 629/2008). The World Health Organization (WHO) has set a limit for toxic element intakes based on body weight (bw). Their recommendations on intake limitations set as a provisional tolerable weekly intake (PTWI) values are: 0.007 mg/kg bw for Cd, 0.025 mg/kg bw for Pb, 0.0016 mg/kg bw for Hg, 0.015 mg/kg bw for As. The WHO recommendations set as a provisional tolerable daily intake (PTDI) values are: 0.50 mg/kg bw for Cu and 1.0 mg/kg bw for Zn. In the USA, tolerable upper intake level for Ni is reported as 1 mg/day (FNB 2001). The US Food and Drugs Administration (FDA) recommended 120 mg/kg daily intake of Cr for foods and feeds. According to the European Scientific Committee on Foods (SCF) the Dietary Reference Intake for Se is 55 μg daily. Even when concentrations of elements do not exceed safe limits, there is still a potential for their bioaccumulation over a long period of time and associated chronic toxicity. The majority of conducted TE accumulation research in mycology deals with the analysis of content in fungal FB and their substrate. Concerning the medicinal

236

M. Karaman et al.

species of interest in this chapter, the most studied are C. comatus and species within the genera Pleurotus and Ganoderma, while only scarce literature data exist for the species S. commune, T. versicolor, and H. erinaceus (Table 8.1). Both edible and medicinal fungi, C. comatus showed prominent ability to concentrate various elements from its environment, especially Zn, Cu, Fe, Mn, Cr, and Ni (Table 8.1). This species stands out with the highest recorded levels of As (410 mg/kg dw), Se (410 mg/kg dw), and Hg (144 mg/kg dw) compared to other medicinal species analyzed in the chapter (Koch et al. 2000; Niedzielski et al. 2017; Nowakowski et al. 2020). In addition, this medicinal mushroom species successfully absorbs and accumulates Cd and Pb in concentrations which may exceed permissible levels for edible mushrooms (García et al. 2009; Melgar et al. 2009; Niedzielski et al. 2017). Fungi belonging to the genera Trametes have a capacity to concentrate a broad range of trace metals. Species T. versicolor was found to absorb to a significant extent Cd, Cu, Cr, Ni, and Pb (Table 8.1). In the extensive screening study of 36 elements in 12 cultivated fungal species accessible in Polish markets, T. versicolor displayed highest content of La (0.13 mg/kg dw), while H. erinaceus had the highest amount of In (7.5 mg/kg dw) and Bi (1.6 mg/kg dw) (Niedzielski et al. 2017). Substrate supplementation experiments showed the ability of H. erinaceus to concentrate Hg and accumulate Se and As (Niedzielski et al. 2014; Gąsecka et al. 2016a, b; Mleczek et al. 2015; Rzymski et al. 2016). Sporocarps of S. commune collected from the trees growing at various distances from high-frequency roads in urban areas concentrated: Cd, Co, Cr, Cu, Mn, Ni, Zn, Hg, and especially Pb (Škrbić et al. 2012). In this study, as well as the one from the Fruška Gora mountain, in Serbia (Karaman 2002; Karaman and Matavulj 2005), S. commune was recognized as superaccumulator of Fe (2451.25 mg/kg dw and 2666.76 mg/kg dw, respectively), indicating the high affinity of this species to accumulate Fe regardless of the habitat in which it grows (urban or forest areas). In the work of Karaman (2002)and Karaman and Matavulj (2005), this medicinal fungus also exhibited high content of Zn (139.25 mg/kg dw). The most comprehensive study dealing with the element content (62 elements) in species of the genus Ganoderma was conducted on ten species cultivated in China and Poland as well as with wild growing species in Poland (Marek et al. 2017). The highest content of most analyzed elements among species was observed for cultivated G. pfeifferi and G. sinense and wild growing G. resinaceum. The level of contaminants in most of the studied species was low apart from the Cd level (4.71 mg/kg) found in G. pfeifferi from Polish cultivation and Al (1208 mg/kg dw), Pb (7.4 mg/kg), and rare-earth elements content determined in G. sinense from Chinese cultivation. Among all medicinal fungi presented in this chapter, the highest levels of Fe, Al, Mn, Zn, Ni, Cr, Cd, and V are reported in G. pfeifferi and G. carnosum (Yalcin et al. 2020), but it was concluded that weekly consumption of these mushrooms (1.5 g per week) still does not put the consumers at risk. As previously reported, fungal species belonging to the genera Ganoderma and Pleurotus, available in trade, can contain higher Pb levels compared to those observed in various other cultivated mushroom species (Huang et al. 2015; Siwulski

8 Diversity, Chemistry, and Environmental Contamination of Wild Growing. . .

237

Table 8.1 Literature data on the trace elements content (mg/kg dw) in the FB of medicinal mushrooms Species

El.

Range of C (mg/kg dw)

Range of C El. (mg/kg dw)

C. comatus

Cu Fe

7.8–147.3 94–3640

Ag 3.85 Al 31.2

G. lucidum

Other Ganoderma-s

P. ostreatus

H. erinaceus

Mn 11.1–103 Ni 0.1–58.6

As 0.1–1 Cd 0.08–15.3

Zn Cr Se Cu

4.85–473 1.8–38.60 2.05–36.4 7.24–137.96

Hg 0.78–144 Pb 0.27–30.5

Fe Mn Ni Zn Cr Se Cu

V

0.48–4.6

29.21–2290.92 21.54–76.36 4.3–101.32 34.87–103.26 3.98–136.33 2.47 15.9–291

Al As Cd Hg Pb

19.95–500 1.12–1.1 0.13–0.39 3.2 0.36–3.87

V

506–549

Fe Mn Ni Zn Cr Se Cu Fe Mn Ni Zn

64.96–14,344 43.57–1223 19.57–100 25–28 4.42–172.2 5.3–6.1 5.2–47.1 54–682 6.27–76.2 1.5–145 29.8–142

Ag Al As Cd Hg Pb V Al Ag As Cd

99–109 2182–4845 0.8–0.84 3.68–41.07 1.1–1.21 3.53–113.24 0.55–1.69 20.6–47.74 0.22 Mn > Zn > Cu > Ni > Se > Co. Comparative study revealed that Na, Mg, P, and Ca contents in cultivated samples were greater than those in wild samples. Kadnikova et al. (2015) reported metal concentration of A. auricula-judae in the following order: Ca > K > Na > Mg > Fe > Zn > Co/Ni/Cu/Mn. In case of A. polytricha, the minerals are present as Ca > Na > K > Mg > Fe > Mn > Zn > Cu (Manjunathan et al. 2011). Total 15 minerals are present in A. thailandica where K is the most abundant macroelement (K > P > Mg  Ca > Na). Alongside, Fe is the major microelement and the rest of components are present in the descending order of Zn > Mn  Ni  Cu  Cr (Bandara et al. 2017). Auricularia cornea contains potassium as the most abundant macro element followed by magnesium, calcium, and finally sodium. Among microelements, iron is present in adequate amount in Auricularia which indicates that consumption of the mushroom may be beneficial for iron deficiency related diseases. Karun et al. (2018) depicted that cooking adversely affects seven minerals (sodium, potassium, calcium, magnesium, phosphorus, iron, and copper) in A. auricula. However, Na/K ratio (0.32 uncooked, 0.47 cooked) and Ca/P ratio (2.01 uncooked, 1.88 cooked) in A. auricula are favorable for human health. The Na/K ratio 1 helps to prevent loss of calcium in urine. Such mineral content in cultivated samples varies with the nature of substrate used. For instance, the ash content of A. polytricha cultivated on a sawdust substrate containing Zea mays stalk was superior to that of control (Liang et al. 2019). In a separate study, effect of corn stalks as a cultivation substitution material (20–80%) for sawdust on nutrient profile of A. auricula was analyzed. Results reported that addition of corn stalks increased protein, ash, copper, and iron contents in black fungus, but reduced extent of magnesium, manganese, zinc and colloidal substances (Yao et al. 2019). The mineral content in A. polytricha could also be manipulated by using different supplements. For instance, Ca content of fruit body grown on sawdust medium (beech sawdust:rice bran ¼ 4:1) was increased by supplementation of 1–5% of Ca carbonate or Ca phosphate. Conversely, Mg content cold be incremented by applying 0.5% of Mg hydroxide, Mg carbonate, Mg sulfate, and Mg chloride (Tabata and Ogura 2003).

11

Auricularia spp.: from Farm to Pharmacy

321

11.3.7 Vitamins Mushrooms appear to be good sources of vitamins like thiamin (B1), riboflavin (B2), niacin (B3), biotin, and ascorbic acid (vitamin C), but a great deal of species specificity exists. Vitamins A, D, and E are relatively uncommon (Breene 1990; Kakon et al. 2012). Macrofungi are consisted of moderately high amounts of folates at concentrations similar to those found in vegetables (Cheung 2010). However little information on the vitamin contents of ear mushrooms is available. Research done till date shows that A. auricula contains ergosterol, provitamin of ergocalciferol, at the level of 19 mg/100 g mushroom dry matter (Breene 1990). Ergocalciferol (provitamin D) can be converted into vitamin D in the presence of sunlight (Cheung 2010). Rebecca et al. (2020) detected vitamin E in A. cornea in negligible amount, i.e. 0.59 mg/100 g.

11.4

Medicinal Effects of Auricularia spp.

Numerous extracts and isolated compounds obtained from Auricularia species have been investigated for bioactivity. The mushrooms have been detected to possess a large variety of biological functions, including antioxidant, antimicrobial, anticoagulant, antitumor, hypoglycemic effect, enhancing immunity, hypolipidemic activity, antiaging, and so on. The following section reviews the multifunctional properties of Auricularia spp. in detail.

11.4.1 Antioxidant Activity Aging, obesity, and detrimental lifestyle choices often cause stress on the body resulting in oxidative damage to tissues. Superoxide radicals, hydroxyl radicals, and hydrogen peroxide damage DNA, provoke lipid peroxidation, and impair enzymes as well as structural proteins. The stress on body results in oxidative damage to tissues and promotes development of cancer, cardiovascular and neurological diseases, diabetes, cataracts, and rheumatoid arthritis (Khatua et al. 2013, 2017). Although organisms own defense system to protect; but they are not sufficient to prevent free radical damage. Hence antioxidants are employed to ameliorate the situation where many synthetic compounds, such as butylated hydroxyanisole and butylated hydroxytoluene, have shown potential downside. As a result, natural antioxidants are preferred in food applications (Finkel and Holbrook 2000; Ren et al. 2014). In this context, several studies have reported antioxidant effect of Auricularia spp. in terms of half maximal effective concentrations or EC50 values as summarized in Table 11.4.

A. fuscosuccinea (White variety) A. polytricha

A. auricula-judae

Name of mushroom A. auricula

Methanol extract Methanol extract Methanol extract Methanol extract Methanol extract

Boiled extract 95% Ethanol extract Hot water extract

Water extract

Extract/ active component Heteroglycan

ND ND ND ND

ND

ND

ND

ND

2 9.01 mg/ mL 0.4 mg/ mL 0.51 mg/ mL 0.373 mg/ mL 6.11 mg/ mL

ND

ND

1 0.73 mg/ mL 0.05 mg/ mL 0.08 mg/ mL 0.05 mg/ mL ND

0.19 mg/ mL 0.15 mg/ mL 0.63 mg/ mL 0.13 mg/ mL 13 mg/ mL ND

ND

ND

ND

ND

ND

ND

ND 3.65 mg/ mL

ND

4 1.23 mg/ mL ND

ND

3 3.29 mg/ mL ND

1.71 (mg of GAE/g of sample)

ND

0.58 mg/ mL 0.6 mg/mL

ND

3.47 mg/ mL

ND

ND

ND

5 ND

500 hm of MDA/mg of phenolics

ND

0.58 mg/mL

0.3 mg/mL

ND

7.35 mg/mL

ND

ND

ND

6 ND

ND

ND

ND

ND

ND

7 0.07 mg/ mL 0.31 mg/ mL 0.57 mg/ mL 0.4 mg/ mL ND

ND

2.26 mM TE/g 1.82 mM TE/g ND

14.88 (mgGAE/ g) ND

ND

ND

ND

8 ND

Ao and Deb (2019) Puttaraju et al. (2006)

Lin et al. (2013)

Ao and Deb (2019) Lin et al. (2013)

Packialakshmi et al. (2017)

References Zeng et al. (2012) Acharya et al. (2004)

Table 11.4 Antioxidant activity of Auricularia spp. as presented by EC50 values. (1) Superoxide radical scavenging, (2) Hydroxyl radical scavenging, (3) DPPH radical scavenging, (4) ABTS radical scavenging, (5) Chelating of ferrous ion, (6) Reducing power, (7): Inhibition of lipid oxidation, (8) Total antioxidant activity

322 S. Khatua et al.

ND

ND

Chloroform

Hot water

ND

ND

ND

ND

ND

ND

ND

ND

0.34 mg/ mL 21 mg/ mL 0.05 mg/ mL 0.65 mg/ mL 0.07 mg/ mL

ND

31.58 mg/ mL 9.7 mg/ mL

ND

ND

4.63 mg/ mL 0.83 mg/ mL 14 mg/ mL ND

ND

ND

ND

ND

ND

ND

ND

5.6 (mg of GAE/g of sample) ND

ND

ND not determined, TE trolox equivalent, GAE gallic acid equivalent, MDA malondialdehyde

Auricularia sp.

A. thailandica

ND

ND

ND

ND

ND

ND

Hot water extract Methanol extract Aqueous extract 70% ethanol

90% ethanol extract Water extract

ND

ND

ND

ND

ND

335.5 hm of MDA/mg of phenolics ND

ND

ND

ND

ND

ND

6.77 mg/ mL ND

ND

ND

ND

ND

ND

ND

ND

ND

ND

ND

Gebreyohannes et al. (2019)

Packialakshmi et al. (2016) Bandara et al. (2017)

Wong et al. (2013) Puttaraju et al. (2006)

11 Auricularia spp.: from Farm to Pharmacy 323

324

S. Khatua et al.

Fan et al. (2007) extracted crude polysaccharides (AAP) from fruit bodies of A. auricula, developed AAP blended bread, analyzed physical qualities and antioxidant activity of breads with different levels of substitution of AAP flour. They observed that with regard to loaf weight, height, and volume, up to 9% AAP flour could be included in the formulation without interfering with sensory acceptance of the bread. Moreover, incorporation of AAP markedly increased antioxidant property of the bread as tested by 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) scavenging method broadening utilization of AAP in health-promoting sector. A water-soluble crude polysaccharidic fraction was isolated from A. auricula. Conversely, 80% ethanolic fraction was prepared using dried powder of hawthorn (Crataegus pinnatifida) fruit. Further a newly functional formula diet was postulated containing 80% of crude polysaccharide and 20% fruit extract. The functional diet and carbohydrate fraction were used at the same concentration to determine radical scavenging effect. Results showed that functional diet presented superior DPPH• scavenging and superoxide radical (O2•) quenching effects than that of polysaccharide. Besides protective effect of low-density lipoprotein (LDL) oxidation was also dramatically enhanced in functional diet in comparison to polysaccharide (Luo et al. 2009b). After 2 years, the same research team revealed bioactivity of another functional formula diet (AHP) consisting of polysaccharides from A. auricula (AAP), polyphenolic compounds from Hawthorn (Crataegus), and Pueraria radix in the ratio of 5:3:2. Compared with AAP, hydroxyl (OH•) and O2• scavenging effects of AHP were significantly elevated. The same trend was also followed in inhibition of Cu2+induced LDL peroxidation assay. The treatment of AAP executed protection against LDL oxidation by extending lag phase significantly from 30 to 91 min. However, the outcome of AHP treatment was superior to AAP, by elongating the lag phase further to 240 min. Such excellent antioxidative potential might be explained by the introduction of polyphenolic compounds into the diet as well as the synergistic effects among components (Luo et al. 2011). A neutral polysaccharide and an acidic polysaccharide were isolated from A. auricula-judae by hot water and ultrasonic-assisted extraction. Further each of the carbohydrate chain was sulfated successfully and evaluated for antioxidant activity in a comparative manner. Results showed that the sulfated derivatives presented better O2• scavenging property than nonsulfated samples. The similar effect was also reflected in scavenging OH•, quenching 20 -azinobis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical and inhibition of lipid peroxidation assays; although overall outcome was not much impressive as EC50 values were not readable in most of the methods (Zhang et al. 2011b). A water-soluble polysaccharide was extracted from A. auricula-judae with assistance from ultrasonics and purified (AAP I-a). The backbone was composed mainly of mannose where other monomers were presented in the order of arabinose > glucose > xylose ~ galactose > rhamnose. The polysaccharide treatment increased thymus index and spleen index vitality of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) and reduce content of peroxidation product— malondialdehyde (MDA). Polysaccharide supplementation also enhanced blood

11

Auricularia spp.: from Farm to Pharmacy

325

serum, heart, and liver antioxidant enzyme activity. Interestingly consumption of the polysaccharide showed no noticeable physical alteration to the examined vital organs or on body weight of treated aged mice suggesting in vivo antiaging effect of AAP I-a (Zhang et al. 2011a). Yang et al. (2011) extracted crude polysaccharide (AAP) from A. auricula and modified by carboxymethylation to improve water solubility as well as bioactivity. The sample was purified (CMAAP) and the main fraction (CMAAP22) was collected. CMAAP22 was found to be composed of mannose and glucose in the molar ratio of 1.06:1 with an average molecular weight of 3.4  106 Da. Carboxymethylated derivative (CMAAP and CMAAP22) exhibited improved scavenging of OH•, DPPH•, and ABTS radicals compared to AAP. The antioxidant effect decreased in the following order of CMAAP22 > CMAAP > AAP indicating carboxymethylated derivatives have a noticeable effect on quenching of free radicals. A deproteinized heteropolysaccharide with molecular weight of 2.77  104 Da was prepared from A. auricula by microwave-assisted extraction (95  C, 25 min, 860 W, pH 7). The bio-polymer was observed as a spherical lump where backbone was mainly composed by (1 ! 3) linked glucose. The macromolecule exhibited strong ABTS, DPPH, superoxide, and hydroxyl radical scavenging properties. In addition, the polysaccharide effectively inhibited lipid oxidation of egg yolk homogenate and exhibited strong reducing power. The remarkable antioxidant activity may be attributed to low molecular weight of the polysaccharide (Zeng et al. 2012). Li et al. (2012) isolated three fractions using acidic, water, and alkaline solvents from a number of mushrooms including A. auricula. All the fractions from ear mushroom consisted of carbohydrate and protein where extent of the molecules was presented in the highest amount in aqueous preparation. Subsequently the water fraction presented better potential in ABTS radical and OH• quenching assays. While acidic extract exhibited the highest effect in inhibition of lipid peroxidation method. Crude polysaccharide fraction was isolated from A. auricula-judae by hot water extraction and later protein was removed by Sevag reagent. To reduce wastage, an optimum condition for extraction was identified at a ratio of liquid to solid of 70 mL/ g, 4 h, 90  C and four times resulting in the best yield of 6.89%. Further, the polymers were subjected to different antioxidant assays, namely radical scavenging (ABTS, DPPH•, OH•, O2•) and reducing method. The extract exhibited effective potency in a dose-dependent manner where EC50 values were lower than 5 mg/mL in most of the tests (Cai et al. 2015). Khaskheli et al. (2015) isolated two polysaccharidic fractions, namely AAPF and AAPP from the fruit bodies of A. auricula and pickled product, respectively. Compositional analysis showed dominance of glucose in AAPF, while AAPP was mainly consisted of arabinose linked by β-glycosidic bond. Evaluation of antioxidant activity showed that AAPF possessed better DPPH• scavenging effect; conversely, superior OH• and ABTS radical quenching activities as well as reducing power were exhibited by AAPP. In a different study, water-soluble polysaccharides (AAP1, AAP2, AAP3, AAP4, and AAP5) were extracted from cultivated A. auricula using alkali solvent and

326

S. Khatua et al.

deproteinized. All the fractions exhibited effective radical scavenging (DPPH•, O2•, and OH•), metal chelating, and reducing power capacities. Alongside, the polysaccharides increased life span, alleviated SOD and catalase activities, reduced generation of reactive oxygen species (ROS) in oxidative stress state of Caenorhabditis elegans. Comparatively, the strongest antioxidant activity was executed by AAP1 consisting arabinose, xylose, 2-deoxy-D-glucose, mannose, glucose, and N-acetyl-D-glucosamine in molar ratio of 1:0.44:0.33:1.67:1:0.17 (Xu et al. 2016). A hot water extract of A. auricula-judae was investigated for antioxidant efficacy and amount of phytochemical components was determined as well. The extract exhibited strong antioxidant activity in all the assays where EC50 values were in the decreasing order of reducing power > OH• scavenging > DPPH• quenching > chelating ability of Fe2+ > inhibition of β-carotene bleaching. The preparation also showed promising effect in total antioxidant assay. The fraction was found to contain high amount of phenol followed by flavonoid which might have played a key role (Packialakshmi et al. 2017). Ma et al. (2018) isolated water fraction from A. auricula and degraded effectively with the help of solution plasma process (SPP) and H2O2. Furthermore, antioxidant experiments revealed that the degraded polymers exerted greater DPPH• scavenging and metal chelating effects. The observation could be justified as SPP irradiation reduced intrinsic viscosity of AAP and elevated bioactivity. Acharya et al. (2004) isolated three fractions, namely water, boiled, and ethanolic fractions from fresh A. auricula fruit bodies and compared their antioxidant activities. Comparatively the aqueous extract presented superior potential in O2• scavenging and inhibition of lipid peroxidation as evident by the lowest EC50 values. Conversely, ethanolic preparation executed better activity in OH• quenching assay followed by crude water extract. Boonsong et al. (2016) performed comparative study of antioxidant activity of A. auricula collected from local market using three different extractants such as water, 50% (v/v) ethanol, and diethyl ether. The fraction isolated by hydrothermal process presented the best effect in terms of DPPH• scavenging, reducing power, and chelating ability. It could be reasoned by the presence of total phenolic and flavonoid compounds in sufficient amount in the preparation. Methanolic extracts from fresh, oven-dried, and freeze-dried fruit bodies as well as mycelium of cultivated A. auricula-judae were evaluated for their antioxidant capacities. Fraction of freeze-dried basidiocarps had the strongest scavenging activity of DPPH• when compared to the other preparations tested. The extract of ovendried fruit bodies also showed effective potency, whereas that of mycelium was relatively a poor free radical scavenger. Similar trend was also followed in case of ferric-reducing antioxidant power (FRAP) assay where decreasing order of potency was as follows: freeze-dried fruit bodies > fresh fruit bodies ~oven-dried fruit bodies > mycelium. When total phenolic content in the tested formulations was computed, freeze-dried fruit bodies extract consisted of the highest phenolic content than that of other fractions, while the lowest extent was detected in mycelium extract signifying positive correlation between phenolic content and antioxidant activity. It

11

Auricularia spp.: from Farm to Pharmacy

327

could be justified as freeze-drying causes development of ice crystals within fruit body matrix resulting in greater rupture of cell structure and better solvent extraction. Hence the observation suggests that method of processing of fresh basidiocarps had an effect on antioxidant potential (Kho et al. 2009). Auricularia auricula fruit bodies were utilized to prepare 70% ethanol extract and further a dichloromethane fraction was isolated. The fraction exhibited potent DPPH• scavenging activity in a dose-dependent manner with EC50 of less than 3 mg/mL (Reza et al. 2014). Yu and Oh (2016) isolated three organic fractions from A. auricula-judae to determine antioxidant effect. Among the preparations, ethanol extract presented the best effect in DPPH• and ABTS radical scavenging activities. Conversely acetone fraction presented moderate effect in comparison with ethyl acetate preparation. The effect could be justified by quantity of polyphenol which was present in satisfactory amount in ethanolic preparation. Conversely, flavonoid was detected in the decreasing order of ethyl acetate > acetone > ethanol. Butkhup et al. (2018) collected 25 wild edible mushrooms from natural habitat of Northeastern Thailand. All the gathered macrofungi were analyzed for their antioxidant activities and for that 60% methanol fraction was prepared. Results showed that the fraction from A. auricula exhibited moderate effect in DPPH• scavenging and FRAP assays in comparison to other investigated taxa. It might be due to presence of phenol and flavonoid in the fraction in lesser extent. Crude polysaccharides isolated from A. cornea exhibited DPPH radical scavenging activity. The macromolecules at the level of 10 mg/mL were able to scavenge 40% radical. Fourier transform infrared spectroscopy (FTIR) analysis indicated the fraction was consisted of β-glucan (Ren et al. 2014). One low molecular weight polysaccharide of 2.8  104 Da was isolated from the fruiting body of A. polytricha. The pure polysaccharide exhibited potent activity in OH• scavenging with EC50 value below 3 mg/mL (Sun et al. 2010a). Four purified polysaccharides, namely APPsA-1, APPsB-1, APPsB-2, and APPsC-1 were isolated from A. polytricha basidiocarps by hot water process. Composition analysis revealed that mannose was the major element in carbohydrate backbone followed by galactose. Besides, uronic acid was also detected in all the polymer chains except APPsA-1. Results of antioxidant assays showed that all fractions except APPsA-1 exhibited antioxidant activities in terms of chelating ability of Fe2+, O2• scavenging assay, and OH• quenching method with EC50 values lower than 1 mg/mL. The outcome might be related to extent of uronic acid as the stronger antioxidant activity was presented by those polysaccharides which contained higher uronic acid (Sun et al. 2010b). Packialakshmi et al. (2016) isolated hot water fraction from A. polytricha which was found to be enriched in phenols and flavonoids. The extract presented excellent antioxidant activity in several assays where the activity was in the decreasing order of lipid peroxidation inhibition > β-carotene bleaching inhibition > ABTS radical scavenging > N,N-dimethyl-1,4-diaminobenzene (DMPD) radical quenching > phosphomolybdenum reducing antioxidant power > cupric reducing antioxidant capacity methods.

328

S. Khatua et al.

Free and bound phenolics of A. polytricha powder were extracted using 80% chilled ethanol and alkaline-hydrolysis. The amounts of free and bound phenolics were detected as 474.4 μg gallic acid equivalent (GAE)/g sample DW and 70.7 μg GAE/g sample DW. Both the fractions inhibited DPPH•; however, antioxidant capacity of free phenolic extract was much higher than that of bound phenolic extract. Correlation analysis indicated that content of total phenolics in the alcoholic extracts mainly contributed to antioxidant capacity (Hung and Nhi 2012). Wong et al. (2013) prepared 90% ethanol extracts from five edible mushrooms of Malaysia separately and tested their antioxidant activity. Among them, A. polytricha exhibited the best potential in DPPH• quenching assay with EC50 of 31.58 mg/mL concentration. Consistently, the extract also showed the highest metal chelating effect. The outcome might be linked to extent of phenolics as A. polytricha extract was found to be consisted of the highest amount of phenol (6.03 mg GAE/g dry matter) and flavonoid (6.95 mg quercetin equivalent/g dry matter). Park et al. (2015) reported antioxidant activities of 55 mushrooms. For that, they prepared culture media containing mycelia which was further extracted with 40% ethanol. Analysis showed that the fraction of A. polytricha exhibited potent DPPH• scavenging, reducing power and lipid oxidation inhibitory activities with EC50 values less than 10 mg/mL concentration. Moreover the extract presented the best reducing power in comparison with other investigated macrofungi. Two different solutions were prepared using ethanol and distilled water as solvent in order to prepare extracts from A. polytricha. When antioxidant capacities were compared, the aqueous fraction displayed higher capacity than ethanolic preparation as determined by total antioxidant status. The antioxidant activity of distilled water and organic extracts was found to be 0.91 μmol Trolox equivalent/L and 0.73 μmol Trolox equivalent/L, respectively (Avcı et al. 2016). Puttaraju et al. (2006) determined antioxidantive potential of water and methanolic extracts from 23 macrofungal species naturally grown in different geographic locations of India. The extractive yield of aqueous fraction from A. polytricha was better than organic fraction which might be due to extraction of phenolic compounds in higher amount. Both the preparations were consisted of tannic acid, gallic acid, protocatechuic acid, and gentisic acid which cumulatively presented in higher amount in aqueous fraction. As a result, the water extract presented superior antioxidant activity in terms of reducing power, DPPH• scavenging, and inhibition of lipid peroxidation. Comparative study with other analyzed mushrooms showed that the fractions from A. polytricha exhibited moderate activity. A comparative study on DPPH• scavenging activity has been performed using methanol extracts of ten wild edible mushrooms. Among them, ear mushrooms showed moderate activity as evident by high EC50 values. However, A. polytricha exhibited better potency than A. auricula-judae which might be due to presence of phenol and flavonoid in higher extent in the former fraction (Ao and Deb 2019). Four polysaccharides were isolated from A. cornea, A. polytricha, and A. auricula separately which were later deproteinized and decolorized. All the polymers were consisted mainly of mannose followed by galactose and arabinose. Besides presence of fucose, uronic acid, and pyran ring structure was also evident. Molecular weight

11

Auricularia spp.: from Farm to Pharmacy

329

of the isolated macromolecules ranged from 1.26  106 to 6.9  105 Da. The carbohydrate chains under investigation exhibited potent activity where the effect decreased in the order of A. polytricha > A. auricula > A. cornea. Interestingly, the outcome in DPPH•, O2•, OH• quenching assays was found to be enhanced with increase in molecular weight of the macromolecule. Conversely, fucose and galactose were identified to be negatively associated with FRAP method (Su and Li 2020). Lin et al. (2013) tested antioxidant activity of methanol extracts from three gelatinous mushrooms including cultivated A. polytricha and white variety of A. fuscosuccinea. Analysis showed that fraction from A. fuscosuccinea presented the best potential in DPPH• scavenging, chelating ability of Fe2+, reducing power, and total antioxidant assays. While A. polytricha also exhibited effective activity which was lower than A. fuscosuccinea but superior to the other investigated macrofungus. White variety of A. fuscosuccinea possessed the highest SOD activity (2.1 U/mg), whereas glutathione reductase activity (7.97 U/g) was the best in case of A. polytricha. All the prepared fractions were mainly composed of phenolics and flavonoids where the contents were in the highest amounts in white variety of A. fuscosuccinea. It could thus be assumed that the phenolics played a key role behind the antioxidant activity of the newly cultivated mushroom. Mau et al. (2001) examined the antioxidant properties of methanol extracts from several ear mushrooms commercially available in Taiwan including black ear (A. mesenterica), red ear (A. polytricha), jin ear (A. fuscosuccinea, brown strain), and snow ear (A. fuscosuccinea, white strain). Overall snow ear mushroom presented the most effective property in all investigating assays, namely reducing power and OH• quenching assays. Conversely, red ear executed the best effect in conjugated diene method. The outcome could be justified by extent of bioactive compounds as snow ear mushroom consisted of the highest amount of phenol and tocopherol resulting in satisfactory extractive yield of the fraction. The extract was also consisted of ascorbic acid in moderate quantity. Bandara et al. (2017) domesticated A. thailandica and isolated two fractions to investigate antioxidant activity. Overall methanol extract exhibited better DPPH• and ABTS radical scavenging properties than aqueous fraction which might be presence of phenolics in higher quantity. Three fractions were prepared from Auricularia sp. and investigated for their ability to scavenge DPPH•. All the extracts showed considerable antioxidant activities that increased in a dose-dependent manner. Of the preparations, 70% ethanol fraction exhibited the highest scavenging activity followed by chloroform extract. While hot water preparation presented the most inferior efficacy as evident by the highest EC50 value (Gebreyohannes et al. 2019).

330

S. Khatua et al.

11.4.2 Antimicrobial Activity Currently, growing emergence of drug-resistant bacterial strain is a serious problem in the world. Abundant use of antibiotics and acquired mutations assisting bacterial survival have contributed to the non-susceptibility of microorganisms to commonly used drugs (Oli et al. 2020). While it is impossible to prevent bacterial evolution, it is important to choose the most appropriate compounds minimizing development of drug-resistant strains. Thus there will forever be a need for novel antimicrobial agents to outwit bacteria and other pathogens (Ren et al. 2014). In this context, several studies have reported antimicrobial effect of Auricularia spp. in terms of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values as well as zone of inhibition as summarized in Table 11.5. A number of articles have been published till date describing antimicrobial effect of A. auricula-judae with special emphasis on its organic fraction. Yu and Oh (2016) isolated three fractions from the mushroom using various solvents (acetone, ethyl acetate, and ethanol) and their bioactivity was investigated using disc diffusion method. The acetone extract consisting polyphenol in the highest concentration showed the best effect against all the tested pathogens, namely Bacillus subtilis, Escherichia coli, Enterobacter cloacae, Micrococcus luteus, Pseudomonas aeruginosa, and Staphylococcus aureus. The least efficacy was presented by ethyl acetate fraction as it was not able to inhibit three tested bacteria. Bacillus subtilis showed the most susceptible nature, while S. aureus presented more resistant quality. The observation contradicts with Han et al. (2018) depicting ethyl acetate fraction as the most promising antibacterial preparation in comparison with ethanol and acetone extracts. All the preparations were able to inhibit growth of nine oral bacteria that cause dental caries and periodontal diseases (S. aureus, Streptococcus mutans, Streptococcus sanguinis, Streptococcus sobrinus, Streptococcus criceti, Streptococcus ratti, Streptococcus anginosus, Actinomyces viscosus, and Actinomyces israelii). Among the investigated pathogens, A. viscosus emerged as the most susceptible microorganism. Sukmawati et al. (2019) isolated 96% ethanolic extract from A. auricula which was further subjected to fractionation using n-hexane, ethyl acetate, and methanol-water solvents. Each extract was tested for antimicrobial activity by microdilution technique against four pathogenic bacteria. Based on the result it could be said that ethyl acetate fraction possessed the best antimicrobial activity against S. aureus, E. coli, Bacillus cereus, and P. aeruginosa. Among the tested microbes, S. aureus showed the most susceptibility nature as evident by the lowest MIC value. Observation under scanning electron microscopy (SEM) indicated exposure of the fraction caused a noticeable change in shape and size of S. aureus. Compositional analysis revealed presence of tannin in the ethyl acetate fraction that might have played a role behind antimicrobial properties. In a separate study, a comparative analysis between water and ethanol fractions of A. auriculajudae was performed. Among the investigated bacteria, B. subtilis, S. aureus, and Salmonella typhi presented quite susceptible nature in contrast to E. coli and P. aeruginosa. Qualitative phytochemical screening analysis revealed presence of

11

Auricularia spp.: from Farm to Pharmacy

331

Table 11.5 Antibacterial activity of Auricularia spp. as determined by MIC and MBC values (mg/mL) and zone of inhibition (mm) Name of mushroom A. Auricula

Extract/ active compound Ethanol extract

Cold water extract

A. Auriculajudae

Ethanol extract

Tris buffer protein extract

Tested microorganism Bacillus cereus Salmonella typhi Proteus mirabilis Klebsiella pneumoniae Escherichia coli C. albicans Bacillus cereus Proteus mirabilis Klebsiella pneumoniae Streptococcus pneumonia Escherichia coli C. albicans Bacillus subtilis (MTCC 736) Salmonella typhi (MTCC 3216) Staphylococcus aureus (MTCC 3160) Escherichia coli (MTCC 40) Pseudomonas aeruginosa (MTCC 7837) Staphylococcus aureus Escherichia coli Pseudomonas aeruginosa Klebsiella pneumoniae Bacillus subtilis Candida albicans Trichophyton schoenleinii

MIC ND ND

MBC ND ND

Zone of inhibition 7.7 4.7

ND

ND

3.11

ND

ND

1.77

ND ND ND ND

ND ND ND ND

1.66 4.89 4.22 2.1

ND

ND

1.46

ND

ND

4.7

ND ND 12.5

ND ND ND

2.62 9.1 ND

12.5

ND

ND

12.5

ND

ND

50

ND

ND

50

ND

ND

0.05

ND

3.66

0.02 0.05

ND ND

6 4

0.05

ND

2.33

0.05 0.05

ND ND

3 3.33

0.05

ND

2.33

References Nwachukwu and Uzoeto (2010)

Deka et al. (2017)

Oli et al. (2020)

(continued)

332

S. Khatua et al.

Table 11.5 (continued) Name of mushroom

Extract/ active compound Warm aqueous protein extract

Acetone

Ethanol extract

Tested microorganism Staphylococcus aureus Escherichia coli Pseudomonas aeruginosa Klebsiella pneumoniae Bacillus subtilis Candida albicans Trichophyton schoenleinii Staphylococcus aureus (KCTC 1927) Streptococcus mutans (KCTC 3065) Streptococcus sanguinis (KCTC 3284) Streptococcus sobrinus (KCTC 3308) Streptococcus criceti (KCTC 3640) Streptococcus ratti (KCTC 3655) Streptococcus anginosus (KCTC 3983) Actinomyces viscosus (KCTC 5531) Actinomyces israelii (KCTC 9054) Staphylococcus aureus Streptococcus mutans Streptococcus sanguinis

MIC 0.05

MBC ND

Zone of inhibition 3.66

0.02 0.05

ND ND

3.66 2.66

0.05

ND

2.33

0.05 0.05

ND ND

3 1.66

0.05

ND

2

1.88–3.75

ND

ND

3.75

ND

ND

1.88–3.75

ND

ND

3.75

ND

ND

0.94–1.88

ND

ND

1.88–3.75

ND

ND

1.88

ND

ND

0.94–1.88

ND

ND

1.88

ND

ND

1.88–3.75

ND

ND

3.75

ND

ND

1.88–3.75

ND

ND

References

Han et al. (2018)

(continued)

11

Auricularia spp.: from Farm to Pharmacy

333

Table 11.5 (continued) Name of mushroom

Extract/ active compound

Ethyl acetate extract

A. polytricha

Methanol extract

Methanol and hexane extracts

Tested microorganism Streptococcus sobrinus Streptococcus criceti Streptococcus ratti Streptococcus anginosus Actinomyces viscosus Actinomyces israelii Staphylococcus aureus Streptococcus mutans Streptococcus sanguinis Streptococcus sobrinus Streptococcus criceti Streptococcus ratti Streptococcus anginosus Actinomyces viscosus Actinomyces israelii Bacillus cereus

MIC 3.75

MBC ND

Zone of inhibition ND

1.88–3.75

ND

ND

1.88–3.75

ND

ND

1.88–3.75

ND

ND

0.94–1.88

ND

ND

1.88

ND

ND

0.94–1.88

ND

ND

3.75

ND

ND

0.94

ND

ND

1.88

ND

ND

0.94–1.88

ND

ND

1.88

ND

ND

0.94–1.88

ND

ND

0.23

ND

ND

0.47–0.94

ND

ND

3.75

ND

Gbolagade and Fasidi (2005)

Escherichia coli

3

ND

Proteus vulgaris

5.5

ND

Staphylococcus aureus Staphylococcus aureus (MTCC 73)

7

ND

12 (HDM), 7 (FDM) 18 (HDM), 13 (FDM) 10 (HDM), 5 (FDM) 7 (HDM)

0.78

ND

ND

Singh and Tripathi (2018)

References

(continued)

334

S. Khatua et al.

Table 11.5 (continued) Name of mushroom

Auricularia sp.

Extract/ active compound

Chloroform

70% ethanol

Hot water

Tested microorganism Klebsiella pneumoniae (MTCC 109) Escherichia coli (MTCC 739) Cryptococcus neoformans (ATCC 3204) E. coli (clinical isolate) K. pneumoniae (ATCC 13883) P. aeruginosa (clinical isolate) P. aeruginosa (ATTC 27853) MRSA (ATCC 33591) S. aureus (ATCC 25923) C. albicans (clinical isolate) C. parapsilosis (ATCC 90018) E. coli K. pneumoniae P. aeruginosa P. aeruginosa MRSA S. aureus C. albicans C. parapsilosis E. coli K. pneumoniae P. aeruginosa P. aeruginosa MRSA S. aureus C. albicans C. parapsilosis

MIC 0.78

MBC ND

Zone of inhibition ND

1.56

ND

ND

1.56

ND

ND

2

2

ND

1.33

1.33

ND

2

2

ND

1.67

1.67

ND

1

1.33

ND

1

1

ND

1.33

2

ND

1.33

2

ND

1.33 1 1.67 1.33 1 0.83 1.33 1 1 0.83 1.33 1.33 1 0.83 1 0.83

1.33 1.33 1 1.33 1 0.83 1.33 1.33 1.17 0.8 1 0.83 1 0.67 1.33 1

ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND ND

ND not determined, HDM hole diffusion method, FDM filter paper disc method

References

Gebreyohannes et al. (2019)

11

Auricularia spp.: from Farm to Pharmacy

335

tannin, saponin, steroid, terpenoid, and flavonoid in the fractions (Deka et al. 2017). The report was in accord to Nwachukwu and Uzoeto (2010) describing S. typhi and P. aeruginosa as the most resistant bacteria to ethanol, hot and cold water extracts of A. auricula. Overall, the organic fraction being enriched in bioactive components showed a wide spectrum of antimicrobial effect against Gram-negative bacteria (E. coli, P. aeruginosa, Klebsiella pneumoniae, Proteus mirabilis, S. typhi), Gram positive bacteria (B. cereus, S. aureus, Streptococcus pneumoniae), and yeast (Candida albicans) where the cold water fraction presented the least activity. In contrast to secondary metabolites, less attention has been paid on primary metabolites. Recently a crude polysaccharide from A. auricula-judae was investigated for antimicrobial effect. The macromolecules exhibited potential against food borne pathogens, S. aureus and E. coli. The inhibitory effect against S. aureus was consistent when pH ranged between 5.5 and 9 in testing solution and even at high temperature (120  C for 15 min) indicating heat resistance nature of the sample. However, the extract was not effective enough to render growth of other investigated bacteria (B. subtilis and M. luteus) and fungi (Saccharomyces cerevisiae and Aspergillus niger) (Cai et al. 2015). Oli et al. (2020) aimed to determine the bioactive contents of A. auricula-judae and evaluated antimicrobial effect of its protein extract against some selected pathogens. For that, Tris buffer and warm aqueous protein extracts were prepared where both the fractions showed antimicrobial activities against studied pathogens (B. subtilis, E. coli, P. aeruginosa, K. pneumoniae, S. aureus, and C. albicans) except for Trichophyton mentagrophytes, Microsporum gypseum, and Microsporum ferrugineum. Comparatively E. coli was detected as the most sensitive microorganism to Tris and warm aqueous extracts. The phytochemical analysis of crude extracts revealed carbohydrate and protein as the major components. Alongside, A. polytricha has also been used to determine antimicrobial effect; however, reports are scarce. Literature survey revealed that methanol extract from the mushroom possesses inhibitory effect against pathogenic bacteria (B. cereus, E. coli, S. aureus, K. pneumoniae, Proteus vulgaris) and fungal strain (Cryptococcus neoformans). It might be due to presence of phytochemicals such as phenols, flavonoids, ascorbic acid, carotene, and lycopene in higher extent in the organic fraction (Gbolagade and Fasidi 2005; Singh and Tripathi 2018). However ethanol preparation from cloud ear exhibited potent activity against P. aeruginosa along with other studied microbes such as E. coli, E. faecalis, and C. albicans. In this case, S. aureus appeared to be quite resistant as evident by minimum inhibition zone. In contrast, water extract from the mushroom could not inhibit growth of any microorganism (Avcı et al. 2016). Wong et al. (2013) prepared ethanol extracts from five different edible mushrooms and tested for their antibacterial activities against both Gram positive (S. aureus and M. luteus) and Gram-negative (E. coli and P. aeruginosa) strains, using Kirby–Bauer disk-diffusion method. Results showed that A. polytricha exhibited potent activity against all investigated microbes where zone of inhibition ranged from 5 to 15 mm. S. aureus and P. aeruginosa exhibited susceptibility, while other two bacteria presented comparatively resistant nature. Overall, A. polytricha presented better potential than other macrofungi under study.

336

S. Khatua et al.

Gebreyohannes et al. (2019) prepared three extracts from Auricularia sp. using chloroform, 70% ethanol and water solvents and tested against six bacterial species (including clinical isolates and standard strains) as well as two yeast species. All the fractions presented potent activity against tested pathogens where MIC and MBC values ranged from 0.83 mg/mL to 2 mg/mL and 0.67–2 mg/mL, respectively. Overall, Gram-negative bacteria, namely E. coli and P. aeruginosa presented more resistant nature in comparison with Gram positive microbes. Of all investigated extracts, hot water fraction showed the strongest antibacterial activity particularly against S. aureus. Protein free polysaccharide was isolated from A. auricula which was further graded into two fractions. All three bio-polymers were then chemically modified by chlorosulfonic acid-pyridine method. Further they were added with Newcastle disease virus (NDV) into cultivation system of chicken embryo fibroblast in three manners, pre-, post- and simultaneous-adding polysaccharide with NDV, respectively. All three sulfated polymers exhibited positive response as they could prevent, treat NDV infection and directly kill NDV. Interestingly modified macromolecules exerted superior efficacy than that of native polymer confirming that sulfation modification could enhance antiviral activity of polysaccharide (Nguyen et al. 2012). To determine anti-human immunodeficiency virus (HIV)-1 effect of A. polytricha, Sillapachaiyaporn et al. (2019) sequentially extracted the basidiocarps initially with hexane, then ethanol and at last with cold water. Result demonstrated that hexane extract could inhibit HIV-1 replication by blocking respective protease activity (EC50 of 0.8 mg/mL). Further four purified components (two triacylglycerols, linoleic acid and ergosterol) were isolated from the crude hexane extract. All the compounds exhibited HIV-1 protease inhibition activity, but their potential was inferior to the original fraction, suggesting synergistic effect.

11.4.3 Cytotoxic, Antitumor, and Anticancer Effect Cancer is deliberated as humanitarian disaster that encompasses a complex group of more than 100 different types of disorders. During onset of the process, a normal cell is transformed into malignant form via genetic mutation that may be caused by exposure to cigarette smoke or ultraviolet radiation (Patel and Goyal 2012). As a result, damaged cells undergo an uncontrolled proliferation and promptly produce an irregular mass called tumor. Eventually the cells get separated from parent lump, invade surrounding tissues, and migrate through lymphatic or blood system. Further these cells set up secondary foci at distant sites, responsible for 90% of cancer causing deaths (Song et al. 2013). At present, it is estimated that around 12.7 million people are diagnosed with cancer annually across the globe, while by 2030 over 21 million new cancer cases are expected among them 13 million may expire (Bhanot et al. 2011). To ameliorate the condition, therapeutic medicines are available in market, although they exhibit unsatisfactory consequences as they cause

11

Auricularia spp.: from Farm to Pharmacy

337

severe side effects. In this backdrop, natural products derived edible mushrooms might play a pivotal role in chemoprevention (Khatua et al. 2019, 2021). A comparative analysis on cytotoxicity of three extracts of A. auricula was performed by Li et al. (2012). Results showed that alkaline fraction exhibited the most aggressive nature towards HeLa cell growth inhibition (21.44%). The acidic preparation also showed effective potential by reducing 15.13% cell population where water fraction displayed the lowest affinity. Conversely, all three fractions presented similar kind of cytotoxic effect (16.14–19.45%) towards HepG2 cell where the aqueous fraction exhibited the best effect. Interestingly, the fractions presented lower cytotoxic effect on normal human endothelial cell line (ECV304) indicating cancer cell specific activity. Similar observation has also been reported by Reza et al. (2014) comparing cytotoxic activity of 100 Korean wild plants and three mushrooms including A. auricula-judae. Seventy percent ethanolic extract from A. auricula-judae exhibited the most potent inhibitory activity against P388D1 macrophage tumor cell line by inhibiting growth of 42.21% in treatment of 1 mg/mL concentration. The organic fraction executed potent cytotoxic activities on Sarcoma 180, human NSCLC NCI H358 (bronchoalveolar) and SNU 1 (gastric carcinoma) cell lines as well where the effect was about 1.5 times greater than P388D1 cell. In contrast to the organic preparation, water fraction from the mushroom exhibited lower efficacy. A linear water-soluble, branched (1 ! 3)-β-D-glucan consisting a single helical chain was isolated from A. auricula. The polysaccharide exhibited strong inhibitory activity against implanted Sarcoma 180 (S180) solid tumor in mice. Researchers further investigated correlation between structural features and antitumor potential. They assumed that attachment of poly-hydroxy groups to the bio-polymer backbone might enhance pharmacological property. While partial introduction of carboxymethyl group into glucan failed to augment the effect (Misaki et al. 1981). At the same time, two kinds of acidic heteroglycans were isolated by hot aqueous 70% ethanol and hot water extracts from wild A. auricula-judae. Both the polymers were glucuronoxylomannans containing O-acetyl groups (Ukai et al. 1982). Similar kind of carbohydrate chain was also isolated from Auricularia sp. (Japanese local name Yu ji, Chinese local name Yū ěr). All the macromolecules were tested for antitumor activity against subcutaneously implemented S180 in mice by intraperitoneal administration. Among them, considerable activity was noted in case of Auricularia sp., while other two samples portrayed lower potential (Ukai et al. 1983). More recently, a water-soluble β-glucan (AAG) was isolated from A. auricula-judae that contained 19% glucuronic acid with Mw of 2.88  105. The polymer was incubated with Acinar cell carcinoma (ACC) tumor cells to evaluate antitumor effect and result showed dose-dependent cytotoxic effect. In vivo result showed AAG significantly inhibited tumor growth where the dose 20 mg/kg exhibited the best effect. The histological section of tumor tissues showed nucleus atrophy, chromatin condensation, cell shrinkage, plasma membrane blabbing, and formation of membrane-enclosed apoptotic bodies in AAG-treated mice. Further analysis revealed that the injection of AAG in S-180 tumor tissue section caused augmentation of expression of Bax, while decreased level of Bcl-2 dramatically. The

338

S. Khatua et al.

immunohistochemical results indicated that AAG could induce apoptosis in S-180 tumor cell by upregulating Bax and downregulating Bcl-2 (Ma et al. 2010). In case of A. polytricha, a crude polysaccharide was isolated and separated into three parts, namely APPI, APPII, and APPIII to test their antitumor effect on S180 bearing mice. Amongst them, only APPII showed significant antitumor effect and thus was selected for further purification (APPIIA and APPIIB). The result of antitumor test (in vivo) revealed that only the fraction APPIIA possesses the bioactivity where the tumor growth inhibition ratio was about 53.6% (Yu et al. 2009). In another study, β-glucan with average molecular weight of about 1.2  106 Da (AAFRC) was isolated from A. polytricha. The macromolecule significantly inhibited growth of transplantable S180 in mice with inhibitory rate of 43.61%. The treatment also reduced average tumor weight of mice from 2.367 to 1.382 g. In addition, no signs of toxicity were observed in the mice treated with the polysaccharide on the base of body weight and microscopic examination of individual organs (Song and Du 2012). A crude polysaccharidic fraction was isolated from A. polytricha basidiocarps by hot water process. The macromolecules induced cytotoxicity in human lung cancer A549 cells in a dose-dependent manner where 50% cellular growth was prohibited by the treatment of 28.07 μg/mL after 48 h. Exposure of the extract also induced apoptotic cell death, affected DNA synthesis and arrested cell cycle progression at G0/G1 phase. The outcome was mediated by reduced expression of cyclin A, cyclin D, and cyclin-dependent kinase (CDK)2, as well as the alleviated level of p21 and p53. Further investigation highlighted involvement of mitochondrial pathway as co-incubation of cells with the preparation caused release of cytochrome c that in turn activated caspase-9, -3, and poly (ADP-ribose) polymerase (PARP) cleavage. Additionally, the fraction displayed a repressing effect on lung tumorigenesis by decreasing growth of A549 xenografts in nude mice (Yu et al. 2014). Reza et al. (2014) prepared 70% ethanol extract from A. auricula-judae and obtained dichloromethane, ethyl acetate, butanol, and water fractions. All the preparations exhibited cytotoxic activities against NCl H358 and SNU1 in a dosedependent manner. Comparatively in case of NCl H358, the effect was observed in the order of dichloromethane > butanol > ethanol > ethyl acetate > water fraction. Similar trend was also followed in case of SNU1 except ethanol extract presenting the lowest efficacy. To further evaluate ability of dichloromethane to promote apoptosis, mRNA expression was measured. Reverse transcriptase-PCR showed that the treatment downregulated expression of BCl-2 and alleviated level of p53 in both the cell lines.

11.4.4 Immune-Modulation Activity Immunomodulatory drug modifies response of the immune system by increasing (immunostimulators) or decreasing (immunosuppressives) production of serum antibodies. Thus immunostimulators are prescribed when defense mechanism needs to

11

Auricularia spp.: from Farm to Pharmacy

339

be boosted against infectious diseases, tumors, immunodeficiency, and alteration in antibody transfer, so forth. Conversely immunosuppressive drugs are utilized to reduce the response against transplanted organs and to treat autoimmune diseases (Bascones-Martinez et al. 2014). Various medicines available for controlling immune response; however, they are associated with adverse effects. Hence goal of the present research is to achieve increased pharmacological response and the lowest degree of unwanted side effects (Khatua and Acharya 2018, 2019a, b). Nguyen et al. (2012) extracted crude total AAP (AAPct) from A. auricula by water decoction and ethanol precipitation method, then purified in turn by removing proteins to obtain total AAP (AAPt). Column chromatography was used to grade AAPt into AAP1 and AAP2. Three sulfated AAP (sAAP): (sAAPt, sAAP1, and sAAP2) were prepared by chlorosulfonic acid–pyridine method. Further effects of all these isolated molecules on chicken peripheral lymphocytes proliferation were determined and compared. The results showed that sAAPt and sAAP1 demonstrated better effect. 14-day-old chickens were injected, respectively, with sAAPt, sAAP1, AAPt, and AAP1 at the first vaccination of ND vaccine, once a day for 3 days. After 7, 14, 21, and 28 days of the first vaccination, peripheral lymphocytes proliferation and antibody titer were noted. Overall the best efficacy was executed by sAAPt indicating potency to be used as a component of immunopotentiator. Cyclophosphamide (CTX) is an immunosuppressive agent that is used to treat cancers; although it can adversely alter gut microbiota modulation and mucosal barrier breakdown. To determine whether pure polysaccharide from A. auricula could ameliorate the condition, the macromolecule was administrated to mice treated with CTX. Result showed that the polysaccharide treatment significantly enhanced immune organ indexes, signifying protective effect on host immune system. CTX inhibited production of immune-related cytokines (IL-2, IFN-γ, IL-10, IL-4, and TNF-α), where the treatment with carbohydrate reversed the situation. Besides, the natural product significantly increased level of tight junction proteins, namely Claudin-1, Occludin, and ZO1, suggesting that the drug under study could effectively restore intestinal barrier function. The polysaccharide also regulated composition of gut microbiota and enhanced synthesis of short-chain fatty acids in immunosuppressed mice (Kong et al. 2020). A dichloromethane extract of A. auricula-judae was isolated by steeping the powder in 80% ethanol and then subjecting the powder in CHCl2. The fraction was dissolved in PBS (10–100 μg/mL) and incubated with RAW 264.7 cells treated with LPS (1 μg/mL) for 24 h. Study indicated that the extract under investigation markedly reduced nitric oxide (NO) synthesis and expressions of inflammatory cytokines (IL-6, TNF-α, and IL-1β) in LPS-treated murine RAW 264.7 macrophages indicating the fraction could possibly ameliorate inflammation (Damte et al. 2011). To determine immune-modulatory effect of A. polytricha, a protein of molecular mass of ~13.4 kDa and isoelectric point (pI) of ~5.1 was purified from fruiting body. Amino acid composition of the protein indicated that it was comprised of large quantities of threonine. The protein at the dose of 2.5–20 μg/mL increased accumulation of nitrite and TNF-α production by LPS-activated cells. The protein alone significantly increased IFN-γ levels in cultured soup of treated murine splenocytes

340

S. Khatua et al.

and also promoted proliferation of the cells. The protein was demonstrated to reduce cell proliferation when murine splenocytes were stimulated with mitogen ConA (Sheu et al. 2004). Treatment of polysaccharide from A. polytricha enhanced mRNA transcription level of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and inducible nitric oxide synthase (iNOS) in a dose-dependent manner. Exposure of the macromolecule also aggrandized protein expression level of iNOS that might inhibit tumor markedly (Luo et al. 2009a).

11.4.5 Hypolipidemic/Hypocholesterolemic Effect Hypercholesterolemia is a serious metabolic disorder being characterized by abnormally high lipid (triglyceride and cholesterol) and lipoprotein (low-density lipoprotein-cholesterol or LDL-C and very low-density lipoprotein-cholesterol or VLDL-C) levels in blood. It is a major risk factor in hypertension, atherosclerosis, ischemic heart disease, and other cardiovascular disorders, which are the most frequent causes of death in developed world (Zhao et al. 2015). At present, the main treatment involves smoking cessation, exercise, proper diet, and medication (Wan et al. 2020). Conventional lipid-lowering drugs include statins, fibrates, bile-acid sequestrants, and nicotinic acid. However, they have limited efficacies and cause severe side effects including polyneuropathy, rhabdomyolysis, and myopathy which still need to be overcome. Thus, more efficacious and safer anti-hypercholesterolemic agents are highly needed (Yu et al. 2017). To evaluate effect of A. auricula, rats were fed with two semisynthetic hypercholesterolemic diets (1.5% cholesterol and 5% fat) each containing 5% dried powder of the mushroom. After 4 week of mushroom diet consumption, the serum total cholesterol and LDL cholesterol concentrations were found to be decreased by 17% and 24%, respectively. Besides the treatment caused augmentation in the levels of fecal neutral steroids and bile acids by 39% and 46%, respectively. The researcher assumed that presence of β-glucan in the mushroom inhibited formation of micelles in small intestine of rats and thus lowered cholesterol absorption (Cheung 1996). Luo et al. (2009b) fed mice cholesterol enriched diet in combination with a functional diet. The formula was prepared by mixing water-soluble crude polysaccharide from A. auricula (80%) and 80% ethanol extract from hawthorn fruit in a ratio of 4:1. The diet effectively lowered serum total cholesterol (TC) and atherogenic index, improved serum and hepatic antioxidant status demonstrating potent hypolipidemic effect. Chen et al. (2011) determined effects of A. auricula ethanol extract (AAE) on the serum lipid profiles, hepatic lipid profiles, antioxidant status, and fecal excretion of neutral cholesterol and bile acids in ICR mice fed with CED. The AAE made with this purification process contained more than 16% (g/g) A. auricula polyphenolic compounds. In this experiment, administration of AAE to the CED-fed ICR mice showed no significant difference on levels of weight gain, food intake, and feeding

11

Auricularia spp.: from Farm to Pharmacy

341

efficiency. CED intake led to an increase of cholesterol content both in serum and liver. Oral administration of AAE had a distinct cholesterol lowering effect by decreasing the levels of serum TC, hepatic TC and TG, accordingly reduced the risk of CHD. AAE was also able to decrease AI significantly, contributing to the lower risk in pathology of hyperlipidemia and atherosclerosis. To elucidate the underlying mechanism, hepatic HMG-CoA reductase activity was investigated which was found to be lower after AAE treatment. Administration of AAE could significantly reduce levels of MDA, lipid peroxides, and aggrandized activities of hepatic SOD and TAC. To evaluate effect of A. polytricha on cholesterol metabolism, rats were fed with a cholesterol diet plus 5% ground dried mushroom for 30 days. Analytical data of mushroom preparation showed presence of 10.56% water, 7.8% protein, 2.2% fat, 86.98% sugar as well as crude fiber and 3.02% ash. The treatment reduced plasma cholesterol level, although the overall outcome was lower than other investigated mushrooms, namely Agaricus bisporus and Lentinus edodes (Kaneda and Tokuda 1966). A glycoprotein with a molecular size of 32 kDa was isolated from a submerged mycelial culture of A. polytricha. Mannose was identified as the major component in the carbohydrate backbone followed by galactose. To determine lipid-lowering effect, the macromolecule was fed rats at the levels of 50–100 mg/kg body weight. Result showed that levels of plasma triacylglycerol, total cholesterol, and low-density lipoprotein (LDL) cholesterol steadily decreased with increasing concentration of the polymer (Yang et al. 2002). Budinastiti et al. (2018) designed a research to analyze impact of cloud ear fungus broth on total cholesterol, LDL, and HDL level of Wistar rats that have been given reused cooking oil. Results showed that the fraction from A. polytricha could lower the total cholesterol content as much as 43.39% and LDL cholesterol as much as 49.78% and increased the HDL cholesterol content as much as 55.73% on mouses. Zhao et al. (2015) adopted response surface methodology to optimize extraction parameters for isolation of soluble polysaccharide from A. polytricha. To determine bioactivity, the macromolecule was orally administered to hypercholesterolemic rats for 28 days at two different doses, i.e. 4.5 mg/kg BW and 9.0 mg/kg BW. Both the treatments significantly decreased serum levels of total cholesterol, triglycerides, and LDL cholesterol.

11.4.6 Antidiabetic/Hypoglycemic Effect Diabetes mellitus (DM), a serious disorder of carbohydrate metabolism, is a clinical syndrome characterized by hyperglycemia (high level of glucose in blood), high glycated hemoglobin, and an elevated risk of morbidity and mortality (Gad-Elkareem et al. 2019). There are mainly two types, namely type 1 or insulindependent diabetes mellitus (IDDM) (resulting from selective destruction of insulinproducing β cells in pancreas) and type 2 (T2DM) or non-insulin-dependent diabetes

342

S. Khatua et al.

mellitus (NIDDM) (resulting from insulin resistance and impaired insulin secretion). Most of the cases are T2DM where symptoms include hunger, increased thirst, frequent urination, fatigue, and blurred vision. According to the report presented by International Diabetes Federation (IDF) in 2015, T2DM affects more than 200 million people worldwide which may reach 642 million by 2024 (Khan et al. 2018). The currently available modern drugs used for the DM treatment are often associated with limitations such as high cost, inadequate efficacy, and toxicity (Alema et al. 2020). Hence there is a growing need for development of novel strategies with fewer side effects, such as ethnobotanical medications (Gad-Elkareem et al. 2019). In this backdrop, Yuan et al. (1998) isolated a crude polysaccharide fraction by hot water process from A. auricula-judae to determine NIDDM effect. Dietary supplementation of the polysaccharide at 3% level reduced plasma glucose concentration and urinary glucose excretion. The diet caused increase in hepatic glycogen content that might in turn contributed in suppression of postprandial high serum glucose and insulin levels and improve glucose tolerance in KK-Ay mice. The supplementation caused slight decrease in food consumption (14%) resulting in decline in water intake (21%). The hypoglycemic effect of the fraction under investigation might be partially related to its viscosity. Takeujchi et al. (2004) fed KK-Ay mice a diet encompassing fat along with 5% water extract from A. auricula-judae for 3 weeks. The treatment caused decrease in food uptake, energy expenditure, and water consumption without causing change in body weight. Besides the drug under study resulted in diminished blood glucose level suggesting hypoglycemic effect of the extract. A model of T2DM using high-fat diet and low-dose streptozotocin (STZ) was established to investigate antidiabetic effects of A. auricula polysaccharides simulated hydrolysates. The sample was administered intragastrically (i.g.) at the dose of 0.15 g/kg BW to diabetic Wistar rats. After 4 weeks of administration, fasting blood glucose (FBG) was found to decrease by 23.7%. Besides the treated group showed reduction of 14.6% in blood glucose level measured 120 min after administration of glucose, compared with diabetic control rats. Significant increment of glucagon-like peptide-1 (GLP-1) level was also noticed indicating that the drug might partly restore apoptosis in pancreatic islet cells induced by STZ. Moreover, untreated rats developed obvious clinical diabetes signs including polydipsia, polyphagia, polyuria, and body weight loss which were found to improve in the treated group. Administration of the sample also resulted in significant diminution in low-density lipoproteincholesterol (LDL-C) level (Lu et al. 2018).

11.4.7 Hepatoprotective Effect The term hepatic disease signifies cells, tissues, or liver function damage that can be induced by biological factors, autoimmune diseases, and due to different chemicals like high dose of some drugs, toxic compounds [carbon tetrachloride (CCl4)], and

11

Auricularia spp.: from Farm to Pharmacy

343

unquestionably excessive consumption of alcohol. Despite enormous advances in modern health-care system, there is no completely effective drug aiding in regeneration of hepatic cells. Additionally some drugs have shown potency to induce adverse effects. It is thus need of the hour to identify less toxic and more effective pharmaceuticals for treatment of hepatic diseases (Madrigal-Santillán et al. 2014). Wang et al. (2018) evaluated hepatoprotective effects of A. cornea polysaccharides (APS) and enzymatic-extractable APS (EAPS) on acute alcohol-induced alcoholic liver diseases (ALD). The acute alcohol injection resulted in elevation in activities of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT), which were decreased by the samples. Besides both APS and EAPS had effects on improving lipid metabolism, again EAPS showed superior effect than APS. Interestingly administration of polysaccharides in enhancing activities of superoxide dismutase (SOD), GSH peroxide (GSH-Px), and catalase (CAT) and decreasing lipid peroxidation of malondialdehyde (MDA) contents could be observed as well, demonstrating that drugs under study had potential effects on remitting alcohol-induced oxidative stress. After administration of APS or EAPS at different dosages, hepatic TC and triacylglycerols (TG) levels were significantly reduced. Furthermore, the acute alcohol injection induced enhancement of hepatic CYP2E1 contents which were diminished by the polysaccharides. Results also revealed that administration of alcohol promoted levels of inflammatory mediators (iNOS, COX-2, IL-1β, TNF-α and IL-6 in liver, and IL-1β, TNF-α, and IL-6 in plasma) which were decreased by the treatment of APS or EAPS. Compared with the regular and orderly architectures of mice in negative control group, ALD mice exhibited severe damages including incomplete morphology, necrosis, massive fatty changes, and different size. Liver sections of mice administrated with APS or EAPS showed more or less normal cellular architecture. Overall study indicated both fractions especially EAPS had potential effects on protection liver tissue against acute alcohol toxicity. Chellappan et al. (2016) isolated an aqueous extract of the fruiting bodies of A. polytricha to evaluate protective effect against paracetamol-induced liver toxicity in rats. Results showed that extract treatment significantly attenuated chemical induced increase in AST, TG, ALT, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), total bilirubin and cholesterol and augmented diminished total protein in a dose-dependent manner.

11.4.8 Anticoagulant Activity Platelet aggregation and blood coagulation are crucial events in pathogenesis of ischemic diseases. The process results in formation of thrombin. Platelets are readily activated and aggregate in response to diverse endogenous substances and activated platelets participate in the propagation of thromboembolism leading to ischemic diseases. Till date, several therapeutic agents have been used in order to prevent and treat thromboembolic disorders. Heparin has been the most commonly used

344

S. Khatua et al.

antithrombotic drug; although it may be accompanied by side effects such as bleeding complications. Researchers are thus searching for other possible heparin substitutes (Yoon et al. 2003). Yoon et al. (2003) performed a comparative study on anticoagulant activity of three extracts of A. auricula. Result showed that the alkali fraction prepared with 0.1N NaOH had a higher anticoagulant activity than acid and water formulations. The preparation was further fractionated and isolated polysaccharide exhibited a higher anticoagulant activity than the original extract. Further a nonsulfated polysaccharide was isolated from the edible mushroom that catalyzed thrombin inhibition by antithrombin and inhibited platelet aggregation and blood clotting ex vivo (Yoon et al. 2003). In another study, a substance was isolated from the aqueous extract of A. polytricha that could inhibit platelet aggregation. The component was later identified to be adenosine and was suggested to be responsible for low incidence of arteriosclerosis among Asians who consumed A. polytricha regularly (Miles and Chang 2004).

11.4.9 Anti-Pesticide Effect Carbofuran (2,3-dihydro-2,2-dimethyl-7-benzofuranyl-N-methyl carbamate; CF) is one of the pesticides commonly used to combat mites, insects, and nematodes in soil for vegetables, fruits, and forest crops. The chemical is extremely toxic and thus exposure of the carbamate results in serious health issues. Despite that, the chemical is now used widely in agricultural and household purposes contaminating environment and causing adverse health effects of wildlife, animals, and human. Oxidative stress has been suggested as a mechanism of CF toxicity; henceforth, exogenous supply of antioxidants might improve the situation (Hossen et al. 2018). In a recent study, Hossen et al. (2018) isolated 95% ethanol extract from A. polytricha which was found to contain mainly gallic acid followed by vanillic acid. Oral administration of CF (1 mg/kg) decreased total body weight gain which was found to be improved in treated group (CF + extract). The chemical also caused adverse effect on mean relative liver weight of the rats compared to normal control group which was increased after administration of the fraction. Exposure to CF was associated with significant decrease in erythrocytic parameters which alleviated in mushrooms and CF-treated rats indicating immunostimulatory effect of A. polytricha. Furthermore, there were also significant increases in leukocyte counts and liver function biomarker levels in serum in the CF-treated group which were ameliorated after co-treatment of the mushroom extract. Further, histomorphological observations in liver and kidney tissues also confirmed protective effects of the studied fraction on CF-induced toxicity. Endosulfan is another insecticide that is present as pollutant in all types of ecosystems including water, air, ground, and at sites near to far from application zone. Accumulation of these residues causes significant effect on soil microbiota and

11

Auricularia spp.: from Farm to Pharmacy

345

prevents production of organic crops. Despite that the chemicals are still used in many countries on important crops. In this background, two strains (ECS-0201 and ECS-0210) of white rot fungi, A. fuscosuccinea demonstrated excellent potential to reduce endosulfan. The activity was performed by cell-free culture broths at temperature 26  C within 8 days. Phenol oxidase and laccase activities were detected in the extracts signifying their role in transformation process. The mushroom thus could be an excellent candidate for endosulfan biodegradation (Yanez-Montalvo et al. 2016).

11.4.10

Other Biological Activity

Proliferation of vascular smooth muscle cell (VSMCs) is known as a potential progression in cardiovascular diseases including hypertension, atherosclerosis, and restenosis. Consequently, the inhibition of proliferation of VSMCs at earlier stage plays a vital role to prevent these diseases. In this background, Luo et al. (2011) prepared a functional diet (AHP) containing polysaccharides from A. auricula, polyphenolic compounds from Hawthorn (Crataegus), and Pueraria radix as stated earlier. Results showed that AHP inhibited proliferation of VSMCs induced by oxidized low-density lipoprotein (oxLDL) in a time and dose-dependent manner. Besides both AAP and AHP could elevate NO production in oxLDL damaged VSMCs by 36% and 74%, respectively, compared with model cell. In a separate study, Pisuena et al. (2003) isolated lectins from ten mushrooms and agglutination assay was performed using whole human blood as well as animal blood (calf, dog, cat, and monkey). The lectin extracted from A. auricula was detected as a glycoprotein containing 3.15% total sugar with molecular weight of 640 kDa. It showed the strongest agglutinating activity among all the studied fungi where the sample did not seem to prefer any specific blood type. The potential decreased with increment of purification level indicating a direct relation between the effect and amount of protein needed for agglutination. Maximum activity was recorded between 0 and 60  C and the effect was destroyed at 90  C possibly due to denaturation of the lectin. Huang et al. (2011) isolated extract from A. auricula-judae to determine effect on lifespan of Drosophila melanogaster. Results suggested that the fraction at the level of 5–20 mg/mL elevated lifespan in male flies. While the preparation at the concentration of 20 mg/mL showed a marked increase in average lifespan, half death time, and maximum lifespan in female flies indicating potential antiaging effect of the mushroom. Interestingly, Mycology Research Laboratories (United Kingdom) have manufactured and commercialized A. auricula-judae in the form of Auricularia MRL™—a dietary supplement which supports immune system and maintains homeostasis (Varghese et al. 2019). Moreover, researchers have found a platelet aggregating inhibitor from crude dialysates of aqueous A. polytricha extracts (Hammerschmidt 1980; Hokama and Hokama 1981). Hokama et al. (1983) reported a blastogenic inhibitory factor extracted from A. polytricha, which suppresses the incorporation of 3H-thymidine in mitogen-induced blood mononuclear cells in vitro.

346

S. Khatua et al.

Extracts of fresh A. polytricha exhibited anti-dementia effect as they inhibited activity of BAC1 (beta site APP cleaving enzyme) that causes release of toxic β-amyloid peptide in brain (Bennett et al. 2013). Water extract of the same mushroom has shown amelioration effect on hepatic injury in an animal model of non-alcoholic fatty liver disease (NAFLD). The effect might be attributed to attenuating inflammatory response, oxidative stress, and lipid deposition (Chiu et al. 2014). A. polytricha also exhibited antinociceptive characteristics. Subcutaneous injection of four compounds isolated from A. polytricha reduced acetic acid-induced writhing in mice (Koyama et al. 2002). Zhou et al. (2013) reported purification, structure characterization, and antimutagenic activity in vivo of a 0.9% NaCl solution-soluble polysaccharide (SSP) from mycelia of A. polytricha. Analysis showed that SSP is a glucan with an average molecular weight of about 9.30  105 Da. The macromolecules significantly prevented micronuclei in polychromatic erythrocytes and reticulocytes of mice indicating antimutagenic activity. Wong et al. (2013) prepared ethanol extracts from five different mushrooms and tested in a brine shrimp (Artemia franciscana) assay to determine their cytotoxic activity. Outcome revealed that the fraction from A. polytricha was able to kill larvae of brine shrimps with median lethal concentration (LC50) of 115.8 μg/mL. Among the mushrooms tested, A. polytricha revealed the lowest cytotoxicity, approximately sevenfold lesser than control suggesting safely consumption of the species in large quantities.

11.5

Conclusion

Auricularia spp. are suitable for a wide range of applications; although there is little research being done and the available knowledge is fragmented. Many studies focused on cultivation strategies of A. polytricha manipulating mycelial culture, spawn production, and substrate formation parameters, where effect of farming on nutraceutical properties remains elusive. Proximate composition profiling revealed that edible members have varying contents of proteins, essential amino acids, polysaccharides, crude fibers, unsaturated fatty acids, and mineral substances, while exploration on vitamin extent is limited. Apart from dietary constituents, the taxa are also blessed with enumerable bioactive compounds with diverse medicinal values. The macrofungi executed promising antioxidant, antibacterial, antiviral, anti-fungal, anti-inflammatory, antidiabetic, hypercholesterolemic, immuneenhancing, anticoagulant, antitumor, and anticancer properties, among others. In this context, A. auricula-judae is in limelight where majority of the studies were designed to explore antioxidant property. More diverse and detailed research on medicinal prospects and pure bioactive compound thus required. Overall the present review concludes that supplementation of edible, wild, or cultivated Auricularia spp. as a dietary composition may become a natural adjuvant for prevention and treatment of several human health diseases.

11

Auricularia spp.: from Farm to Pharmacy

347

References Acharya K, Samui K, Rai M, Dutta BB, Acharya R (2004) Antioxidant and nitric oxide synthase activation properties of Auricularia auricula. Indian J Exp Biol 42:538–540 Afiukwa CA, Oko AO, Afiukwa JN, Ugwu OPC, Ali FU, Ossai EC (2013) Proximate and mineral element compositions of five edible wild grown mushroom species in Abakaliki, southeast Nigeria. Res J Pharm, Biol Chem Sci 4(2):1056–1064 Ahila Devi P, Veeralakshmi S, Prakasam V, Vinothini M (2013) Saw dust and wheat bran substrates for the cultivation of new wood ear mushroom (Auricularia polytricha (Mont.) Sacc). Am Eurasian J Agric Environ Sci 13(12):1647–1649 Alema NM, Periasamy G, Sibhat GG, Tekulu GH, Hiben MG (2020) Antidiabetic activity of extracts of Terminalia brownii Fresen. stem bark in mice. J Exp Pharmacol 12:61–71 Alvarenga RLM, Naves LRR, Xavier-Santos S (2015) The genus Auricularia Bull. ex Juss. (Basidiomycota) in Cerrado (Brazilian Savanna) areas of Goiás state and the Federal District, Brazil. Mycosphere 6(5):532–541 Ao T, Deb CR (2019) Nutritional and antioxidant potential of some wild edible mushrooms of Nagaland, India. J Food Sci Technol 56(2):1084–1089 Avcı E, Çağatay G, Avcı GA, Suiçmez M, Cevher ŞC (2016) An edible mushroom with medicinal significance; Auricularia polytricha. Hittite J Sci Eng 3(2):111–116 Bandara AR, Chen J, Karunarathna S, Hyde KD, Kakumyan P (2015) Auricularia thailandica sp. nov. (Auriculariaceae, Auriculariales) a widely distributed species from Southeastern Asia. Phytotaxa 208(2):147–156. https://doi.org/10.11646/phytotaxa.208.2.3 Bandara AR, Karunarathna SC, Mortimer PE, Hyde KD, Khan S, Kakumyan P, Xu J (2017) First successful domestication and determination of nutritional and antioxidant properties of the red ear mushroom Auricularia thailandica (Auriculariales, Basidiomycota). Mycol Prog 16:1029– 1039 Bandara AR, Rapior S, Mortimer PE, Kakumyan P, Hyde KD, Xu J (2019) A review of the polysaccharide, protein and selected nutrient content of Auricularia, and their potential pharmacological value. Mycosphere 10(1):579–607 Bandara AR, Mortimer PE, Vadthanarat S, Xingrong P, Karunarathna SC, Hyde KD, Kakumyan P, Xu J (2020) First successful domestication of a white strain of Auricularia cornea from Thailand. Stud Fungi 5(1):420–434 Bascones-Martinez A, Mattila R, Gomez-Font R, Meurman JH (2014) Immunomodulatory drugs: oral and systemic adverse effects. Med Oral Patol Oral Cir Bucal 19(1):e24–e31 Bennett L, Sheean P, Zabaras D, Head R (2013) Heat-stable components of wood ear mushroom, Auricularia polytricha (higher Basidiomycetes), inhibit in vitro activity of beta secretase (BACE1). Int J Med Mushrooms 15(3):233–249 Bhanot A, Sharma R, Noolvi MN (2011) Natural sources as potential anti–cancer agents: a review. Int J Phytomed 3:9–26 Boa E (2004) Wild edible fungi: a global overview of their use and importance to people. FAO, Rome Boonsong S, Klaypradit W, Wilaipuna P (2016) Antioxidant activities of extracts from five edible mushrooms using different extractants. Agric Nat Resour 50:89–97 Breene WM (1990) Nutritional and medicinal value of specialty mushrooms. J Food Prot 53(10): 883–894 Budinastiti R, Sunoko HR, Widiastiti NS (2018) The effect of cloud ear fungus (Auricularia polytricha) on serum total cholesterol, LDL And HDL levels on Wistar rats induced by reused cooking oil. In: E3S Web of Conferences, vol 31, p 06006 Bulliard JBF (1787) Herbier de la France 7:336 Butkhup L, Samappito W, Jorjong S (2018) Evaluation of bioactivities and phenolic contents of wild edible mushroom from northeastern Thailand. Food Sci Biotechnol 27:193–202

348

S. Khatua et al.

Cai M, Lin Y, Luo Y, Liang H, Sun P (2015) Extraction, antimicrobial, and antioxidant activities of crude polysaccharides from the wood ear medicinal mushroom Auricularia auricula-judae (Higher Basidiomycetes). Int J Med Mushrooms 17(6):591–600 Carrasco J, Zied DC, Pardo JE, Preston GM, Pardo-Giménez A (2018) Supplementation in mushroom crops and its impact on yield and quality. AMB Express 8:146 Carvalho CSM, Sales-Campos C, Andrade MCN (2010) Mushrooms of the Pleurotus genus: a review of cultivation techniques. Interciencia 35(3):177–182 Chellappan DK, Ganasen S, Batumalai S, Candasamy M, Krishnappa P, Dua K, Chellian J, Gupta G (2016) The protective action of the aqueous extract of Auricularia polytricha in paracetamol induced hepatotoxicity in rats. Rec Pat Drug Deliv Formul 10:72–76 Chen G, Luo Y-C, Ji B-P, Li B, Su W, Xiao Z-L, Zhang G-Z (2011) Hypocholesterolemic effects of Auricularia auricula ethanol extract in ICR mice fed a cholesterol-enriched diet. J Food Sci Technol 48(6):692–698 Cheung PCK (1996) The hypocholesterolemic effect of two edible mushrooms: Auricularia auricula and Tremella fuciformis in hypercholesteremic rats. Nutr Res 16:1721–1725 Cheung PCK (2010) The nutritional and health benefits of mushrooms. Nutr Bull 35:292–299 Cheung PCK (2013) Mini-review on edible mushrooms as source of dietary fiber: preparation and health benefits. Food Sci Human Wellness 2:162–166 Chiu W-C, Yang H-H, Chiang S-C, Chou Y-X, Yang H-T (2014) Auricularia polytricha aqueous extract supplementation decreases hepatic lipid accumulation and improves antioxidative status in animal model of nonalcoholic fatty liver. Biomedicine (Taipei) 4(2):12 Crisan EV, Sands A (1978) Nutritional value. In: Chang ST, Hayes WA (eds) The biology and cultivation of edible mushrooms. Academic Press, New York, NY, pp 137–168 Damte D, Reza MA, Lee S-J, Jo W-S, Park S-C (2011) Anti-inflammatory activity of dichloromethane extract of Auricularia auricula-judae in RAW264.7 cells. Toxicol Res 27(1):11–14 Debnath S, Halam V, Das P, Saha AK (2018) Proximate composition, effects of carbon and nitrogen sources on biomass and exopolysaccharides (epss) production of Auricularia auricula-judae. Vegetos 31(3):30–36 Deka AC, Sarma I, Dey S, Sarma TC (2017) Antimicrobial properties and phytochemical screening of some wild macrofungi of Rani-Garbhanga Reserve Forest area of Assam, India. Adv Appl Sci Res 8(3):17–22 Devi MB, Singh SM, Singh NI (2015) Biomass production in Auricularia spp. (Jew’s ear) collected from Manipur, India. Int J Curr Microbiol App Sci 4(6):985–989 Fan SH, Zhang SH, Yu L, Ma L (2007) Evaluation of antioxidant property and quality of breads containing Auricularia auricular polysaccharide flour. Food Chem 101(3):1158–1163 Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of aging. Nature 408:239– 247 Gad-Elkareem MAM, Abdelgadir EH, Badawy OM, Kadri A (2019) Potential antidiabetic effect of ethanolic and aqueous-ethanolic extracts of Ricinus communis leaves on streptozotocin induced diabetes in rats. PeerJ 7:e6441 Gbolagade JS, Fasidi IO (2005) Antimicrobial activities of some selected Nigerian mushrooms. Afr J Biomed Res 8:83–87 Gebreyohannes G, Nyerere A, Bii C, Sbhatu DB (2019) Investigation of antioxidant and antimicrobial activities of different extracts of Auricularia and Termitomyces species of mushrooms. Sci World J 2019:7357048 Hammerschmidt DE (1980) Szechwan purpura. N Engl J Med 302:1191–1193 Han S-R, Yu S-C, Lee J-H, Jung S-H, Lim K-O, Oh T-J (2018) Antimicrobial activity of various solvent extracts of Auricularia auricula-judae against oral bacteria. Indian J Public Health Res Dev 9(11):862–869 Hokama Y, Hokama JL (1981) In vitro inhibition of platelet aggregation with low dalton compounds from aqueous dialysates of edible fungi. Res Commun Chem Pathol Pharmacol 31:177– 180

11

Auricularia spp.: from Farm to Pharmacy

349

Hokama Y, Cripps C, Hokama JL, Abad MA, Sato L, Kimura LH (1983) A potent naturally occurring low-molecular weight blastogenic inhibitory factor from edible black tree fungus. Res Commun Chem Pathol Pharmacol 41:157–160 Hossen MS, Prince MMB, Tanvir EM, Chowdhury MAZ, Rahman MA, Alam F, Paul S, Saha M, Ali MY, Bhoumik NC, Karim N, Gan SH, Khalil MI (2018) Ganoderma lucidum and Auricularia polytricha mushrooms protect against carbofuran-induced toxicity in rats. Evid Based Complement Alternat Med 2018:6254929 Huang B-H, Yung K-H, Chang S-T (1985) The sterol composition of Volvariella volvacea and other edible mushrooms. Mycologia 77(6):959–963 Huang M, Liu J, Zhang S, Mei X, Yang X (2011) Effects of bioactive extracts from four edible mushrooms on the lifespan of Drosophila melanogaster. Mycology 2(1):54–58 Hung PV, Nhi NNY (2012) Nutritional composition and antioxidant capacity of several edible mushrooms grown in the Southern Vietnam. Int Food Res J 19(2):611–615 Irawati D, Hayashi C, Takashima Y, Wedatama S, Ishiguri F, Iizuka K, Yoshizawa N, Yokota S (2012) Auricularia polytricha using sawdust based substrate made of three Indonesian commercial plantation species, Falcataria moluccana, Shorea sp., and Tectona grandis. Micol Aplicada Int 24(2):33–41 Jo WS, Kim DG, Seok SJ, Jung HY, Park SC (2014) The culture conditions for the mycelial growth of Auricularia auricula-judae. J Mushrooms 12:88–95 Johnsy G, Sargunam D, Dinesh MG, Kaviyarasan V (2011) Nutritive value of edible wild mushrooms collected from the Western Ghats of Kanyakumari District. Botany Res Int 4(4): 69–74 Jonathan SG, Bawo DDS, Adejoye DO, Briyai OF (2009) Studies on biomass production in Auricularia polytricha collected from Wilberforce Island, Bayelsa State, Nigeria. Am J Appl Sci 6(1):182–186 Kadnikova IA, Costa R, Kalenik TK, Guruleva ON, Yanguo S (2015) Chemical composition and nutritional value of the mushroom Auricularia auricula-judae. J Food Nutr Res 3(8):478–482 Kakde RB, Gaikwad RS (2014) Diversity of wood decay fungi at Mantha, Jalna (MS) India. Biosci Discov 5(2):230–236 Kakon AJ, Choudhury MBK, Saha S (2012) Mushroom is an ideal food supplement. J Dhaka Natl Med Coll Hosp 18(01):58–62 Kaneda T, Tokuda S (1966) Effect of various mushroom preparations on cholesterol levels in rats. J Nutr 90:371–376 Karun NC, Sridhar KR, Ambarish CN (2018) Nutritional potential of Auricularia auricula-judae and Termitomyces umkowaan–the wild edible mushrooms of south-western India. In: Gupta VK, Treichel H, Shapaval V, Antonio de Oliveira L, Tuohy MG (eds) Microbial functional foods and nutraceuticals, 1st edn. John Wiley & Sons Ltd., New York, NY, pp 281–301 Kavishree S, Hemavathy J, Lokesh BR, Shashirekha MN, Rajarathnam S (2008) Fat and fatty acids of Indian edible mushrooms. Food Chem 106:597–602 Khan SM, Mirza JH, Khan MA (1991) Physiology and cultivation of wood’s ear mushroom Auricularia polytricha (Mont.) Sacc. In: Maher MJ (ed) Science and cultivation of edible fungi. Balkema, Rotterdam, pp 573–578 Khan MF, Rawat AK, Khatoon S, Hussain MK, Mishra A, Negi DS (2018) In vitro and in vivo antidiabetic effect of extracts of Melia azedarach, Zanthoxylum alatum, and Tanacetum nubigenum. Integr Med Res 7:176–183 Khaskheli SG, Zheng W, Sheikh SA, Liu Y, Wang Y-F, Khaskheli AA, Huang W (2014) Effects of rehydration ratio on the quality of Auricularia auricula-judae mushroom. J Food Nutr Res 2(8): 469–475 Khaskheli SG, Zheng W, Sheikh SA, Khaskheli AA, Liu Y, Soomro AH, Feng X, Sauer MB, Wang YF, Huang W (2015) Characterization of Auricularia auricula polysaccharides and its antioxidant properties in fresh and pickled product. Int J Biol Macromol 2015:387–395

350

S. Khatua et al.

Khatua S, Acharya K (2018) Water soluble antioxidative crude polysaccharide from Russula senecis elicits TLR modulated NF-κB signalling pathway and pro-inflammatory response in murine macrophages. Front Pharmacol 9:985 Khatua S, Acharya K (2019a) Alkali treated antioxidative crude polysaccharide from Russula alatoreticula potentiates murine macrophages by tunning TLR/NF-κB pathway. Sci Rep 9:1713 Khatua S, Acharya K (2019b) Crude polysaccharides from two Russuloid myco-food potentiates murine macrophage by tuning TLR/NF-κB pathway. In: Sen R, Mukherjee S, Paul R, Narula R (eds) Biotechnology and biological sciences. CRC Press (Taylor & Francis Ltd), London, pp 281–286 Khatua S, Paul S, Acharya K (2013) Mushroom as the potential source of new generation of antioxidant: a review. Res J Pharm Technol 6(5):496–505 Khatua S, Ghosh S, Acharya K (2017) Laetiporus sulphureus (Bull.: Fr.) Murr. as food as medicine. Pharmacogn J 9(6):s1–s15 Khatua S, Chandra S, Acharya K (2019) Expanding knowledge on Russula alatoreticula, a novel mushroom from tribal cuisine, with chemical and pharmaceutical relevance. Cytotechnology 71(1):245–259 Khatua S, Sen Gupta S, Ghosh M, Tripathi S, Acharya K (2021) Exploration of nutritional, antioxidative, antibacterial and anticancer status of Russula alatoreticula: towards valorization of a traditionally preferred unique myco-food. J Food Sci Technol 58:2133. https://doi.org/10. 1007/s13197-020-04723-9 Kho YS, Vikineswary S, Abdullah N, Kuppusamy UR, Oh HI (2009) Antioxidant capacity of fresh and processed fruit bodies and mycelium of Auricularia auricula-judae (Fr.) Quél. J Med Food 12(1):167–174 Khurena FK, Amwana SO, Luo TX, Kibet ML, Opuru FE (2020) Bioactive analysis of Auricularia delicata: extraction, purification, and characterization of polysaccharides from Auricularia delicata-Morocco forest. Int J Appl Sci Eng Dev 1(3):19–27 Kobayashi Y (1981) The genus Auricularia. Bull Natl Sci Mus 7(2):41–67 Kong X, Duan W, Li D, Tang X, Duan Z (2020) Effects of polysaccharides from Auricularia auricula on the immuno-stimulatory activity and gut microbiota in immunosuppressed mice induced by cyclophosphamide. Front Immunol 11:595700 Koyama K, Akiba M, Imaizumi T (2002) Antinociceptive constituents of Auricularia polytricha. Planta Med 68:284–285 Kumar R, Tapwal A, Pandey S, Borah RK, Borah D, Borgohain J (2013) Macro-fungal diversity and nutrient content of some edible mushrooms of Nagaland, India. Nus Biosci 5:1–7 Li X, Wang Z, Wang L, Walid E, Zhang H (2012) In vitro antioxidant and anti-proliferation activities of polysaccharides from various extracts of different mushrooms. Int J Mol Sci 2012: 5801–5817 Liang C-H, Wu C-Y, Lu P-L, Kuo Y-C, Liang Z-C (2019) Biological efficiency and nutritional value of the culinary-medicinal mushroom Auricularia cultivated on a sawdust basal substrate supplement with different proportions of grass plants. Saudi J Biol Sci 26:263–269 Lin W-Y, Yang MJ, Hung L-T, Lin L-C (2013) Antioxidant properties of methanol extract of a new commercial gelatinous mushrooms (white variety of Auricularia fuscosuccinea) of Taiwan. Afr J Biotechnol 12(43):6210–6221 Lu JV, Tang AV (1986) Cellulolytic enzymes and antibacterial activity of Auricularia polytricha. J Food Sci 51(3):668–669 Lu A, Shen M, Fang Z, Xu Y, Yu M, Wang S, Zhang Y, Wang W (2018) Antidiabetic effects of the Auricularia auricular polysaccharides simulated hydrolysates in experimental type-2 diabetic rats. Nat Prod Commun 13(2):195–200 Luo X, Yu MY, Jiang N, Xu XY, Zeng J, Zheng LY (2009a) Effects of Auricularia polytricha polysaccharide on mouse macrophage cytokine and iNOS gene expression. Jun Wu Xi Tong 28: 435–439

11

Auricularia spp.: from Farm to Pharmacy

351

Luo YC, Chen G, Li B, Ji BP, Guo Y, Tian F (2009b) Evaluation of antioxidative and hypolipidemic properties of a novel functional diet formulation of Auricularia auricula and Hawthorn. Innov Food Sci Emerg Technol 10:215–221 Luo Y, Xiao Z, Wang Q, Li B, Li B (2011) Antioxidant activities and inhibitory effects of Auricularia auricular and its functional formula diet against vascular smooth muscle cell in vitro. Food Nutr Sci 2:265–271 Ma ZC, Wang JG, Zhang L, Zhang YF, Ding K (2010) Evaluation of water soluble β-D-glucan from Auricularia auricular-judae as potential anti-tumor agent. Carbohydr Polym 80:977–983 Ma F, Wu J, Li P, Tao D, Zhao H, Zhang B, Li B (2018) Effect of solution plasma process with hydrogen peroxide on the degradation of water-soluble polysaccharide from Auricularia auricula. II: solution conformation and antioxidant activities in vitro. Carbohydr Polym 198: 575–580 Madrigal-Santillán E, Madrigal-Bujaidar E, Álvarez-González I, Sumaya-Martínez MT, GutiérrezSalinas J, Bautista M, Morales-González Á, González-Rubio MG, Aguilar-Faisal JL, MoralesGonzález JA (2014) Review of natural products with hepatoprotective effects. World J Gastroenterol 20(40):14787–14804 Manjunathan J, Subbulakshmi N, Shanmugapriya R, Kaviyarasan V (2011) Proximate and mineral composition of four edible mushroom species from South India. Int J Biodivers Conserv 3(8): 386–388 Mau J-L, Wu K-T, Wu Y-H, Lin Y-P (1998) Nonvolatile taste components of ear mushrooms. J Agric Food Chem 46:4583–4586 Mau JL, Chao GR, Wu KT (2001) Antioxidant properties of methanolic extracts from several ear mushrooms. J Agric Food Chem 49:5461–5467 Miao J, Regenstein JM, Qiu J, Zhang J, Zhang X, Li H, Zhang H, Wang Z (2020) Isolation, structural characterization and bioactivities of polysaccharides and its derivatives from Auricularia-A review. Int J Biol Macromol 150:102–113 Miles PG, Chang ST (2004) Mushrooms: cultivation, nutritional value, medicinal effect, and environmental impact. CRC Press, Boca Raton, FL Misaki A, Kakuta M, Sasaki T, Tanaka M, Miyaji H (1981) Studies on interrelation of structure and antitumor effects of polysaccharides: antitumor action of periodate-modified, branched (1!3)[beta]-glucan of Auricularia auricula-judae, and other polysaccharides containing (1!3)glycosidic linkages. Carbohydr Res 92(1):115–129 Montoya-Alvarez AF, Hayakawa H, Minamya Y, Fukuda T (2011) Phylogenetic relationships and review of the species of Auricularia (fungi: basidiomycetes) in Colombia. Caldasia 33(1):55–66 Neela S, Fanta SW (2019) Review on nutritional composition of orange-fleshed sweet potato and its role in management of vitamin: a deficiency. Food Sci Nutr 7:1920–1945 Nguyen TL, Chen J, Hu Y, Wang D, Fan Y, Wang J, Abula S, Zhang J, Qin T, Chen X, Chen X, Khakame SK, Dang BK (2012) In vitro antiviral activity of sulfated Auricularia auricula polysaccharides. Carbohydr Polym 90:1254–1258 Nwachukwu E, Uzoeto HO (2010) Antimicrobial activity of some local mushrooms on pathogenic isolates. J Med Plant Res 4:2460–2465 Oli AN, Edeh PA, Al-Mosawi RM, Mbachu NA, Al-Dahmoshi HOM, Al-Khafaji NSK, Ekuma UO, Okezie UM, Saki M (2020) Evaluation of the phytoconstituents of Auricularia auriculajudae mushroom and antimicrobial activity of its protein extract. Eur J Integr Med 38:101176 Onyango BO, Palapala VA, Arama PF, Wagai SO, Gichimu BM (2011) Morphological characterization of Kenyan native wood ear mushroom [Auricularia auricula (L. ex Hook.) Underw.] and the effect of supplemented millet and sorghum grains in spawn production. Agric Biol J N Am 2(3):407–414 Packialakshmi B, Sudha G, Charumathy M (2016) Bioactive constituents and antioxidant efficacy of Auricularia polytricha. Asian J Pharm Clin Res 9(1):125–129 Packialakshmi B, Sudha G, Charumathy M (2017) Studies on phytochemical compounds and antioxidant potential of Auricularia auricula-judae. Int J Pharm Sci Res 8(8):3508–3515

352

S. Khatua et al.

Park KM, Kwon KM, Lee SH (2015) Evaluation of the antioxidant activities and tyrosinase inhibitory property from mycelium culture extracts. J Evid Based Complementary Altern Med 2015:616298 Patel S, Goyal A (2012) Recent developments in mushrooms as anti–cancer therapeutics: a review. 3 Biotech 2:1–15 Pisuena M-EV, Mojica E-RE, Merca FE (2003) Isolation and partial characterization of non-blood specific lectins from Auricularia auricular (Hook) Underw. and Polyporus sp. Asia Life Sci 12(2):97–110 Priya RU, Geetha D (2016) Cultural and physiological studies on black ear mushrooms, Auricularia polytricha (Mont.) Sacc. and Auricularia auricula (L.) Underw. Mushroom Res 25(2):125–131 Priya RU, Geetha D, Darshan S (2016) Biology and cultivation of black ear mushroom–Auricularia spp. Adv Life Sci 5(22):10252–10254 Puttaraju NG, Venkateshaiah SU, Dharmesh SM, Urs SMN, Somasundaram R (2006) Antioxidant activity of indigenous edible mushrooms. J Agric Food Chem 54(26):9764–9772 Rahman MA, Masud AA, Lira NY, Shakil S (2020) Proximate analysis, phytochemical screening and antioxidant activity of different strains of Auricularia auricula-judae (ear mushroom). Int J Tradit Complement Med 5:29 Rebecca RJ, Zhang J, Zhao W, Liu Y, Wasantha KL, Wang S (2020) The compositional and nutritional inventory of naturally mutant strain Auricularia cornea var. Li. edible mushroom from China. Prog Nutr 22(1):323–329 Ren L, Hemar Y, Perera CO, Lewis G, Krissansen GW, Buchanan PK (2014) Antibacterial and antioxidant activities of aqueous extracts of eight edible mushrooms. Bioact Carbohydr Diet Fibre 3:41–51 Reza MA, Hossain MA, Lee SJ, Yohannes SB, Damte D, Rhee MH, Jo WS, Suh JW, Park SC (2014) Dichloromethane extract of the jelly ear mushroom Auricularia auricula-judae (higher Basidiomycetes) inhibits tumor cell growth in vitro. Int J Med Mushrooms 16(1):37–47 Sachin KM, Tendulkar AV (2016) Suitability of growing the wood ear mushroom A. polytricha in Tamil Nadu by low cost substrates and to assess its yield potential at different locations. Int J Biochem Biotechnol 5(2):660–664 Sękara A, Kalisz A, Grabowska A, Siwulski M (2015) Auricularia spp.—mushrooms as novel food and therapeutic agents—a review. Sydowia 67:1–10 Shan H, Sun X, Yang HC, Liu FY, Wang B, Chai L, Luan J (2019) Proximate compositions and bioactive compounds of cultivated and wild Auricularia auricular from northeastern China. Eur J Nutr Food Saf 11(4):175–186 Sheu F, Chien P-J, Chien A-L, Chen Y-F, Chin K-L (2004) Isolation and characterization of an immunomodulatory protein (APP) from the Jew’s Ear mushroom Auricularia polytricha. Food Chem 87:593–600 Sillapachaiyaporn C, Nilkhet S, Ung AT, Chuchawankul S (2019) Anti-HIV-1 protease activity of the crude extracts and isolated compounds from Auricularia polytricha. BMC Complement AlternMed 19:351 Singh S, Tripathi A (2018) Antimicrobial and phytochemical properties of methanol and hexane extract of non-gilled mushrooms collected from North-Western Himalayas. Int J Pharm Sci Res 9(4):1174–1182 Siwulski M, Jasińska A, Sobieralski K, Sas-Golak I (2011) Comparison of chemical composition of fruiting bodies of some edible mushrooms cultivated on sawdust. Ecol Chem Eng A 18(1): 89–96 Song G, Du Q (2012) Structure characterization and antitumor activity of an α, β-glucan polysaccharide from Auricularia polytricha. Food Res Int 45(1):381–387 Song F-Q, Liu Y, Kong X-S, Chang W, Song G (2013) Progress on understanding the anticancer mechanisms of medicinal mushroom: Inonotus obliquus. Asian Pac J Cancer Prev 14:1571– 1578 Su Y, Li L (2020) Structural characterization and antioxidant activity of polysaccharide from four Auriculariales. Carbohydr Polym 229:115407

11

Auricularia spp.: from Farm to Pharmacy

353

Sukmawati IK, Susilawati E, Putri SD (2019) Antibacterial activity of extracts and fractions of wood ear mushroom (Auricularia auricula). Pharmaciana 9(1):157–166 Sun YX, Li TB, Liu JC (2010a) Structural characterization and hydroxyl radicals scavenging capacity of a polysaccharide from the fruiting bodies of Auricularia polytricha. Carbohydr Polym 80:377–380 Sun YX, Liu JC, Kennedy JF (2010b) Purification, composition analysis and antioxidant activity of different polysaccharide conjugates (APPs) from the fruiting bodies of Auricularia polytricha. Carbohydr Polym 82:299–304 Tabata T, Ogura T (2003) Absorption of calcium and magnesium to the fruit body of Aragekikurage (Auricularia polytricha (Mont.) Sacc.) from sawdust culture media supplemented with calcium and magnesium salts. Food Sci Technol Res 9(3):250–253 Takeujchi H, He P, Mooi L (2004) Reductive effect of hot-water extracts from woody ear (Auricularia auricula-judae Quel.) on food intake and blood glucose concentration in genetically diabetic KK-Ay mice. J Nutr Sci Vitaminol (Tokyo) 50:300–304 Teke NA, Kinge TR, Bechem E, Nji TM, Ndam LM, Mih AM (2018) Ethnomycological study in the Kilum-Ijim mountain forest, Northwest Region, Cameroon. J Ethnobiol Ethnomedicine 14: 25 Thatoi H, Singdevsachan SK (2014) Diversity, nutritional composition and medicinal potential of Indian mushrooms: a review. Afr J Biotechnol 13(4):523–545 Ukai S, Morisaki S, Goto M, Kiho T, Hara C, Hirose K (1982) Polysaccharides in fungi. VII. Acidic heteroglycans from the fruiting bodies of Auricularia auricula-judae. Chem Pharm Bull 30: 635–649 Ukai S, Kiho T, Hara C, Morita M, Goto A, Imaizumi N, Hasegawa Y (1983) Polysaccharides in fungi: XIII. Antitumor activity of various polysaccharides isolated from Dictyophora indusiata, Ganoderma japonicum, Cordyceps cicadae, Auricularia auricula-judae and Auricularia sp. Chem Pharm Bull 31:741–749 Valverde ME, Hernández-Pérez T, Paredes-López O (2015) Edible mushrooms: improving human health and promoting quality life. Int J Microbiol 2015:376387 Varghese R, Dalvi YB, Lamrood PY, Shinde BP, Nair CKK (2019) Historical and current perspectives on therapeutic potential of higher basidiomycetes: an overview. 3 Biotech 9:362 Wan P, Chen D, Chen H, Zhu X, Chen X, Sun H, Pan J, Cai B (2020) Hypolipidemic effects of protein hydrolysates from Trachinotus ovatus and identification of peptides implied in bile acidbinding activity using LC-ESIQ-TOF-MS/MS. RSC Adv 10:20098 Wang X, Lan Y, Zhu Y, Li S, Liu M, Song X, Zhao H, Liu W, Zhang J, Wang S, Jia L (2018) Hepatoprotective effects of Auricularia cornea var. Li. polysaccharides against the alcoholic liver diseases through different metabolic pathways. Sci Rep 8:7574 Wangkheirakpam SD, Joshi DD, Leishangthem GD, Biswas D, Deb L (2018) Hepatoprotective effect of Auricularia delicata (Agaricomycetes) from India in rats: biochemical and histopathological studies and antimicrobial activity. Int J Med Mushrooms 20(3):213–225 Wong F-C, Chai T-T, Tan S-L, Yong A-L (2013) Evaluation of bioactivities and phenolic content of selected edible mushrooms in Malaysia. Trop J Pharm Res 12(6):1011–1016 Wu Q, Tan Z, Liu H, Gao L, Wu S, Luo J, Zhang W, Zhao T, Yu J, Xu X (2010) Chemical characterization of Auricularia auricular polysaccharides and its pharmacological effect on heart antioxidant enzyme activities and left ventricular function in aged mice. Int J Biol Macromol 46:284–288 Wu F, Yuan Y, Malysheva VF, Du P, Dai Y-C (2014) Species clarification of the most important and cultivated Auricularia mushroom “Heimuer”: evidence from morphological and molecular data. Phytotaxa 186(5):241–253 Wu F, Yuan Y, He S-H, Bandara AR, Hyde KD, Malysheva VF, Li D-W, Dai Y-C (2015a) Global diversity and taxonomy of the Auricularia auricula-judae complex (Auriculariales, Basidiomycota). Mycol Prog 14:95 Wu F, Yuan Y, Rivoire B, Dai Y-C (2015b) Phylogeny and diversity of the Auricularia mesenterica (Auriculariales, Basidiomycota) complex. Mycol Prog 14:42

354

S. Khatua et al.

Xing-Hong W, Chaobin Z, Pedro F, Changhe Z (2016) Screening and characterization of Auricularia delicate strain for mushroom production under tropical temperature conditions to make use of rubberwood sawdust. Res J Biotechnol 11(11):26–37 Xu C-P, Yun J-W (2003) Optimization of submerged-culture conditions for mycelia growth and exo-biopolymer production by Auricularia polytricha (wood ears fungus) using the methods of uniform design and regression analysis. Biotechnol Appl Biochem 38:193–199 Xu S, Zhang Y, Jiang K (2016) Antioxidant activity in vitro and in vivo of the polysaccharides from different varieties of Auricularia auricula. Food Funct 7(9):3868–3879 Yanez-Montalvo AF, Sánchez JE, Vazquez-Duhalt R, Cruz-Lopez L, Calixto-Romo MA (2016) Degradation of endosulfan by strains of Auricularia fuscosuccinea. Sydowia 68:7–15 Yang BK, Ha JY, Jeong SC, Jeon YJ, Ra KS, Das S, Yun JW, Song CH (2002) Hypolipidemic effect of an exo-biopolymer produced from submerged mycelia culture of Auricularia polytricha in rats. Biotechnol Lett 24:1319–1325 Yang LQ, Zhao T, Wei H, Zhang M, Zou Y, Mao GH, Wu X (2011) Carboxymethylation of polysaccharides from Auricularia auricula and their antioxidant activities in vitro. Int J Biol Macromol 49:1124–1130 Yao H, Liu Y, Ma ZF, Zhang H, Fu T, Li Z, Li Y, Hu W, Han S, Zhao F, Wu H, Zhang X (2019) Analysis of nutritional quality of black fungus cultivated with corn stalks. J Food Qual 2019: 9590251 Ying J-Z, Mao X-L, Xu YC (1987) Icones of medicinal fungi from China. Science Press, Beijing Yoon SJ, Yu MA, Pyun YR, Hwang JK, Chu DC, Juneja LR, Mourão PAS (2003) The nontoxic mushroom Auricularia auricula contains a polysaccharide with anticoagulant activity mediated by antithrombin. Thromb Res 112(3):151–158 Yu S-C, Oh T-J (2016) Antioxidant activities and antimicrobial effects of extracts from Auricularia auricula-judae. J Korean Soc Food Sci Nutr 45(3):327–332 Yu MY, Xu XY, Qing Y, Luo X, Yang ZR, Zheng LY (2009) Isolation of an anti-tumor polysaccharide from Auricularia polytricha (jew’s ear) and its effects on macrophage activation. Eur Food Res Technol 228:477–485 Yu Y-J, Choi K-H, Jeong J-S, Lee G-K, Choi S-R (2013) Study on characteristic of mycelial culture in ear mushroom. J Mushroom Sci Prod 11(1):15–20 Yu J, Sun R, Zhao Z, Wang Y (2014) Auricularia polytricha polysaccharides induce cell cycle arrest and apoptosis in human lung cancer A549 cells. Int J Biol Macromol 68:67–71 Yu Z, Xu H, Yu X, Sui D, Lin G (2017) Hypolipidemic effects of total flavonoid extracted from the leaves of Actinidia kolomikta in rats fed a highfat diet. Iran J Basic Med Sci 20:1141–1148 Yuan ZM, He PM, Cui JH, Takeuchi H (1998) Hypoglycemic effect of water soluble polysaccharide from Auricularia auricula-judae Que. on genetically diabetic KK-Ay mice. Biosci Biotechnol Biochem 62:1898–1903 Yuan Y, Wu F, Si J, Zhao Y-F, Dai Y-C (2019) Whole genome sequence of Auricularia heimuer (Basidiomycota, Fungi), the third most important cultivated mushroom worldwide. Genomics 111(1):50–58 Zambrano MV, Dutta B, Mercer DG, MacLean HL, Touchie MF (2019) Assessment of moisture content measurement methods of dried food products in small-scale operations in developing countries: a review. Trends Food Sci Technol 88:484–496 Zeng WC, Zhang Z, Gao H, Jia LR, Chen WY (2012) Characterization of antioxidant polysaccharides from Auricularia auricular using microwave-assisted extraction. Carbohydr Polym 89: 694–700 Zhang H, Wang Z, Zhang Z, Wang X (2011a) Purified Auricularia auricular-judae polysaccharide (AAP I-a) prevents oxidative stress in an ageing mouse model. Carbohydr Polym 84(1): 638–648 Zhang H, Wang Z-Y, Yang L, Yang X, Wang X, Zhang Z (2011b) In vitro antioxidant activities of sulfated derivatives of polysaccharides extracted from Auricularia auricular. Int J Mol Sci 12(5):3288–3302

11

Auricularia spp.: from Farm to Pharmacy

355

Zhang YX, Bau T, Ohga S (2018) Biological characteristics and cultivation of fruit body of wild edible mushroom Auricularia villosula. Kyushu Univ Inst Rep 63:5–14 Zhang J, Sun T, Wang S, Zou L (2020) Transcriptome exploration to provide a resource for the study of Auricularia heimuer. J For Res 31(5):1881–1887 Zhao S, Rong C, Liu Y, Xu F, Wang S, Duan C, Chen J, Wu X (2015) Extraction of a soluble polysaccharide from Auricularia polytricha and evaluation of its anti-hypercholesterolemic effect in rats. Carbohydr Polym 122:39–45 Zhao Y, Liang W, Zhang D, Li R, Cheng T, Zhang Y, Liu X, Wong G, Tang Y, Wang H, Gao S (2019) Comparative transcriptome analysis reveals relationship of three major domesticated varieties of Auricularia auricula-judae. Sci Rep 9:78 Zhou J, Chen Y, Xin M, Luo Q, Gu J, Zhao M, Xu X, Lu X, Song G (2013) Structure analysis and antimutagenic activity of a novel salt-soluble polysaccharide from Auricularia polytricha. J Sci Food Agric 93:3225–3230 Zurbano LY (2018) Mycelial growth and fructification of earwood mushroom (Auricularia polytricha) on different substrates., in: 4th International Research Conference on Higher Education. KnE Soc Sci 3(6):799–814

Chapter 12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals Uzma Altaf, S. A. J. Hashmi, and Yash Pal Sharma

Abstract Considerable elucidations and intensive research attempted on the immense nutritional values and effective health augmenting properties of mushrooms are dynamically extending as per present day needs. Mushrooms have been acknowledged as the treasure trove of nutrients including high quality proteins, polysaccharides, triterpenes, polyunsaturated fatty acids, dietary fiber, sterols, secondary metabolites, mineral substances, and vitamins. These constituents play a significant role in significantly preventing and curing various health problems, ailments and dreaded diseases such as immunodeficiency, inflammation, cancer, hyperlipidemia, hypercholesterolemia, obesity, hypertension, fungal, bacterial, and viral infections. The present review article endeavors to provide the information and correlate the health effects with underlying biological mechanisms of mushroom nutraceuticals. It tends to be affirmed that augmentation of a dietary composition by inclusion of mushrooms possesses the potential of being a natural adjuvant for the alleviation of multiple chronic diseases. Keywords Health benefits · Malnutrition · Mushroom pharmaceuticals · Diseases

Abbreviations AP-1 CMP DPPH HIV IL MAPK NADH NF-κB ROS

Activator protein-1 Coprinus comatus mycelium polysaccharide 2, 2-diphenyl-1-picrylhydrazyl Human immunodeficiency virus Interleukin Mitogen activated protein kinases Nicotinamide adenine dinucleotide hydrogen Nuclear factor kappa light chain enhancer of activated B cells Reactive oxygen species

U. Altaf · S. A. J. Hashmi · Y. P. Sharma (*) Department of Botany, University of Jammu, Jammu, Jammu and Kashmir, India © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_12

357

358

TNF TLR TRP

12.1

U. Altaf et al.

Tumor necrosis factor Toll like receptor Tyrosinase related protein

Introduction

From earliest times, humankind has been dependent to a greater extent on plants for food, fodder, medicine, timber, clothing, etc. However, the pressure on remnant vegetation and its conservation estate turned out to be more severe with the expanding global populace coupled with the decline in arable land because of rapid industrialization and urbanization. Population rise and poverty paved way to food insecurity which eventually led to malnutrition. This greatest global health challenge of malnutrition linked to high-cost care, disease, and death makes it necessary to focus and rely on auxiliary forest edible resources such as mushrooms which can enhance nutritional security and lower the incidence of malnutrition (Isanaka et al. 2019; Thakur 2020). Mushrooms are considered as treasured macrofungi and nowadays are used as dietary food, dietary supplement, a new class of drugs called “mushroom pharmaceuticals,” and cosmeceuticals (Rathore et al. 2017; Taofiq et al. 2019). These properties are due to their rich measures of significant nutrients and bioactive constituents such as polysaccharides, proteins, glycoproteins, polyphenols, terpenes, polyunsaturated fatty acids (PUFAs), vitamins, viz. niacin, riboflavin, calciferol, etc. (Maiti et al. 2008; Valverde et al. 2015; Dasgupta et al. 2019; Khatua and Acharya 2019; Maity et al. 2020). Besides these, they are good source of dietary fiber (Cheung 2013) and are gluten-free with low calorific value containing low content of simple sugars, sodium, and fats. The presence of polyphenolic compounds makes them an excellent source of antioxidants having ability of scavenging free radicals (Heleno et al. 2015a, b; Sharma et al. 2019). The inclusion of mushrooms in daily diet can alleviate some serious diseases, for example, heart and nervous problems, cancer, etc. The studies concerning compositions of nutritional and bioactive constituents of mushrooms have been expanded significantly in the past several years (Thatoi and Singdevsachan 2014; Ruthes et al. 2016; Maity et al. 2019; Khatua and Acharya 2020; Gao et al. 2021). In this context, an overview of the nutritional composition and medicinal benefits of mushrooms is given. Also, mushroom bioactive nutraceuticals and their functioning mechanisms are summed up in the chapter. Large scale cultivation of mushrooms started towards the start of twentieth century and numerous species belonging to Pleurotus. Lentinula, Auricularia, and Flammulina were commercially cultivated (Singh et al. 2017). Worldwide, cultivated mushrooms have become popular with China being the largest mushroom producer and exporter followed by the USA and Netherlands (Li 2012). Mushroom farming is now practiced in more than 100 countries and production is increasing at

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

359

an annual rate of 6–7% which has led to significant impacts on livelihoods and poverty eradication (Gupta et al. 2018). Out of the estimated 2.2–3.8 million fungal species on globe, more than 148,000 species have been identified and described so far (Antonelli et al. 2020). All these fungi have diverse habits, occupy varied habitats, and grow under variable environmental conditions. India is a biodiversity rich region with varied edaphic, environmental, and climatic conditions comprising of diverse forests. These forests harbor high macrofungal diversity with north-western Himalaya (NWH), Eastern Himalaya, Western and Eastern Ghats, etc. as the major macrofungal diversity hotspots. North-western Himalaya (NWH) is a rich repository of unexplored macrofungal wealth owing to the varied topographical and climatic conditions which provide congenial environment for their lavish growth. Macrofungal species which are potential source of food and medicine have been well documented from NWH regions, viz. Agaricus campestris, Auricularia auricula-judae, Boletus edulis, Calvatia bovista, Cantharellus cibarius, Coprinus comatus, Cordyceps militaris, Fomes fomentarius, Ganoderma lucidum, Geopora arenicola, Helvella elastica, Hericium erinaceus, Hydnum repandum, Lactarius deliciosus, Morchella conica, M. deliciosa, M. esculenta, Ophiocordyceps sinensis, Pleurotus sapidus, Rhizopogon luteolus, Sparassis crispa, Termitomyces badius, T. heimii, T. microcarpus, T. radicatus, Verpa biochemica (Atri et al. 1995; Kumar and Sharma 2011; Vishwakarma et al. 2011; Lalotra et al. 2016; Shameem et al. 2017; Dorjey et al. 2016, 2017, 2019; Yangdol et al. 2017; Bhatt et al. 2018; Sharma et al. 2019, 2020; Altaf et al. 2020; Altaf and Sharma 2020). Furthermore, mushroom consumption has risen recently because of constant advancement in cultivation and storage developments which facilitate their utilization throughout the year. In NWH, several studies have been carried out on mushroom cultivation and their biochemical characterization, viz. Auricularia polytricha, Calocybe indica, Hypsizygus tessulatus, H. ulmarius, Lentinula edodes, Lentinus cladopus, L. sajor-caju, L. squarrosulus, Pleurotus citrinopileatus, P. djamor, P. eryngii, P. ostreatus, P. sajor-caju, and P. sapidus (Upadhyay and Rai 1999; Atri and Lata 2013; Mishra et al. 2013; Lata and Atri 2017; Kaur and Atri 2019). Some medicinal mushrooms reported from Jammu and Kashmir are shown in Figs. 12.1 and 12.2.

12.2

Bioactive Molecules from Mushrooms

As far as food nutrition is concerned, inclusion of mushrooms into the diet and the studies concerning functioning mechanisms and health benefits of mushroom nutraceuticals have become an intriguing interest. Worldwide, various researchers have investigated their bioactive molecules, their preparatory processes and structural characteristics which can be also used for exploitation of new drugs during the course of biotechnological processes (Valverde et al. 2015). Ribosome inactivating proteins, dietary fibers, proteases, protease inhibitors, and hydrophobins include some representative achievements (Wang et al. 2014). Moreover, in the development

360

U. Altaf et al.

Fig. 12.1 Medicinal mushrooms: (a) Fruiting body of Sparassis crispa, (b) small lobed basidiocarps of Schizophyllum commune, (c) Russula brevipes, (d) Rhizopogon roseolus, (e) Basidiocarps arising in bunch in Pleurotus sapidus, (f) Lentinus tigrinus. (Source: Author)

of potential functional foods with high nutritional qualities, more studies are focusing on the bioactive nutraceuticals such as polysaccharides, proteins, phenolic compounds, terpenes, ergosterols, etc. The present review discusses the health benefits of various bioactive compounds obtained from mushrooms.

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

361

Fig. 12.2 Mushrooms growing in nature: (a) Helvella elastica, (b) Geopora arenicola, (c) translucent basidiocarps of Auricularia sp., (d) Laccate pileus observed in Ganoderma lucidum, (e) Ascocarp of Morchella esculenta, (f) Mushrooms Flammulina velutipes. (Source: Author)

12.2.1 Polysaccharides from Mushrooms Mushroom inferred polysaccharides are among the most widely recognized potent compounds comprising monosaccharide residues which are joined by glycosidic linkages. Glucose, fructose, mannose, galactose, xylose, fucose, and trehalose are the most prevalent monosaccharides in the mushroom derived polysaccharides (Valverde et al. 2015). β-linked glucose backbone polysaccharides have greater variability of molecular structures, thus offer the highest capacity for kinds of biological information as compared to proteins and nucleic acids. The high

362

U. Altaf et al.

molecular weight (500–2000 kDa) mushroom polysaccharides have been reported to be more biologically active compared to low molecular weight polysaccharides (Chaturvedi et al. 2018). Mushroom polysaccharides comprise two groups, homopolysaccharides (comprising of only one type of monosaccharides) and heteropolysaccharides (comprising of different types of monosaccharides). The structural variability of mushroom heteropolysaccharides is due to the different types of glycosidic linkages on the basis of their sequence of monosaccharides (Ruthes et al. 2016). The most common polysaccharides are the glucans which are potent antitumor polysaccharides present in fungal cell walls (Pandya et al. 2018; Chaitanya et al. 2019). The first mushroom polysaccharide isolated was lentinan from Lentinus edodes in Japan which exhibits anticancer and immune-modulating activity (Ikekawa et al. 1969). Some of the mushroom polysaccharides include calocyban, pleuran, ganoderan, and schizophyllan from Calocybe indica, Pleurotus spp., Ganoderma lucidum, and Schizophyllum commune, respectively. These polysaccharides are demonstrated and contemplated as the excellent representatives of Dglucans with the common (1-3) or (1-6) β-linked glucose backbones and distinguished by different patterns and degree of branches (Wang et al. 2014). The polysaccharide schizophyllan (Polysaccharide Kerstin) and lentinan (Polysaccharide peptide) have been utilized in cancer immunotherapy (Lindequist et al. 2005; Reis et al. 2017). The various studies on potential abilities of mushroom polysaccharides on biological activities are shown in Table 12.1. The mechanism of polysaccharide antitumor action through mediation of thymus dependent immune response involves the stimulation of cytotoxic macrophages, neutrophils, natural killer cells, chemical messengers (cytokines such as interleukins, interferons, and colony stimulating factors), and monocytes triggering the complementary and acute phase responses (Maity et al. 2021). The activation of different immune cells, viz. natural killer cells, cytotoxic macrophages, cytokines (colony stimulating factors, interferons, interleukins, neutrophils, monocytes) determine the top three activities, viz. antitumor, immunomodulatory, and anti-inflammatory related to mushroom polysaccharides (Wasser 2011). Due to the antitumor properties exhibited by mushroom polysaccharides, they are used in chemotherapies for pancreatic, liver, colorectal, and gastric cancers to decrease the incidence of adverse effects and improve quality of life by extending the survival period of patients (Yang et al. 2019). The activation of various mechanisms of host immune responses has been shown to be related to antitumor activity of mushroom polysaccharides, for example, different host responses were triggered by β-glucans which exhibited distinct affinities towards LacCer, CR3, dectin-1, and scavenger receptors (Andrea et al. 2015). Excellent inhibiting activity was exhibited by polysaccharides from Agaricus bisporus against human breast cancer. Strong immunomodulatory characteristics are exhibited by proteoglycans extracted from Agaricus blazei which are known to upregulate the maturation of dendritic cells, thus are therapeutically significant in controlling cancers (Kim et al. 2005). The polysaccharide composition of Agaricus brasiliensis mostly constituted β-glucans and polysaccharide extract was reported to exhibit programmable immunomodulation through the reduction of

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

363

Table 12.1 Some of the health promoting mushroom polysaccharides Fungal species Agaricus bisporus

Characteristics Homogeneous polysaccharide

Astraeus hygrometricus Auricularia auriculajudae Calocybe indica

Polysaccharides Heteropolysaccharide, β-Dglucans

Antitumorous activity

Heteropolysaccharide

Antioxidant and anti-aging properties, increases the activities of SOD, CAT, and GPx. Exhibits antidiabetic nephropathic disabilities Anticancerous activity

Coprinus comatus Cordyceps militaris Coriolus versicolor

Polysaccharides

Entoloma lividoalbum

Polysaccharides PS-I and PS-II, β-glucan

Flammulina velutipes

Polysaccharides, heteropolysaccharide, homogeneous polysaccharide

Ganoderma lucidum

Beta-D-glucan, polysaccharides ganoderon A, ganoderon B, homogeneous polysaccharide

Macrolepiota dolichaula Morchella importuna

Fucogalactan

Pleurotus djamor

Health benefits Immune-stimulatory activity, inhibit the expression of IL-1 and COX-2 Stimulation of macrophages

Beta-D-glucans, cordycepic acid Polysaccharides PSK, PSP

Polysaccharides

Galactoglucan

Antiviral effect on HIV and cytomegalovirus in vitro and anticancerous activity Immunostimulating, protective role in lymphocytes, macrophage activation, splenocyte and thymocyte proliferation Antifungal and antibacterial Antitumor activity, increases the macrophage proliferation, and enhances phagocytic activity Neuroprotective activity, elevating the expression of connexion 36 and p-CaMK II Immunostimulative, antitumorous activity, exhibits antidiabetic activity by enhancing insulin sensitivity through regulation of inflammatory cytokines Immunostimulant Macrophage stimulation and enhances phagocytosis of RAW 264.7 cells Antioxidant properties

References Smiderle et al. (2013) Mallick et al. (2009) Sagar et al. (2007), Bandara et al. (2019) Govindan et al. (2014)

Gao et al. (2021) Sagar et al. (2007) Sagar et al. (2007) Maity et al. (2014a, b, 2015)

Sagar et al. (2007), Yang et al. (2015), Govindan et al. (2016)

Sagar et al. (2007), Xu et al. (2017)

Samanta et al. (2015) Wen et al. (2019)

Maity et al. (2020) (continued)

364

U. Altaf et al.

Table 12.1 (continued) Fungal species Pleurotus eryngii

Characteristics Heteropolysaccharide

Russula albonigra Russula alatoreticula Termitomyces eurhizus

β-glucan Polysaccharide Polysaccharides

Health benefits Exhibiting antitumorous activity by inducing the cell cycle arrest at the S-phase Immunostimulant and exhibits antioxidant activity Immunomodulation through activation of macrophages Anticancerous activity against indomethacin induced gastric ulceration in mice

References Ren et al. (2016)

Nandi et al. (2014) Khatua and Acharya (2019) Chatterjee et al. (2013)

lipopolysaccharide induced pro-inflammatory cytokine synthesis (Smiderle et al. 2011). Potential antitumorous activity was shown by single helical polysaccharide, β-D-glucan from A. auricula-judae (Zhang and Yang 1995). In vitro modern cell culture experiments depict free radical scavenging activity by polysaccharide extracts from mycelium or fruiting bodies of Auricularia auricula-judae, thus demonstrate polysaccharides to be potent antioxidants (Kho et al. 2009; PiljacZegarac et al. 2011; Cai et al. 2015; Choi et al. 2019). The structural characteristics and immunomodulatory action (Nitric oxide (NO) and interleukin (IL)-10 increased) of two exopolysaccharides CEPSN-1 and CEPSN-2 isolated from submerged culture of A. auricula-judae have been determined (Zhang et al. 2018). β-D-glucan from A. auricula-judae exhibits antitumor activity when modified chemically and made water soluble (Bandara et al. 2019). Polysaccharides from Coprinus comatus increased activity of hepatic and mitochondrial antioxidant enzymes, such as glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) (Zhao et al. 2019). Polysaccharides from mycelium of C. comatus (CMP) exhibits antidiabetic nephropathic abilities by decreasing blood glucose level due to the typical structure of major monosaccharides of galactose, configuration of α-pyrinose, and proper molecular weights (Gao et al. 2021). Abnormal activation of p13k/Akt and wnt/β-catenin signaling pathways leads to abnormal proliferation of mesangial cells and renal interstitial fibrosis in diabetic patients. CMP from C. comatus can ameliorate diabetic nephropathy by blocking these signaling pathways (Bose et al. 2017). Polysaccharides (PS-I and PS-II) from Entoloma lividoalbum were reported to be immunostimulants (Maity et al. 2014a, b). Water soluble β-glucan isolated from edible mushroom E. lividoalbum is considered an immunostimulating agent as it enhances macrophage activation and proliferation of thymocytes and splenocytes (Maity et al. 2015). De Jesus et al. (2018) reported water soluble β-D-glucans having potential in wound-healing capacity obtained from Fomitopsis betulina. The β-glucan polysaccharides from Ganoderma lucidum binds to TLR-4 receptor which results in activation of NF-κB through mediation of macrophage activation (Underhill et al. 1999; Cao et al. 2018). Differentiation of murine splenic B cells into IgM secreting plasma cells is induced by proteoglycans

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

365

isolated from G. lucidum through stimulation of activation marker of B cells (Kim et al. 2003; Wang et al. 2019). Immuno-stimulatory activities were demonstrated by triple helical polysaccharide isolated from Hericium erinaceus by inducing TNF-α expression and NO production (Lee et al. 2009). Due to the specific configuration and high affinity for cell receptors, polysaccharides from Ganoderma lucidum, Lentinus velutinus, and Russula griseocarnosa exhibit anticancerous activities against cervical carcinoma cells (HeLa and SiHa) (Yuan et al. 2017; Udchumpisai and Bangyeekhun 2019). Inhibitory activities are shown by polysaccharides from Lentinus edodes, Gleoestereum incarnatum, and Lentinus velutinus against liver cancer cells (HepG2) (Udchumpisai and Bangyeekhun 2019). Polysaccharides from Morchella esculenta exhibit anticancerous activities against colon cancer cells (HT-29) and polysaccharide MIPW 50-1 isolated from M. importuna stimulates macrophages and increases phagocytosis of RAW 264.7 cells as well as secretion of IL-6, TNF-α, and NO (Liu et al. 2016; Wen et al. 2019). Through MAPK and p38 signaling pathway, polysaccharides extracted from Phellinus linteus help in dendritic cell maturation by activating TLR receptors (Lull et al. 2005). Galactoglucan isolated from Pleurotus djamor demonstrated antioxidant properties by exhibiting DPPH hydroxyl scavenging activity (Maity et al. 2020). β-glucan from Russula albonigra showed immunomodulatory and antioxidative properties (Nandi et al. 2014). Khatua and Acharya (2019) isolated crude polysaccharide from Russula alatoreticula which activates macrophages through TLR/NF-κB pathway. Polysaccharides rich extract from Termitomyces eurhizus caused reduction of myeloperoxidase activity and modulation of cyclooxygenase enzymes (COX-1 and COX-2) which eventually led to increased production of prostaglandin E2 (PE2). These factors caused ulcer healing in indomethacin induced gastric ulceration in mice (Chatterjee et al. 2013). The vast majority of the mushroom polysaccharides have been proved as dietary fibers and displayed an interaction process with the colonized microbiota in gastrointestinal tracts which could alter their different variations and consequently impact the host health. These regulate gut microbiota as well the gastrointestinal function (Jayachandran et al. 2017). In particular, the stimulatory effects on the propagation of specific bacterial groups and the production of beneficial compounds by those bacterial groups mainly the short chain fatty acids (SCFAs) such as acetate, butyrate, valerate acid, and propionate are due to their absorption of polysaccharides as energy source after degradation of polysaccharides by the gut microbiota (Zhu et al. 2016; Ma et al. 2017). The functional mechanisms of mushroom polysaccharides can be revealed by studying the alterations of mushroom polysaccharides on gut microbiota. The human gut health was improved after utilization of β-glucans extracted from mushrooms by colonized gut microbiota and specifically changing the plentitude of bacteria including lactic acid bacteria and bifidobacteria (Wong et al. 2005). During the fermentation process, Ganoderma lucidum polysaccharides owed the ability of increasing the abundance of Bifidobacteria (Yamin et al. 2012). In addition, due to the daily augmentation of Ganoderma lucidum polysaccharide strain S3, the growth and abundance of the bacteria, viz. Lactobacillus, Roseburia,

366

U. Altaf et al.

and Lachnospiraceae got enhanced, thereby providing health benefits to host (Li et al. 2016).

12.2.2 Bioactive Proteins from Mushrooms Proteins and bioactive proteins are significant nutraceuticals in mushrooms with various health benefits such as digestion enhancement, exogenic nutritional constituent absorption, and immune function modulation to aid the host defending the pathogen invasions and inhibition of some enzyme activities (Valverde et al. 2015). Since last century various proteins and peptides have been identified from the common mushrooms, namely Agaricus bisporus, Coprinus comatus, Flammulina velutipes, Ganoderma lucidum, Pleurotus cornucopiae, P. ostreatus, Sparassis latifolia (Lam and Ng 2001; Wang and Ng 2006; Wong et al. 2008; Zhao et al. 2014; Zhang et al. 2015; Chandrasekaran et al. 2016; Chu et al. 2017; He et al. 2017; Ismaya et al. 2020). Most of the bioactive proteins and peptides among the list literatures have been demonstrated of being potential candidates which show antitumor, antiviral, immunomodulatory, anti-inflammatory activities and suppress the tumor invasion or metastases (Lin et al. 2010; Puri et al. 2012; Alves et al. 2013; Chatterjee et al. 2017). Mushroom proteins and peptides with medicinal potential, namely lectins, fungal immunomodulatory proteins (FIPs), laccases, ribosome inactivating proteins (RIPs), and ribonucleases have been determined (Xu et al. 2011). Lectins and FIPs are the two main category proteins as illustrated by the researches over recent years around the globe shown in Table 12.2. Mushroom lectins comprise families like β-trefoil fold, galectin like fold, and actinoporin-like fold (Hassan et al. 2015). Lectins specifically glycoproteins or nonimmune proteins which bind to carbohydrates of cell surface possess significant activities, viz. antiviral, antitumor, antibacterial, immunomodulatory properties (Singh et al. 2014, 2020). Abmb, mannose binding protein, isolated from Agaricus bisporus is a recently discovered lectin-like protein that exhibits agglutinating activity of red blood cells/RBCs when occurring in complex with mushroom tyrosinase (Ismaya et al. 2020). Lectin from Ganoderma applanatum exhibited antitumorous activity causing pro-apoptosis in colon adenocarcinoma cells (HT-29) (Kumaran et al. 2017). Both anti-proliferative activity towards cancer cells and mitogenic activity towards sperm cells have been demonstrated by lectins from Ganoderma carpense and Polyporus adjusta. Antibacterial activity against E. coli, Pseudomonas aeruginosa was shown by lectin from Sparassis latifolia (Chandrasekaran et al. 2016). Likewise, lectins extracted from Volvariella volvacea stimulate transcriptional expression of IL 4, TNF-α, IFN-γ, IL3, and IL2 receptors and exhibits mitogenic activity towards human peripheral lymphocytes (Ng 2004). Moderate temperatures are suitable for activation of lectins; however, few thermostable lectins have also been reported from Agaricus bitorquis (Zhao et al. 2019), Clitocybe

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

367

Table 12.2 Some of the recently discovered bioactive proteins and peptides from various fungi Fungal species Agaricus bisporus

Characteristics Lectin

Cerrena unicolor Ganoderma applanatum

Laccases Lectin

Ganoderma atrum

FIPs

Ganoderma lucidum

Laccases

Hohenbuehelia serotina Hypsizigus marmoreus

Ribonuclease

Inonotus baumii Lignosus rhinocerotis

Laccases

RIPs

FIP-Lrh

Pholiota squarrosa

Lectin

Pleurotus eous

Lectins

Ramaria formosa Sparassis latifolia

Ribonuclease

Termitomyces clypeatus

Cibacron blue affinity eluted protein (CBAEP)

Lectin

Health benefits Agglutination of red blood cells in combination with mushroom tyrosinase Apoptosis in leukemia cells Pro-apoptosis and cytotoxic activity in colon adenocarcinoma cells (HT-29), thus exhibiting antitumorous activity Exhibits antitumorous activity by inhibiting proliferation and causing cell death in breast cancer cells Exhibits antitumorous activity by causing cell cycle arrest at the G1/S transition phase and increasing apoptosis in breast cancer cells Inhibition of HIV-1 reverse transcriptase activity, thus demonstrating antiviral properties Inhibitory activity against HIV-1 reverse transcriptase Growth inhibition in leukemia and hepatoma cells in humans and several fungi Antitumor activity, inhibition of proliferation in L1210 and HepG2 cells Anticancerous activity, cytotoxic effect on MCF-7, HeLa, and A549 cancer cell lines Able to differentiate between primary and metastatic colon cancer tissues in the expression of α 1-6 fucosylation Inhibitory growth in K562, SK-NMC, MCF-7, and HEP-2 cell lines Inhibitory activity against HIV-1 reverse transcriptase Exhibiting antibacterial activity against Escherichia coli, Pseudomonas aeruginosa Immunomodulation by enhancing natural killer (NK) cell activity against NK-sensitive tumor cell line (YAC-1)

References Ismaya et al. (2020) Matuszewska et al. (2016) Kumaran et al. (2017)

Li et al. (2017), Xu et al. (2016)

Wang and Ng (2006) Zhang et al. (2014) Lam and Ng (2001) Sun et al. (2014) Pushparajah et al. (2016) Singh et al. (2010) Mahajan et al. (2002) Zhang et al. (2015) Chandrasekaran et al. (2016) Maiti et al. (2008)

368

U. Altaf et al.

nebularis (Pohleven et al. 2009), Inocybe umbrinella (Zhao et al. 2009), Russula lepida (Zhang et al. 2010). Fungal immunomodulatory proteins are the mushroom bioactive proteins which are utilized as adjuvants for treatment of tumor owing to their remarkable activity in repressing the invasion metastasis of tumor cell lines (Lin et al. 2010). The strong antitumor effect was exhibited by FIP “fve” extracted from Flammulina velutipes. The protein exhibited potent adjuvant properties enhancing peripheral blood lymphocyte and T-helper type 1 antigen-specific immune responses (Ng 2004). FIPs from Ganoderma atrum exhibited antitumorous activity by inhibiting proliferation and apoptosis in breast cancer cells by causing cell cycle arrest at the G1/S transition phase (Xu et al. 2016). Cytotoxic effect on MCF-7, HeLa, and A549 cancer cell lines by FIP-Lrh from Lignosus rhinocerotis was reported by Pushparajah et al. (2016). FIPs from Volvariella volvacea can induce the expression of both TH1 and TH2 specific cytokines (Hsu et al. 1997). By eliminating one or more adenosine residues from rRNA, RIPs could inactivate ribosomes. Various studies have confirmed the RIPs owing the ability to inhibit HIV-1 reverse transcriptase activity (Puri et al. 2012). RIP “Calcaelin” from Calvatia caelata demonstrated anti-proliferative activity towards breast cancer cells and anti-mutangenic activity towards spleen cells (Ng 2004). Growth inhibition in hepatoma and leukemia cells in humans was exhibited by RIP from Hypsizigus marmoreus (Lam and Ng 2001). Significant inhibition has been found by ribonucleases extracted from mushrooms in the growth of Pseudomonas aeruginosa, P. fluorescens, and Staphylococcus aureus at the RNA level (Alves et al. 2013). Ribonucleases from Hohenbuehelia serotina and Ramaria Formosa exhibited inhibitory activity against HIV-1 reverse transcriptase (Zhang et al. 2014, 2015). In addition, ribonucleases extracted from Pleurotus sajor-caju exhibited anti-proliferative action on leukemia and hepatoma cells and demonstrated antimutagenic activity on mouse spleen cells (Ng 2004). Laccases, the widespread class of enzymes have been related to the morphogenesis of organisms, pathogenesis, and immunogenesis (Xu et al. 2011). Apoptosis in leukemia cells was exhibited by laccases isolated from Cerrena unicolor (Matuszewska et al. 2016). Laccases from Ganoderma lucidum caused antiviral activity by inhibiting HIV-1 reverse transcriptase activity (Wang and Ng 2006). Proliferation in L1210 and HepG2 cells was inhibited by laccases from Inonotus abaumi (Sun et al. 2014). Function studies especially focused on most of the identified proteins and peptides are mainly involved in antitumor and immunomodulation activities like human leukemia T cells, HepG2 cells, and breast cancer MCF7 cells; on the contrary the antiviral studies were the inhibition effects on the reverse transcription of the immunodeficiency virus (HIV-1) (Ma et al. 2018). Proteoglycans (0–500 μg/mL) isolated from Phellinus linteus were reported to increase the proliferation rate of B-lymphocytes and expression of co-stimulatory molecules, namely CD80 and CD86. The process of immunomodulatory activities has been reported to involve protein kinase C (PKC) and protein tyrosinase kinase (PTK) signaling pathways (Kim et al. 2003). According to Kim et al. (2006), a novel polysaccharide-protein

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

369

enhanced B-cell proliferation and modified macrophages and NK cells in in vitro conditions. In addition, the health benefits induced by functional proteins and peptides through regulation of gut microbiota have also been studied and illustrated and have increased over the last few years. The study on correlations between mushroom isolated proteins and peptides and gut microbiota was lacking and is gaining momentum in the recent years. Extensive research indicated that immune functions could be improved by HEP3 protein, a simple band protein isolated from Hericium erinaceus through regulating the composition and metabolism of gut microbiota in mice. In addition HEP3 protein also displayed immunomodulatory activity in lipopolysaccharide activated RAW 264.7 macrophages through decreasing the excessive production of cytokines (Diling et al. 2017). Researches in this aspect require in-depth and further study in the coming years which will reveal the novel mechanisms of mushroom proteins and peptides on human health modulation.

12.2.3 Phenolic Compounds from Mushrooms Phenolic compounds, one of the major essential groups of secondary metabolites, comprise aromatic rings with one or more hydroxyl groups (Apak et al. 2007). They have been demonstrated to exhibit antioxidant properties both in vitro and in vivo (Ferreira et al. 2009). Their mechanism of antioxidative action occurs in different ways. Most importantly, by virtue of being exceptional hydrogen or electron donors, polyphenols can act as antioxidants by stabilizing reactive oxygen species and protecting cells against damage. Likewise, they are able to chelate those elements (Cu, Fe) which can produce reactive oxygen species. Additionally, they inhibit the formation of free radicals through the inhibition of enzymes mainly oxidases such as cyclooxygenase, microsomal monooxygenase, lipoxygenase, and NADH oxygenase as well as S-glutathione transferase or C protein kinase (Ferreira et al. 2009). The profoundly active and antioxidative phenolic compounds found in mushrooms are gallic, p-coumaric acid, p-hydroxybenzoic, protocatechuic, cinnamic, and caffeic acids (Reis et al. 2012; Muszynska et al. 2013; Gąsecka et al. 2018). Positive correlation has been established between antioxidant activities of mushroom extract and their phenolic content (Puttaraju et al. 2006; Chirinang and Intarapichet 2009). The antioxidant activities of the phenolic substances present in various mushroom species have been tested in various investigations and study results have shown high content of phenolic compounds in mushrooms and their extracts. Total polyphenols as major antioxidant components were found in methanolic extract of Grifola frondosa (Mau et al. 2002). Lee et al. (2007) described total phenols as the antioxidant compounds in Hypsizigus mushrooms. Analysis of phenolic composition by HPLC in Agaricus brasiliensis revealed presence of rutin, gallic acid, catechin, and caffeic acid which contribute to its antioxidant activity (Abah and Abah 2010). The antioxidant activities of six different Boletus spp., viz. B. edulis, B. purpureus, B. reticulates, B. satanas, Boletus aereus and B. rhodoxanthus were investigated by Heleno et al. (2011). The correlation was

370

U. Altaf et al.

found between total phenol content and antioxidant activity of Armillaria mellea with the reducing power and the scavenging effect on superoxide anions (Lung and Chang 2011). The phenolic derivatives in several species of Agaricus were determined, viz., A. blazei, A. campestris, A. silvaticus, A. arvensis, A. bisporus, and A. bitorquis by Gąsecka et al. (2018) and their antioxidant activities assessed by DPPH radical scavenging test were found to be directly proportional to their phenolic content. Phenolic acid is the main phenolic compound found in mushrooms, demonstrating antioxidant activity because of the phenolic hydrogen. Enhancement of antioxidant activity has been found because of hydroxyl substitutions at para and ortho position. Two p-terphenyls indicating potent inhibition effects on lipid peroxidation have been found in Paxillus panuoides. Phenolic compounds, viz. p-hydroxybenzoic, protocatechuic, cinnamic, and p-coumaric acids were first reported in Imleria badia, tests of linoleic acid oxidation (99.2%) revealed correlation between composition of phenolic compounds and high antioxidant activity (Reis et al. 2012). However, phenolic acids such as caffeic, ferulic, protocatechuic, and p-coumaric have also been reported (Liu et al. 2013). The concentration of one of the most active antioxidants, i.e. caffeic acid was found to be higher (approximately up to 15 μg/g dw) in macrofungal species such as Agaricus bisporus, Boletus edulis, Calocybe gambosa, Hygrophorus marzuolus, and Lactarius deliciosus (Reis et al. 2012; Muszynska et al. 2013). Antioxidant activities of p-Hydroxybenzoic acid against free radicals and antimicrobial action against pathogenic fungi and bacteria have been reported by Rice-Evans et al. (1996) and Heleno et al. (2013), respectively. Likewise the other bioactivities, for example, antimutagenic and estrogenic properties were also reported (Pugazhendhi et al. 2005). Several bioactivities such as antimicrobial (Alves et al. 2013) and antioxidant (Ferreira et al. 2009) have also been exhibited by protocatechuic acid. Tannic acid, catechin, and gallic acid are the polyphenols which are reported to interact with steroid receptors, consequently changing transmembrane potential of mitochondria and depending on cell systems ultimately increases or reduces the ROS activation (Wei et al. 2008). Carvajal et al. (2012) reported gallic and syringic as dominant organic acids in fruiting bodies of Agaricus brasiliensis. Polyphenols such as resveratrol and curcumin were reported to improve cell survival by acting as efficient quenchers of 1O2 (Das and Das 2002; Celaje et al. 2011). The lipophilic molecules, resveratrol and curcumin mix very well between membrane lipids and lipoproteins, thus their levels in blood are detected less in comparison to tissues (Timmers et al. 2012). Phenolic compounds also exhibit anticancerous activities by demonstrating direct cytotoxicity towards cancer cells. Complete growth inhibition of HeLa cells was demonstrated by Hericenone A and B from Hericium erinaceus at 100 μg/mL and 6.3 μg/mL concentration, respectively. The potent cytotoxicity of Hericenone B may be because of γ-lactam and its N-substituent (Kawagishi et al. 1990). The polyphenols present in ethyl acetate extract of Inonotus sanghuang have been demonstrated to show antioxidant and anti-inflammatory effects against bleomycin induced acute lung injury in mice (Su et al. 2019). Lovastatin which shows hypocholesterolemic properties by inhibiting hydroxymethylglutary-CoA reductase has been extracted from sporocarps of Cantherellus cibarius and Imleria badia (Kała

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

371

et al. 2020). Cinnamic acid has been reported to show antitumorous activity, having the capacity for cell growth inhibition in a lung cancer cell line (NCI-H460) (Vaz et al. 2012). Apart from above cell line, cinnamic acid showed the cytotoxicity against the colon (HCT15) and cervical (HeLa) carcinoma cell lines (Heleno et al. 2014a). Additionally, cinnamic acid was reported to show antimicrobial action against fungi and Gram positive and Gram negative bacteria (either collection microorganisms or clinical isolates) (Alves et al. 2013; Heleno et al. 2013). The antioxidant activity and antitumor activities against breast carcinoma cell lines MCF7 and NCI-H460 HCT15 by coumaric acid were reported by Rice-Evans et al. (1996) and Heleno et al. (2014a), respectively. Heleno et al. (2014b) reported antibacterial and antifungal activity of p-coumaric acid. In another similar study by Lou et al. (2012), p-coumaric acid exhibited bactericidal activity by disrupting cell membranes of bacteria and binded to genomic DNA, thus inhibiting cellular functions and consequently resulting in cell death. Caffeic and ferulic acids were also reported to show antimicrobial activity against pathogenic bacteria and fungi (Alves et al. 2013). Thus, looking at all the promising bioactivities and realizing that mushrooms are rich reservoirs of these molecules, we can presume that mushrooms are a decent choice for our everyday diet. Flavonoids are representatives of phenolic compounds that have been reported to be effective scavengers (Ferreira et al. 2009; Butkhup et al. 2018). Basic structure of flavonoids comprises a flavan nucleus which consists of two benzene rings (A&B) combined by an oxygen containing pyran ring (C). In the recent work on Sanghuangporus sanghuang, seven core genes have been found to be involved in flavonoid biosynthesis (Shao et al. 2019). Flavonols, flavanones, flavanols, flavones, and isoflavones are the six common subclasses of flavonoids (Renaud and de Lorgeril 1992; Farkas et al. 2004; Manach et al. 2004). Flavonoids have been reported in several mushrooms such as Lactarius piperatus (Barros et al. 2007); Lentinus edodes, Volvariella volvacea, Auricularia auricular-judae (Boonsong et al. 2016), Boletus edulis, Geopora arenicola, Morchella deliciosa, Sparassis crispa (Lalotra et al. 2016), Morchella conica, Rhizopogon luteolus (Altaf et al. 2020). Various flavonoids like hesperetin, formometin, myricetin, catechin, biochanin, resveratrol, kaempferol, quercetin, anthocyanins have been reported in mushrooms (Ferreira et al. 2009; Khoo et al. 2017). Flavonoids can decrease membrane fluidity and can modify peroxidation kinetics (Arora et al. 2000). The antioxidant activity at low dosage of quercetin has been reported by Vargas and Burd (2010). Regarding the assimilation and bioavailability of quercetin, its aglycosylated form leads to the formation of lipophilic molecule which can be effectively absorbed through epithelia of colon cells (Murota and Terao 2003; Lagunes and Trigos 2015). Tel et al. (2012) reported mushroom flavonoids to have cholinesterase inhibiting activity and antioxidant activities.

12.2.4 Terpenes from Mushrooms Terpenes, a cluster of volatile unsaturated hydrocarbons have been categorized as monoterpenoids, sesquiterpenoids, diterpenoids, and triterpenoids (Duru and Ayan

372

U. Altaf et al.

2015). They have been extracted from mushrooms widely and exhibit numerous pharmacological activities, viz. anti-cholinesterase (Dundar et al. 2015), antioxidant (Boonsong et al. 2016), anti-inflammatory (Elsayed et al. 2014), antiviral (Asakawa et al. 2014), anticancer (Song et al. 2013; Klaus et al. 2016), and antimalarial (Öztürk et al. 2015) activities. Diterpenoids that have been isolated from mushrooms are cyathane type though a large portion of the triterpenoid compounds from mushrooms are distinguished as lanostane type (Duru and Ayan 2015). Neuroprotective effects have been demonstrated by diterpenoid isolated from Antrodia camphorata (Huang et al. 2005). A sesquiterpenoid from Astraeus hygrometricus exhibited anticancerous activity in vitro in liver cells through modulation of antiapoptotic Bcl-2 family proteins, thus inducing mitochondria mediated apoptosis (Dasgupta et al. 2019). Antifungal activity is demonstrated by diterpenoid “Crinipellis” isolated from Crinipellis rhizomaticola (Han et al. 2018). Neocyathins K-R (1-8), eight new polyoxygenated cyathane diterpenoids have been isolated from inedible mushroom Cyathus africanus which demonstrates neurotrophic and anti-neuroinflammatory properties (Wei et al. 2018). Flammulinolides and Flammulinol are the sesquiterpenoids that have been found in Flammulina velutipes and their toxicity against three tumor cell lines specifically KB, HeLa, and HepG2 was tested (Wang et al. 2012). Lanostane, the triterpenoid compound mostly isolated from the mushrooms has been shown effective against cancer. Several triterpenes, namely lanostane type triterpenic acids, lucidenic acids, ganoderic acids have been extracted from fruiting bodies of Ganoderma lucidum (Mckenna et al. 2002; Iwatsuki et al. 2003; Tang et al. 2006; Akihisa et al. 2007). Kimura et al. (2002) reported ganoderic acid F inhibiting angiogenesis that had been induced by tumor, thus exhibiting antimetastatic activity. Gao et al. (2002) reported anticancerous activity of lucialdehydes B and C (triterpenes with lanostane skeleton) isolated from Ganoderma lucidum towards LLC, Sarcoma 180, T-47D, and Sarcoma Meth-A cell lines. In addition to that, methyl ganoderate A acetonide and n-butyl ganoderate H, the lanostane triterpenes from Ganoderma lucidum exhibited antiacetylcholinesterase activity. Henceforth paves another way to utilize them as a potential drug for the treatment of Alzheimer’s and related neurodenegerative diseases by the pharmaceutical companies (Lee et al. 2011). Lanostane triterpenoids from cultivated sporocarps of Ganoderma casuarinicola exhibited anti-tuberculosis and antimalarial activities (Isaka et al. 2020). Also, Inonotus obliquus was reported to be source of triterpenes and sterols, namely inotodiol, trametenolic acid, and ergosterol (Park et al. 2005; Van et al. 2009; Ma et al. 2013). Lentinellic acid from Lentinellus omphalodes exhibited antibacterial activity and inhibits protein synthesis in Ehrlich ascetic carcinomas (Rahi and Malik 2016). Triterpenoids from Naematoloma fasciculare inhibit proliferation of human cancer cell lines, viz. HCT-15, SK-MEL-2A549, and SK-OV-3 (Kim et al. 2013). Terpenes (five monoterpenoids and two sesquiterpenoids) from Pleurotus species revealed antiinflammatory activities and also positive outcomes were found for their cytotoxicity against cancer line (Wang et al. 2013). For curing degenerative diseases, these terpenes can be efficaciously utilized in developing drugs. Terpenes along with their biological activities are given in Table 12.3.

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

373

Table 12.3 Terpenes isolated from different fungal species and their health benefits Fungal species Antrodia camphorata Astreus hygrometricus

Clitopilus passeckerianus Crinipellis rhizomaticola Coprinellus radians Cyathus africanus Cyathus striatus

Flammulina velutipes Ganoderma lucidum

Ganoderma casuarinicola Inonotus obliquus Lentinellus omphalodes

Characteristics Diterpenoid

Health benefits Neuroprotective effects

References Huang et al. (2005)

Sesquiterpenoid

Dasgupta et al. (2019)

Diterpenoid

Exhibiting anticancerous activity through modulation of antiapoptotic Bcl-2 family proteins Exhibits antibiotic activity

Nagabushan (2010)

Diterpenoid

Exhibits antifungal activity

Han et al. (2018)

Diterpenoids

Antitumorous activity

Ou et al. (2012)

Diterpenoids

Neurotrophic and antineuroinflammatory Enhances nerve growth factor (NGF)-mediated neurite outgrowth in rat pheochromocytoma (PC-12) cells Antitumorous activity

Wei et al. (2018)

Diterpenoids

sesquiterpenoids Triterpenoids

Triterpenoids Triterpenoid Lentinellic acid

Pleurotus eryngii Marasmius alliaceus Naematoloma fasciculare

Diterpenoids

Stereum hirsutum

Sesquiterpenoid

Sesquiterpenoid Triterpenoids

Bai et al. (2015)

Sagar et al. (2007)

Inhibiting angiogenesis induced by tumor, thus exhibiting anticancerous activity, active against HIV-1, exhibits antiinflammatory response Anti-tuberculosis and antimalarial activity Antihyperglycemic

Gao et al. (2002), Sagar et al. (2007), Dudhgaonkar et al. (2009)

Antibacterial activity and inhibits protein synthesis in Ehrlich ascetic carcinomas Cytotoxicity against two human cancer lines Anticancerous activity

Rahi and Malik (2016)

Inhibition in proliferation of human cancer cell lines, viz. HCT-15, SK-MEL-2A549, and SK-OV-3 Exhibits antioxidant activity

Kim et al. (2013)

Isaka et al. (2020) Ying et al. (2014)

Wang et al. (2012) Anke et al. (1981)

Ma et al. (2014)

374

U. Altaf et al.

12.2.5 Polyunsaturated Fatty Acids (PUFAs) from Mushrooms PUFAs are the most prevalent lipids in mushrooms which contribute to the lowering of serum cholesterol (Valverde et al. 2015). Ergosterol, the main sterol produced by mushrooms demonstrates the substantial antioxidant properties (Guillamón et al. 2010). Bok et al. (1999) reported glycosylated ergosterol peroxide from methanolic extracts of Cordyceps sinensis inhibited proliferation of WM-1341, K562, HL-60, Jurkat, and RPMI-8226 tumor cell lines. The immunomodulation and antiviral activities were demonstrated by ergosterol peroxide isolated from Cryptoporus volvatus against porcine deltacoronavirus. In vitro, this virus was inhibited by downregulating NF-κB and p38/MAPK signaling pathways (Duan et al. 2021). Apoptosis in HT29 cells by anticancer sterol isolated from Sarcodon aspratus has been demonstrated by Kobori et al. (2006) by inducing cyclin dependent kinase inhibitor 1A expression which causes cell cycle arrest. Moreover, the essential role of diet rich in sterols has been reported to prevent cardiovascular diseases (Kalač 2013). Linoleic acid displays numerous physiological functions especially the suppression of expression of pro-inflammatory cytokines including IL-1β, IL-6, TNF-α, and NOS2 in RAW 264.7 cells and inhibiting NO production, thus reducing inflammatory level (Saiki et al. 2017). Also, the decreasing impact on the Alzheimer’s disease is correlated with its inhibitory effects on the acetylcholinesterase (Ach E) and butyrylcholinesterase (BCh E) (Öztürk et al. 2014). Tocopherols, the another polyunsaturated fatty acids were detected in mushrooms, considered as potent natural antioxidants producing free radical scavenging peroxyl components from different reactions. These antioxidants possess higher biological activity for protection against cardiovascular, microbial, and degenerative malfunctions (Heleno et al. 2012, 2015a, b; Jaworska et al. 2015). Also, α-tocopherol is known for the downregulation of MNP-1 expression by suppression of AP-1. Besides this, it is also an important anti-wrinkle and anti-hyperpigmentation agent as it inhibits enzyme tyrosinase (Masaki 2010).

12.3

Conclusions

Mushrooms are considered as valuable, suitable, and complete dietary food depending on its richness in proteins, polysaccharides, and other functional constituents with multiple bioactivities. Accordingly, the primary bioactive mushroom nutraceuticals along with their host health benefits are described. Based on the immense nutritional supremacy mushrooms can also be utilized as the proficient material in the immune strength enhancement, reducing and averting the chances of cancer development, tumor cell growth inhibition, protecting the nervous system from the damage of aging, etc. Furthermore, worldwide the fundamental consideration of the researchers was to estimate the probiotic potential of mushrooms

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

375

particularly the correlations between the structure regulation of gut microbiota and host health problems including gut inflammation, obesity, colonic cancer, and neurological diseases. Also the immunomodulation, antiviral and anti-inflammatory properties of mushroom extracts can be best suitable for treating COVID-19 infection and severe lung inflammation that follows the infection. Overall, it could be affirmed that the health benefit spectrum provided by the mushrooms was heterogenous and it is anticipated that with the advancements and current knowledge in molecular nutrition and nutrigenomics, mushrooms could be consumed for everyday supplementation as compared to other nutraceutical foods. In view of the global rise in population, shrinking natural resources, increased malnutrition and pandemics, expanding applications, and maximizing the advantages of mushroom nutraceuticals need to be intensified, which could increase a better comprehension in the course of development of functional foods. Further aspects focusing on their genomic studies are still needed in the future as the genomic datasets will be a vital tool for various molecular investigations to promote biology based medicine or drug discovery. Moreover, the biosynthesis of biologically active compounds can also be studied by identification of genes and pathways that may enhance our understanding of predicted gene function. Acknowledgements We are grateful to the Head, Department of Botany (UGC-SAP II DRS II), University of Jammu, Jammu and Kashmir, for providing the laboratory facilities. The first author gratefully acknowledges the financial support from Council of Scientific and Industrial Research (CSIR), New Delhi.

References Abah SE, Abah G (2010) Antimicrobial and antioxidant potentials of Agaricus bisporus. Adv Biol Res 4(5):277–282 Akihisa T, Nakamura Y, Tagata M et al (2007) Anti-inflammatory and anti-tumor promoting effects of triterpene acids and sterols from the fungus Ganoderma lucidum. Chem Biodivers 4:224– 231. https://doi.org/10.1002/cbdv.200790027 Altaf U, Sharma YP (2020) Morphological and molecular characterization of two Pleurotus species from Jammu and Kashmir, India. J Mycol Plant Pathol 50(1):97–104 Altaf U, Lalotra P, Sharma YP (2020) Nutritional and mineral composition of four wild edible mushrooms from Jammu and Kashmir, India. Indian Phytopathol 73:313–320. https://doi.org/ 10.1007/s42360-020-00230-1 Alves MJ, Ferreira ICFR, Froufe HJC et al (2013) Antimicrobial activity of phenolic compounds identified in wild mushrooms, SAR analysis and docking studies. J Appl Microbiol 115:346– 357. https://doi.org/10.1111/jam.12196 Andrea CR, Fhernanda RS, Marcello I (2015) D-Glucans from edible mushrooms: a review on the extraction, purification and chemical characterization approaches. Carbohydr Polym 117:753– 761. https://doi.org/10.1016/j.carbpol.2014.10.051 Anke T, Watson WH, Giannetti BM et al (1981) Antibiotics from basidiomycetes XIII the alliacols A and B from Marasmius alliaceus. J Antibiot 34(10):1271–1277 Antonelli A, Fry C, Smith RJ et al (2020) State of the world’s plants and fungi 2020. Royal Botanic Gardens, Kew. https://doi.org/10.34885/172

376

U. Altaf et al.

Apak R, Güçlü K, Demirata B et al (2007) Comparative evaluation of various total antioxidant capacity assays applied to phenolic compounds with the CUPRAC assay. Molecules 12:1496– 1547. https://doi.org/10.3390/12071496 Arora A, Byrem TM, Nair MG et al (2000) Modulation of liposomal membrane fluidity by flavonoids and isoflavonoids. Arch Biochem Biophys 373:102–109. https://doi.org/10.1006/ abbi.1999.1525 Asakawa Y, Nagashima F, Hashimoto T (2014) Pungent and bitter, cytotoxic and antiviral terpenoids from some bryophytes and inedible fungi. Nat Prod Commun 9:409–417. PMID: 24689227 Atri NS, Lata (2013) Studies for culturing and cultivation of Lentinus cladopus Lév. Mycosphere 4(4):675–682. https://doi.org/10.5943/mycosphere/4/4/3 Atri NS, Saini SS, Kaul G (1995) Taxonomic studies on north Indian agarics - the genus Termitomyces. Mushroom Res 4:7–10 Bai R, Zhang CC, Yin X et al (2015) Striatoids A–F, cyathane diterpenoids with neurotrophic activity from cultures of the fungus Cyathus striatus. J Nat Prod 78:783–788. https://doi.org/10. 1021/np501030r Bandara A, Rapior S, Mortimer PE et al (2019) A review of the polysaccharide, protein and selected nutrient content of Auricularia, and their potential pharmacological value. Mycosphere 10(1): 579–607. https://doi.org/10.5943/mycosphere/10/1/10 Barros L, Baptista P, Ferreira ICFR (2007) Effect of Lactarius piperatus fruiting body maturity stage on antioxidant activity measured by several biochemical assays. Food Chem Toxicol 45: 1731–1737. https://doi.org/10.1016/j.fct.2007.03.006 Bhatt RP, Singh U, Uniyal P (2018) Healing mushrooms of Uttarakhand Himalaya, India. Curr Res Environ Appl Mycol 8(1):1–23. https://doi.org/10.5943/cream/8/1/1 Bok JW, Lermer L, Chilton J et al (1999) Antitumor sterols from the mycelia of Cordyceps sinensis. Phytochemistry 51:891–898. https://doi.org/10.1016/s0031-9422(99)00128-4 Boonsong S, Klaypradi W, Wilaipun P (2016) Antioxidant activities of extracts from five edible mushrooms using different extractants. Agric Nat Res 50:89–97. https://doi.org/10.1016/j.anres. 2015.07.002 Bose M, Almas S, Prabhakar S (2017) Wnt signaling and podocyte dysfunction in diabetic nephropathy. J Investig Med 65:1093–1101. https://doi.org/10.1136/jim-2017-000456 Butkhup L, Samappito W, Jorjong S (2018) Evaluation of bioactivities and phenolic contents of wild edible mushrooms from northeastern Thailand. Food Sci Biotechnol 27:193–202. https:// doi.org/10.1007/s10068-017-0237-5 Cai M, Lin Y, Luo YL et al (2015) Extraction, antimicrobial, and antioxidant activities of crude polysaccharides from the wood ear medicinal mushroom Auricularia auricular-judae (higher basidiomycetes). Int J Med Mushrooms 17:591–600. https://doi.org/10.1615/ intjmedmushrooms.v17.i6.90 Cao Y, Xu X, Liu S et al (2018) Ganoderma: a cancer immunotherapy review. Front Pharmacol 9: 1–29. https://doi.org/10.3389/fphar.2018.01217 Carvajal AESS, Koehnlein EA, Soares AA et al (2012) Bioactives of fruiting bodies and submerged culture mycelia of Agaricus brasiliensis (A. blazei) and their antioxidant properties. LWT Food Sci Technol 46(2):493–499. https://doi.org/10.1016/j.lwt.2011.11.018 Celaje JA, Zhang D, Guerrero AM et al (2011) Chemistry of trans-resveratrol with singlet oxygen: [2 + 2] addition, [4 + 2] addition, and formation of the phytoalexin moracin M. Org Lett 13: 4846–4849. https://doi.org/10.1021/ol201922u Chaitanya M, Jose A, Ramalingam P (2019) Multi-targeting cytotoxic drug leads from mushrooms. Asian Pac J Trop Med 12:531–536. https://doi.org/10.4103/1995-7645.272482 Chandrasekaran G, Lee YC, Park H et al (2016) Antibacterial and antifungal activities of lectin extracted from fruiting bodies of the Korean cauliflower medicinal mushroom, Sparassis latifolia (Agaricomycetes). Int J Med Mushrooms 18:291–299. https://doi.org/10.1615/ IntJMedMushrooms.v18.i4.20

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

377

Chatterjee A, Khatua S, Chatterjee S et al (2013) Polysaccharide-rich fraction of Termitomyces eurhizus accelerate healing of indomethacin induced gastric ulcer in mice. Glycoconj J 30:759– 768. https://doi.org/10.1007/s10719-013-9479-5 Chatterjee S, Sarma MK, Deb U et al (2017) Mushrooms: from nutrition to mycoremediation. Environ Sci Pollut Res 24:19480–19493. https://doi.org/10.1007/s11356-017-9826-3 Chaturvedi VK, Agarwal S, Gupta KK et al (2018) Medicinal mushroom: boon for therapeutic applications. Biotech 8:334. https://doi.org/10.1007/s13205-018-1358-0 Cheung PC (2013) Mini-review on edible mushrooms as source of dietary fiber: preparation and health benefits. Food Sci Human Wellness 2:162–166. https://doi.org/10.1016/j.fshw.2013. 08.001 Chirinang P, Intarapichet KO (2009) Amino acids and antioxidant properties of the oyster mushrooms, Pleurotus ostreatus and Pleurotus sajor-caju. Sci Asia 35:326–331. https://doi.org/10. 2306/scienceasia1513-1874.2009.35.326 Choi YJ, Park IS, Kim MH et al (2019) The medicinal mushroom Auricularia auricula-judae (Bull.) extract has antioxidant activity and promotes procollagen biosynthesis in HaCaT cells. Nat Prod Res 33(22):3283–3286. https://doi.org/10.1080/14786419.2018.1468332 Chu PY, Sun HL, Ko JL et al (2017) Oral fungal immunomodulatory protein - Flammulina velutipes has influence on pulmonary inflammatory process and potential treatment for allergic airway disease: a mouse model. J Microbiol Immunol Infect 50:297–306. https://doi.org/10. 1016/j.jmii.2015.07.013 Das KC, Das CK (2002) Curcumin (diferuloylmethane), a singlet oxygen (1O2) quencher. Biochem Biophys Res Commun 295:62–66. https://doi.org/10.1016/s0006-291x(02)00633-2 Dasgupta A, Dey D, Ghosh D et al (2019) Astrak urkurone, a sesquiterpenoid from wild edible mushroom, targets liver cancer cells by modulating Bcl2 family proteins. IUBMB Life 71(7): 992–1002. https://doi.org/10.1002/iub.2047 De Jesus LI, Smiderle LIFR, Ruthes AC et al (2018) Chemical characterization and wound healing property of a beta-D-glucan from edible mushroom Piptoporus betulinus. Int J Biol Macromol 117:1361–1366. https://doi.org/10.1016/j.ijbiomac.2017.12.107 Diling C, Chaoqun Z, Jian Y et al (2017) Immunomodulatory activities of a fungal protein extracted from Hericium erinaceus through regulating the gut microbiota. Front Immunol 8:666–679. https://doi.org/10.3389/fimmu.2017.00666 Dorjey K, Kumar S, Sharma YP (2016) Desert puffballs from Ladakh trans-Himalaya (J&K), India - the genus Bovista and Calvatia. Indian Phytopathol 69(1):87–92 Dorjey K, Kumar S, Sharma YP (2017) Eight coprinoid macromycetes (Agaricaceae & Psathyrellaceae) from trans-Himalayan region of Ladakh (J&K), India. Indian J For 40(1): 47–61 Dorjey K, Kumar S, Sharma YP (2019) High altitude morels from Ladakh trans-Himalaya (J&K), India. J Non-Timber Prod 26(3):123–129 Duan C, Ge X, Wang J et al (2021) Ergosterol peroxide exhibits antiviral and immunomodulatory abilities against porcine deltacoronavirus (PDCoV) via suppression of NF-κB and p38/MAPK signaling pathways in vitro. Int Immunopharmacol 93:107317. https://doi.org/10.1016/j.intimp. 2020.107317 Dudhgaonkar S, Thyagarajan A, Sliva D (2009) Suppression of the inflammatory response by triterpenes isolated from the mushroom Ganoderma lucidum. Int Immunopharmacol 9(11): 1272–1280. https://doi.org/10.1016/j.intimp.2009.07.011 Dundar A, Okumus V, Ozdemir S et al (2015) Antioxidant, antimicrobial, cytotoxic and anticholinesterase activities of seven mushroom species with their phenolic acid composition. J Hortic 2:1–6. https://doi.org/10.4172/2376-0354.1000161 Duru ME, Ayan GTC (2015) Biologically active terpenoids from mushroom origin: a review. Rec Nat Prod 9:456–483 Elsayed EA, El Enshasy H, Wadaan MA et al (2014) Mushrooms: a potential natural source of antiinflammatory compounds for medical applications. Mediat Inflamm 2014:8085841. https://doi. org/10.1155/2014/805841

378

U. Altaf et al.

Farkas O, Jakus J, Heberger K (2004) Quantitative structure–antioxidant activity relationships of flavonoid compounds. Molecules 9:1079–1088. https://doi.org/10.3390/91201079 Ferreira ICFR, Barros L, Abreu RMV (2009) Antioxidants in wild mushrooms. Curr Med Chem 16: 1543–1560. https://doi.org/10.2174/092986709787909587 Gao JJ, Min BS, Ahn EM et al (2002) New triterpene aldehydes, lucialdehydes A-C, from Ganoderma lucidum and their cytotoxicity against murine and human tumor cells. Chem Pharm Bull 50:837–840. https://doi.org/10.1248/cpb.50.837 Gao Z, Kong D, Cai W et al (2021) Characterization and anti-diabetic nephropathic ability of mycelium polysaccharides from Coprinus comatus. Carbohydr Polym 251:1–12. https://doi. org/10.1016/j.carbpol.2020.117081 Gąsecka M, Magdziak Z, Siwulski M et al (2018) Profile of phenolic and organic acids, antioxidant properties and ergosterol content in cultivated and wild growing species of Agaricus. Eur Food Res Technol 244:259–268. https://doi.org/10.1007/s00217-017-2952-9 Govindan S, Keeper C, Jaba P et al (2014) Calocybe indica polysaccharides alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress induced by D-galactose in mice. In: Proceedings of 8th International Conference on Mushroom Biology and Mushroom Products (ICMBMP8), New Delhi, India. ICAR - Directorate of Mushroom Research, Solan, pp 394–406 Govindan S, Johnson EER, Christopher J et al (2016) Antioxidant and anti-aging activities of polysaccharides from Calocybe indica var, APK2. Exp Toxicol Pathol 68:329–334. https://doi. org/10.1016/j.etp.2016.04.001 Guillamón E, García-Lafuente A, Lozano M et al (2010) Edible mushrooms: role in the prevention of cardiovascular diseases. Fitoterapia 81(7):715–723. https://doi.org/10.1016/j.fitote.2010. 06.005 Gupta S, Summuna B, Gupta M et al (2018) Edible mushrooms: cultivation, bioactive molecules, and health benefits. In: Mérillon J-M, Ramawat KG (eds) Bioactive molecules in food. Reference series in phytochemistry. Springer, New York, NY Han JW, Oh M, Lee YJ et al (2018) Crinipellins A and I, two diterpenoids from the basidiomycete fungus Crinipellis rhizomaticola, as potential natural fungicides. Molecules 23(9):2377–2388. https://doi.org/10.3390/molecules23092377 Hassan MAA, Rouf R, Tiralongo E et al (2015) Mushroom lectins: specificity, structure and bioactivity relevant to human disease. Int J Mol Sci 16:7802–7838. https://doi.org/10.3390/ ijms16047802 He M, Su D, Liu Q et al (2017) Mushroom lectin overcomes hepatitis B virus tolerance via TLR6 signaling. Sci Rep 7:5814. https://doi.org/10.1038/s41598-017-06261-5 Heleno SA, Barros L, Sousa MJ et al (2011) Targeted metabolites analysis in wild Boletus species. LWT Food Sci Technol 44(6):1343–1348. https://doi.org/10.1016/j.lwt.2011.01.017 Heleno SA, Barros L, Martins A et al (2012) Phenolic, polysaccharidic, and lipidic fractions of mushrooms from northeastern Portugal: chemical compounds with antioxidant properties. J Agric Food Chem 60:4634–4640. https://doi.org/10.1021/jf300739m Heleno SA, Ferreira ICFR, Esteves AP et al (2013) Antimicrobial and demelanizing activity of Ganoderma lucidum extract, p-hydroxybenzoic and cinnamic acids and their synthetic acetylated glucuronide methyl esters. Food Chem Toxicol 58:95–100. https://doi.org/10.1016/j.fct. 2013.04.025 Heleno SA, Ferreira ICFR, Calhelha RC et al (2014a) Cytotoxicity of Coprinopsis atramentaria extract, organic acids and their synthesized methylated and glucuronate derivatives. Food Res Int 55:170–175 Heleno SA, Ferreira ICFR, Ćirić A et al (2014b) Coprinopsis atramentaria extract, organic acids, synthesized glucuronated and methylated derivatives as antibacterial and antifungal agents. Food Funct 5:2521–2528. https://doi.org/10.1039/c4fo00490f Heleno SA, Barros L, Martins A et al (2015a) Nutritional value, bioactive compounds, antimicrobial activity and bioaccessibility studies with wild edible mushrooms. LWT Food Sci Technol 63:799–806

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

379

Heleno SA, Martins A, Queiroz MJRP et al (2015b) Bioactivity of phenolic acids: metabolites versus parent compounds: a review. Food Chem 173:501–513. https://doi.org/10.1016/j. foodchem.2014.10.057 Hsu HC, Hsu CI, Lin RH et al (1997) Fip-vvo, a new fungal immunomodulatory protein isolated from Volvariella volvacea. Biochem J 323:557–565. https://doi.org/10.1042/bj3230557 Huang NK, Cheng JY, Lai WL et al (2005) Antrodia camphorata prevents rat pheochromocytoma cells from serum deprivation induced apoptosis. FEMS Microbiol Lett 244(1):213–219. https:// doi.org/10.1016/j.femsle.2005.01.048 Ikekawa T, Uehara N, Maeda Y et al (1969) Antitumor activity of aqueous extracts of edible mushrooms. Cancer Res 29:734–735 Isaka M, Chinthanom P, Rachtawee P et al (2020) Lanostane triterpenoids from cultivated fruiting bodies of the wood-rot basidiomycete Ganoderma casuarinicola. Phytochemistry 170:112225. https://doi.org/10.1016/j.phytochem.2019.112225 Isanaka S, Barnhart DA, McDonald CM et al (2019) Cost-effectiveness of community-based screening and treatment of moderate acute malnutrition in Mali. BMJ J 4:e001227. https://doi. org/10.1136/bmjgh-2018-001227 Ismaya WT, Tjandrawinata RR, Rachmawati H (2020) Lectins from the edible mushroom Agaricus bisporus and their therapeutic potentials. Molecules 25:2368–2384. https://doi.org/10.3390/ molecules25102368 Iwatsuki K, Akihisa T, Tokuda H (2003) Lucidenic acids P and Q, methyl lucidenate P, and other triterpenoids from the fungus Ganoderma lucidum and their inhibitory effects on Epstein–Barr virus activation. J Nat Prod 66:1582–1585. https://doi.org/10.1021/np0302293 Jaworska G, Pogó K, Berna E et al (2015) Nutraceuticals and antioxidant activity of prepared for consumption commercial mushrooms Agaricus bisporus and Pleurotus ostreatus. J Food Qual 38:111–122. https://doi.org/10.1111/jfq.12132 Jayachandran M, Xiao J, Xu B (2017) A critical review on health promoting benefits of edible mushrooms through gut microbiota. Int J Mol Sci 18:1934–1946. https://doi.org/10.1111/jfq. 12132 Kała K, Kryczyk-Poprawa A, Rzewińska A et al (2020) Fruiting bodies of selected edible mushrooms as a potential source of lovastatin. Eur Food Res Technol 246:713–722. https:// doi.org/10.1007/s00217-020-03435-w Kalač P (2013) A review of chemical composition and nutritional value of wild growing and cultivated mushrooms. J Sci Food Agric 93(2):209–218. https://doi.org/10.1002/jsfa.5960 Kaur B, Atri NS (2019) Evaluation of amino acid and fatty acid profile of Pleurotus sapidus - an edible mushroom from India. Mushroom Res 28(1):53–60 Kawagishi H, Ando M, Mizuno T (1990) Hericenone A and B as cytotoxic principles from the mushroom Hericium erinaceum. Tetrahedron Lett 31:373–376 Khatua S, Acharya K (2019) Alkali treated antioxidative crude polysaccharide from Russula alatoreticula potentiates murine macrophages by tunning TLR/NF-κB pathway. Sci Rep 9: 1713. https://doi.org/10.1038/s41598-018-37998-2 Khatua S, Acharya K (2020) A new edible mushroom with a new hope. In: Current updates in life sciences. Elsevier, Amsterdam, pp 344–353 Kho YS, Vikineswary S, Abdullah N et al (2009) Antioxidant capacity of fresh and processed fruit bodies and mycelium of Auricularia auricula-judae (Fr.) Quel. J Med Food 12:167–174. https:// doi.org/10.1089/jmf.2007.0568 Khoo HE, Azlan A, Tang ST, Lim SM (2017) Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits. Food Nutr Res 61: 1361779. https://doi.org/10.1080/16546628.2017.1361779 Kim GY, Park SK, Lee MK et al (2003) Proteoglycan isolated from Phellinus linteus activates murine B lymphocytes via protein kinase C and protein tyrosine kinase. Int Immunopharmacol 3:1281–1292. https://doi.org/10.1016/S1567-5769(03)00115-2

380

U. Altaf et al.

Kim YW, Kim KH, Choi HJ et al (2005) Anti-diabetic activity of beta-glucans and their enzymatically hydrolyzed oligosaccharides from Agaricus blazei. Biotechnol Lett 27:483–487. https:// doi.org/10.1007/s10529-005-2225-8 Kim YO, Park HW, Kim JH et al (2006) Anti cancer effect and structural characterization of endopolysaccharide from cultivated mycelia of Inonotus obliquus. Life Sci 79:72–80. https://doi.org/ 10.1016/j.lfs.2005.12.047 Kim KH, Moon E, Choi SU et al (2013) Lanostane triterpenoids from the mushroom Naematoloma fasciculare. J Nat Prod 76:845–851 Kimura Y, Taniguchi M, Baba K (2002) Antitumor and antimetastatic effects on liver of triterpenoid fractions of Ganoderma lucidum: mechanism of action and isolation of an active substance. Anticancer Res 22(6):3309–3318. https://doi.org/10.1021/np300801x Klaus A, Kozarski M, Vunduk J (2016) Antibacterial and antifungal potential of wild basidiomycete mushroom Ganoderma applanatum. Lek Sirovine 36:37–46. https://doi.org/10.5937/ leksir1636037K Kobori M, Yoshida M, Ohnishi-Kameyama M (2006) 5alpha, 8alpha-epidioxy-22E-ergosta-6, 9 (11), 22-trien-3 betaol from an edible mushroom suppresses growth of HL60 leukemia and HT29 colon adenocarcinoma cells. Biol Pharm Bull 29:755–759 Kumar S, Sharma YP (2011) Diversity of wild mushrooms from Jammu and Kashmir (India). In: Proceedings of the 7th International Conference on Mushroom Biology and Mushroom Products (ICMBMP7), vol 1, pp 568–577 Kumaran S, Pandurangan AK, Shenbhagaraman R et al (2017) Isolation and characterization of lectin from the artist’s conk medicinal mushroom, Ganoderma applanatum (Agaricomycetes) and evaluation of its antiproliferative activity in HT-29 colon cancer cells. Int J Med Mushrooms 19:675–684. https://doi.org/10.1615/IntJMedMushrooms.2017021274 Lagunes I, Trigos A (2015) Photo-oxidation of ergosterol: indirect detection of antioxidants photosensitizers or quenchers of singlet oxygen. J Photochem Photobiol B 145:30–34. https:// doi.org/10.1016/j.jphotobiol.2015.02.014 Lalotra P, Bala P, Kumar S, Sharma YP (2016) Biochemical characterization of some wild edible mushrooms from Jammu and Kashmir. Proc Natl Acad Sci India Sect B Biol Sci 88:539–545. https://doi.org/10.1007/s40011-016-0783-2 Lam SK, Ng TB (2001) Hypsin, a novel thermostable ribosome-inactivating protein with antifungal and antiproliferative activities from fruiting bodies of the edible mushroom Hypsizigus marmoreus. Biochem Biophys Res Commun 285(4):1071–1075. https://doi.org/10.1006/bbrc. 2001.5279 Lata, Atri NS (2017) Amino acid profile of a basidiomycetous edible mushroom Lentinus sajorcaju. Int J Pharm Pharm Sci 9(9):250–257. https://doi.org/10.22159/ijpps.2017v9i9.18856 Lee Y, Huang G, Liang Z et al (2007) Antioxidant properties of three extract from Pleurotus citrinopileatus. LWT Food Sci Technol 40(5):823–833 Lee I, Seo J, Kim J et al (2009) Lanostane triterpenes from the fruiting bodies of Ganoderma lucidum and their inhibitory effects on adipocyte differentiation in 3T3-L1 cells. J Nat Prod 73: 172–176. https://doi.org/10.1021/np900578h Lee I, Ahn B, Choi J et al (2011) Selective cholinesterase inhibition by lanostane triterpenes from fruiting bodies of Ganoderma lucidum. Bioorg Med Chem Lett 21:6603–6607. https://doi.org/ 10.1016/j.bmcl.2011.04.042 Li Y (2012) Present development situation and tendency of edible mushroom industry in China. In: Zhang J, Hexiang W, Mingjie C (eds) Proceedings of 18th Congress of the International Society of Mushroom Science. China Agriculture Press, Beijing, pp 1–9 Li K, Zhuo C, Teng C et al (2016) Effects of Ganoderma lucidum polysaccharides on chronic pancreatitis and intestinal microbiota in mice. Int J Biol Macromol 93:904–912. https://doi.org/ 10.1016/j.ijbiomac.2016.09.029 Li S, Liu H, Wang W et al (2017) Antioxidant and anti-aging effects of acidic extractable polysaccharides by Agaricus bisporus. Int J Biol Macromol 106:1297–1306. https://doi.org/10. 1016/j.ijbiomac.2017.08.135

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

381

Lin C, Sheu G, Lin Y et al (2010) A new immunomodulatory protein from Ganoderma microsporum inhibits epidermal growth factor mediated migration and invasion in A549 lung cancer cells. Process Biochem 45:1537–1542. https://doi.org/10.1016/j.procbio.2010.06.006 Lindequist U, Niedermeyer THJ, Jülich WD (2005) The pharmacological potential of mushrooms. Evid Based Complement Alternat Med 2:285–299. https://doi.org/10.1093/ecam/neh107 Liu J, LiangJia L, JuanKan J et al (2013) In vitro and in vivo antioxidant activity of ethanolic extract of white button mushroom (Agaricus bisporus). Food Chem Toxicol 51:310–316. https://doi. org/10.1016/j.fct.2012.10.014 Liu C, Sun Y, Mao Q et al (2016) Characteristics and antitumor activity of Morchella esculenta polysaccharide extracted by pulsed electric field. Int J Mol Sci 17:986. https://doi.org/10.3390/ ijms17060986 Lou Z, Wang H, Rao S et al (2012) p-Coumaric acid kills bacteria through dual damage mechanisms. Food Control 25:550–554. https://doi.org/10.1016/j.foodcont.2011.11.022 Lull C, Wichers HJ, Savelkoul HFJ (2005) Antiinflammatory and immunomodulating properties of fungal metabolites. Mediat Inflamm 2005:63–80. https://doi.org/10.1155/MI.2005.63 Lung MY, Chang YC (2011) Antioxidant properties of the edible basidiomycete Armillaria mellea in submerged cultures. Int J Mol Sci 12(10):6367–6384. https://doi.org/10.3390/ijms12106367 Ma L, Chen H, Dong P et al (2013) Anti-inflammatory and anticancer activities of extracts and compounds from the mushroom Inonotus obliquus. Food Chem 139:503–507. https://doi.org/ 10.1016/j.foodchem.2013.01.030 Ma K, Li C, Han J (2014) New benzoate derivatives and hirsutane type sesquiterpenoids with antimicrobial activity and cytotoxicity from the solid-state fermented rice by the medicinal mushroom Stereum hirsutum. Food Chem 143:239–245. https://doi.org/10.1016/j.foodchem. 2013.07.124 Ma G, Kimatu BM, Zhao L et al (2017) In vivo fermentation of a Pleurotus eryngii polysaccharide and its effects on fecal microbiota composition and immune response. Food Funct 8:1810–1821. https://doi.org/10.1039/c7fo00341b Ma G, Yang W, Zhao L et al (2018) A critical review on the health promoting effects of mushrooms nutraceuticals. Food Sci Human Wellness 7(2):125–133. https://doi.org/10.1016/j.fshw.2018. 05.002 Mahajan RG, Patil SI, Mohan DR et al (2002) Pleurotus eous mushroom lectin (PEL) with mixed carbohydrate inhibition and antiproliferative activity on tumor cell lines. J Biochem Mol Biol Biophys 6:341–345. https://doi.org/10.1080/1025814021000008558 Maiti S, Bhutia SK, Mallick SK (2008) Antiproliferative and immunostimulatory protein fraction from edible mushrooms. Environ Toxicol Pharmacol 26(2):187–191. https://doi.org/10.1016/j. etap.2008.03.009 Maity P, Nandi AK, Sen IK (2014a) Heteroglycan of an edible mushroom Entoloma lividoalbum: structural characterization and study of its protective role for human lymphocytes. Carbohydr Polym 114:157–165. https://doi.org/10.1016/j.carbpol.2014.07.080 Maity P, Samanta S, Nandi AK et al (2014b) Structure elucidation and antioxidant properties of a soluble β-d-glucan from mushroom Entoloma lividoalbum. Int J Biol Macromol 63:140–149. https://doi.org/10.1016/j.ijbiomac.2013.10.040 Maity P, Sena IP, Majia PK (2015) Structural, immunological, and antioxidant studies of β-glucan from edible mushroom Entoloma lividoalbum. Carbohydr Polym 123:350–358. https://doi.org/ 10.1016/j.carbpol.2015.01.051 Maity GN, Maity P, Choudhuri I et al (2019) Structural studies of a water insoluble β-glucan from Pleurotus djamor and its cytotoxic effect against PA1, ovarian carcinoma cells. Carbohydr Polym 222:114990. https://doi.org/10.1016/j.carbpol.2019.114990 Maity GN, Maity P, Khatua S et al (2020) Structural features and antioxidant activity of a new galactoglucan from edible mushroom Pleurotus djamor. Int J Biol Macromol 168:743. https:// doi.org/10.1016/j.ijbiomac.2020.11.131

382

U. Altaf et al.

Maity P, Sen IK, Chakraborty I et al (2021) Biologically active polysaccharide from edible mushrooms: a review. Int J Biol Macromol 172:408–417. https://doi.org/10.1016/j.ijbiomac. 2021.01.081 Mallick SK, Bhutia SK, Maiti TK (2009) Macrophage stimulation by polysaccharides isolated from barometer earthstar mushroom, Astraeus hygrometricus (Pers.) Morgan (Gasteromycetideae). Int J Med Mushrooms 11(3):237–248 Manach C, Scalbert A, Morand C et al (2004) Polyphenols: food sources and bioavailability. Am J Clin Nutr 79:727–747. https://doi.org/10.1093/ajcn/79.5.727 Masaki H (2010) Role of antioxidants in the skin: anti-aging effects. J Dermatol Sci 58:85–90. https://doi.org/10.1016/j.jdermsci.2010.03.003 Matuszewska A, Karp M, Jaszek M et al (2016) Laccase purified from Cerrena unicolor exerts antitumor activity against leukemic cells. Oncol Lett 11:2009–2018. https://doi.org/10.3892/ol. 2016.4220 Mau J, Lin H, Song S (2002) Antioxidant properties of several specialty mushrooms. Food Res Int 35(6):519–526. https://doi.org/10.1016/S0963-9969(01)00150-8 McKenna D, Jones K, Hughes K (2002) Reishi botanical medicines: the desk reference for major herbal supplements, 2nd edn. The Haworth Herbal Press, Binghamton, NY, pp 825–855 Mishra KK, Pal RS, Kumar RA et al (2013) Antioxidant properties of different edible mushroom species and increased bioconversion efficiency of Pleurotus eryngii using locally available casing materials. Food Chem 138:1557–1563. https://doi.org/10.1016/j.foodchem.2012.12.001 Murota K, Terao J (2003) Antioxidative flavonoid quercetin: implication of its intestinal absorption and metabolism. Arch Biochem Biophys 417:12–17. https://doi.org/10.1016/s0003-9861(03) 00284-4 Muszynska B, 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 Scientiarum Polonorum Hortorum Cultus 12(4):107–116 Nagabushan H (2010) Retapamulin: a novel topical antibiotic. Indian J Dermatol Venereol Leprol 76(1):77–79. https://doi.org/10.4103/0378-6323.58693 Nandi AK, Samanta S, Maity S (2014) Antioxidant and immunostimulant β-glucan from edible mushroom Russula albonigra (Krombh.) Fr. Carbohydr Polym 99:774–782. https://doi.org/10. 1016/j.carbpol.2013.09.016 Ng TB (2004) Peptides and proteins from fungi. Peptides 25:1055–1073. https://doi.org/10.1016/j. peptides.2004.03.013 Ou YX, Li YY, Qian XM, Shen YM (2012) Guanacastane-type diterpenoids from Coprinus radians. Phytochem 78:190–196 Öztürk M, Tel G, Öztürk FA et al (2014) The cooking effect on two edible mushrooms in Anatolia: fatty acid composition, total bioactive compounds, antioxidant and anticholinesterase activities. Rec Nat Prod 8(2):189–194 Öztürk M, Tel CG, Muhammad AA et al (2015) Mushrooms: a source of exciting bioactive compounds. Stud Nat Prod Chem 45:363–456. https://doi.org/10.1016/B978-0-444-63473-3. 00010-1 Pandya U, Dhuldhaj U, Sahay NS (2018) Bioactive mushroom polysaccharides as antitumor: an overview. Nat Prod Res 33:2668. https://doi.org/10.1080/14786419.2018.1466129 Park YM, Won JH, Kim YH et al (2005) In vivo and in vitro anti-inflammatory and antinociceptive effects of the methanol extract of Inonotus obliquus. J Ethnopharmacol 101:120–128. https:// doi.org/10.1016/j.jep.2005.04.003 Piljac-Zegarac J, Samec D, Piljac A (2011) Antioxidant properties of extracts of wild medicinal mushroom species from Croatia. Int J Med Mushrooms 13:257–263. https://doi.org/10.1615/ IntJMedMushr.v13.i3.50 Pohleven J, Obermajer N, Sabotic J et al (2009) Purification, characterization and cloning of a ricin B-like lectin from mushroom Clitocybe nebularis with antiproliferative activity against human leukemic T cells. Biochem Biophys Acta 1790:173–181. https://doi.org/10.1016/j.bbagen.2008. 11.006

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

383

Pugazhendhi D, Pope GS, Darbre PD (2005) Oestrogenic activity of p-hydroxybenzoic acid (common metabolite of paraben esters) and methylparaben in human breast cancer cell lines. J Appl Toxicol 25:301–309. https://doi.org/10.1002/jat.1066 Puri M, Kaur I, Perugini MA et al (2012) Ribosome-inactivating proteins: current status and biomedical applications. Drug Discov Today 17:774–783. https://doi.org/10.1016/j.drudis. 2012.03.007 Pushparajah V, Fatima A, Chong C et al (2016) Characterisation of a new fungal immunomodulatory protein from tiger milk mushroom, Lignosus rhinocerotis. Sci Rep 6:30010. https://doi. org/10.1038/srep30010 Puttaraju NG, Venkateshaiah SU, Dharmesh SM et al (2006) Antioxidant activity of indigenous edible mushrooms. J Agric Food Chem 54:9764–9772. https://doi.org/10.1021/jf0615707 Rahi DK, Malik D (2016) Diversity of mushrooms and their metabolites of nutraceutical and therapeutic significance. J Mycol 10:1–18. https://doi.org/10.1155/2016/7654123 Rathore H, Prasad S, Sharma S (2017) Mushroom nutraceuticals for improved nutrition and better human health: a review. PharmaNutrition 5:35–46. https://doi.org/10.1016/j.phanu.2017.02.001 Reis F, Martins A, Barros L et al (2012) Antioxidant properties and phenolic profile of the most widely appreciated cultivated mushrooms: a comparative study between in vivo and in vitro samples. Food Chem Toxicol 50:1201–1207. https://doi.org/10.1016/j.fct.2012.02.013 Reis FS, Martins A, Vasconcelos MH et al (2017) Functional foods based on extracts or compounds derived from mushrooms. Trends Food Sci Technol 66:48–62. https://doi.org/10.1016/j.tifs. 2017.05.010 Ren D, Wang N, Guo J et al (2016) Chemical characterization of Pleurotus eryngii polysaccharide and its tumor inhibitory effects against human hepatoblastoma HepG-2 cells. Carbohydr Polym 138:123–133. https://doi.org/10.1016/j.carbpol.2015.11.051 Renaud SC, de Lorgeril M (1992) Wine, alcohol, platelets, and the French paradox for coronary heart disease. Lancet 339:1523–1526. https://doi.org/10.1016/0140-6736(92)91277-f 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/10.1016/08915849(95)02227-9 Ruthes AC, Smiderle FR, Iacomini M (2016) Mushroom heteropolysaccharides: a review on their sources, structure and biological effects. Carbohydr Polym 136:358–375. https://doi.org/10. 1016/j.carbpol.2015.08.061 Sagar A, Gautam C, Sehgal AK (2007) Studies on some medicinal mushrooms of Himachal Pradesh. Indian J Mushrooms 25:8–14 Saiki P, Kawano Y, Van Griensven LJ et al (2017) The anti-inflammatory effect of Agaricus brasiliensis is partly due to its linoleic acid content. Food Funct 8:4150–4158 Samanta S, Nandi AK, Sen IK (2015) Studies on antioxidative and immunostimulating fucogalactan of the edible mushroom Macrolepiota dolichaula. Carbohydr Res 413:22–29. https://doi.org/10.1016/j.carres.2015.05.006 Shameem N, Kamili AN, Ahmad M et al (2017) Antimicrobial activity of crude fractions and morel compounds from wild edible mushrooms of north western Himalaya. Microb Pathog 105:356– 360. https://doi.org/10.1016/j.micpath.2017.03.005 Shao Y, Guo H, Zhang J et al (2019) The genome of the medicinal macrofungus Sanghuang provides insights into the synthesis of diverse secondary metabolites. Front Microbiol 10:3035. https://doi.org/10.3389/fmicb.2019.03035 Sharma YP, Sharma R, Khatua S et al (2019) Morphotaxonomy and comparative mycochemical study and antioxidant activity of hydromethanol, infusion and decoction extracts from Russula brevipes Peck. Indian Phytopathol 72:445–452. https://doi.org/10.1007/s42360-019-00173-2 Sharma R, Sharma YP, Kumar S et al (2020) Diversity and distribution of wild fleshy fungi in district Jammu, J&K, India. Indian For 146(6):524553 Singh RS, Bhari R, Kaur HP (2010) Mushroom lectins: current status and future perspectives. Crit Rev Biotechnol 30:99–126. https://doi.org/10.3109/07388550903365048

384

U. Altaf et al.

Singh SS, Wang H, Chan YS et al (2014) B. Lectins from edible mushrooms. Molecules 20:446– 469. https://doi.org/10.3390/molecules20010446 Singh M, Kamal S, Sharma VP (2017) Status and trends in world mushroom production-I. Mushroom Res 26(1):1–20 Singh RS, Walia AK, Kennedy JF (2020) Mushroom lectins in biomedical research and development. Int J Biol Macromol 151(15):1340–1350. https://doi.org/10.1016/j.ijbiomac.2019.10.180 Smiderle FR, Ruthes AC, van Arkel J et al (2011) Polysaccharides from Agaricus bisporus and Agaricus brasiliensis show similarities in their structures and their immunomodulatory effects on human monocytic THP-1 cells. BMC Complement Altern Med 11:58. https://doi.org/10. 1186/1472-6882-11-58 Smiderle FR, Alquini G, Tadra-Sfeir MZ et al (2013) Agaricus bisporus and Agaricus brasiliensis (1!6)-d-glucans show immunostimulatory activity on human THP-1 derived macrophages. Carbohydr Polym 94:91–99. https://doi.org/10.1016/j.carbpol.2012.12.073 Song FQ, Liu Y, Kong XS, Chang W et al (2013) Progress on understanding the anticancer mechanisms of medicinal mushroom: Inonotus obliquus. Asian Pac J Cancer Prev 14:1571– 1578. https://doi.org/10.7314/apjcp.2013.14.3.1571 Su X, Liu K, Xie Y et al (2019) Mushroom Inonotus sanghuang alleviates experimental pulmonary fibrosis: implications for therapy of pulmonary fibrosis. Biomed Pharmacother 133:110919. https://doi.org/10.1016/j.biopha.2020.110919 Sun J, Chen QJ, Zhu MJ et al (2014) An extracellular laccase with antiproliferative activity from the sanghuang mushroom Inonotus abaumii. J Mol Catal B Enzym 99:20–25 Tang W, Jian-Wen L, Wei-Ming Z et al (2006) Ganoderic acid T from Ganoderma lucidum mycelia induces mitochondria mediated apoptosis in lung cancer cells. Life Sci 80:205–211. https://doi. org/10.1016/j.lfs.2006.09.001 Taofiq O, Rodrigues F, Barros L et al (2019) Agaricus blazei Murrill from Brazil: an ingredient for nutraceutical and cosmeceutical applications. Food Funct 10:565–572. https://doi.org/10.1039/ C8FO02461H Tel G, Apaydın M, Duru ME et al (2012) Antioxidant and cholinesterase inhibition activities of three Tricholoma species with total phenolic and flavonoid contents: the edible mushrooms from Anatolia. Food Anal Methods 5:495–504. https://doi.org/10.1007/s12161-011-9275-4 Thakur MP (2020) Advances in mushroom production: key to food, nutritional and employment security: a review. Ind Phytopathol 73:377. https://doi.org/10.1007/s42360-020-00244-9 Thatoi H, Singdevsachan SK (2014) Diversity, nutritional composition and medicinal potential of Indian mushrooms: a review. Afr J Biotechnol 13:523–545. https://doi.org/10.5897/AJB2013. 13446 Timmers S, Auwerx J, Schrauwen P (2012) The journey of resveratrol from yeast to human. Aging 4:1–3. https://doi.org/10.18632/aging.100445 Udchumpisai W, Bangyeekhun E (2019) Purification, structural characterization, and biological activity of polysaccharides from Lentinus velutinus. Mycobiology 48(1):51–57. https://doi.org/ 10.1080/12298093.2019.1693482 Underhill DM, Ozinsky A, Hajjar AM et al (1999) The Toll-like receptor 2 is recruited to macrophage phagosomes and discriminates between pathogens. Nature 401:811–815. https:// doi.org/10.1038/44605 Upadhyay RC, Rai RD (1999) Cultivation and nutritive value of Lentinus squarrosulus. Mushroom Res 8:35–38 Valverde ME, Hernández-Pérez T, Paredes-López O (2015) Edible mushrooms: improving human health and promoting quality life. Int J Microbiol 2015:376387 Van Q, Nayak BN, Reimer M et al (2009) anti-inflammatory effect of Inonotus obliquus, Polygala senega L., and Viburnum trilobum in a cell screening assay. J Ethnopharmacol 125:487–493 Vargas AJ, Burd R (2010) Hormesis and synergy: pathways and mechanisms of quercetin in cancer prevention and management. Nutr Rev 68:418–428

12

Therapeutic Potential of Mushroom Bioactive Nutraceuticals

385

Vaz JA, Almeida GM, Ferreira ICFR et al (2012) Clitocybe alexandri extract induces cell cycle arrest and apoptosis in a lung cancer cell line: identification of phenolic acids with cytotoxic potential. Food Chem 132:482–486. https://doi.org/10.1016/j.foodchem.2011.11.031 Vishwakarma MP, Bhatt RP, Gairola S (2011) Some medicinal mushrooms of Garhwal Himalaya, Uttarakhand, India. Int J Med Aromat Plants 1(1):33–40 Wang H, Ng T (2006) A laccase from the medicinal mushroom Ganoderma lucidum. Appl Microbiol Biotechnol 72:508–513. https://doi.org/10.1007/s00253-006-0314-9 Wang YQ, Bao L, Yang XL et al (2012) Four new cuparene-type sesquiterpenes from Flammulina velutipes. Helv Chim Acta 95:261–267. https://doi.org/10.1002/hlca.201100289 Wang S, Bao L, Zhao F et al (2013) Isolation, identification, and bioactivity of monoterpenoids and sesquiterpenoids from the mycelia of edible mushroom Pleurotus cornucopiae. J Agric Food Chem 61:5122–5129. https://doi.org/10.1021/jf401612t Wang XM, Zhang J, Wu LH et al (2014) A mini-review of chemical composition and nutritional value of edible wild grown mushroom from China. Food Chem 151:279–285. https://doi.org/10. 1016/j.foodchem.2013.11.062 Wang G, Wang L, Zhou J et al (2019) The possible role of PD-1 protein in Ganoderma lucidum– mediated immunomodulation and cancer treatment. Integr Cancer Ther 18:1–13. https://doi.org/ 10.1177/1534735419880275 Wasser SP (2011) Current findings, future trends, and unsolved problems in studies of medicinal mushrooms. Appl Microbiol Biotechnol 89:1323–1332. https://doi.org/10.1007/s00253-0103067-4 Wei S, Helsper JPFG, van Griensven LJLD (2008) Phenolic compounds present in medicinal mushroom extracts generate reactive oxygen species in human cells in vitro. Int J Med Mushrooms 10:1–13. https://doi.org/10.1615/IntJMedMushr.v10.i1.20 Wei J, Guo WH, Cao CY et al (2018) Polyoxygenated cyathane diterpenoids from the mushroom Cyathus africanus, and their neurotrophic and anti-neuroinflammatory activities. Sci Rep 8: 2175. https://doi.org/10.1038/s41598-018-20472-4 Wen Y, Peng D, Li C et al (2019) A new polysaccharide isolated from Morchella importuna fruiting bodies and its immunoregulatory mechanism. Int J Biol Macromol 15:8–19. https://doi.org/10. 1016/j.ijbiomac.2019.06.171 Wong KH, Won KY, Kwan HS et al (2005) Dietary fibers from mushroom sclerotia: 3. In vitro fermentability using human fecal microflora. J Agric Food Chem 53:9407–9412. https://doi.org/ 10.1021/jf051080z Wong JH, Wang H, Ng T (2008) Marmorin, a new ribosome inactivating protein with antiproliferative and HIV-1 reverse transcriptase inhibitory activities from the mushroom Hypsizigus marmoreus. Appl Microbiol Biotechnol 81:669–674. https://doi.org/10.1007/ s00253-008-1639-3 Xu X, Yana H, Chen J et al (2011) Bioactive proteins from mushrooms. Biotechnol Adv 29(6): 667–674. https://doi.org/10.1016/j.biotechadv.2011.05.003 Xu H, Kong YY, Chen X et al (2016) Recombinant FIP-gat, a fungal immunomodulatory protein from Ganoderma atrum, induces growth inhibition and cell death in breast cancer cells. J Agric Food Chem 64:2690–2698. https://doi.org/10.1021/acs.jafc.6b00539 Xu S, Dou Y, Ye B et al (2017) Ganoderma lucidum polysaccharides improve insulin sensitivity by regulating inflammatory cytokines and gut microbiota composition in mice. J Funct Foods 38: 545–552. https://doi.org/10.1016/j.jff.2017.09.032 Yamin S, Shuhaimi M, Arbakariya A et al (2012) Effect of Ganoderma lucidum polysaccharides on the growth of Bifidobacterium spp. as assessed using real-time PCR. Int Food Res J 19: 1199–1205 Yang W, Yu J, Zhao L et al (2015) Polysaccharides from Flammulina velutipes improve scopolamine-induced impairment of learning and memory of rats. J Funct Foods 18:411–422 Yang M, Belwal T, Devkota HP et al (2019) Trends of utilizing mushroom polysaccharides (MPs) as potent nutraceutical components in food and medicine: a comprehensive review. Trends Food Sci Technol 92:94–110

386

U. Altaf et al.

Yangdol R, Kumar S, Sharma YP (2017) Some pyronemataceous macrofungi from Ladakh (J&K), India. Curr Res Environ Appl Mycol 7(4):293–300. https://doi.org/10.5943/cream/7/4/6 Ying YM, Zhang LY, Zhang X et al (2014) Terpenoids with alphaglucosidase inhibitory activity from the submerged culture of Inonotus obliquus. Phytochemistry 108:171–176. https://doi.org/ 10.1016/j.phytochem.2014.09.022 Yuan Y, Liu Y, Liu M et al (2017) Optimization extraction and bioactivities of polysaccharide from wild Russula griseocarnosa. Saudi Pharm J 25(4):523–530. https://doi.org/10.1016/j.jsps.2017. 04.018 Zhang L, Yang L (1995) Properties of Auricularia auricula-judae β-D-glucan in dilute solution. Biopolymers 36:695–700. https://doi.org/10.1002/bip.360360603 Zhang R, Zhang G, Hu D et al (2010) A novel ribonuclease with antiproliferative activity from fresh fruiting bodies of the edible mushroom Lyophyllum shimeiji. Biochem Genet 48:658–668. https://doi.org/10.1007/s10528-010-9347-y Zhang R, Zhao L, Wang H et al (2014) A novel ribonuclease with antiproliferative activity toward leukemia and lymphoma cells and HIV-1 reverse transcriptase inhibitory activity from the mushroom, Hohenbuehelia serotina. Int J Mol Med 33:209–214. https://doi.org/10.3892/ ijmm.2013.1553 Zhang R, Tian G, Zhao Y et al (2015) A novel ribonuclease with HIV-1 reverse transcriptase inhibitory activity purified from the fungus Ramaria Formosa. J Basic Microbiol 55:269–275. https://doi.org/10.1002/jobm.201300876 Zhang Y, Zeng Y, Men Y (2018) Structural characterization and immunomodulatory activity of exopolysaccharides from submerged culture of Auricularia auricular-judae. Int J Biol Macromol 115:978–984. https://doi.org/10.1016/j.ijbiomac.2018.04.145 Zhao JK, Wang HX, Ng TB (2009) Purification and characterization of a novel lectin from the toxic wild mushroom Inocybe umbrinella. Toxicon 53:360–366. https://doi.org/10.1016/j.toxicon. 2008.12.009 Zhao S, Rong CB, Kong C et al (2014) A novel laccase with potent antiproliferative and HIV-1 reverse transcriptase inhibitory activities from mycelia of mushroom Coprinus comatus. Biomed Res Int 2014:417461. https://doi.org/10.1155/2014/417461 Zhao H, Li H, Lai Q et al (2019) Antioxidant and hepatoprotective activities of modified polysaccharides from Coprinus comatus in mice with alcohol-induced liver injury. Int Biol Macromol 15:476–485. https://doi.org/10.1016/j.ijbiomac.2019.01.067 Zhu KX, Nie SP, Tan LH et al (2016) A polysaccharide from Ganoderma atrum improves liver function in type 2 diabetic rats via antioxidant action and short-chain fatty acids excretion. J Agric Food Chem 64:1938–1944. https://doi.org/10.1021/acs.jafc.5b06103

Chapter 13

Potential Uses of Mushrooms as Dietary Supplement to Enhance Memory Chitra Arya

Abstract Memory is the ability of an individual to record the information and recall it whenever needed. A complex network of numerous nerve cells and cortex of brain helps us to store memory captured in the form of words/pictures/olfactory signals, etc. Hippocampus helps in converting short form of memory into long term. By continuous learning we memorize the things and in an accident or disease there is loss of memory, stress and anxiety can lead to depression and ill health. Just like herbs (i.e. tea—Camellia sinensis (L.) Kuntze) stimulates the nerves of our brain the use of certain mushrooms like Hericium, Ganoderma, Lentinula, Psilocybe helps in brain-boosting and cognitive impairments. Mushrooms and their bioactive compounds present in the mycelial extract help in lowering the blood pressure, change the mood and control the progression of Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). Stressful conditions are often associated with loss of memory and other cognitive functions, which may lead to threats of schizophrenia and Alzheimer’s disease. In traditional or alternative system of medicine, numerous plants and fungi have been used to alleviate memory impairment both in healthy individuals and those with disease states which are now recognized as specific cognitive disorders. An ethnomycological approach has provided leads to identify mushrooms and their bioactive compounds that may have potential to modulate cognitive abilities by different modes of action. A variety of therapeutic targets have been identified as relevant in the treatment of cognitive disorders, and neuroprotection against glutamateinduced overstimulation of N-methyl-D-aspartate (NMDA) receptors, by the use of NMDA receptor modulators. Other activities considered to be relevant in the alleviation of cognitive impairment include anti-inflammatory, antioxidant and estrogenic activities. Psychedelics produced by hallucinogenic mushrooms can cause physical changes in brain, even to the cellular as well as molecular levels, which is the primary component. These psychedelics when exposed to neuron cells help to create new outgrowths of the

C. Arya (*) Phytochemistry Laboratory, Department of Botany, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_13

387

388

C. Arya

neuron network in the brain. These new connections help in brain functioning. Proactive compounds like hericenones (from mushroom) and erinacines (from mycelium) of lion’s mane, cordycepin from Cordyceps, lentinan from Lentinula help in stress alleviation, induce sound sleep and enhance the memory by stimulating the brain and avoiding shrinking of neurons in the cortex. Keywords Memory · Mushrooms · Dietary supplements · Hericium · Ganoderma · Cordyceps

13.1

Introduction

In traditional systems of medicine the plants like Brahmi (Centella asiatica (L.) Urban), Neer brahmi (Bacopa monnieri L.), Shankhpushpi (Evolvulus alsinoides L.), Maiden hair tree (Ginkgo biloba L.) and almond (Prunus amygdalus Batsch.) have been used to alleviate memory impairment both in healthy and diseased individuals, which are now recognized as specific cognitive disorders such as Alzheimer’s disease (AD), Parkinson’s disease (PD) and amyotrophic lateral sclerosis (ALS). It is suggested that almonds possess a memory enhancing activity in view of its positive effect on the retention of special memory in scopolamineinduced amnesia (Batool et al. 2015). Scientists found that the almonds lowered the serum cholesterol level in rats. They have also found to elevate the Ach level in the brain and ultimately improve the memory (special and avoidance) of rats. Potential of almonds in the management of cognitive dysfunction has been studied by Kulkarni et al. (2010). Complex mixture of components, with biological activities in relation to cognitive function, is reported from leaves of Ginkgo biloba L. (Field and Vadnal 1998) but the mechanisms of action are not well characterized. Among the many plants reputed to enhance cognitive function in a variety of traditional medicines including Ayurvedic, Chinese, European, African and South American, relatively few have been extensively studied to determine any pharmacological basis for their historical uses. The paper provides details of some of the mushrooms that have been used traditionally for their cognitive enhancing effects. Mention of Soma in Veda’s is supposed to be procured from a mushroom Amanita muscaria (L.) Lam. A number of hallucinogenic fungi have been identified by Ethnomycologists, which were used in past to cure the mental disorders. A variety of therapeutic targets have been identified as relevant in the treatment of cognitive disorders, including modulation of the cholinergic system, which may be achieved by the inhibition of acetylcholinesterase (AChE) and neuroprotection against glutamate-induced overstimulation of N-methyl-D-aspartate (NMDA) receptors, by the use of NMDA receptor modulators. Other activities considered to be relevant in the alleviation of cognitive impairment include anti-inflammatory, antioxidant and estrogenic activities. Role of macrofungi belonging to higher fungal groups of Basidiomycota and Ascomycota is well established in food and pharmacy industry. They have been called as ‘meat of the forest’ or ‘meat of the poor’ in certain countries (Dimitrijevic

13

Potential Uses of Mushrooms as Dietary Supplement to Enhance Memory

389

et al. 2018). Mushrooms are rich in protein (19–35%), carbohydrate (50–65%) and fat (2–6%) (Wang et al. 2014). To date about 2000 edible and medicinal fungi have been characterized (Meenu and Xu 2019; Lu et al. 2020). Truffles, morals and boletes are edible and more delicious, while Cordyceps, Lentinula and Ganoderma are medicinally more useful. Auricuaria auricula (L.) Underw. (wood ear fungus known as ‘Uchina’ in Manipuri) was the first mushroom to be grown commercially in China. Currently the mushroom production is the sixth largest agricultural industry there (Pan et al. 2019). Other important countries producing mushrooms include the USA, Poland, Netherlands, Spain and Canada (Singh 2017). The production has increased many times in India during the last two decades. Efforts are made to cultivate these in submerged cultures as well (Lu et al. 2020). Clinical trials have suggested that many mushrooms are neuroprotective (Zhang et al. 2017; Phan et al. 2015, 2017; Mori et al. 2009). Better cognitive performance of 70–74 years old Norwegian was reported with mushroom consumption (Nurk et al. 2010) and 19% reduced risk of dementia was recorded among Japanese people having food supplemented with mushrooms three times in a week or more (Zhang et al. 2017).

13.2

Nervous System, Neurons and Memory in Human Beings

Human nervous system consists of brain lodged in cranial cavity with 12 pairs of cranial nerves. It has two large paired cerebral hemisphere with corpus callosum present at bottom. Each hemisphere has four lobes. Although the suri and sulci vary somewhat in different cerebral hemisphere, they are recognizable in all hemisphere. On convex surface of the brain the central and lateral sulci are most important. The central sulcus is the precentral gyrus and frontal lobe. Parietal lobe has also superior and inferior parietal lobules (Johns 2014). The cerebral hemisphere are outgrown from upper end of the hollow neural tube and are themselves hollow. Each contains a cavity called a lateral ventricle, which has its anterior horn in the frontal lobe continues back and sends a posterior horn towards the occipital lobe and most of the thickness of the wall of a cerebral hemisphere is composed of white matter, but on inner surface or adjustment to central ventricle is grey matter as of spinal cord the largest forms corpus striatum. While the nerve cells in cerebral hemisphere from pallium or cerebral cortex of covers the inner surface of gyriad dips down into sulci, and about two-thirds of the cortex is hidden in sulci. All parts of the cerebral cortex do not have the same function. In both the motor and the sensory areas the lower limb is represented towards the top and upper limb is represented lower on the lateral surface and the face, tongue and larynx on the lowest part. The body is thus essentially represented upside down and each cortex controls the opposite side of the body. The injuries to brain tumour and blockage of vessels may create a variety of symptoms (Vega 2020). Central nervous system (brain and spinal cord) is made up

390

C. Arya

of neurons and glia cells. The electrical and chemical signals are transmitted by neurons. These messenger cells have tree like dendrites and long tail called axon. Researches done by Altman (1962), Kaplan (1979) and Nottebohm (1985) on rat, monkey and birds, respectively, proved that neurons can be produced late in the life cycle as well. Nottebohm (1985) believed that during mating season in birds new neurons were added which helped them to learn new songs to attract females. Brain pathways for song control in canaries have been described. A large forebrain nucleus, hyperstriatum ventralis, pars caudalis (HVc), projects to the robust nucleus of the archistriatum (RA). RA projects to the caudal half of the hypoglossal nucleus of the medulla, which houses the motor neurons that innervate the vocal control organ (syrin~). Neurons in nucleus HVc respond to sound, including that of conspecific ~ong. HVc neurons also start firing before and during song production. Removal of HVc results in aberrant song (Nottebohm et al. 1976). HVc is involved in a perceptual and motor involvement in singing. Treatment of adult ovariectomized females with DHT by itself does not induce song. But, DHT will induce song in adults with intact ovaries. The song developed by adult female canaries treated with testosterone is male-like in structure, but has only one-third or less as many different syllable types as the song of adult males. The summer and early fall period of song instability in adult male canaries corresponds to a time of lowered plasma testosterone levels. Gage and Eriksson showed that the adult human brain produced new neurons. There are three types of neurons: sensory, motor and inter-neurons. How these neurons communicate with each other with astrocyte and oligo-dendrocytes (glia cells) by making connections is what makes each of us unique in how we think, feel and act. New neurons can develop, can travel to different locations in body and when dead macrophages eat them to clear the debris (Kempermann and Gage 1999). The memory creation is associated with the strengthening of existing connections or the growth of new connections between neurons. First, the olfactory nerve is located very close to the amygdala, the area of the brain that is connected to the experience of emotion as well as emotional memory. In addition, the olfactory nerve is very close to the hippocampus, which is associated with memory as you learned earlier in this article. The actual ability to smell is highly linked to memory (Mouly and Sullivan 2010). Human brain is unique as the cerebral cortex has 125 trillion synapses. A study further reported that 1 synapse can store 4.7 bits of information, thus cerebral cortex can have 74 TB memory. An average adult human brain can store 2.5 million GB digital memory. To compare the Yahoo’s 2 PB computational centre, which can process 24 billion events a day is a full 20% smaller than the capacity of a single human brain (Reber 2010).

13.2.1 Stress and Sleep Sleep is an important part of our daily routine. Just like food provides energy to body, a good quality sleep helps in relieving mental stress and both REM and

13

Potential Uses of Mushrooms as Dietary Supplement to Enhance Memory

391

non-REM sleep help in memory consolidation. If we are awake for a very long time the mind fails to concentrate and our mood is lost. Sleep plays an important role in learning new information (Rasch and Born 2013). Sleep promoting cells within the hypothalamus and the brain stem produce a brain chemical called GABA, which acts to reduce the activity of arousal centres in the hypothalamus and the brain stem (Brown et al. 2012). The brain stem especially the pons and medulla plays a prominent role in REM sleep. Signals are send to relax muscles essential for body posture and limb movements, so that we do not act out our dreams. Pineal gland receives signals from supra chiasmatic nucleus (SCN) of the hypothalamus and increases production of hormone melatonin, which helps to induce sleep. The thalamus acts as a relay for the information from the senses to the cerebral cortex. During most stages of sleep, the thalamus becomes quiet, letting you tune out external world. But during REM sleep, the thalamus is active, sending the cortex images, sounds and other sensations that we enjoy during our dreams. The basal forebrain promotes sleep and wakefulness. Release of adenosine helps in sleep drive, while caffeine blocks the actions of adenosine, thus avoids sleepiness.

13.2.2 How to Avoid Stress and Have Good Sleep? Sleep is a complex and dynamic process that affects how you function in different ways. The sleep is important to avoid risks of high blood pressure, cardiovascular diseases, diabetes, depression and obesity. Sleep plays a housekeeping role and keeps the tissues and body fit for different metabolic functions. Two internal biological mechanisms, circadian rhythms and sleep-wake homeostasis regulate our sleep. The homeostatic sleep drive reminds the body to sleep after a certain time and regulates sleep intensity. This sleep drive gets stronger every hour you are awake and causes you to sleep longer and more deeply after a period of sleep deprivation. With our fatigue factors responsible are food and medicine intake, outer environment like temperature and light intensities. Exposure to light can make it difficult to fall asleep (McCauley et al. 2021). People are advised to have fixed timings to go to bed. Avoid caffeine or nicotine like compounds immediately before going to bed. Keep your body relaxed, take a warm bath if needed, use light music but not working on computer or watching T.V. keep the lights off or very dim in bed room. Do not lie in bed awake, if you are not feeling tired try to read a book or listen music you will get relaxed and then sleep. It has been recommended that walking in the evening or doing some exercise to get body physically tired or doing gardening work may induce better sleep. Sleep pattern changes with age a small baby may sleep 16 h a day but for most of us 7–8 h sleep is good. After 60 years the sleep is less and interrupted by awakenings. Taking alcohol for better sleep is not advisable. Better to consult a doctor if not comfortable with sleep.

392

C. Arya

13.2.3 The Role of Genes in Sleep Nerve signalling chemicals neurotransmitters that shape the sleep and help in awakening include acetylcholine, histamine, adrenaline, cortisol and serotonin. Gamma-aminobutyric acid (GABA) is a naturally occurring amino acid that works as a neurotransmitter in your brain. GABA is considered an inhibitory neurotransmitter because it blocks, or inhibits, certain brain signals and decreases activity in your nervous system. Scientists have identified genes involved with sleep and sleep disorders, including genes that control the excitability of neurons, and clock genes such as Per, Tim and Cry that influence our circadian rhythms and the timing of sleep. Different genes have been identified with such sleep disorders as familial advanced sleep phase disorder, narcolepsy and restless legs syndrome. Some of the genes expressed in the cerebral cortex and other brain areas change their level of expression between sleep and wake. Several genetic models, including fruit fly and zebrafish, are helping scientists to identify molecular mechanisms and genetic variants involved in normal sleep and sleep disorders.

13.3

Power of Plants to Alter Consciousness

Many plants and their extracts are used to enhance pleasure, forgetfulness, sleep, visions, etc. The importance of the Soma plant in Vedic religion is mentioned in Atharva Veda (8:7:20) and Rig Veda (1:30:4) (Arya and Arya 2007). The botanical identity of Soma is under question. Numerous candidates have been nominated, some of these include Ephedra, Sarcostemma, Periploca, Cannabis and Rheum (Brough 2009). Wasson (1969) considered Amanita muscaria as the divine mushroom. Plants like Papaver somniferum (poppy), Nicotiana tabacum (tobacco), Coffea arabica (coffee), Camellia sinensis (tea) Rosmarinus officinalis (rosemary) Mistletoe (Viscum, Phoradendron and Arceuthobium, members of Santalaceae), Mandrax officinarum (Mandrak) were used to change the mood. Pyridine alkaloids are present in the leaves of tobacco, opium, betel nut and saguaro (Carnegiea gigantea), opium and morphine act on sensory nerve cells of cerebrum and produce dreams and visions in the subject (Sabnis and Daniel 1990). Cannabis (Cannabis sativus L.) and nutmeg (Myristica fragrance Houtt.) have non-nitrogenous active principles. Another plant with red wood and thick growth of leaves, Coca (Erythroxylum coca Lam.), a native of Andes, Amazon, Peru, Bolivia, Ecuador, Indonesia and Ceylon. The leaves contain an alkaloid cocaine (isolated in 1885). Pyrrolidine, also known as tetrahydropyrrole, is an organic compound with the molecular formula (CH2)4NH. It is a cyclic secondary amine, also classified as a saturated heterocycle. It is a colourless liquid that is miscible with water and most organic solvents. It has a characteristic odour that has been described as ‘ammoniacal, fishy and shellfish-like’. A nitrogenous bicyclic organic alkaloid compound tropane called cocaine. The chemical is absorbed by drinking, smoking or rubbing in

13

Potential Uses of Mushrooms as Dietary Supplement to Enhance Memory

393

gums. Cocaine (C17H21NO4) is a powerfully addictive, psychoactive, stimulant drug. Cocaine acts as adrenaline, it causes elation accompanied by hallucination. It is used in religious ceremonies and administered to relief from pain just like morphine (Yearout 1977). Biologically, the effect occurs in the midbrain region called the ventral tegmental area (VTA). Neuronal fibres from the VTA connect to the nucleus accumbens, an area of the brain responsible for rewards. Animal studies show that levels of a brain chemical (neurotransmitter) known as dopamine are increased in this area. The use of cocaine can interfere with this process, allowing dopamine to accumulate and send an amplified ‘reward’ signal to the brain, resulting in the euphoria described by users. Some users report feelings of restlessness, irritability and anxiety. Some users increase their dose to intensify and prolong the euphoric effects. Users can also become more sensitive to the anaesthetic and convulsant effects, and this increased sensitivity may explain some deaths occurring after apparently low doses (Drent et al. 2012; NIDA 2021). Kaani tribes of Kerala used Trichopus zeylanicus Gaertn. a small herb, included in the family Dioscoreaceae having flavonoid glycoside, which is used as stress or fatigue reliever. The herb grows on sandy soil near rivers and streams in shady places in lowland and intermediate altitude of Agasthya hills in Western Ghats (Pushpangadan et al. 1995).

13.4

Divinity in Mushrooms

The different species of Psilocybe, Conocybe and Stropharia exhibit the psychotomimetic properties. These mushrooms native of Mexico are part of religious ceremonies of Indians. The brown mushroom Psilocybe mexicana with a bluish stain near the base of the stipe. The active compounds present are 4-hydroxy-dimethyl tryptamines like psilocybine and psilocine. The psilocybin is unique having phosphorus containing indole derivative (Hofmann 1959). These mushrooms exhibited psychomimetic properties when taken orally.

13.5

Memory and Use of Mushrooms

Feng et al. (2019) studied the cognitive impairment in citizens of Singapore using modified mini-mental state examination (SM-MMSE) developed by Feng et al. (2019). Clinical Dementia Rating (CDR) was administered. The participants who consumed greater than 2 portions of mushroom per week had lower odds of having mild cognitive impairment (MCI). Certain components in mushrooms such as hericenones, erinacines, scabronines and dictyrophorine may promote the synthesis of nerve growth factors (NGF) (Mori et al. 2009) in mushrooms including amyloid-β and phosphorylate tall and acetylcholinesterase which protect brain from

394

C. Arya

neurodegeneration (Phan et al. 2015). At present, Hericium erinaceus (Bull.) Purs. is widely used as a dietary supplement. Nevertheless, the lack of standardization strongly affects the quality and bioactivity of the final product, only a few molecules have been reported to stimulate NGF release, namely erinacines A–I from mycelium (the most studied being erinacine A and hericenones C–D from sporophores). To obtain this specific target on neuroprotection, the standardization process of dietary supplements therefore relies on the selective detection and quantification of such molecules. A major problem at this concern is the availability of pure analytical standards. A study was conducted to analyse and compare different stages of H. erinaceus (mycelium, primordium and sporophore) sampled in Tuscany (Italy), in order to detect the presence and to quantify the concentration of the target bioactive metabolites erinacine A and hericenones C and D (Corana et al. 2019). The erinacines in H. erinaceus are a group of cyathane-type diterpenoids, including 20 members of 24 diterpenoids described by Tang et al. (2015). To date, 15 erinacines (A, B, C, D, E, F, G, H, I, P, Q, J, K, R, S) are isolated from the mycelium of H. erinaceus and eight out of 15 show neuroprotective properties, such as enhancing NGF release (erinacines A–I) and managing neuropathic pain (erinacine E), while the others have different pharmacological activities (Kawagishi et al. 1994; Ma et al. 2008). A thione derivative of histidine, ergo thioneine (ET), has a cyto-protective effect (Cheah and Halliwell 2012). While humans cannot produce ET it can be absorbed from mushroom diet and stored in body and the brain via a specific transporter OCTN1 (organic cation transporter novel-type 1) (Tschirka et al. 2018). Plasma level of ET was lower in persons with MCI which may be a risk factor for neurodegeneration and increase in ET through consumption of mushrooms promoted cognitive health and neurodegeneration in ageing (Feng et al. 2019). Some of the well-known medicinal mushrooms include caterpillar fungus, Reishi, Chaga, Shiitake, etc. Lion’s mane or Hericium erinaceus with its thin white tendrils is compared to sea food in China. It has a wide range of antiinflammatory and brain-boosting benefits, which decrease sleep disorders and improve REM sleep. It is said that Chinese Buddhist monks used Hericium powder in tea to increase their brain power. Millions of people suffer with depression and anxiety. Hericium has antidepressant properties (Kawagishi et al. 1996). Animal studies have revealed the increase in neuron production in the hippocampus, the part of our brain which regulates emotions. Extract of Hericium exhibited a reversion of frailty cognitive decline during ageing (Ratto et al. 2019). Up to now, about 70 different secondary metabolites have been isolated from either sporophore or mycelium or both. Lion’s mane mushroom is used in form of powder or capsules with a dose of 0.5–1.0 g/day. It can be administered through a coffee, tea or hot chocolate. It can be used in mushroom soup or in cake. Usually mushroom powder is better than mycelium extract with erinacines. The breast feeding ladies and pregnant women are advised to seek medical approval before consuming this mushroom on daily basis. In Italy when Rossi et al. (2019) added H. erinaceus to the daily diet of wild-type mice for 2 months the general locomotor activity increased but had no effect on spatial memory. It was recorded that oral supplementation of Hericium resulted into

13

Potential Uses of Mushrooms as Dietary Supplement to Enhance Memory

395

specific and selective improvements in recognition without altering spatial working memory. Recognition memory can be modelled as a dual process. In this model, the perirhinal cortex supports the recognition of individual items as part of circuit involved in familiarity with an encountered stimulus, whereas the hippocampus supports recollected associations and relationships between stimuli (Rossi et al. 2019).

13.6

Role of Mushrooms in Neurodegenerative Diseases

Oxidative stress has been implicated in the progression of a number of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s diseases (PD) and amyotrophic lateral sclerosis (ALS). Oxygen is vital for life but is also potentially dangerous, and a complex system of checks and balances exists for utilizing this essential element. Oxidative stress is the result of an imbalance in pro-oxidant/ antioxidant homeostasis that leads to the generation of toxic reactive oxygen species. The systems in place to cope with the biochemistry of oxygen are complex, and many questions about the mechanisms of oxygen regulation remain unanswered. However, this same complexity provides a number of therapeutic targets, and different strategies, including novel metal-protein attenuating compounds, aimed at a variety of targets have shown promise in clinical studies (Barnham et al. 2004). Hypercholesterolemia had been implicated as one of the stark hallmarks of AD. Recent AD control guidelines have suggested lifestyle modification to slow down the progression of AD. In the present study, hot water extract of Ganoderma lucidum (200 mg/kg body weight) was fed to the hypercholesterolemic and AD model rats for 8 weeks (Rahman et al. 2020). Nonspatial memory and learning abilities of the model animals were assessed using novel object recognition (NOR) test, rotarod test and locomotor/open-field test. Then, the animals were sacrificed and transmission electron micrograph (TEM) view of the hippocampal neurons was assessed. In all the nonspatial memory and learning tests, the G. lucidum HWE fed rats performed better indicating improved memory and learning abilities. TEM view showed regular arrangement of the neurons in the G. lucidum HWE fed rats compared with those of the deranged arrangement of the AD rats. The mushroom extract might have aided in restoring the memory and learning abilities of the AD model animals through maintaining neuronal structure and function. Thus, G. lucidum could be suggested as a medico-therapeutic agent against AD. Oxidation of proteins can lead to unfolding or conformational changes in the protein, thereby exposing more hydrophobic residues to an aqueous environment, which may lead to loss of structural or functional activity including aggregation and accumulation of oxidized proteins as cytoplasmic inclusions, as reported in AD (Stadtman and Berlett 1997). Oxidatively modified proteins may affect the normal physiological processes by disrupting cellular functions such as alterations in protein expression and gene regulation, protein turnover, modulation of cell signalling, induction of apoptosis and necrosis, etc. (Butterfield and Stadtman 1997). A redox

396

C. Arya

proteomics approach was used to identify specific oxidatively modified brain proteins such as carbonylated, nitrated, (4-hydroxy-2-trans nonenal) HNE-bound and glutathionylated brain proteins in neurodegenerative diseases including AD and models thereof (Boyd-Kimball et al. 2005, 2006; Castegna et al. 2002a, b; Sultana et al. 2006). These diseases are characterized by extensive oxidative damage to lipids, proteins and DNA. This damage can lead to cell death by a variety of different mechanisms, either by deactivating important process or by upregulating toxic cascades. Further, Aβ models of AD strongly support the notion that oxidative stress induced by Aβ may be a driving force in AD pathogenesis. Studies conducted on the earliest stage of AD, MCI, may elucidate the mechanism(s) leading to AD pathogenesis by identifying early markers of the disease and to develop therapeutic strategies to slow or prevent the progression of AD (Sultana et al. 2009). Oxidative stress is the result of an imbalance in the pro-oxidant/antioxidant homeostasis leading to the generation of toxic reactive oxygen species (ROS). ROS have a normal metabolic role in cell signalling and are generated by the interaction of oxygen with redox-active metal ions. As ROS can be damaging both metals and ROS are tightly regulated. Genetics has identified Aβ, α-synuclein and (superoxide dismutase) SOD as playing a pivotal role in AD, PD and ALS, respectively. These proteins are the major components of the deposits associated with these diseases. All these proteins have been shown to interact with redox-active metal ions with the subsequent generation of ROS. Aβ will coordinate copper and iron and generate H2O2 with the further generation of ROS through Fenton chemistry. Α-synuclein regulates the uptake of vesicular dopamine, and a breakdown in this process allows the build-up of dopamine in the cytoplasm. Dopamine coordinates iron and induces the formation of ROS. Destabilization of the active site of SOD allows a corruption of the antioxidant enzyme such that it becomes pro-oxidant. Excitotoxicity is a downstream consequence of calcium dysregulation as a result of unregulated ROS. Drug targeting this toxicity (Meantime in AD, Amantadine in PD and Riluzole in ALS) has modest clinical benefit. The antioxidant α-tocopherol has shown clinical promise against AD. Inhibiting metalmediated redox processes has shown benefit in mouse models of AD and PD and encouraging promise in a small phase II clinical trial for AD. Effect of Cordyceps militaris (CM) extract on the passive avoidance test was performed on rats to confirm the effect of the CM extract on the representative types of memory and to evaluate memory function (Lee et al. 2011). Rats in all groups performed acquisition trials without an electric challenge, to make sure there were no physiological defects (i.e. motor function) or intrinsic cognitive impairments prior to the scopolamine-induced impairments. The times for the acquisition trials, indicated by the latency times for entering the dark compartment, were not significantly different in the different groups. After the acquisition trials, the effect of the CM extract on the retention latency, indicated by the latency times for entering the dark compartment, was measured 24 h after applying an electric shock in the dark box of the passive avoidance test. In the retention, it was shown that the CM200 + SCO (scopolamine-induced and saline-treated) group and CM300 + SCO group had

13

Potential Uses of Mushrooms as Dietary Supplement to Enhance Memory

397

significantly increased latencies when entering the dark compartment for retention as compared to those of the SCO group (Klinkenberg and Blokland 2010). The study was performed to evaluate the effect of CM on neurite outgrowth in Neuro2A mouse neuroblastoma cells and scopolamine-induced learning and memory deficits in rats (Iwase et al. 2001). Pre-treatment with CM (5–20 μg/mL) for 1 h was sufficient to stimulate primary neurite sprouting and extension of Neuro2A cells after 24 h cultivation in a dose-dependent manner. The CM also increased choline acetyltransferase expression in differentiated Neuro2A cells. Administration of CM significantly reversed the scopolamine-induced deficit in memory, and it alleviated decrease in cholinergic immunoreactivity in the hippocampus. It was demonstrated that in vitro neuritogenesis of Neuro2A cell lines by CM constitutes a potential clue that could help to explain in vivo improvement of memory functions using the behavioural tasks. These results suggest that CM is strongly effective in protecting against memory-related neuronal degeneration in the brain and retarding the progression of memory deficits associated with various neurodegenerative diseases. The well replicated amnesic effect of scopolamine, a non-selective muscarinic cholinergic receptor antagonist, is interpreted as a principal consequence of a blockade of post-synaptic muscarinic M1 transmission, which leads to disruption of the function of the hippocampus in the working memory (Iwase et al. 2001). The decrease of the activity of cholinergic neurons or acetylcholine content in the hippocampal terminals has been directly related to alterations in hippocampal functioning and cholinergic dysfunction (Ohara et al. 1997). It is evident from results that the chronic administration of SCO produced severe deficits in cognitive functioning in addition to decreased (choline acetyltransferase) ChAT immune activity in the hippocampus (Cheng et al. 2011). According to the cholinergic hypothesis, memory impairments in patients with senile dementia are due to a selective and irreversible deficiency in the cholinergic functions of the brain (Giacobini 2002). It was found by Cheng et al. (2011) that a bioactive component of CM, cordycepin, was effective in ameliorating neurodegenerative changes and protecting gerbil hippocampal neurons from ischemic injury. However, whether oral administration of CM on spatial memory affects the cognitive functions is not investigated. When discussing the neuropathological features of memory and cognitive dysfunction, as observed mainly, in patients with AD, the cholinergic deficit has been considered a primary cause (Hasselmo 2006). Accordingly, various cholinergic drugs exert their therapeutic effects by counteracting the acetylcholine deficits and consequently enhancing the acetylcholine levels in the brain (Drever et al. 2007). It is likely that the observed amelioration in the deficits in spatial learning capability demonstrated by the CM-treated rats may be associated with the increased release of ACh. The beneficial effects of the CM extract could be related to increases in central cholinergic function (Lee et al. 2011). Recently, neurogenesis has been reported to play an important role in spatial memory. Its specific contribution to spatial memory, evaluated in the water maze, has been seen as evidence for therapeutic approaches using the treatment of herbal medicine or natural products (Crandall et al. 2004; Zhang et al. 2008). The function of the CM extract in the formation of the synaptic connection and modulation of cholinergic neurons in the brain could contribute to the enhancement of memory

398

C. Arya

function. The results demonstrated that the CM extract promoted neurite outgrowth and enhanced neuronal function. Specifically, CM extract induced ACh release and improved cognitive behaviour related to memory. Therefore, the CM extract may possibly be used as a new effective substance for preventing memory loss and cholinergic dysfunction, as observed in AD.

13.7

Conclusion

Different species of mushrooms are edible and used as medicine to cure various diseases. The fungi like Psilocybe, Conocybe and Stropharia exhibit the psychotomimetic properties. These mushrooms have been used in religious ceremonies. The bioactive secondary metabolite psilocybine is unique having phosphorus containing indole derivative. These mushrooms exhibited psychomimetic properties when taken orally. Mycologists have reported that certain bio-components present in mushrooms such as hericenones, erinacines, scabronines and dictyrophorine may promote the synthesis of nerve growth factors (NGF). At present, products from Ganoderma lucidum (Curtis) P. Karst. and Hericium erinaceus (Bull.) Purs. are widely used as dietary supplements for anti-ageing, rejuvenating and energy boosting properties. The role of many of these fungi in age-associated disorders and enhancing memory is being investigated. Nevertheless, the lack of standardization strongly affects the quality and bioactivity of the final product, only a few molecules have been reported to stimulate NGF release, namely erinacines A–I from mycelium. More researches are needed to determine their role in enhancing memory, medicinal uses and developing cultivation technologies to ensure their availability.

References Altman J (1962) Are neurons formed in the brains of adult mammals. Science 135(3509): 1127–1128. https://doi.org/10.1126/science.135.3509.1127 Arya A, Arya C (2007) Medicinal mushrooms for healthy life. In: Daniel M, Arya A, Raole VM (eds) Herbal technology. Scientific Pub. (India), Jodhpur, pp 63–68 Barnham KJ, Masters CL, Bush AI (2004) Neurodegenerative diseases and oxidative stress. Nat Rev Drug Discov 3:205–214 Batool Z, Sadir S, Liaquat L, Tabassum S (2015) Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia. Brain Res Bull 120:63. https://doi.org/10.1016/ j.brainresbull.2015.11.001 Boyd-Kimball D, Castegna A, Sultana R, Poon HF, Petroze R, Lynn BC, Klein JB, Butterfield DA (2005) Proteomic identification of proteins oxidized by Abeta (1–42) in synaptosomes: implications for Alzheimer’s disease. Brain Res 1044:206–215. https://doi.org/10.1016/j.brainres. 2005.02.086

13

Potential Uses of Mushrooms as Dietary Supplement to Enhance Memory

399

Boyd-Kimball D, Poon HF, Lynn BC, Cai J, Pierce WM Jr, Klein JB, Ferguson J, Link CD, Butterfield DA (2006) Proteomic identification of proteins specifically oxidized in Caenorhabditis elegans expressing human Abeta (1–42): implications for Alzheimer’s disease. Neurobiol Aging 27:1239–1249. https://doi.org/10.1016/j.neurobiolaging.2005.07.001 Brough J (2009) Soma and Amanita muscaria. Bull Sch Orient Afr Stud 34:331–362 Brown RE, Basheer R, McKenna JT, Stecker RE et al (2012) Control of sleep and wakefulness. Physiol Rev 92(3):1087–1187. https://doi.org/10.1152/physrev.00032.2011 Butterfield DA, Stadtman ER (1997) Protein oxidation processes in aging brain. Adv Cell Aging Gerontol 2:161–191. https://doi.org/10.1016/S1566-3124(08)60057-7 Castegna A, Aksenov M, Aksenova M, Thongboonkerd V, Klein JB, Pierce WM, Booze R, Markesbery WR, Butterfield DA (2002a) Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part I: creatine kinase BB, glutamine synthase, and ubiquitin carboxyterminal hydrolase L-1. Free Radic Biol Med 33:562–571. https://doi.org/ 10.1016/S0891-5849(02)00914-0 Castegna A, Aksenov M, Thongboonkerd V, Klein JB, Pierce WM, Booze R, Markesbery WR, Butterfield DA (2002b) Proteomic identification of oxidatively modified proteins in Alzheimer’s disease brain. Part II: dihydropyrimidinase-related protein 2, alpha-enolase and heat shock cognate 71. J Neurochem 82:1524–1532. https://doi.org/10.1046/j.1471-4159.2002.01103.x Cheah IK, Halliwell B (2012) Ergothioneine; antioxidant potential, physiological function and role in disease. 477. Biochim Biophys Acta 1822:784–793 Cheng LL, Chen XN, Wang Y, Yu L, Kuang X, Wang LL, Yang W, Du JR (2011) Z-ligustilide isolated from Radix Angelicae sinensis ameliorates the memory impairment induced by scopolamine in mice. Fitoterapia 82:1128–1132 Corana F, Cesaroni V, Mannucci B, Baiguera RM, Picco AM, Savino E, Ratto D, Perini C, Kawagishi H, Girometta CE, Paola Rossi P (2019) Array of metabolites in Italian Hericium erinaceus mycelium, primordium, and sporophore. Molecules 24:3511. https://doi.org/10.3390/ molecules24193511 Crandall J, Sakai Y, Zhang J, Koul O, Mineur Y, Crusio WE, McCaffery P (2004) 13-cis-Retinoic acid suppresses hippocampal cell division and hippocampal-dependent learning in mice. Proc Natl Acad Sci U S A 101:5111–5116 Dimitrijevic MV, Mitic VD, Jovanovic OP, Stankov Jovanovic VP, Nikolic JS, Petrovic GM, Stojanovic GS (2018) Comparative study of fatty acids profile in eleven wild mushrooms of boletaceae and russulaceae families. Chem Biodivers 15(1):e1700434. https://doi.org/10.1002/ cbdv.201700434 Drent M, Wijnen P, Bast A (2012) Interstitial lung damage due to cocaine abuse: pathogenesis, pharmacogenomics and therapy. Curr Med Chem 19(33):5607–5611. https://doi.org/10.2174/ 092986712803988901 Drever BD, Anderson WG, Johnson H, O’Callaghan M, Seo S, Choi DY, Riedel G, Platt B (2007) Memantine acts as a cholinergic stimulant in the mouse hippocampus. J Alzheimers Dis 12:319– 333 Feng L, Cheah IK, Ng MM, Li J, Chan SM, Lim SL, Mahhendran R, Kua EH, Halliwell B (2019) The association between mushroom consumption and mild cognitive impairment: a communitybased cross-sectional study in Singapore. J Alzheimers Dis 2019:1–10. https://doi.org/10.3233/ JAD-180959 Field BH, Vadnal R (1998) Ginkgo biloba and memory: an overview. Nutr Neurosci 1(4):255–267. https://doi.org/10.1080/1028415X.1998.11747236. PMID: 27414695 Giacobini E (2002) Long term stabilizing effect of cholinesterase inhibitors in the therapy of Alzheimer’s disease. J Neural Transm Suppl 62:181–187 Hasselmo ME (2006) The role of acetylcholine in learning and memory. Curr Opin Neurobiol 16:710–715 Hofmann A (1959) Psilocybin und Psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen. Helvetica Chemica Acta 42:1557–1572

400

C. Arya

Iwase T, Ojika K, Matsukawa N, Nishino H, Yamamoto T, Okada H, Fujimori O, Ueda R (2001) Muscarinic cholinergic and glutamatergic reciprocal regulation of expression of hippocampal cholinergic neurostimulating peptide precursor protein gene in rat hippocampus. Neuroscience 102:341–352 Johns P (2014) Functional neuroanatomy. In: Clinical neuroscience. Elsevier, Amsterdam, pp 27–47. https://doi.org/10.1016/B978-0-443-10321-6.00003-5 Kaplan J (1979) Growth and development of infant squirrel, monkeys during the first six months of life. In: Ruppenthal G (ed) Nursery care of nonhuman primates. Plenum Press, New York, NY, pp 153–164 Kawagishi H, Shimada A, Shirai R, Okamoto K, Ojima F, Sakamoto H, Ishiguro Y, Furukawa S (1994) Erinacines A, B and C strong stimulators of nerve growth factor (NGF)-synthesis from the mycelia of Hericium erinaceum. Tetrahedron Lett 35:1569–1572 Kawagishi H, Shimada A, Hosokawa S et al (1996) Erinacines E, F, and G stimulators of nerve growth factor (NGF)-synthesis, from the mycelia of Hericium erinaceum. Tetrahedron Lett 37(41):7399–7402. https://doi.org/10.1016/0040-4039(96)01687-5 Kempermann G, Gage FH (1999) New nerve cells for the adult brain. Sci Am 280:48–53. https:// www.jstor.org/stable/26058240 Klinkenberg I, Blokland A (2010) The validity of scopolamine as a pharmacological model for cognitive impairment: a review of animal behavioral studies. Neurosci Biobehav Rev 34(8): 1307–1350. https://doi.org/10.1016/j.neubiorev.2010.04.001 Kulkarni KS, Kastura SB, Mengi SA (2010) Efficacy of the Prunus amygdalus (almonds) nuts in scopolamine induced amnesia in rats. Indian J Pharmacol 42:168–173 Lee B, Park J, Shin H, Kwon S, Yeom M, Sur B, Kim S, Kim M, Lee H, Yoon SH, Hahm DH (2011) Cordyceps militaris improves neurite outgrowth in Neuro2A cells and reverses memory impairment in rats. Food Sci Biotechnol 20(6):1599–1608. https://doi.org/10.1007/s10068-0110221-4 Lu H, Lou H, Hu J, Liu Z, Chen Q (2020) Macrofungi: a review of cultivation strategies, bioactivity, and application of mushrooms. Compr Rev Food Sci Food Saf 19:2333–2356. https://doi.org/10.1111/1541-4337.12602 Ma BJ, Zhou Y, Li LZ, Li HM, Gao ZM, Ruan Y (2008) A new cyathanexyloside from the mycelia of Hericium erinaceum. Z Naturforsch 63b:1241–1242 McCauley ME, McCauley P, Riedy SM, Banks S et al (2021) Fatigue risk management based on self-reported fatigue: expanding a biomathematical model of fatigue-related performance deficits to also predict subjective sleepiness. Transp Res Part F Traffic Psychol Behav 79:94–106. https://doi.org/10.1016/j.trf.2021.04.006 Meenu M, Xu B (2019) Application of vibrational spectroscopy for classification, authentication and quality analysis of mushroom: a concise review. Food Chem 289:545–557. https://doi.org/ 10.1016/j.foodchem.2019.03.091 Mori K, Inatomi S, Ouchi K, Azumi Y, Tuchida T (2009) Improving effects of the mushroom Yamabushi-take (Hericium erinaceus) on mild cognitive impairment: a double-blind placebocontrolled clinical trial. Phytother Res 23:367–372 Mouly AM, Sullivan R (2010) The neurobiology of olfaction: memory and plasticity in the olfactory system: from infancy to adulthood. CRC Press/Taylor & Francis, Boca Raton, FL National Institute of Drug Abuse (2021) Cocaine drug facts. Drug Facts 2021:1–7 Nottebohm F (1985) Neuronal replacement in adulthood. Ann N Y Acad Sci 457:143–161. https:// doi.org/10.1111/j.1749-6632.1985.tb20803.x Nottebohm F, Stokes TM, Leonard CM (1976) Central control of song in the canary, Serinus canarius. J Comp Neurol 165:457–486 Nurk E, Refsum H, Drevon CA, Tell GS, Nygaard HA, Engedal K, Smith AD (2010) Cognitive performance among the elderly in relation to the intake of plant foods. The Hordaland Health Study. Br J Nutr 104:1190–1201

13

Potential Uses of Mushrooms as Dietary Supplement to Enhance Memory

401

Ohara T, Tanaka K, Fukaya H, Demura N, Iimura A, Seno N (1997) SDZ ENA 713 facilitates central cholinergic function and ameliorates spatial memory impairment in rats. Behav Brain Res 83:229–233 Pan J, Ai F, Shao P, Chen H, Gao H (2019) Development of polyvinyl alcohol/β-cyclodextrin antimicrobial nanofibers for fresh mushroom packaging. Food Chem 300:125249. https://doi. org/10.1016/j.foodchem.2019.125249 Phan CW, David P, Naidu M, Wong KH, Sabaratnam V (2015) Therapeutic potential of culinarymedicinal mushrooms for the management of neurodegenerative diseases: diversity, metabolism, and mechanism. Crit Rev Biotechnol 35:355–368 Phan CW, Pamela D, Vikineswary S (2017) Edible and medicinal mushrooms: emerging brainfood for the mitigation of neurodegenerative diseases. J Med Food 20:1–10 Pushpangadan P, Rajasekharan S, Subramaniam A, Latha P, Evans DA, Raj R (1995) Further on the pharmacology of Trichopus zeylanicus. Anc Sci Life 14:127–135 Rahman MA, Hossain S, Abdullah N, Aminudin N (2020) Lingzhi or reishi medicinal mushroom, Ganoderma lucidum (agaricomycetes), ameliorates nonspatial learning and memory deficits in rats with hypercholesterolemia and Alzheimer’s disease. Int J Med Mushrooms 22(11): 1067–1078. https://doi.org/10.1615/IntJMedMushrooms.2020036354 Rasch B, Born J (2013) About sleep’s role in memory. Physiol Rev 93(2):681–766. https://doi.org/ 10.1152/physrev.00032.2012 Ratto D, Corana F, Mannucci B, Priori EC, Cobelli F, Roda E, Ferrari B, Occhinegro A, Di Iorio C, De Luca F (2019) Hericium erinaceus improves recognition memory and induces hippocampal and cerebellar neurogenesis in frail mice during aging. Nutrients 11:715 Reber P (2010) What is the memory capacity of human brain? Sci Am Mind Neurosci. https://doi. org/10.1038/scientificamericanmind0510-70 Rossi P, Cesaroni V, Savino E (2019) Dietary supplementation of lion’s mane medicinal mushroom, Hericium erinaceus (Agaricomycetes), and spatial memory in wild-type mice. Int J Med Mushrooms 20:485–494. https://doi.org/10.1615/IntJMedMushrooms.2018026241 Sabnis SD, Daniel M (1990) A phytochemical approach to economic botany. Kalyani Pub., Ludhiyana, p 483 Singh R (2017) A review on different benefits of mushroom. IOSR J Pharm Biol Sci 12(1): 107–111. https://doi.org/10.9790/3008-120102107111. e-ISSN:2278-3008, p-ISSN:2319-7676 Stadtman ER, Berlett BS (1997) Reactive oxygen-mediated protein oxidation in aging and disease. Chem Res Toxicol 10:485–494. https://doi.org/10.1021/tx960133r Sultana R, Boyd-Kimball D, Poon HF, Cai J, Pierce WM, Klein JB, Merchant M, Markesbery WR, Butterfield DA (2006) Redox proteomics identification of oxidized proteins in Alzheimer’s disease hippocampus and cerebellum: an approach to understand pathological and biochemical alterations in AD. Neurobiol Aging 27:1564–1576. https://doi.org/10.1016/j.neurobiolaging. 2005.09.021 Sultana R, Perluigi M, Butterfield DA (2009) Oxidatively modified proteins in Alzheimer’s disease (AD), mild cognitive impairment and animal models of AD: role of Abeta in pathogenesis. Acta Neuropathol 118(1):131. https://doi.org/10.1007/s00401-009-0517-0 Tang HY, Yin X, Zhang CC, Jia Q, Gao JM (2015) Structure diversity, synthesis, and biological activity of cyathane diterpenoids in higher fungi. Curr Med Chem 22:2375–2391 Tschirka J, Kreisor M, Betz J, Grundemann D (2018) Substrate selectivity check of the ergothioneine transporter. 489. Drug Metab Dispos 46:779–785 Vega J (2020) An overview of frontal lobe damage, symptoms of dysfunction can be physical, behavioural, or cognitive. Brain and nervous system stroke medically reviewed by Claudia C., online on Very well Health Wang XM, Zhang J, Wu LH, Zhao YL, Li T, Li JQ, Liu HG (2014) A mini-review of chemical composition and nutritional value of edible wild-grown mushroom from China. Food Chem 151:279–285. https://doi.org/10.1016/j.foodchem.2013.11.062

402

C. Arya

Wasson RG (1969) Soma, divine mushroom of immortality. Mouton, Harcourt, Brace and World, Inc, The Hague, p 381 Yearout F (1977) The power of plants. John Murray, London, p 288 Zhang CL, Zou Y, He W, Gage FH, Evans RM (2008) A role for adult TLX positive neural stem cells in learning and behaviour. Nature 451:1004–1007 Zhang S, Tomata Y, Sugiyama K, Sugawara Y, Tsuji I (2017) Mushroom consumption and incident dementia in elderly Japanese: the Ohsaki Cohort 2006 Study. J Am Geriatr Soc 65:1462–1469

Chapter 14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps Arun Arya

Abstract Fungi are eukaryotic nonchlorophyllous simple microorganisms classified under Kingdom Mycota. They have unicellular or filamentous branched tube like body termed mycelium made up of chitin or callose. Earlier these organisms were placed with plants, but since they consume food by absorption with the help of enzymes and do not perform photosynthesis, they were shifted to a separate group. Study of fungi is called mycology. This term is derived from study of mushrooms. Knowledge of many of these fungal organisms can be obtained through beautiful postage stamps released by different nations. Collection and display of stamps on a particular topic is termed thematic philately. This popular hobby related to mushrooms is thus termed mycophilately. Braun Lucien of France, founding father of thematics, differentiated for the first time between traditional and thematic philately in 1949. According to him traditional philately studies stamps from physical angle, i.e. shades, perforations overprints, etc. while thematic philately studies it from the angle of motive, culture, art, history, and education. In the collection first day covers and postal stationary can be included but it should pass through mail and written account should be limited. The fungi has played a definite role in human welfare. Discovery of Koch’s postulates and his germ theory and Penicillin by Sir Alexander Flaming is depicted in postage stamps. A large number of beautiful edible and poisonous mushrooms have appeared on stamps. The paper describes details of stamps depicting significance of fungi in food and sustainable ecosystems. The beauty of mushrooms hopes to inspire the readers and celebrate their significance in the art of philately. Keywords Beauty · Diversity · Uses · Fungi · Mushrooms · Postage stamps · First day cover (FDC)

Supplementary Information The online version of this chapter (https://doi.org/10.1007/978-98116-6257-7_14) contains supplementary material, which is available to authorized users. A. Arya (*) Department of Botany and Environmental Studies, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_14

403

404

14.1

A. Arya

Introduction: Mycophilately

Mycophilately undoubtedly owes much of its current popularity to the articles published by Ing (1976) and Moss and Dunkley (1986) and other philatelists. A number of stamps with fungi in their designs have been mentioned in these lists as well as in a recently published catalogue of fungi on stamps (Greenewich 1997, please see the online Supplementary Annexure 14.1). Some of the information on a number of previously listed and printed stamps on fungi and mushrooms is reported here. Mushroom-forming fungi exhibit a tremendous variety of morphological, physiological, and behavioral traits. Though science had taken up the challenge to relate these traits to functions in the twentieth century, such deliberations became much rarer in recent decades. In the review presented here we aim at reviving this research area, particularly in regard to ecological implications. We have therefore compiled fruit body traits with their evidenced or suggested functions. Some traits have no immediate functional meaning, but many are suggestive of some ecological importance. Many traits serve more than one function, and traits interact in the sense of trade-offs, patterns that reflect the economy of fungal design. In conclusion, the review comes up with well and little-known mushroom properties and the numerous gaps in attributing traits to functions. Now why don’t you browse through this Fungi on Stamps Web and look for other items of interest? Several stamps depicting fungi have been reported from off-shore islands which have dubious postal validity. Several such stamps are not accorded catalogue status by the Stanley Gibbons catalogues (Molitoris et al. 1990). This chapter describes the postal stamps, miniature sheets, and first day cover released by different countries on mushrooms.

14.1.1 Philately: Art and Science of Stamp Collection Fungi on Stamp by Bruce Ing, the exhibits arranged by Dr Hilda Canter-Lund and Mr. C.J. La Touche at the Society’s FUNGI ‘73 Exhibition created a good deal of interest and the Editor of the Bulletin readily agreed to publish a short catalogue of stamps depicting fungi. Altogether 93 stamps have been issued to date, from 20 countries. The first of these was the unusual Japanese issue of 1948, but the first to show a fungal portrait was the set from Rumania in 1958. Fifty-five species are represented and it is not surprising to note that, with several central African, East Asian, and eastern European states involved, 37 of these are eaten with considerable relish. Examples are the parasol, St. George’s, Chinese white and field mushrooms, Shii-take, chanterelle, morel, boletes, and the termite fungi. Several poisonous species are included of which Death Cap and Fly Agaric need no comment (Fig. 14.1). In contrast a yeast, Penicillium, and a stinkhorn also appeared in the list (Coetzee 1993). Collecting stamps on a subject is termed Thematic collection.

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

405

Fig. 14.1 Poisonous mushroom: Stamps on Amanita muscaria (picture source: Timir Shah)

The first stamp was issued in Britain in 1840 and first stamp shop was opened in Tuileries Garden, Paris in 1860. In 1856 an Englishmen Edward Stanley Gibbons persuaded his father to allocate a corner of pharmacy shop for stamp dealing (Aggersberg 1991). Today Stanley Gibbons is an international company. It is Birmingham stamp dealer Edward Loines Pemberton, who has been fairly described as the father of scientific philately. In 1869 Royal Philatelic Society and in 1975 Baroda Philatelic Society were formed, it is managed by President Mr. Prashant Pandya and Secretary Mr. Timir Shah.

14.1.2 Stamps: Certain Fungi and Their Discoveries Fungi are nonchlorophyllous simple organisms classified under Kingdom Mycota. They have unicellular or filamentous eukaryotic structure. Many of the fungal organisms produce large fruiting bodies which can be seen by naked eyes and collected by hands and are termed as mushrooms. Most of these fungi belong to Asco or Basidiomycetes group. Discovery of Penicillin, the wonder drug from Penicillium notatum, a member of Talaromyces of Ascomycotina, by Alexander Fleming in 1928 has been a great victory of modern biology and medicine. This was a chance discovery in 1928 which resulted in a Nobel Prize for him in Physiology

406

A. Arya

Fig. 14.2 (a–d) Postage stamps of edible and poisonous Mushrooms (source: author)

and Medicine in 1945. He has discovered that growth of bacteria could be inhibited by a mold called Penicillium. Figure 14.2b shows a picture of Penicillium the fungus on which Alexander worked and a stamp from Mexico. There are more than 6500 antibiotics known today. Mexico brought a blue colored stamp in 1981 to commemorate the birth century of this Nobel laureate. Sir Alexander Fleming was born on 6 August 1881, in Lochfield, Scotland.

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

407

Fungi are chemical and enzymatic geniuses, generating complex molecules often compatible with human physiology. Lion’s Mane Hericium mushroom produces nerve growth compounds able to cross the blood–brain barrier and stimulates nerve cell growth. When consumed as a liposomal preparation, it can apparently reverse the damage of neurologically degenerative diseases, for instance, Parkinson’s disease patients have seen their tremors disappear, their sense of smell return, their gait improve, as well as other findings. Another mushroom, Psilocybe, is now the newly resurrected research darling—curing alcohol, nicotine, and cocaine addictions, helping treatment-resistant depression, easing the emotional pain of terminal cancer— with new arenas of study popping up, well, like mushrooms (Fig. 14.3).

14.1.3 Soma and Mushrooms on Stamps Vedas tell us about Soma drink, which may be made from Amanita or Psilocybe like hallucinogenic mushrooms. Gods, priests, and people in ancient times derived special strength by consuming these fungi. French philosopher Voltair has said, “Vedas are the most precious gift for which the West has ever been indebted to the East.” Atharva Veda is full of herbal plants and products. There are 5987 mantras. A mantra from 8th chapter says Mumuchana ayoshadhayo agne vairshwa naradadhi. Bhumi santanwatiriti yasan raja vanaspatih.

Herbs produced from earth relieve us from alimentary diseases and keep us healthy. Soma is king of these herbs. The extract of this Soma-ras medicine should keep our body and mind fit. Sam Veda is third Veda with 1875 verses, out of these only 99 do not belong to Rig Veda. Verse 861 says, “Soma” is cleaned, washed, soaked in water, cut into pieces and crushed under stones and juice is extracted and taken as drink. It brings peace, happiness and prosperity generating wisdom to rightly perform our duties. “May you enter into the innermost consciousness of my soul with intense exhilaration, I pray,” such is the prayer to Soma. It is said that soma referred in Vedas was not a fermented product like wine. The process of making wine from date and grapes by using yeast is quite old. The term “ferment” comes from the Latin word fervere, which means “to boil.” Fermentation was described by late fourteenth century alchemists, but not in the modern sense. The scientific investigation on fermentation started in 1600. In ancient times mushrooms have been thought to have special powers. The Pharaohs of Egypt prized mushrooms as delicacy. Holy Ramayana tells us that when Lakshaman was injured, hanuman on the advice of Sushain Vaidya went in search of a luminous fungi or a mushroom and brought Kishkindha mountain. Archeological excavations conducted in 1991 from Alps have revealed that Iceman was using fungi like Piptoporus and Fomes for igniting the fire some

408

A. Arya

Fig. 14.3 (a) Tropical mushrooms from Antigua and Barbados. First day cover released on 26 March, 2001 (source: author). (b) Stamps on Amanita mushrooms (source: Timir Shah). (c) ISRAEL 2002 FDC Mushrooms MIGDAL HA-EMEK, A. muscaria and other mushrooms. (d) First day cover showing edible mushrooms on the stamps of Ciskei (South Africa) 19-3-1987— stamps of Boletus edulis, Macrolepiota zeyheri, Termitomyces sp., Russela capensis. (e) First day cover showing poisonous mushrooms on the stamps of Ciskei (South Africa) 1988—stamps of Amanita phalloides, Chlorophyllum molybdites, A. muscaria, and A. Pantherina

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

409

6000 years back. Literature has revealed that parts of certain fungi after treatment with sodium nitrate were used as fuse for bullets and explosives used in land mines.

14.1.4 Stamps Showing Mycologists at Work Mycologists are the scientists who study fungi—a stamp set commemorating the discoverer of penicillin (Sir Alexander Fleming) was issued by Mauritius in 1978 and similar commemoratives have also been issued by several African countries since that date, such as St Thomas and Prince Islands 2003 and 2007, Guinea 2002, though I am not convinced that the two portraits shown in the Mozambique 2002 Minisheet MS1665, one clean shaven and one bearded, really are both of Alexander Fleming! This frequent commemoration of Fleming is right and proper, given the colossal difference that antibiotics made to the health of humanity, but Fleming was a bacteriologist, and the usual story is that the fungus drifted into his attention in a temporarily deserted laboratory (Fig. 14.2b shows a blue colored stamp of Alexander Fleming from Mexico). An Englishman who worked at the University of Manitoba and was a renowned experimental mycologist and plant pathologist together with a souvenir sheet with a stamp showing a portrait of Elsie Maud Wakefield (an English mycologist and plant pathologist at the Royal Botanic Gardens, Kew), while the sheet displays a portrait of Anton de Bary (considered to be a founding father of modern mycology and plant pathology) (Fig. 14.4a). A brief biography and picture of Louis Pasteur appears on a souvenir sheet issued by the Democratic Republic of the Congo 2006 (Fig. 14.4b).

14.2

Pigments: Imparting Beautiful Colors to the Mushrooms

Many fungi, especially the mushrooms are visible from long distances, they possess characteristic colors. They produce a wide variety of secondary metabolites and compounds like quinones, carotenoids, betacyanins, alkaloids, xanthones, biphenyls, melanin, etc. (Jan and Karel 2011). Various pigments and other bio-constituents show important activities like antioxidative, free radical scavenging, anticarcinogenic, immunomodulatory, antiviral, and antibacterial that have generated intensive research interest. The important groups of pigments present in mushrooms are as follows.

410

A. Arya

Fig. 14.4 (a) Heinrich Anton de Bary a mycologist and father of modern plant pathology along with Elsie Wakefield—2011. (b) Miniature sheet from Congo depicting Biochemist Louis Pasteur with mushroom Lactarius—2006

14.2.1 Quinones Most of us are familiar with the ubiquitous plastoquinones, ubiquinones, and tocopherols and vitamin K. Species within the order Polyporales are saprotrophic and most of them wood-rotters. The Polyporaceae are a family of such wood-decay fungi that contain pigments mostly derived from polyporic acids and terphenylquinones. The dark red polyporic acid, the parent compound of numerous terphenylquinones and related compounds, is the major component of Hapalopilus nidulans (Fr.) P. Karst. Betulinans A and B are two simple terphenylquinones recently found in the plant pathogen Lenzites betulina (L.) Fr. (Gill 1999). The striking yellowish or orange-colored fruiting bodies of the wood-rotting edible mushroom Laetiporus sulphureus (Bull.) Murrill belonging to the Fomitopsidaceae family contains non-isoprenoid polyene known as laetiporic acid A (predominantly

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

411

occurring as the 7-cis-isomer and 2-dehydro-3-deoxylaetiporic acid A as the main pigments (Davoli et al. 2005)). Cortinarius the largest genus of agarics (1000 spp.), the genera Agaricus L., Leucoagaricus Locq. ex Singer and Macrolepiota Singer of the Agaricaceae, including the common mushroom A. bisporus (J.E. Lange) Imbach, contain the glutamic acid derived hydrazine agaritine that may be enzymatically oxidized at the C-4 hydroxymethyl group to the corresponding formyl and carboxyl derivatives, which are hydrolyzed to 4-(hydroxymethyl) phenylhydrazine and 4-carboxymethylbenzoic acid, respectively. 4-(Hydroxymethyl) phenylhydrazine is oxidized to the corresponding diazonium cation. The metabolic fate of agaritine has been linked with the carcinogenicity of the mushroom (Walton et al. 2001). The yellow pigment characteristic of the yellow-staining A. xanthodermus Genev. and of some other Agaricus species is caused by another azaquinone metabolite. Tricholoma contain a range of anthraquinones like fallacinol, bright yellow dimeric anthraquinone. Boletales possess diverse colors that are mainly derived from terphenylquinones and pulvinic acids. Terphenylquinones, exemplified by polyporic acid and atromentin, are mainly produced by wood-rotting higher fungi growing on various deciduous trees but in other higher fungi, they only appear sporadically. However, atromentin is the key intermediate for many conversions leading to more highly hydroxylated terphenylquinones, hydroxypulvinic acids, cyclopentenones, and related compounds. In the intact fruit bodies, atromentin occurs in the form of its colorless precursors leucomentins.

14.2.2 Carotenoids Carotenoids are not widespread in higher fungi as they are in plants; nevertheless, they have been isolated from several yellow pigmented Cantharellus Juss. (Cantharellaceae). The golden chanterelle C. cibarius Fr. pigment mixture was found to consist mainly of CE¼B2-carotene and also present were the xanthophyll—canthaxanthin that was found in the pink to red-orange cinnabar chanterelle, C. cinnabarinus (Schwein.) Schwein. as the main pigment.

14.2.3 Betacyanins The striking orange-red pigments of the cap of fly agaric, Amanita muscaria are a mixture of the purple betacyanin muscapurpurin, orange betaxanthins muscaurins and yellow muscaflavin. Muscaurin I and muscaurin II are derived from unusual non-protein amino acids, ibotenic acid and stizolobic acid, respectively, and are the major agaric pigments. Pigments named muscaurins III-VII are mixtures of pigments derived from common amino acids. Muscaurin III is a mixture of vulgaxanthin I,

412

A. Arya

known as (S)-glutamine-betaxanthin, miraxanthin III, known as (S)-aspartic acidbetaxanthin, and a betaxanthin derived from 2-aminoadipic acid. Muscaurin IV is a mixture of vulgaxanthin I and miraxanthin III (Li and Oberlies 2005). Apart from carotenoids, only a few lower terpenoids are colored compounds. The color of the injured flesh as well as of the latex of several Lactarius Pers. (Russulaceae) species own to their color changes to sesquiterpenoids. The fruiting body of L. deliciosus (L. ex Fr.) S. F. Gray is first carrot-colored, but slowly turns green. The L. deterrimus Gröger fruit body is pale peach colored and becomes apricot colored with a grayish green intensity on aging, on cutting L. deterrimus yields saffron or orange-colored latex. These color changes are due to sesquiterpenoids derived from azulene (guaiazulene). Ochroleucins are the main pigments of the fruiting bodies of the Common Yellow Russula, Russula ochroleuca Pers., and R. viscida Kudrna. The labile yellow ochroleucin A is rapidly transformed to the stable red ochroleucin B (Sontag et al. 2006).

14.3

Edible and Poisonous Mushrooms (Toadstools)

Collection of mushrooms from nature is termed Fungal foray. “Soma” the divine drink is supposed to be obtained from mushrooms. These are rich in protein and because of high folic acid content they are extremely beneficial for blood formation. Mushroom may be edible or poisonous. There has been a long association of toads in medieval mushrooms as well as with contemporary art, literature, and folklore. The term “toadstool” is literally a mushroom upon which a toad can sit. In fairy tales, toadstools were often associated with little gnomes of the forest, as well as frogs and toads. The mushrooms most often pictured with toads are a poisonous species with the classic umbrella cap and long stem, such as the Fly Agaric (Amanita muscaria). These have a bright red cap with white spots and emit an odor that actively attracts flies. Outer surface of pileus shows fragments of veil. Toads are attracted to the mushroom to eat the flies. A souvenir sheet from Singapore (with detail) honoring the story of Thumbelina by Hans Christian Andersen depicts the typical appearance of the “toadstools” with red with white spots with one stamp showing a toad.

14.4

Mushrooms on Postage Stamps

Ing (1976) stated that the first stamp issued to show images of fungi, and specifically portraits of mushrooms, was the set issued by Romania over the 12th to 30th July 1958 (Fig. 14.2b last stamp), closely followed by the Czechoslovakian set issued on 6th October 1958 and the set issued by Poland on 8th May 1959. Since that time more than 5000 stamps have been issued showing illustrations of fungi, mostly illustrations of mushrooms and similar macroscopic fungal fruit bodies (list enclosed

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

413

as online Supplementary Annexure 14.1) (Moss 1992, 1993, 1998; Moss and Pegler 2003). Few of these fungi are briefly illustrated here. The stamp issue liked most is the gloriously self-indulgent Guinea 2009 series called “Mushrooms on stamps,” which features a collective sheet 175  98 mm, of six 5000-Guinean franc stamps showing previous issues from Australia, Afghanistan, Andorra, and France. The set also includes a souvenir sheet, 142  107 mm with a single stamp of 29000-Guinean franc face value showing an issue from the Faroe Islands. Poland printed a set of eight stamps on mushrooms (Fig. 14.2d first two triangular stamps) and Kampuchea in 1985 printed a set of six stamps (Fig. 14.2c, d last stamps).

14.4.1 Amanita Many species are of unknown edibility, especially in countries such as Australia, where many fungi are little-known. The name is possibly derived from Amanus (Ancient Gr.: Ἁμανóς), a mountain in Cilicia. The genus Amanita was first published with its current meaning by Christiaan Hendrik Persoon in 1797. Under the International Code of Botanical Nomenclature, Persoon’s concept of Amanita, with A. muscaria (L.) Pers. as the type sp., has been officially conserved against the older Amanita Boehm (1760), which is considered a synonym of Agaricus L. The genus Amanita contains about 600 species of agarics, including some of the most toxic known mushrooms found worldwide. This genus is responsible for approximately 95% of the fatalities resulting from mushroom poisoning, with the death cap accounting for about 50% on its own. The most potent toxin present in these mushrooms is α-amanitin. The genus also contains many edible mushrooms, but mycologists discourage mushroom hunters, other than knowledgeable experts, from selecting any of these for human consumption. Nonetheless, in some cultures, the larger local edible species of Amanita are mainstays of the markets in the local growing season. Samples of this are Amanita zambiana and other fleshy species in Central Africa, A. basii and similar species in Mexico, A. caesarea and the “Blusher” Amanita rubescens in Europe, and A. chepangiana in South-East Asia. Other species are used for coloring sauces, such as the red A. jacksonii, with a range from eastern Canada to eastern Mexico. Edible species of Amanita include Amanita fulva, Amanita vaginata (grisette), Amanita calyptrata. Although some species of Amanita are edible, many fungi experts advise against eating a member of Amanita unless the species is known with absolute certainty. Because so many species within this genus are so deadly toxic, if a specimen is identified incorrectly, consumption may cause extreme sickness and possibly death. Inedible species of Amanita include Amanita albocreata (ringless panther), Amanita atkinsoniana, Amanita citrina (false death cap), Amanita excelsa, Amanita flavorubescens, Amanita franchetii, Amanita longipes, Amanita onusta, Amanita

414

A. Arya

Table 14.1 Postage stamps on different Amanita mushrooms S. No. 1. 2. 3. 4. 5. 6. 7. 8. 9.

Amanita species Amanita phalloides Amanita muscaria Amanita phalloides Amanita muscaria Amanita muscaria Amanita caesarea Amanita citrine Amanita pantherina Amanita caesarea

Year 8th May 1959 1974 1974

Place/country Poland—A set of eight stamps Germany, DDR issued in 1974 (Nr.Fsc:27408Nr. Yvert:1613/0Nr.) Germany Republic of Argentina

1986

Russia five stamps Romania set of 10 one gray and red colored stamp 20

1988 1985

Cuba Kampuchea

1994

Nepal—Red color (Rs. 4)

rhopalopus, Amanita silvicola, Amanita sinicoflava, Amanita spreta, and Amanita volvata. Some poisonous species include Amanita brunnescens, Amanita ceciliae, Amanita cokeri (Coker’s amanita), Amanita crenulata, Amanita farinosa (eastern American floury amanita), Amanita frostiana, Amanita muscaria (fly agaric), Amanita pantherina (panther cap), and Amanita porphyria. Members of the Phalloidieae are notable for their toxicity, containing toxins known as amatoxins, which can cause liver failure and death. These include the death cap A. phalloides; species known as destroying angels, including A. virosa, A. bisporigera, and A. ocreata; and the fool’s mushroom, A. verna. More recently, a series in the subgenus Lepidella has been found to cause acute kidney failure, including A. smithiana of northwestern North America, A. pseudoporphyria of Japan, and A. proxima of Southern Europe. Russia brought a set of five stamps Ядовитые грибы—Мухомор красный Red colored three poisonous mushrooms—Amanita muscaria issued in 1986 of 5 к denomination (Table 14.1).

14.4.2 Armillaria Armillaria mellea is widespread in northern temperate zones. It has been found in North America, Europe and northern Asia, and it has been introduced to South Africa. The fungus grows parasitically on a large number of broadleaf trees. It fruits in dense clusters at the base of trunks or stumps. Alternatively, when infected

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

415

roots come into contact with uninfected ones the fungal mycelium may grow across. The rhizomorphs invade the trunk, growing between the bark and the wood and causing wood decay, growth reduction and mortality. In 1893, the American mycologist Charles Horton Peck reported finding Armillaria fruiting bodies that were “aborted,” in a similar way to specimens of Entoloma abortivum. It was not until 1974 that Roy Watling showed that the aborted specimens included cells of both A. mellea and E. abortivum. He thought that the Armillaria was parasitizing the Entoloma, a plausible hypothesis given its pathogenic behavior. However, a 2001 study by Czederpiltz, Volk, and Burdsall showed that the Entoloma was in fact the microparasite. The whitish-gray malformed fruit bodies known as carpophoroids were the result of E. abortivum hyphae penetrating the Armillaria and disrupting its normal development. The main part of the fungus is underground where a mat of mycelial threads may extend for great distances termed as the rhizomorph (Czederpiltz et al. 2001). The mushrooms have a taste that has been described as slightly sweet and nutty, with a texture ranging from chewy to crunchy, depending on the method of preparation. Parboiling mushrooms before consuming removes the bitter taste present in some specimens and may reduce the amount of gastrointestinal irritants. According to one guide, they must be cooked before eating. Drying the mushrooms preserves and intensifies their flavor, although reconstituted mushrooms tend to be tough to eat. The mushrooms can also be pickled and roasted. Several bioactive compounds have been isolated and identified from the fruit bodies. The triterpenes 3β-hydroxyglutin-5-ene, friedelane-2α,3β-diol, and friedelin were reported in 2011. Indole compounds include tryptamine, L-tryptophan, and serotonin. Cytotoxic compounds Melleolides present in it are made from orsellinic acid and protoilludane sesquiterpene alcohols via esterification. A polyketide synthase gene, termed ArmB, was identified in the genome of the fungus, which was found expressed during melleolide production. The gene shares ca. 42% similarity with the orsellinic acid synthase gene (OrsA) in Aspergillus nidulans. Characterization of the gene proved it to catalyze orsellinic acid in vitro. It is a non-reducing iterative type 1 polyketide synthase. Co-incubation of free orsellinic acid with alcohols and ArmB showed cross-coupling activity. Mongolia released a stamp of Armillaria mellea in 1985.

14.4.3 Boletus Boletus edulis was first described in 1782 by the French botanist Pierre Bulliard and still bears its original name. B. edulis is the type species of the genus Boletus. In Rolf Singer’s classification of the Agaricales mushrooms, it is also the type species of section Boletus, a grouping of about 30 related boletes united by several characteristics: a mild tasting, white flesh that does not change color when exposed to air; a smooth to distinctly raised, netted pattern over at least the uppermost portion of the stem; a yellow-brown or olive-brown spore print; white tubes that later become

416

A. Arya

Fig. 14.5 Colorful Boletus edulis (Czechoslovakia—1958, Armenian Republic—2013). Boletus clopus (Malagasy—1990) Boletus satanus from Germany

yellowish then greenish, which initially appear to be stuffed with cotton; and cystidia that are not strongly colored. Molecular analysis published in 1997 established that the bolete mushrooms are all derived from a common ancestor and established the Boletales as an order separate from the Agaricales. The generic name is derived from the Latin term bōlētus “mushroom,” which was borrowed in turn from the Ancient Greek βωλίτης, “terrestrial fungus.” Ultimately, this last word derives from bōlos/βῶλoς “lump,” “clod,” and, metaphorically, “mushroom.” The βωλίτης of Galen, like the boletus of Latin writers like Martial, Seneca, and Petronius, is often identified as the much prized Amanita caesarea. The specific epithet edulis in Latin means “eatable” or “edible.” Common names for mushroom B. edulis vary by region. The standard Italian name, porcino (pl. porcini), means porcine; fungo porcino, in Italian, echoes the term suilli, literally “hog mushrooms,” a term used by the Ancient Romans and still in use in southern Italian terms for this species. The derivation has been ascribed to the resemblance of young fruit bodies to piglets, or to the fondness pigs have for eating them. It is also known as “king boletes.” The English penny bun refers to its rounded brownish shape. The cap of this mushroom is 7–30 cm broad at maturity. Slightly sticky to touch, it is convex in shape when young and flattens with age. The color is generally reddishbrown fading to white in areas near the margin and continues to darken as it matures. The under surface of the cap is made of thin tubes, the site of spore production; they are 1–2 cm deep and whitish in color (Fig. 14.5). Boletus edulis has a cosmopolitan distribution, concentrated in cool-temperate to subtropical regions. It is common in Europe—from northern Scandinavia, south to the extremities of Greece and Italy—and North America. It has been recorded growing under Pinus and Tsuga in Sagarmatha National Park in Nepal, as well as in the Indian forests of Arunachal Pradesh. Boletus edulis is known to be able to tolerate and even thrive on soil that is contaminated with toxic heavy metals, such as soil that might be found near metal smelters. The mushroom’s resistance to heavy-metal toxicity is conferred by a biochemical called a phytochelatin—an oligopeptide whose production is induced after exposure to metal. Phytochelatins are chelating agents, capable of forming multiple bonds with the metal; in this state, the metal cannot normally react with

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

417

other elements or ions and is stored in a detoxified form in the mushroom tissue. Considered a choice edible, particularly in France, Germany, Poland, and Italy, it was widely written about by the Roman writers Pliny the Elder and Martial, although ranked below the esteemed Amanita caesarea. When served suilli instead of boleti, the disgruntled Martial wrote: sunt tibi boleti; fungos ego sumo suillos (Ep. iii. 60). (“You eat the choice boletus, I have mushrooms that swine grub up.”) A 1998 estimate suggests the total annual worldwide consumption of Boletus edulis and closely related species (B. aereus, B. pinophilus, and B. reticulatus) to be between 20,000 and 100,000 tons. The results of some studies suggest that unknown components of the soil microflora might be required for B. edulis to establish a mycorrhizal relationship with the host plant. B. edulis mushrooms are 9% carbohydrates, 3% fat, and 7% protein. Chitin, hemicellulose, and pectin-like carbohydrates—all indigestible by humans—contribute to high proportion of insoluble fiber in B. edulis. They also have high content of B vitamins, tocopherols, selenium, a trace mineral, although the bioavailability of mushroom-derived selenium is low. Boletus edulis fruit bodies contain diverse phytochemicals, including 500 mg of ergosterol per 100 g of dried mushroom and ergothioneine. The fruit bodies contain numerous polyphenols, especially a high content of rosmarinic acid, aroma compounds giving B. edulis mushrooms their characteristic fragrance include some 100 components, such as esters and fatty acids. In a study of aroma compounds, 1-octen-3-one was the most prevalent chemical detected in raw mushrooms, with pyrazines having increased aroma effect and elevated content after drying. Scott 1790, the Devil’s Bolete (Boletus satanas), is one of six British endangered species shown in this set of stamps. The others include a rodent, an orchid, a bird, a snail, and an insect. The Presentation Pack issued by the Royal Mail tells a lot more about all of these endangered organisms and the work that is being done to help them recover. For the bolete there is a beautiful color photo of two buttons in the wild and a chart showing only six known locations left in Britain where it has been found recently. It is mycorrhizal with Beech trees (Fagus sylvatica) which are only found in Southern England and loss of habitat appears to be the main problem. Poland on 8th May, 1959 (Nr. Fsc:25903Nr. Scott:842/49Nr. Yvert:959/66Nr. Michel:1093/00) issued a set of eight postage stamps depicting Amanita phalloides 20, 2 stamps, Boletus luteus 30, 2 stamps, Boletus edulis 40, Lactarius deliciosus 60 GR. In 1988 Cuba published stamp of Boletus satanas, mushroom is shown white colored with red colored lower surface. It has pores on lower surface. Mongolia has issued a large stamp on B. aurantiacus. Costa Rica released a set of two delicious mushrooms Boletus edulis and Morchella esculenta (Fig. 14.6).

14.4.4 Coprinus Coprinus mushrooms are common wild mushrooms that appear in the summer and the fall. They liquefy as they mature and for this reason have to be eaten soon after they are picked. If Coprinus mushrooms that you collect turn to black goo before you

418

A. Arya

Fig. 14.6 Certain stamps showing Morchella and Ascomycetes member Gyromitra (source: Timir Shah)

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

419

have a chance to cook them, you can use the liquid as semi-permanent ink. The most popular species, C. comatus, is known as the Shaggy Mane or Lawyer’s Wig for the appearance of the surface of the large, white caps. This is a delicious edible that often comes up in large groups. A related species (C. atramentarius), the Inky cap mushroom, is smaller, less attractive, and also edible, but it contains a compound that interferes with the metabolism of alcohol and can cause a violent reaction if you consume alcohol after eating it. Researchers at the University of Florida reported in 2017 that a shaggy mane mushroom protein known as Y3 could bind with proteins on the surface of a certain type of leukemia cell. This action triggered a cascade of enzymes that killed 90% of the leukemia cells, suggesting that the Y3 protein and the mushroom might be promising candidates for new treatments for leukemia. Lab tests elsewhere have suggested that Coprinus mushrooms have antitumor and antiviral effects, as well as the ability to modulate immune system activity. Some research has found that C. comatus may help lower blood sugar. They absorb toxic heavy metals like Hg, Cd, and As from soil, including cadmium, mercury, and arsenic. They may be useful in cleaning up contaminated sites. Another plus: the antioxidant properties of Coprinus species can help neutralize pollution-triggered oxidative stress. C. comatus is one of the several mushrooms included in a line of skin-care products. It protects skin health and can help reduce dryness and sensitivity. Kampuchea released two stamps, i.e. Coprinus comatus and C. micaceus in 1985.

14.4.5 Inocybe Inocybe is a large genus of mushroom-forming fungi with over 1400 species, including all forms and variations. Members of Inocybe are mycorrhizal, and some evidence shows that the high degree of speciation in the genus is due to adaptation to different trees and perhaps even local environments. The name Inocybe means “fibrous hat.” It is taken from the Greek words ἴς (in the genitive ἴνoς, meaning “muscle, nerve, fiber, strength, vigor”) and κύβη (“head”). The genus was first described as Agaricus trib. Inocybe by the famous Swedish scholar Elias Magnus Fries in volume 1 of his work, Systema mycologicum (1821), and verified in the volume 2 of his book Monographia Hymenomycetum Sueciae in 1863. The small to medium size pileus is in the small, thin, big fleshy, initially stretched conical or bellshaped, then flattened, or flattened, or with a fairly prominent sharp or flattened gurgle in the center. It is not hygrophanous and has a dry appearance. In the beginning, the edge often shows a pale, curving curve, and in the old age does not show short radial cracks to the depths. Coloring is at first on almost all white to graywhitish varieties. Some retain color, others change, varying between ocheryellowish and brown, various shapes, even lilac-like to purple. The lamellas are dense, thick, and bulky, with short intermediate legs at the edge and only weakly attached to the foot, almost loose. Coloring is in many white starters, which becomes mature gray-brown, ocher-brown, or gray-olive. The edges are whitish or white-

420

A. Arya

flocked. The spores are brownish, tiny, normally oval to slightly ellipsoidal, often elongated in the form of almonds or beans (Clypeus tuberculous or star-shaped subgenus), smooth, never verrucous, and germ-free. Basidias are tertrasporics. Cisterns with or without crystalline fossil are fusiform, bulging in the middle and with a tumbling at the top. Inocybe species are not considered suitable for consumption; While the vast majority of Inocybes are toxic, seven rare species of Inocybe are hallucinogenic, having been found to contain psilocybin, including Inocybe aeruginascens which also contains aeruginascine (N,N,N-trimethyl-4-phosphoryloxytryptamine). In a 1905 publication, Norwegian botanist Axel Gudbrand Blytt (1843–1898) described this toxic toadstool, giving it the scientific binomial name Inocybe erubescens, by which name it is generally referred to today. Synonyms of I. erubescens include I. patouillardii Bres. (stamp from Cuba in 1988) and it was by this name that the deadly fiber cap was generally referred to in field guides until quite recently (although the English common name most often used by the non-scientific community at that time was the Red-staining Fiber cap). This is a deadly poisonous toadstool and large enough for inexperienced foragers to consider these toadstools worth collecting for food. That makes it very dangerous indeed. Under no circumstances should I. erubescens be included in collections of fungi intended for human consumption, it is deadly as its common name suggests. Cuba has issued a beautiful stamp of Inocybe patouillardii released in 1988 (Fig. 14.2a 3rd stamp toward left side).

14.4.6 Leccinum The cap is orange-red and measures up to 20 cm. Its flesh is white, bruising at first burgundy, then grayish or purple-black. The underside of the cap has very small, whitish pores that bruise olive-brown. The stem measures 10–18 cm tall and 2 cm thick and can bruise blue-green. It is whitish, with short, rigid projections or scabers that turn to brown to black with age. L. aurantiacum can be found fruiting during summer and autumn in forests throughout Europe and North America. The association between fungus and host tree is mycorrhizal. In Europe, it has traditionally been associated with poplar trees. Some debate exists about the classification of L. aurantiacum and L. quercinum as separate species. According to authors who do not recognize the distinction, L. aurantiacum is also found among oak trees. Additionally, L. aurantiacum has been recorded with various other deciduous trees, including beech, birch, chestnut, willow, and trees of the genus Tilia. This is a favorite species for eating and can be prepared as other edible boletes. Its flesh turns very dark on cooking. It is a member of the Boletaceae. Due to a number of poisonings and the difficulty identifying species, Leccinum species are considered by some as possibly not safe to eat. This species also needs to be cooked well (not parboiled) or else it may cause vomiting or other negative effects. This species can cause problems with digestion if not cooked properly. In Europe, several orange-red

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

421

capped species exist, which differ mainly in habitat. L. albostipitatum grows with aspen and has white scales on the stipe. In coniferous forests, L. vulpinum occurs around pine and spruce trees. In North America, L. insigne grows in aspen or birch stands, while L. atrostipitatum grows in birch stands. Both are edible. An envelope received by Shri O.P. Arya in Premnagar Kanpur from Russia in 1965 depicts a red capped sacker stalk Leccinum auriantiacum this stamp was released in 1964 (Fig. 14.2b).

14.4.7 Lepiota The “lepiotoid mushrooms” include species featuring white spore prints, gills that are free from the stem, partial veils that often leave a ring on the stem—and, under the microscope, smooth, usually dextrinoid spores. They can be very similar to species of Amanita; however, most (though not all) lepiotoid mushrooms are smaller than most amanitas and lack volvas. Additionally, most amanitas are mycorrhizal, while most lepiotoid mushrooms are saprobic—which means they “act” differently; amanitas are associated with trees (with a very few saprobic exceptions), while lepiotoid mushrooms are associated with litter. Identification features that can be assessed without a microscope include colors, an assessment of the texture of the cap surface, bruising and staining reactions, the odor of the crushed flesh, and a close look at the morphology of the stem and the disposition of veil remnants. For this reason the stems of lepiotoid mushrooms should not be handled during the collecting process; ephemeral rings and sheathing shagginess can be easily rubbed away. Most lepiotoid identifications, however, will require microscopic analysis. It is found that both a cross-sectional Roman aqueduct section and a radial cap section that includes the center of the cap are usually required, both mounted in KOH, along with a third slide of mature gill tissue (or a spore print scraping) mounted in Melzer’s reagent. In other words, studying lepiotoid mushrooms under the microscope means a bunch of work. Microscopic features to observe include the structure of the pileipellis, the morphology of the (often boring and hard-to-distinguish) cheilocystidia, and the morphology of the spores. The pileipellis (which Else Vellinga, the most prolific contemporary lepiotoid author, calls the “pileus covering”) must be assessed over the center of the cap, where the pigment has not broken up into scales or patches. As for the spore morphology be prepared for a much more finely honed assessment of spore shapes than is often required in the non-lepiotoid world. Laos in 1985 printed Vintage Mushroom Postage Stamp Set of six stamps. One stamp shows Lepiota procera, an edible Parasol mushroom, another stamp shows Xerocomus subtomentosus. Two stamps of Angola showing collective sheet, 105  122, each with six stamps, all 3.5 million KZr face value depicting Agaricus silvicola and Lapiota custela.

422

A. Arya

14.4.8 Laccaria Laccaria species form a fairly easily recognized group of white-spored mushrooms. The gills are often thick and a little waxy and are usually purple, pinkish, or (Caucasian) flesh-colored. The cap colors range from whitish to, more commonly, orangish brown or reddish brown, while a few species are purple. Laccarias are never slimy, which helps in separating them from the waxy caps, and their gills are attached to the stem but do not run down it, helping distinguish them from clitocyboid mushrooms. Laccarias are mycorrhizal, Laccaria identification is frequently a fairly easy matter of carefully observing the mushroom’s ecology and visible features, but I hasten to add that there is a catch: you must, in some cases, have fresh, young specimens available in order to judge the color (whitish or lilac) of the basal mycelium, since the purplish fuzz notoriously fades to whitish, often doing so fairly early in development. Microscopic analysis is required in order to sift through a few species clusters and includes spore morphology, “prong counting” (determining whether basidia are two- or four-spored), hunting for cheilocystidia, and assessing pileipellis details. Most microscopic features necessary for Laccaria identification can be accomplished with a successful Roman aqueduct section, mounted in KOH (2%) and stained with phloxine. DNA evidence, so far, has upheld Laccaria as a “good” genus, though its precise position among the gilled mushrooms has not been thoroughly resolved. Guyana in 1987 printed a violet colored stamp of mushroom Laccaria amethystina which is found associated with oaks or beech in eastern North America; cap purple, fading to lilac or buff.

14.4.9 Morchella Commonly known as morels this group of delicious mushrooms Morchella belongs to group Ascomycota of fungi. The mushrooms have mycorrhizal association with forest trees. Collected from nature from hilly areas of Kashmir and Himachal Pradesh, India.

14.4.10

Paxillus

Paxillus involutus, commonly known as the brown roll-rim, common roll-rim, or poison pax, is a member of Basidiomycete that is widely distributed across the Northern Hemisphere (Margit and Bresinsky 1999). It has been inadvertently introduced to Australia, New Zealand, South Africa, and South America. Various shades of brown in color, the fruit body grows up to 6 cm high and has a funnelshaped cap up to 12 cm wide with a distinctive inrolled rim and decurrent gills that may be pore-like close to the stipe. Although it has gills, it is more closely related to

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

423

the pored boletes than to typical gilled mushrooms. An antigen in the mushroom triggers the immune system to attack red blood cells. Serious and commonly fatal complications include acute kidney injury, acute respiratory failure, and disseminated intravascular coagulation. The brown roll-rim was described by French mycologist Pierre Bulliard in 1785 as Agaricus contiguus, although the 1786 combination Agaricus involutus of August Batsch is taken as the first valid description. The species gained its current binomial name in 1838 when the “Father of mycology,” Swedish naturalist Elias Magnus Fries erected the genus Paxillus and set it as the type species. In Poland, the mushroom was often eaten after pickling or salting. It was known to be a gastrointestinal irritant when ingested raw but had been presumed edible after cooking. Questions were first raised about its toxicity after German mycologist Julius Schäffer died after eating it in October 1944. About an hour after he and his wife ate a meal prepared with the mushrooms, Schäffer developed vomiting, diarrhea, and fever. His condition worsened to the point where he was admitted to hospital the following day and developed kidney failure, perishing after 17 days. The Paxillus syndrome is better classed as a hypersensitivity reaction than a toxicological reaction as it is caused not by a genuinely poisonous substance but by the antigen in the mushroom. The antigen is still of unknown structure but it stimulates the formation of IgG antibodies in the blood serum. Poisoning symptoms are rapid in onset, consisting initially of vomiting, diarrhea, and abdominal pain. Two compounds that have been identified are the phenols involutone and involutin; the latter is responsible for the brownish discoloration upon bruising. Cuba has a stamp on Paxillus involutus released in 1988. It is a part of seven stamps released on P. involutus, Amanita citrine, Boletus satanas, Tylopilus felleus, Inocybe patouillardii, Amanita muscaria, Hypholoma fasciculare.

14.4.11

Pholiota

In 1984, Upper Volta renamed Burkina Faso, which means “land of honest men,” has significant reserves of gold, but the country has faced domestic and external concern over the state of its economy and human rights. A former French colony, it gained independence as Upper Volta in 1960. A stamp released in 1985 depicts Pholiota mutablitis (Fig. 14.7).

14.4.12

Pleurotus: Oyster mushroom

The Pleurotus sajor-caju also popularly known by its common name as gray oyster mushroom, and this name was obtained for the physical appearance which resembled an oyster shell. It was first isolated from India this strain has been identified to be the best strain for cultivation in tropical and subtropical regions. In Malaysia,

424

A. Arya

Fig. 14.7 Certain stamps showing Tricholoma, Agaricus, Pholiota, and Boletus

oyster mushroom are usually consumed as soup, grilled or deep fried and it has a great demand as local street food. Broader on outer side the mushroom has gills and a short stalk on one side of pileus. Among the cultivated species it is easier to grow this lignocellulosic mushroom on a variety of hosts (Fig. 14.8).

14.4.13

Russla

Russula xerampelina, also commonly known as the crab brittle gill or the shrimp mushroom, is a basidiomycete mushroom of the brittle gill genus Russula. Two subspecies are recognized. The fruiting bodies appear in coniferous woodlands in autumn in Northern Europe and North America. Their caps are colored various shades of wine-red, purple to green. Mild tasting and edible, it is one of the most highly regarded brittle gills for the table. It is also notable for smelling of shellfish or crab when fresh. Russula xerampelina was originally described in 1770 as Agaricus xerampelina from a collection in Bavaria by the German mycologist Jacob Christian Schaeffer, who noted the color as fusco-purpureus or “purple-brown.” As the first defined species, it gives its name to the section Xerampelinae, a group of related species within the genus Russula, occasionally all termed R. xerampelina in the past. Russula xerampelina has a characteristic odor of boiled crustacean. The cap is 6–12 cm wide, domed, flat, or with a slightly depressed center, and sticky. The

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

425

Fig. 14.8 A miniature sheet from Thailand showing different Pleurotus species

color is variable, most commonly purple to wine-red, or greenish, and darker toward the center of the cap. There are fine grooves up to a centimeter long running perpendicular to the margin. The gills have a mild to rather bitter taste, narrowly spaced, and turn creamy-yellow on aging specimens. The spore print is creamyyellow to ochre. The oval spores measure 8.8–9.9 by 6.7–7.8 μm and are covered with 1 μm spines. The stipe 4–8 cm long, 1.5–3 cm wide is cylindrical, white or sometimes with a reddish blush, turning ochre or brownish with age. This Russula has been divided into several similar species by some mycologists. However, they all have the singular dark green color reaction to iron salts (iron (II) sulfate) when applied to the flesh and all smell of shellfish. This aroma is quite distinct and becomes stronger with age. The taste of Russula xerampelina is mild.

426

A. Arya

This Russula is considered one of the best edible species of its genus, although the crab, or shrimp taste and smell will persist even when cooking. This is more pronounced and less pleasant in older specimens. The young caps are said to be superb stuffed with any suitable ingredients and are rarely maggoty. Yellow colored beautiful stamp of Russula nepalensis of Rs. 7 was released by Nepal in 1994.

14.4.14

Tricholoma

Tricholoma is a fairly large genus of mycorrhizal gilled mushrooms with white spore prints, fleshy stems, and gills that are attached to the stem, often by means of a slight “notch.” Under the microscope, Tricholoma species have inamyloid spores. Though species of Tricholoma can be found across our continent from spring to fall (and nearly year-round in warm climates), the mushrooms tend to like cooler conditions and are most abundant in montane and northern forests, particularly in the fall. Some species are distinctive—especially those with rings and those with a strong, foul odor reminiscent of coal tar. A few species are brightly colored. But many, many Tricholoma species are gray, grayish, brown, or brownish, and frustratingly similar. The texture of the cap, colors, bruising and discoloring reactions, and odors and tastes separate many of the species. Since the mushrooms are mycorrhizal, paying attention to the trees in the area can go a long way toward identifying your Tricholoma. A few species have distinctive reactions to chemicals. Microscopic features include the presence or absence of cystidia and clamp connections and spore dimensions. Korea in 1993 released a stamp of Tricholoma (Fig. 14.9). Mangolia released a 20s stamp of Tricholoma mangolica, it was a part of four mushroom collection in 1985.

14.5

Other Fungi on Postal Stamps

14.5.1 Clathrus The generic name Clathrus is derived from Ancient Greek κλειθρoν or “lattice,” and the specific epithet is Latin ruber, meaning “red.” The mushroom is commonly known as the “basket stinkhorn,” the “lattice stinkhorn,” or the “red cage.” It was known to the locals of the Adriatic hinterland in the former Yugoslavia as veštičije srce or vještičino srce, meaning “witch’s heart.” Clathrus ruber is a species of fungus in the family phallaceae and the type species of the genus Clathrus. It is commonly known as the latticed stinkhorn, the basket stinkhorn, or the red cage, alluding to the striking fruit bodies that are shaped somewhat like a round or

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

427

Fig. 14.9 A stamp of Tricholoma matsutake from Korea released in 1993

oval hollow sphere with interlaced or latticed branches. The fungus is saprobic, feeding off decaying woody plant material, and is often found alone or in groups in leaf litter on garden soil, grassy places, or on woodchip garden mulches. Although considered primarily a European species, C. ruber has been introduced to other areas and now has a wide distribution that includes all continents except Antarctica. The species was illustrated in the scientific literature during the sixteenth century, but was not officially described until 1729. The fruit body initially appears like a whitish “egg” attached to the ground at the base by cords called rhizomorphs. Clathrus ruber was illustrated in 1560 by the Swiss naturalist Conrad Gesner in his Nomenclator Aquatilium Animantium—Gesner mistook the mushroom for a marine organism. The fungus was first described scientifically in 1729, by the Italian Pier Antonio Micheli in his Nova plantarum genera iuxta Tournefortii methodum disposita, who gave it its current scientific name. The species was once referred to by American authors as Clathrus cancellatus L., as they used a system of nomenclature based on the former American Code of Botanical Nomenclature, in which the starting point for naming species was Linnaeus’s 1753 Species Plantarum. The International Code for Botanical Nomenclature now uses the same starting date, but names of Gasteromycetes used by Christian Hendrik Persoon in his Synopsis Methodica

428

A. Arya

Fungorum (1801) are sanctioned and automatically replace earlier names. Since Persoon used the specific epithet ruber, the correct name for the species is Clathrus ruber. Clathrus ruber is the type species of the genus Clathrus and is part of the group of Clathrus species known as the Laternoid series. The fruit body, or receptacle, bursts the egg open as it expands (a process that can take as little as a few hours) and leaves the remains of the peridium as a cup or volva surrounding the base. The receptacle collapses about 24 h after its initial eruption from the egg. The spores are elongated, smooth, and have dimensions of 4–6 by 1.5–2 μm. Scanning electron microscopy has revealed that C. ruber (in addition to several other Phallales species) has a hilar scar—a small indentation in the surface of the spore where it was previously connected to the basidium via the sterigma. The basidia (spore-bearing cells) are six-spored. “A young person having eaten a bit of it, after 6 h suffered from a painful tension of the lower stomach, and violent convulsions. He lost the use of his speech, and fell into a state of stupor, which lasted for 48 h. After taking an emetic he threw up a fragment of the mushroom, with two worms, and mucus, tinged with blood. Milk, oil, and emollient fomentations were then employed with success.” C. ruber is generally listed as inedible or poisonous in many British mushroom publications from 1974 to 2008. Pigments responsible for the orange to red colors of the mature fruit bodies have been identified as carotenes, predominantly lycopene and beta-carotene—the same compounds responsible for the red and orange colors of tomatoes and carrots, respectively. Poland released a stamp of Clathrus ruber in 1980.

14.5.2 Phallus: Stinkhorn The immature fruit bodies of Phallus species grow underground, are roughly spherical to ovoid, and have a soft or gelatinous surface. The genus was first mentioned in the literature by the Dutch Botanist Hadrianus Junius, who in 1564 wrote a short book published in Delft on the Phallus in Hollandia, describing a mushroom in the form of a penis. He was not convinced that the organism was fungal in nature. Later Linnaeus placed it in fungi. It develops from an egg like structure. It belongs to order Phallales. The outer tissue layer, or peridium, is white to pale, smooth, firm-membranous. The slimy spores, or gleba, is attached to outer surface of mushroom and is colored dark olivaceous to blackish brown. The stalk of Phallus mushrooms are called receptacles: they are upright, cylindrical, hollow, spongy, and bearing roughly bell-shaped cap with irregularly branching ridges on the outer surface.

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

429

14.5.3 Geastrum: Earth Star It is a member of Gasteromycetes of Basidiomycota. The name is derived from geo means earth and aster meaning star, refers to the behavior of the outer peridium. At maturity, the outer layer of the fruiting body splits into segments which turn outward creating a star-like pattern on the ground. The inner peridium is a spore sac. In some species, the outer peridium splits from a middle layer, causing the spore sac to arch off the ground. If the outer peridium opens when wet and closes when dry, it is described as hygroscopic. In some species, the inner peridium is borne on a stalk or pedicel. The columella is a column-like clump of sterile tissue to be found inside the inner peridium. The mouth in most species of “earth stars” is quite prominent, often arising as a small cone at the apex of the inner peridium. It may be even or sulcate (grooved). Geastrum triplex, the collared earth star, is described as one of the most common earth stars in Britain by Pegler et al. (1995) in their beautifully illustrated monograph of British puffballs, earthstars, and stinkhorns (Moss 1996). They are generally not toxic but considered non-edible due to their fibrous texture in the mature stage at which they are generally found (Fig. 14.10b).

14.5.4 Calvatia: Giant Puffball The Calvatia are large puffballs which develop underground when mature they come above the ground and disperse the sports in large number. Species of Calvatia were recorded from different types of soils and substrates including, humicolous soil, grassy soil, sandy soil, on manure, on soils of moist and shady places. The main habitat of this mushroom reported in literature includes forests of Salix alba, Populus nigra, broad leaved forests, coniferous forest, and sal forest. Some of Calvatia spp. were reported to be edible as long as the inside is pure white and it should be consumed within 24 h of harvest. The fruit bodies of Calvatia cyathiformis are edible when young. Two steroids including, Calvasterols A (14α hydroxyergosta-4, 7, 9, 22-tetraen-3, 6-dione) and B (9α, 14α-dihydroxyergosta-4, 7, 22-trien-3, 6-dione) and a novel dimeric steroid and calvasterone were detected from the fungus, Calvatia cyathiformis. Calvacin a new antitumor agent was also reported (Roland et al. 1960). Indigenous knowledge of ethnic tribes for utilization of wild mushrooms including C. gigantea as food and medicine in Similipal biosphere reserve is investigated. The brown colored big medicinal mushrooms belonging to Gasteromycetes are shown in Fig. 14.10a.

430

A. Arya

Fig. 14.10 (a, b) A series of five stamp from Korea and the Mushrooms of the world—a set of six stamps from Ghana

14

Beauty, Diversity, and Utility of Mushrooms on Postage Stamps

431

14.5.5 Rammaria The fungus is large much branched produced on the dead wood the fruiting body is a structure which produces large number of basidiospores and degrades the wood by production of lingo-cellulosic enzymes it is a member of hymenomycetes. It is also called coral fungi (Stamp from Korea Fig. 14.10a).

14.6

Conclusion

Beauty, diversity, utility, and peculiar growth pattern has fascinated the human mind since ancient times. Mushrooms have unfolded the ancient human behavior about their various uses for providing strength, good health and beauty to body. These have been thought to possess chemicals for disease cure and longevity. Many of the countries have released a number of beautiful stamps on different fungi and mycologists to educate the people about their uses and conservation. The chapter presents some of these philatelic objects of human curiosity and objects to provide knowledge about Natures unique creation Lovely Mushrooms. Acknowledgements This is to thank Mr. Prashant Pandya, President, Baroda Philatelic Society for encouragement and Secretary Mr. Timir R. Shah for sharing the pictures of some of the old stamps included in the chapter from his collection.

References Aggersberg DJ (1991) Collect fungi on stamps. In: A Stanley Gibbons thematic catalogue. Stanley Gibbons, St. Heller, p 48. ISBN-10: 0852592930 Coetzee JC (1993) Yet more fungi on stamps. Mycologist 7(1):29–31. https://doi.org/10.1016/ S0269-915X(09)80624-1 Czederpiltz DL, Volk TJ, Burdsall HH Jr (2001) Field observations and inoculation experiments to determine the nature of the carpophoroids associated with Entoloma abortivum and Armillaria. Mycologia 93(5):84151. https://doi.org/10.2307/3761750.JSTOR. PMID 3761750 Davoli P, Mucci A, Schenetti L, Weber RWS (2005) Laetiporic acids, a family of non-carotenoid polyene pigments from fruit-bodies and liquid cultures of Laetiporus sulphureus (Polyporales, Fungi). Phytochemistry 66:817–823 Gill M (1999) Pigments of fungi (Macromycetes). Nat Prod Rep 16:301–317 Greenewich JP (1997) Collect fungi on stamps, 2nd edn. Stanley Gibbons, St. Heller. 96 p. ISBN10: 0852592930, ISBN-13: 978-0852592939 (Stamp Catalogue) Ing B (1976) Fungi on stamps. Bull Br Mycol Soc 10(1):32–37. https://doi.org/10.1016/S00071528(76)80020-X Jan V, Karel C (2011) Pigments of higher fungi: a review. Czech Journal of food. Science 29 (20: 87–102 Li C, Oberlies NH (2005) The most widely recognized mushroom: chemistry of the genus Amanita. Life Sci 78:532–538

432

A. Arya

Margit J, Bresinsky A (1999) Speciation and phylogenetic distances within Paxillus s. str. (Boletales). Plant Biol 1(6):701–705. https://doi.org/10.1111/j.1438-8677.1999.tb00283.x Molitoris HP, Kahl R, Kuthan J (1990) Fungi on stamps. In: Exhibition Contribution EH-4 to the International Mycological Congress, 28th August-3rd September, 1990. University of Regensburg Library (Zentralbibliothek), Regensburg. 48 p Moss MO (1992) A selection of microfungi depicted on postage stamps. Mycologist 6(2):68–71. https://doi.org/10.1016/S0269-915X(09)80452-7 Moss MO (1993) The Doris Rast fungal stamp collection. Mycologist 7(1):28. https://doi.org/10. 1016/S0269-915X(09)80623-X Moss MO (1996) Recent issues of stamps about fungi from Jersey and the Isle of man. Mycologist 10(3):111–112. https://doi.org/10.1016/S0269-915X(98)80005-0 Moss MO (1998) Gasteroid basidiomycetes on postage stamps. Mycologist 12(3):104–106. https:// doi.org/10.1016/S0269-915X(98)80005-0 Moss MO, Dunkley IP (1986) Fungi on stamps 1984-1985. Bull Br Mycol Soc 20(1):63–68. https:// doi.org/10.1016/S0007-1528(86)80020-7 Moss MO, Pegler DN (2003) Recent stamp issues of fungi from New Zealand. Mycologist 17(4): 176–178. https://doi.org/10.1017/S0269915X04004094 Pegler DN, Leessee T, Spooner BM (1995) British Puffballs, Earthstars and Stinkhorns. Royal Botanic Gardens, Kew, pp 108–109 Roland JF, Chmielewicz ZF, Weiner BA, Gross AM et al (1960) Calvacin: a new anti-tumor agent. Science 132:1897 Sontag B, Rüth M, Spitteler P, Arnold N, Steglich W, Reichert M, Bringmann G (2006) Chromogenic meroterpenoids from the mushroom Russula ochroleuca and R. viscida. Eur J Org Chem 2006:1023–1033 Walton K, Coombs MM, Walker R, Ioannides C (2001) The metabolism and bioactivation of agaritine and of other mushroom hydrazines by whole mushroom homogenate and by mushroom tyrosinase. Toxicology 161:165–177

Part II

Biology and Occurrence of Mushrooms

Chapter 15

Citizen for Mushrooms N. S. K. Harsh

Abstract This is a narration of beautiful Asco and Basidiomycetous macro-fungi, by an expert who studied in Kumaun University, Nainital and later joined Forest Research Institute as a scientist. His unique experiences about these fungi will enhance your understanding about mushrooms and will motivate young students to undertake researches on applications and biology of these little known organisms. He worked extensively on wood-decaying fungi of Kumaun Himalaya and has contributed a lot in the field. The first mushroom he identified in the childhood using the manual and after following morphological and microscopic characters was Schizophyllum commune Fr. One of the special characters mentioned in the Fergus’ manual about this mushroom was that its gills curl when it was dry and return to normal when moist. For a young botanist observing this phenomenon under a microscope was very exciting and later helped him to made a huge impact on him and he decided to study these organisms in detail and thus he become a well-known mycologist. Various mushrooms and their unique occurrence in nature can be well understood by his lucid narration. Beautiful pictures clicked by him and his students are included in the chapter, which will give you a pleasant surprise and some interesting aspects. Keywords Mushrooms · Citizens · Fungal foray · Morels · Medicinal uses

Currently working as International Forest Disease (Pathology) Specialist in Asian Development Bank funded Improved Sanitary and Phytosanitary (SPS) Handling in Greater Mekong Subregion (GMS) Trade Project at Vientiane, Laos PDR. N. S. K. Harsh (*) Forest Research Institute, Dehradun, Uttarakhand, India © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_15

435

436

15.1

N. S. K. Harsh

Introduction: Prelude

It was during a candid conversation with Padmashri Shri Anup Shah, a renowned photographer, that I stumbled upon the idea of writing about my tryst with fungi, and particularly what are commonly called as ‘mushrooms’. For the past four decades, I have been studying mycology and forest pathology. The journey has been quite enriching and I am fortunate to have made my contribution in this field in the form of 200 research papers and 7 books. But this isn’t a research paper for a group of mycologists. It is just a collection of my interesting (and somewhat hilarious) experiences that I encountered while studying about mushrooms. I would like to thank Shri Anup Shah for giving me this idea. I also want to thank the editors of the book (Drs. Arya and Katerina Rusevska) who encouraged me to write such an article. Lastly, I would like to thank my lovely wife and children for tolerating my obsession with fungi for all these years. To all the learned mycologists and scholars of fungi, here are my apologies in advance if you don’t like informal yet fun take on mushrooms.

15.2

A Burn in the Foot: First Experience with a Medicinal Mushroom

I remember getting a severe burn on my foot from boiling water when I was just 9 years old. It was way back in 1966 and we used to live in the small town of Almora (Uttarakhand) where medical facilities were scarce in those days. My father went to collect a mushroom from a nearby chir pine (Pinus roxburghii) tree and later applied its powder on the burn. The injury healed within a week. The mushroom was called ‘phuskitumri’ (फुस्कितुमड़ी) (etymology bloated flask shape) and it emitted brown powdery cloud from a hole at the top. I became aware of medicinal properties of mushroom at a very young age, thanks to my father’s traditional knowledge. Later, when I started working with Fungi, I identified it as Astraeus hygrometricus (Pers.) Morgan, a Gasteromycete fungus and the brown powdery cloud as its spores (Fig. 15.1). I also came to know that the same mushrooms are being used by people of Gond tribe in Madhya Pradesh in central India for burns (Harsh et al. 1999). They are even sold as edible mushroom in tribal markets during rainy season (Fig. 15.1b) (Harsh et al. 1993a).

15

Citizen for Mushrooms

437

Fig. 15.1 (a) Astraeus hygrometricus in field and (b) A. hygrometricus being sold in local market. (Photo: Rajesh Kumar a)

15.3

Taste of a Wild Mushroom: First Experience with an Edible Mushroom

It was during one rainy day in August 1969 that my father got us some off white colored wild mushrooms. He had collected it from a pasture ground in Pithoragarh (Uttarakhand). He cooked it for dinner. My first stint with edible mushrooms was amazing and I remember loving the dish. Those were the days when cultivated mushrooms hadn’t arrived in the market in India. My father told me that it was his mother who made him acquainted with this species of edible mushroom. That day, he shared an important scientific fact with me—all wild mushrooms are not edible and some are poisonous too. I have collected the same mushroom from a termite mound, from weekly tribal markets of Mandla in Madhya Pradesh (Harsh et al. 1993a) and from my kitchen garden in FRI Campus Dehradun—identified as Termitomyces microcarpus (Berk. & Broome) R. Heim (Fig. 15.2).

15.4

Joy of Identifying First Mushroom

I joined as a PhD scholar at Botany Department, D. S. B. College, Kumaun University, Nainital in October 1978 and started working on wood-decaying fungi of Kumaun Himalaya. The first collection of wood-decaying fungi from Nainital was brought to the laboratory and I started its identification using a classical manual by Charles L. Fergus (1960) “Illustrated genera of Wood Decaying Fungi”. The first mushroom (fungus) I identified using the manual and after following morphological and microscopic characters was Schizophyllum commune Fr. (Fig. 15.3). One of the

438

N. S. K. Harsh

Fig. 15.2 Termitomyces microcarpus in field

Fig. 15.3 Schizophyllum commune being sold in Shillong market. (Photo by N.S. Bisht)

special characters mentioned in the Fergus’ manual about this mushroom was its gills which curl when it was dry and return to normal when moist. For a novice, observing this phenomenon under a microscope was very exciting. It made a huge impact on me and that was the day I decided on becoming a mycologist.

15.5

Fungal Taxonomist Par Excellence

In April 1979, I, along with my friend (Dr. N. S. Bisht, now in the description wherever friend is mentioned, I mean him) went to the Forest Research Institute, Dehradun for seeking assistance in the identification of wood-decaying fungi that we

15

Citizen for Mushrooms

439

Fig. 15.4 Trametes versicolor. (Photo by Rajesh Kumar)

had collected in past 6 months. When we reached the premises, we were advised by the Head of the Forest Pathology Division, Dr. P. S. Rehill to meet Mr. Balwant Singh, who was a Technical Assistant then. He taught us the techniques and basics of studying wood-decaying fungi. We were in awe with his confidence, ease, and expertise in the way he identified the fungi from our collection. We had thought that we had about 50 different fungi with us but we later learnt through Mr. Balwant Singh that some of them were morphological variants of the same species. There were as many as 15 Trametes versicolor (L.) Lloyd in our collection (Fig. 15.4).

15.6

First Sight of Morels (Gucchi, गुच्छी Mushroom)

In the spring of 1979, my friend and I were on a collection spree of mushrooms in the Government House area in Nainital. Among other mushrooms, we collected some morels and returned to our lab in Botany Department, D. S. B. College. We showed them to our guide Professor B. S. Mehrotra, a renowned mycologist, who was then the Head of the Botany Department. When he saw the morels, he literally jumped with the joy. Perhaps, it was the first time he saw them live. We gave him all the morels which he happily used for cooking. It was also my first encounter with Morchella esculenta (L.) Pers.: Fr. (Fig. 15.5). I then went on to report about some Morchella spp. from Kumaun Himalaya (Harsh et al. 1983).

440

N. S. K. Harsh

Fig. 15.5 Morchella esculenta and a girl having garland of morels. (Photo by Ashwani Tapwal)

15.7

‘Chicken’ of the Woods

We collected a big yellowish orange mushroom identified as Laetiporus sulphureus (Bull.: Fr.) Murr. in July 1979 from a locality in Garam Pani in Nainital district. We took it for photography to a photo studio in Nainital since we did not have the luxury of a camera in those days. The photographer, being a vegetarian, warned us not to bring it to the studio for he mistook it for chicken. We had a hard time convincing him that it was mushroom and not chicken. Then, me and my friends, decided to cook it in the hostel. It came out delicious as it somewhat felt like chicken in taste and texture. Our fellow research scholars who were living in other rooms came to know that we were having wild mushrooms for dinner. But they refused to join us since they were not very sure if it was edible. I jokingly asked them to come to our room to check on us the next morning to see if we were ‘alive’. Next day, they knocked on our door early morning. Upon finding us fit and fine, they straight went to look up for the mushroom dish that we had last night. They grabbed the utensil and finished off the remaining dish in no time. In 2003, I found this mushroom fruiting in a tree of Adenanthera microsperma at Forest Research Institute campus at Dehradun, (where I served as a Scientist). I started collecting it every year from the tree so as to satisfy my culinary interests. I also shared information about this tree with my students at Forest Research Institute University. But ever since I told them, I haven’t been able to collect any mushrooms since they vanish before I reach the tree. Guess I should have kept it a secret! (Fig. 15.6).

15

Citizen for Mushrooms

441

Fig. 15.6 Laetiporus sulphureus—Chicken of the woods

15.8

‘Ghost’ on a Tree

It was during my PhD in Nainital when a citizen came to meet Prof. B. S. Mehrotra with an eerie story. He told him that many people had spotted a strange light coming out of a Horse Chestnut (Aesculus indica) tree near Government House. The locals suspected the involvement of a ghost. Prof. Mehrotra, being my PhD guide, called me and my friend who was also pursuing PhD under him. He asked us to investigate the ‘paranormal activity’. He told us to look for mycelium and rhizomorphs (rootlike structures) at the base of the tree and under the bark. We went there and found white mycelium and thick black rhizomorphs running on the surface as well as under the dead bark of the tree. We brought samples to the laboratory. Prof. Mehrotra then told us that the samples were the rhizomorphs of Armillaria mellea (Vahl.) Quel., ‘honey mushroom’ (Fig. 15.7).These mushrooms cause ‘shoe string’ root rot in the trees which emit bioluminescence (glow) in the night due to the presence of luciferin, luciferase enzyme and oxygen. Voila, the mystery of the ‘ghost’ was finally busted!

15.9

Largest and Heaviest Mushroom

In July 1979, while traveling from Haldwani to Almora in a public bus with my friend, I noticed a large fruit body of a fungus attached to a Myrica nagi (kafal काफ़ल) tree. It was located on a hill near a place called Beerbhatti in Nainital district. My friend somehow arranged his uncle’s official Jeep from Haldwani and we went to the spot. We climbed up the hill to have a look at the tree. With the help of our driver, we managed to detach the large fruit body from the tree. We had a lot of

442

N. S. K. Harsh

Fig. 15.7 Armillaria mellea and its rhizomorphs. (Photo source sultimate-mushroom.com edible58.armillaria mellea.html)

difficulty bringing it down to the jeep since it weighed roughly around 40 kg. We then headed to Bhowali and got down from the jeep. From there, we loaded the fruit body in a public bus to Nainital. The conductor wasn’t very happy with the 40 kg luggage we were carrying. We had to buy another Rs 12 ticket for it so as to take it to Nainital. When we reached the Bus Stand [called Dat (डाट) locally], we had to hire a coolie to take it to the Botany Department, D. S. B. College since it is situated on a steep hill. The coolie had to carry it on his back held with ropes. He charged Rs 40 which was a huge amount for us in those days. The large fruit body of the fungus was identified as Inonotus pachyphloeus (Pat.) Wagner & Fisch. It is still kept at the Botany Department. I always thought it was the heaviest and largest fruit body of any mushroom until my student Dr. Manoj Kumar collected a fruit body of this fungus from Kalsi in Dehradun district and reported about it (Fig. 15.8) (Kumar et al. 2017). My record was thus broken after 38 years!

15.10

Mushroom at the Tree Line

In September 1979, I along with my friends, went on excursion-cum-collection trip to Pindari Glacier situated in Kumaun Himalaya. We collected many wood-decaying fungi enroute. A scarlet red fungus that we collected at 3100 m amsl was the last wood-decaying fungus at tree line identified as Hymenochaete mougeotii (Fr.) Cooke growing on dead branches of Rhododendron campanulatum (Fig. 15.9). This finding helped us to write and publish a paper on the altitudinal distribution of wood-decaying fungi in the Transactions of the British Mycological Society (now Mycological Research) (Harsh and Bisht 1982).

15

Citizen for Mushrooms

443

Fig. 15.8 Inonotus pachyphloeus. (Photo by Manoj Kumar)

15.11

A Hippie Came for Fly Agaric

In late 1970s and early 1980s, hippies used to visit the hills of Kumaun Himalaya. During my Ph. D. days, a local friend in Nainital, came looking for me. Knowing that I worked on mushrooms, he came with a hippie to meet me several times. But I could not meet them since I was always busy with work. One day, we finally managed to meet. After a brief introduction, the hippie inquired about Amanita muscaria (L.) Lam., the fly agaric mushroom occurrence in Nainital (Fig. 15.10). I told him that I had seen that mushroom growing in the forest around Government House. But I warned him that the mushroom was fatally poisonous. Months later, I met my friend again, I asked him if they were able to find A. muscaria. He told me that they could only collect a single fruit body. But when I asked why they needed it,

444

N. S. K. Harsh

Fig. 15.9 Hymenochaete mougeoti. (Source: https://www.houbareni.czoubakozovka_mougeotova)

Fig. 15.10 Amanita muscaria. (Photo by Ashwani Tapwal)

15

Citizen for Mushrooms

445

I was shocked with his reply. He told me that the hippie used to consume a small quantity of the mushroom (A. muscaria) and go into trance for hours. He was so addicted to it that he used to recycle his urine to give back the impact. I regretted to share location of the mushroom with them. I later learnt about the hallucinogenic effect of some mushrooms.

15.12

Decorative Pieces from Mushrooms

The same friend, who introduced me to the hippie, invited me to his house one day. When I went to his place, I noticed a table lamp that he had created from the fruit body of Fomes fomentarius (L.) Fr. He made it after removing the internal tissue and fitting a bulb holder. The fungus is found in Nainital on Betula alnoides trees (Fig. 15.11). In local markets of Nainital, one can always find the fruiting bodies of different fungi attached or glued to the drift wood / bamboo, silver or gold painted as well as ferns or dry leaves mingled and sold as decorative pieces. I commonly found fruit bodies of Hexagonia tenuis (Hook.) Fr. and Microporus xanthopus (Fr.) Kuntze in such pieces (Fig. 15.12).

Fig. 15.11 Fomes fomentarius

446

N. S. K. Harsh

Fig. 15.12 Hexagonia tenuis (by Kiran Bisht) and Microporus xanthopus

Fig. 15.13 Cantharellus cibarius. (Source: Hanekam, Saxifraga-Lucien Rommelaars)

15.13

Monkeys Too Like Mushrooms

During my collection trips in conifer forests in Almora district, I once witnessed monkeys picking up something from the grass and eating. On getting a closer look, I noticed Cantharellus cibarius Fr. growing among the grass which was being

15

Citizen for Mushrooms

447

devoured by them. This mushroom is deliciously edible and also forms ectomycorrhizae with conifers and oaks (Fig. 15.13).

15.14

Not Always Mushroom

Whenever I travel by road, it has always been my habit to look at the trees passing. Once while going back to Almora from Nainital in a public bus in 1979, I spotted a white object on a pine tree near Bhowali. I thought it was a fruiting body of a mushroom. While returning, I asked the driver to stop the bus at the same spot. I got down and went to look for the mushroom. To my utter disappointment, I found it was not a fruiting body but a porcelain object which was used to hold the telephone wire nailed to the tree. I walked back dejectedly to look for another bus to Nainital. After covering around 5 km, I got a wood-decaying fungus Pycnoporellus fulgens (Karst.) Murr. on a dead pine tree. It was reported for the first time from India (Bisht and Harsh 1982). I have realized that it has become my instinct to get attracted to mushrooms wherever I go. Even during leisure trips with my wife and daughters, whenever I spot mushrooms, I start giving out the name and the description of the species, much to their annoyance. Well, I can’t blame them for making fun of me. No wonder they have coined a nickname for me—‘Fungusiya’.

15.15

Forest Fire and Mushrooms

During my stint at Tropical Forest Research Institute, Jabalpur, I once went to Dantewara in Jagdalpur district (now in Chattisgarh state) in 1986. The Divisional Forest Officer of the area was my friend. He took me around in the Sal (Shorea robusta) forest area where a Forest Guard showed the area where fire had occurred. Then he shared a traditional knowledge that the local tribal people say that puttu (पुट्टू Astraeus hygrometricus) fruit more in the following rains after fire in the Sal forests. A. hygrometricus forms ectomycorrhizal association with the roots of S. robusta.

15.16

Mythology and Mushroom

During a study tour in the forests of Mandla district of Madhya Pradesh, I came across a termite mound covered with Termitomyces microcarpus mushroom (also mentioned above) (Fig. 15.14a). Some tribal laborers working there told me that they call it bhat pihri (भातपिहरी) and they eat it after cooking with onion and garlic. One of them said that they do not collect this mushroom from those termite mounds

448

N. S. K. Harsh

Fig. 15.14 (a, b) Termitomyces microcarpus on termite mound and termite mound being worshipped

which they worshipped during Nagpanchami (नागपंचमी), a festival in which snakes (Cobra) are offered milk in India (Fig. 15.14b). I could interpret it as a conservation approach of the tribal for this mushroom.

15.17

Mushrooms Sold in Tribal Markets

During the 1990s, I came to know that wild mushrooms are sold in the tribal markets of Mandla district of Madhya Pradesh. I, along with my students, went there for survey and collected information from five tribal markets. Mostly Termitomyces spp. in estimated quantity of nearly 25,000 kg, were being sold there during rainy season (Fig.15.15a, b). The sale of wild mushrooms provided sustenance to them during lean period when other minor forest produce were not available in the forests. The study led to reporting of ethnomycology in India (Harsh et al. 1993a, b, 1996, 1999; Harsh 2014).

15.18

Innovative Mushroom Drier

I also conducted some ethnomycological studies in tribal areas of Madhya Pradesh (now some parts are in Chattisgarh) during 1990s. We found out that the tribal ladies used to dry the edible mushrooms (mostly Termitomyces spp.) in their homes on an innovative drier by keeping them over a screen made up with bamboo sticks and wire. They hung it about half a meter over the chulha (चूल्हा) (Fig. 15.16). They used to consume the dried mushrooms during off season. For preservation, they dipped

15

Citizen for Mushrooms

449

Fig. 15.15 (a, b) Termitomyces being sold in the market

these mushrooms in turmeric powder solution in water before spreading them on the drier (Harsh et al. 1999).

15.19

Medicinal Mushroom

During our ethnomycological studies, I came across a mushroom identified as Ganoderma lucidum (Leyss) Karst. (Fig. 15.17a) which was being used in tribal medicine and I documented it (Harsh and Rai 1993). Later, I came to realize that it is the medicinal mushroom that has been in use in Chinese Traditional Medicine for

450

N. S. K. Harsh

Fig. 15.16 Innovative mushroom drier. (Source: Harsh et al. 1999)

Fig. 15.17 (a, b) Ganoderma lucidum and its cultivation

long and an economical protocol could be successfully developed for its cultivation (Fig. 15.17b) (Singh et al. 2014).

15

Citizen for Mushrooms

15.20

451

Accidental Discovery

There was a corner outside our Mycology lab of Botany Department in D.S.B. College where the lab attendant used to throw tea leaves after making tea. One day, while drinking tea with friends, I spotted a mushroom growing on that waste and the idea of using used/ waste tea leaves for the culturing of wood-decaying basidiomycetous fungi struck to me. The same was tried with success and published (Bisht and Harsh 1981). Later, I found that fungi could survive in the used tea leaves substrate for more than 5 years though the substrate had become hardened.

15.21

Fairy Ring

I had read about ‘fairy rings’ of mushrooms during my graduation days and was fascinated about their existence. One fine morning during the rainy season of 2007, I saw two ‘fairy rings’ of mushrooms growing in the lawn right outside my official chamber at Forest Research Institute, Dehradun (Fig. 15.18). The joy and excitement on my face was so visible to everyone that my students perhaps thought that I had gone berserk! I identified the mushroom as Marasmius oreades (Bolton) Fr. (Fig. 15.18). Miles to go before I sleep. . . .

15.22

Embarrassing Moments with Mushroom

While teaching fungal taxonomy to M. Sc. Forestry students in 2016, I took them on a field excursion visit in FRI campus to apprise them with the different forms of macro-fungi in field. Out of all mushrooms and wood-decaying fungi that were

Fig. 15.18 Fairy ring and Marasmius oreades

452

N. S. K. Harsh

Fig. 15.19 Phallus indusiatus. (Photo by Rajesh Kumar)

collected, one special mushroom was Phallus indusiatus Vent., the stink horns (Fig. 15.19). I warned the students not to touch it with bare hands because of its foul smell. I asked my students to gather information about the use of fungi they had collected and prepare a presentation based on it. A female student was to collect information about Phallus indusiatus. In the subsequent classes, the students described about the medicinal and edible uses of the fungi they had collected. But the girl who was to collect information about P. indusiatus avoided sharing any information about it on the pretext that she found it of no use. However, I was not convinced with her response and I decided to search about it on Google. I didn’t realize that the computer was attached to an LCD projector. When the results showed up on the screen, it was a big embarrassment for me and other female students while some boys chuckled. The result showed that the (foul) smell of P. indusiatus induced spontaneous orgasms in some women (www.ourbreathingplanet.com “Phallus indusiatus—Astounding mushroom”). I was so embarrassed that I immediately closed the computer. I later called the girl and apologized.

15

Citizen for Mushrooms

15.23

453

Mushroom in an Airport Duty Free Shop?

Isn’t it unusual to see a mushroom fruit body in a duty free shop at an International airport? Well, I saw one at the Siem Reap International Airport, when I had gone for a project in Cambodia. The fruit body was displayed along with wines and chocolates. Some packaged pieces were put up for sale (US$ 63.50 for 500 g) (Fig. 15.20). I could identify it as Phellinus linteus (Berk. & Curt.) Teng. The salesperson told me that it was sold for cancer treatment.

15.24

Discredited

An entomopathogenic fungus was brought by one senior forest officer from Mansarovar where it was being sold. I identified it as Ophiocordyceps (Cordyceps) sinensis G. H. Sung, J. M. Sung, Hywel-Jones & Spatafora, the caterpillar-fungus (कीड़ाजड़ी) which is now collected in the alpine meadows of Uttarakhand by locals when snow starts melting. It fetches a good price of about Rs 12 lakh per kg (Fig. 15.21a, b). My only regret is that when the account about the fungus was published by the officer, the credit for identification was given to someone else.

Fig. 15.20 Phellinus linteus at air port

454

N. S. K. Harsh

Fig. 15.21 (a, b) Ophiocordyceps sinensis. (Photos by A.N. Shukla)

15.25

Conclusion

I wish the description here may motivate some young enthusiasts to study fungi, their taxonomy, myths, beauty and help them discover new compounds and uses. Fungal taxonomists are becoming rarer day-by-day. The hope lies in citizen scientists and explorers. I wish to finish this paper on a lighter note. During my talks, the one question that I often encounter is about how to differentiate between edible and poisonous mushrooms. I caution the audience not to try wild mushrooms for consumption without confirming their identity from those who know about it. But if they still want to try them for dinner, they must inform their neighbors beforehand. If they wake up the next morning, they can testify the edibility of the mushroom species. If they don’t, then the neighbors can establish that the mushrooms were poisonous. Happy mushrooming folks! Acknowledgments I gratefully acknowledge the citizens who familiarized me with the mushrooms and their uses. I offer my heartfelt gratitude to Padmashri Shri Anup Sah, the ace Photoartist of our country who gave the idea to document my encounters with the mushrooms. I thank Dr. Ashwani Tapwal, Scientist at Himalayan Forest Research institute, Simla and Shri Rajesh Kumar, Scientist at Rain Forest Research Institute, Jorhat for kindly sharing photos of some mushrooms from their collection. I wish to express gratitude to my wife and daughters for critically going through this paper and giving useful suggestions. I owe my thanks to Mr. Sreeraj T. K. for editing and improving the flow of the text.

References Bisht NS, Harsh NSK (1981) Use of waste tea leaves as an aid to culture of some wood-rotting fungi. Int Biodeterior Bull 17:19–20 Bisht NS, Harsh NSK (1982) Two new records of wood-decaying fungi from India. Curr Sci 51: 782–785 Fergus CL (1960) Illustrated genera of wood decaying fungi. Burgess Pub, Sheffield, p 132

15

Citizen for Mushrooms

455

Harsh NSK (2014) Fungi from forests for food, medicine and livelihood: conservation issues in India. Fungal Conserv 4:30–34 Harsh NSK, Bisht NS (1982) Altitudinal distribution of some common wood-decaying fungi in Kumaun, India. Trans Br Mycol Soc 79:182–186 Harsh NSK, Rai BK (1993) Use of Ganoderma lucidum in folk medicine. Indian J Trop Biodivers 1:324 Harsh NSK, Joshi MC, Bisht NS, Mehra HS (1983) Studies on the wild edible fungi of Kumaun Hills – I. Class Ascomycetes. Himalayan Res Dev 2:52–56 Harsh NSK, Rai BK, Ayachi SS (1993a) Forest fungi and tribal economy – a case study in Baiga tribe of Madhya Pradesh. J Trop For 9:270–276 Harsh NSK, Tiwari CK, Jamaluddin (1993b) Market potential of wild edible fungi in Madhya Pradesh. Indian J Trop Biodivers 1:93–98 Harsh NSK, Tiwari CK, Rai BK (1996) Forest fungi in the aid of tribal women of Madhya Pradesh. Sustain For 1:10–15 Harsh NSK, Rai BK, Soni VK (1999) Some ethnomycological studies from Madhya Pradesh, India. In: Singh J, Aneja KR (eds) From ethnomycological to fungal biotechnology: exploiting fungi from natural resources for novel products. Plenum Publishing, New York, pp 19–32 Kumar M, Mehra PS, Harsh NSK, Pandey A, Pandey VV (2017) Largest fungal fruit body from India. J Threat Taxa 9:11085–11086 Singh S, Harsh NSK, Gupta PK (2014) A novel method of economical cultivation of medicinally important mushroom, Ganoderma lucidum. Int J Pharm Sci Res 5:2033–2037

Chapter 16

Mushroom Biotechnology: Developing Cultivation Protocol for Four Different Mushrooms and Accessing Their Potential in Pollution Management Ajinkya G. Deshpande and Arun Arya

Abstract The proteinaceous food value of mushrooms is well recognized and it may offer effective and lasting solutions to the problems of child malnutrition and protein supplement in pregnant ladies. Advancements have been made toward understanding mushroom biology, cultivation aspects, using a variety of agro lingo-cellulosic waste, breeding high yielding varieties, medicinal implications and uses of these unique fruiting bodies in bioremediation and waste water management. Mushrooms contain antioxidants and anticancerous chemicals in significant quantities. Use of Chaga mushroom in corona virus disease control has been suggested recently in Russia. After first cultivation of rat ear fungus (Auricularia auricula) in 600 A.D., now more than 20 species are commercially cultivated and protocols to culture about 300 mushrooms is now known. New cultivation methods are developed and discussed for Shiitake mushroom (Lentinula edodes), Lenzites sterioides, Reishi mushroom (Ganoderma lucidum) and Turkey tail (Trametes versicolor). The biological efficiency was 45% for Lentinus and 56% for Reishi in experiments conducted at Botany Department of the M.S. University of Baroda. An increase in yield was recorded when Lentinus mycelium was exposed to blue light and 5–10 ppm Veradix (IBA). The cultivation of medicinal mushroom is profitable as well fascinating since it requires a range of specific environmental conditions such as humidity, temperature, etc. The efforts have been made to eliminate the use of polythene bags by using earthen pots in case of oyster mushroom. A range of substrates have been used to increase the yield and manage agro-waste produced in large quantity in different countries. Cellulose and hemicellulose served as better sources of mushroom production, whereas, in lignin containing substrates the growth was slower. Apart from using substrates, dilute acid soaking of the leaves produced better growth of oyster. Light and temperature levels are also critical for

A. G. Deshpande (*) UK Centre for Ecology and Hydrology, Bush Estate Penicuik, Edinburgh, UK A. Arya Department of Botany, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, Gujarat, India © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_16

457

458

A. G. Deshpande and A. Arya

example Lentinus cultivation required 15–20
C temp, while it was 20–25
C in certain other species. For G. lucidum the temperature required was 30
C. Exposure to light acts as a shock to switch over the mycelium from vegetative to reproductive stage. The efforts are being made to increase number of fruiting bodies by the use of Ni and Sn salts. This chapter deals with spawn production and the advances in cultivation of four medicinal mushrooms made in different parts of the world. Mushrooms breeding and strain improvement has resulted into many new and high yielding strains. Production of oyster mushroom is done in almost all parts of the country, extensive fungal surveys are needed for developing better conservation strategies. Keywords Biotechnology · Mushroom biology · Food · Medicinal uses · Cultivation · Remediation · Heavy metals

16.1

Introduction

Fungi are marvelous and unique creation of nature to sustain it for long. Mushrooms are highly evolved fungi with fruiting bodies. These can be described as, “macrofungi with a distinctive fruiting body, large enough to be seen with naked eye and to be picked by hand” (Chang and Miles 1992). Mushrooms have been recognized by Food and Agriculture Organization as Food, contributing to ameliorate the protein malnutrition in countries which are largely cereal dependent. It is said that during Roman times one of the Caesars described mushroom as, “The foods of the Gods,” and promptly reserved them for himself, his ministers and soldiers. Breeding of edible mushrooms with the latest research methods and technologies will undoubtedly act as a boost for breeders to enhance upon the quality traits of the natural trash burners. In many developing countries of Africa and Asia, large population still lives in tribal or rural areas. In Africa, more than seven in ten poor people live in rural regions and are dependent on small-scale agriculture (IFAD 2001). In the past decade, over 350 million people have been lifted out of poverty, but global poverty remains a massive and predominantly rural phenomenon, with 70% of the developing world’s 1.4 billion extremely poor people living in rural areas. The IFAD report (International Fund for Agricultural Development (IFAD) 2011) also describes challenges, including the high poverty rate in Sub-Saharan Africa and the lack of progress in South Asia. The report underscores threats to rural development posed by climate change, volatile food prices, and natural resource constraints (International Fund for Agricultural Development (IFAD) 2011). If the natural resources base is not managed for the long term, and is exploited for short-term gains, it will never help in economic development on the scale demanded to relieve poverty over past 50 years. The ecosystems have managed to supply food, fuel fodder and fiber and other ecosystem services across the world. The use of fruits, vegetables and mushrooms can aid in providing balanced diet to millions of under-nourished people. Mushrooms were earlier classified as plants, but since they do not use

16

Mushroom Biotechnology: Developing Cultivation Protocol for Four Different. . .

459

light energy and no photosynthesis occurs, they were reclassified as Fungi. However, they can produce several groups of enzyme complexes, which can convert the huge lignocellulosic waste materials into a wide diversity of products. These products have multibeneficial effects for human welfare (e.g., as food, tonic, medicine, feed and fertilizers for plant growth, and at the same time help in protecting and regenerating the environment). Total 148,000 species of fungi have been named to date, of an estimated 2.2–3.8 million. Fungi that might prove useful for bioenergy are therefore more likely to be discovered by broad, high throughput genomic screening programs. Fungi have great potential within the bioenergy sector. A mere 285 of 148,000 described fungal species are assessed on the Red List, equating to 0.2% (Antonelli et al. 2020). Moreover, cultivation and development of edible and medicinal mushrooms can positively generate equitable economic growth that has already had an impact at national and regional levels in this century. Along with ecofriendly agriculture there is a need for sustainable research and development of mushroom production (mushrooms themselves) and mushroom products (mushroom derivatives), which can become a “nongreen revolution” (Chang 1999, 2007). In ancient times, mushrooms have been thought to have special powers. Their use in traditional ancient therapies dates back at least to the Neolithic age (Gargano et al. 2017). The Pharaohs of Egypt prized mushroom as a delicacy. The Egyptians thought mushrooms gave immortality to Pharaohs. It is mentioned in Ramayana that, when Lakshman was injured, Hanuman brought whole Kishkindha Mountain, he was told to search the medicine probably in luminous fungi/mushroom. Vedas tell us about “Soma drink” which may be Amanita or Psilocybe like hallucinogenic mushroom. Contemporary research has validated and documented much of the ancient knowledge on medicinal mushrooms (MM). In Colombia by the year 2004 about 27 different species of Psilocybe type mushrooms were reported (Martinez 2020). In Manizales, Colombia, Psilocybe zapotecorum had been collected. Research on the subject has advanced further and the latest discoveries talk about mushroom cults that were held in countries such as Siberia, Greece, Japan and the exotic islands of Hawaii. The Amanita muscaria cult traced and detected by Robert Gordon Wasson on in the Ojibway tribe in North America is remarkable (Wasson 1980). I had probed the Muisca mushroom cult by a complete study done by with the aid of Carl Ruck and Clark Heinrich. New evidence and study of pieces of the Museo del Oro in Bogota suggest that the mushroom cults were not only practiced by the Muiscas, but also by the Tayronas and the Tolimas. My idea of an Amanita Mushroom Cult in the Muiscas would not have been developed without the encouragement of this wonderful human being, researcher, and tomato lover. The tribes in question which I suggest practiced a mushroom cult are the Tayronas, the Muiscas and the Panches or Tolimas. I will call the last ones Tolimas for the sake of confusion. There is evidence from seeing the pieces of goldsmithing belonging to this particular tribes in the Museo del Oro, being the Tolima ones being the most powerful and less least stylized of all, while the Tayronas show the most artistic progress to the top (Martinez 2020). Ganoderma strains used in oriental folk medicine refer to Reishi (Moncalvo 2000) (Fig. 16.8a). Mushrooms are rich in protein and are classified among

460

A. G. Deshpande and A. Arya

vegetables. Out of 14,000 known mushrooms, 3000 are edible. About 100 mushrooms are commercially cultivated, and only ten species are used at industrial scale. Truffles (Tuber of Ascomycota) are hypogean, most delicious used in gourmet delicacies and are one of the costliest natural products. Being mycorrhizal they grow in close proximity of specific tree roots and are rarely cultivated artificially. More than 700 mushrooms are used in traditional system as medicine. Morchella or Guchhi is India’s most delicious mushroom. Medicinal mushrooms (MM) are comparable to “medicinal plants” and can be defined as macroscopic fungi, used for alleviation of diseases or in balancing a healthy diet. According to definition of herbal drugs dried fruit bodies, mycelia or spores are considered mushroom or fungal drugs (Gargano et al. 2017). MM are used in a variety of ways: (a) (b) (c) (d) (e)

As dietary food Dietary supplement Mushroom pharmaceuticals Natural biocontrol agents for plants Cosmeceuticals

Scientific names of certain mushrooms and their uses are listed in Table 16.1 and Figs. 16.1 and 16.2.

16.2

Wild Edible Mushrooms

In nature besides providing food for man and other animals these eukaryotic microbes play an important role in recycling the carbon, nitrogen and other elements through enzymatic breakdown of lignocellulosic plant waste and animal dung, which serve as substrate for these saprophytic fungi (Chang 1993). Fungi digest the complex substances and utilize these through absorptive nutrition for their growth. Owing to this function of mushrooms, Chang and Miles (1992) advocated the use of mushroom biotechnology to utilize agro-wastes like cereal straw, coffee, and coconut waste. Nisha (2011) made use of waste paper and cotton from offices and labs to produce Pleurotus. Further the spent mass can be utilized to produce cattle/poultry feed or utilized as compost to enhance crop yield. Mushrooms can be present in three ecological habitats (a) saprobic (b) ectomycorrhizal or (c) parasitic as in case of Ganoderma and Heterobasidion. The fruit bodies may be produced above or below ground (hypogean). Archeological record reveals that edible species were associated with people living 13,000 years ago in Chile, but it was in China where consumption of wild fungi was first reliably noted (Boa 2004) (Fig. 16.3). Saini et al. (2018) has reported 126 taxa of Agaricus from India. The fruiting body of Agaricus consists of 85–87% water. It is rich in protein (40–45%), 3–4% carbohydrates, 6–8% dietary fiber, 3–4% lipids, and vitamins. Specially vitamin B1, B2, niacin, ergosterol, and linoleic acid (70–80%), aromatic compound and soluble sugars, arabinose, glucose, and trehalose (Bellini et al. 2003). Potassium is the main mineral in A. brasiliensis (Oliveira et al. 2010). Large amount of alanine

16

Mushroom Biotechnology: Developing Cultivation Protocol for Four Different. . .

461

Table 16.1 Common mushrooms, their scientific names, occurrence/association, and uses S. no. A. 1

Common name Ascomycota Keedajadi/ Caterpillar fungus

Scientific name

Association

Remarks/uses

Ophiocordyceps sinensis (Berk.) Sacc. Cordyceps militaris (l.) Fr. Morchella esculenta (L.)Pers.:Fr. Tuber magnatum Pico

E

Medicinal

M

Edible- delicious

M

Most delicious

M

Edible

S

Edible, High protein 40% of world production

M

Edible only when young

S

Edible

S

Medicinal use

S

Medicinal use

S

Edible

S

Edible 25% of world production

S

Edible

2.

Morels

3.

Truffles

B. 4.

Basidiomycota Boletus Boletus edulis Bull. Button Agaricus mushroom bisporus( JE Lange) Imbach A. brunnescens A. bitorquis (Quél.) Sacc. A. campestris L. Giant Puff Calvatia ball gigantean (Batsch) Lloyd Jew’s ear Auricularia mushroom auricula-judae (Bull.) Quél. Lenzites Lenzites sterioides sterioides(Fr.) Ryv Lions mane Hericium erinaceus (Bull.) Purs. Maitake Grifola mushroom frondosa9 (Dicks) Grey Oyster Pleurotus sajor mushroom caju, (Fr.)Fr. P. florida, (Fr.) P. Kumm. P. ostreatus (Jacq.) P. Kumm. Paddy straw Volvariella volvacea mushroom (Bull.) Singer

5.

6.

7.

6.

7.

8.

9.

10.

(continued)

462

A. G. Deshpande and A. Arya

Table 16.1 (continued) S. no. 11.

12.

13.

14. 15.

16.

Common name Reishi, Ling-zhi

Scientific name G. lucidum (Curtis) P. Karst.

Association S/P

Shaggy Mane or Lawyer's wig Shiitake

Coprinus comatus (O.F. Müll.) Pers.

S

Lentinula edodes (Berk.) Pegler

S

Split gill fungi St George’s mushroom

Schizophyllum commune Fr. Tricholoma gambosum (Fr.) Donk Trametes versicolor (L.) Lloyd

S

Turkey tail

M

S

Remarks/uses Medicinal use, cancer curing properties; Mycoremidiation-used as biosorbent Edible only when young: The coprine—may cause nausea in combination with alcohol. Edible and medicinal—can cure cancer and HIV; 10% of world production Edible; basidiospores may cause allergy Edible

Medicinal; Deterioration of woodwhite-rot fungi

Note: E entomopathogenic, M ectomycorrhizal, P parasitic, S saprobic

Fig. 16.1 Hallucinogenic mushroom Psilocybe. (Source: S.N. Tyagi, Meerut, India)

(11.9%) and tyrosine (2.4%) was present in protein (Kawagishi et al. 1989). Supplementing the substrate with controlled liberation of urea and Mn (II)Cl shortens the crop period from 35 to 28 days for Pleurotus spp. and also increases mushroom productivity (Lelley and Janben 1993). Mushrooms have low energy levels hence beneficial for weight reduction, low purine helps to prevent gout and

16

Mushroom Biotechnology: Developing Cultivation Protocol for Four Different. . .

463

Fig. 16.2 Uses of Pleurotus or Oyster mushroom

Fig. 16.3 Medicinal uses of Ganoderma

rheumatism, low sodium which benefits persons having high blood pressure. Moreover they have a unique flavor and few are delicious. Mushrooms are medicinal foods with eight important amino acids and have higher nutritional values than fish or beef (Chang and Bushnell 1996; Fekadu 2015) (Fig. 16.4).

464

A. G. Deshpande and A. Arya

Mushrooms Habitat

Ecto- mycorrhizal

With Roots Mycorrhizal Difficult to cultivate

Non- mycorrhizal

Under ground Soil Calvatia (saprobe)

Morchella Tricholoma Boletus Ramaria Russula Calvatia (Mycorrhizal)

On Earth Surface Insects Cordyceps Termitomyces

On Earth Surface Soil Lepiota Dictyophora Lepista Melanoleuca On Earth Dung Coprinus Agaricus Agrocybe Stropharia

Above Earth Straw Volvariella

Above Earth Wood Auricularia Pleurotus Lentinus Tremella Hericium Pholiota

Fig. 16.4 Habitat and examples of different mushrooms

Thick leafy vegetation, senescenced leaves and fallen woody material on the forest floor result in prolific growth of saprophytic fungi aided by substrate availability from microbial decomposition of organic matter. Fast growth of temperate tree species such as Pinus and Eucalyptus is possible due to the presence of ectomycorrhizae, which help the roots to access the nutrients immobilized within soil aggregates, otherwise inaccessible even to fine roots. Therefore a large number of ectomycorrhizal fungi and consequently mushrooms occur in temperate forests. Fungi help in seedling establishment. Collection have been made from Sweden, Munich (Germany) and North America. The species collected were Morchella spp. Cantharellus, Tricholoma spp. Boletus edulis and the collection for 1992 season had been 2 million kg at a value of $41.1 million (Kaul 2002). Total world production of mushrooms was 34 billion kg in 2013 (Royse et al. 2017). In India—Agaricus campestris, Cantharellus spp., Coprinus spp., Lantinus subnudus, Termitomyces spp., Tricholoma, Boletus spp. and Tuber spp. are some common mushrooms found in India. In Kashmir out of 175 species of agaricoid and clavarivid fungi 77 were mycorrhizal and were also found elsewhere in India. The gamut of Agaricoid species present in India has been negatively influenced by the replacement of natural forest by exotic trees like conifers, Eucalyptus, Casuarina in the hills of South India. Species of Morchella were collected from nature in Kashmir and Himachal Pradesh and sold in market. Survey conducted in Panchmahal,

16

Mushroom Biotechnology: Developing Cultivation Protocol for Four Different. . .

465

Narmada, Dahod and Vadodara districts showed the presence of Auricularia, Aurificaria, four species of Ganoderma, two species of Lenzites, 12 species of Phellinus and Schizophyllum commune from different forest trees in Gujarat.

16.2.1 Mushroom: The Magic Store of Health Benefits Total commercial mushroom production worldwide has increased more than 21 times in 35 years. From 350,000 tons in 1965 to 7.5 million tons in 2000 (Boa 2004). Edible, medicinal, and wild mushrooms are the three major components of the global mushroom industry. Combined, the mushroom industry was valued at approximately $63 billion in 2013. Cultivated, edible mushrooms are the leading component (54%) accounting for approximately $34 billion, while medicinal mushrooms make up 38% or $24 billion and wild mushroom account for $5 billion or 8% of the total (Royse et al. 2017). According to an old Chinese saying, “medicines and food have a common origin.” Mushroom products are used for food and medicinal purposes (Wasser 2002; Stamets 2000). The term mushroom nutraceuticals has been coined to embody both nutritional and medicinal features. Asian cultures have also used Reishi, rendered in jade, as a talisman worn around the neck. Sometimes, whole dried Reishi are placed in the home to ward off the evil. It may be used to prepare Herbal Meditation tea. The antler-shaped mushroom is the most rare and valuable form of Reishi, known in China for over 4000 years as Ling-Zhi, herbalist called Reishi the herb of spiritual potency and used it promote good health and longevity in Japan. HIV/Aids and antiretrieval drugs derived from mushrooms have been used in Africa. Bioactive compounds of Ganoderma and Lentinus are useful for HIV patients (Bisen et al. 2010). When Ganoderma capsules were given to HIV patients hemoglobin level increased from 0.5 to 1.1 mg. Reishi is used to treat liver disorders, hypertension, arthritis, and other ailments. Reishi Gano is a king of mushroom essence (G. lucidum) widely known as King of herbs. It is effective in: 1. 2. 3. 4. 5.

scanning diseases cleaning toxin regulating body functions recovery of health preserving youthfulness

Members of two Aphyllophorales were collected from the branches of Tamarindus indica and Alangium salvifolium, fungi Trametes gibbosa (Pers.) Fr. and T. lactinea (Berk.) Pat. were found respectively attached to these trees in the Ratanmahal wildlife sanctuary, in Panchmahal district of Gujarat (Arya et al. 2008). Used as MM the fruit bodies of T. gibbosa have the ability to confer a protective effect to blood vessels of rat in the carrageenan assay, suggesting their possible use in pathological disease conditions leading to endothelial damage (Czarnecki and Grzybek 1995). Polysaccharides extracted from the mycelial culture

466

A. G. Deshpande and A. Arya

of T. gibbosa, when administered intraperitoneally into white mice at a dosage of 300 mg/kg inhibited the growth of Sarcoma 180 and Ehrlich solid cancers by 80% and 90%, respectively (Ohtsuka et al. 1973). The petroleum ether and ethyl acetate extract of T. gibbosa were shown to be cytotoxic to human cervix epitheloid carcinoma cell lines (Hela) and human hepatoma cell lines (SMMC-7721) using the MTT-dye assay. The methanolic extract, however, showed weak activity when compared with the flavonoid quercetin (Ren et al. 2006), and was inhibitory (i.e., 0.1%), or a fruiting body with a well-formed pileus (CO2 < 0.1%) will be produced. Fresh air contains 0.03% CO2 and aim for reducing CO2 as close to fresh air as possible, is always desired for production of pileated mushrooms (Chen 1999; Stamets 2000). Humidity is provided by fine mist (3–4 times/day). (g) Harvesting of Fruit Bodies Time from primordia formation to sporophore harvesting, is around 25–30 days. Maturity of fruit body is indicated by the disappearance of the undifferentiated white growth at the edge of the fruiting body (Chen 2002). Cultivation is continued at reduced air humidity (85%) for additional 7–10 days to encourage further growth in pileus thickness and firmness. Harvesting is done by cutting the stalk and cultivation is continued under the optimal growth parameters for second and third flushes, but the subsequent flushes have lower yield, especially the third flush. When logs are left to stand after harvesting, fruiting takes place during the following year, but the yield is reduced to half so the logs used over 2 years are discarded (Chen 2002).

23.2.2 Artificial Cultivation or Synthetic Log/Sawdust/Polybag Technique To meet the gradually increasing demand of G. lucidum as a natural medicine, commercial cultivation of this mushroom has been introduced worldwide. Artificial cultivation of Ganoderma was attempted in 1937 (Perumal 2009). However, the first successful cultivation of Ganoderma was performed in 1969 with the help of a spore separation cultivation method by a Chinese technician in the Institute of Microbiology, Chinese Academy of Sciences, Beijing (Yu and Shen 2003). Different species of Ganoderma need different conditions for growth and cultivation (Mayzumi et al. 1997). (a) Strain Selection Strains of G. lucidum vary widely, and play important role in mushroom cultivation (Chen 2001). Particularly in fruiting temperature and mycelial maturation (early or late; shorter or longer production time). Substrate selectivity, growth rate (some fast strains may produce pre-mature fruiting), quality (shape, size, thickness, color, and aroma, etc.) and yield (high or low). Reishi strains differ in the size, texture, and ornamentation of the “mushroom caps.” Strains differ in the length of their spawn run period and in their tendency to fruit at different temperatures. Certain strains are preferred for indoor vs. outdoor cultivation. One may grow several strains to extend the fruiting season (Escribano et al. 2020).

23

Cultivation Technology of the Fungus Ganoderma lucidum (Curtis) P. Karst

603

(b) Isolation and Procurement of Axenic Culture To obtain the pure culture of Ganoderma lucidum, Potato Dextrose Agar (PDA) culture medium is commonly used. To raise a pure culture, a piece is taken from stipopileal region (connecting stipe and pileus) and dipped in 0.1% HgCl2 sol. for 20–30 s. for disinfection and placed on PDA Petri plates (Rawat 2018). These plates are incubated at 25  2  C until substantial mycelial growth is obtained. (c) Spawn Preparation There are mainly two types of spawn, solid spawn and liquid spawn. Many growers use solid spawn while some prefer liquid spawn. Solid spawn is based on the substrate used, such as grain spawn, sawdust-bran spawn, wood plug spawn etc. (Chen 1999). Liquid mycelial spawn can be made on PD broth or any other formulations. In artificial cultivation mainly wheat grain spawn was used. For grain spawn preparation healthy and clean wheat grains are selected, washed with clean water, boiled in water for 30–40 min. (wheat grains: water, 2:1 w/v) so as to boil them and make soft enough to be pressed within fingers. Excess water is removed through sieving and the grains are allowed to cool. Grains were thoroughly mixed with calcium carbonate (4% w/w) and calcium sulfate (2% w/w) for adjusting pH 5.5 and to avoid lump formation in the grains. Glass bottles (500 mL) or polypropylene bags are filled with about 250 g of grains, and plugged with non-absorbent cotton and then sterilized by autoclaving at 22 psi for 90 min. These bottles are then allowed to cool overnight at room temperature and next day inoculated with culture of G. lucidum and incubated at 25  1  C till the mycelium covers the grains. (d) Substrate Selection and Preparation The most popular ingredient used in synthetic formulations of substrate is saw dust. Artificial cultivation of G. lucidum has been achieved by using the substrates such as cereal grain, sawdust, wood logs (Chang and Buswell 1999; Wasser 2005; Boh et al. 2007), tea waste (Peksen and Yakupoglu 2009), cork residue (Riu et al. 1997), sunflower seed hull (González-Matute et al. 2002), corn cobs (Ueitele et al. 2014), olive oil press cakes (Regori and Pohleven 2014) and wheat straw (Khajuria and Batra 2014). Regardless of the main ingredient used, starch-based supplements such as wheat bran or rice bran are always added to the mixture. These supplements act as nutrient source to provide an optimum growth. Other supplements that are added in lesser quantities include calcium carbonate (CaCO3) and gypsum (CaSO4). These produce a better, more nutritious diet for the reishi mushroom. Most of the formulations include about four parts saw dust and one part wheat or rice bran. Various formulations have been recommended by different researchers for growing G. lucidum. Based upon the cost and availability of substrates, one can select the formulation suggested by various workers. Sawdust 22.5%, paddy straw 67.5%, and rice bran 10% (Veena and Pandey 2011); sawdust 80% and wheat bran 20% (Mehta et al. 2014); rice straw 70% and sawdust 30% (Magday Jr et al. 2014); saw dust 80% and wheat bran 10% (Thakur and Sharma 2015); wheat straw 100% (Cilerdzic et al. 2018). Adjust the water content to 60–65% with the help of moisture analyzer and

604

S. Jandaik and S. K. Gupta

palm test method before sterilization (Kwon and Kim 2004) and pH to 5.5–6.0 using gypsum and lime. Saw dust has to be soaked at least for 1 day and rice straw for 3 h. All the ingredients are thoroughly mixed. (a) Bag Filling and Sterilization Fill 1.5–2 kg of prepared substrate in the polypropylene bags immediately after mixing and wetting the substrate, up to three-fourth capacity. Top of the filled bag is plugged with non-absorbent cotton. The bags are autoclaved at 22 lb psi for 1½–2 h without any delay to avoid fermentation in the bags. (b) Spawning and Spawn Run Spawning is done aseptically after cooling down the substrate. Although various workers such as Rai (2003), Veena and Pandey (2010), and Mehta et al. (2014), have reported use of 3%, 6–8%, and 3% spawn rates respectively for better yield of G. lucidum. However, Bernabé-Gonzalez et al. (2015) reported 2% spawn but for general purpose and successful colonization 3% spawn grain is introduced in the central hole made in the substrate. The inoculated bags are then incubated at 30  1  C under darkness. Top of all inoculated bags is kept closed until the substrate in the bags is fully colonized. Normally spawn run takes place 18–20 days. After complete colonization (when thick mycelial sheet is developed), bags are shifted to cropping room. (c) Cropping Conditions The top portion of the bags is cut open and bags are kept on bamboo or iron shelves in a cropping room to attain the different stages of mushroom growth, i.e., spawn run, primordial initiation, stalk formation, pileus differentiation, and cap maturation. The temperature and relative humidity (RH) are adjusted to 30  1  C and 60–70%, respectively. During the first stage i.e., spawn run period is completed without artificial lighting, during primordial formation stage temperature of 28  1  C and relative humidity of 90–95% along with light exposure of 800 lux for 10–12 h is maintained while reduced humidity of 70–80% and 28  1  C temperature with 800 lux light exposure is preferred during third stage of stalk formation. Temperature of 25  1  C and relative humidity of 85–90% along with light exposure (800 lux) as in case of second and third stage is desirable for pileus differentiation. Reduced relative humidity of 60–65% and temperature of 28  1  C is maintained for proper cap maturation that constitutes the last stage in the development of Ganoderma fruit bodies. Relative humidity is maintained by spraying clean water on the substrate bags and room walls as well as floor, twice or thrice daily to minimize drying of the substrate surfaces. (d) Environmental Requirements for Fruiting After the complete spawn run (bags white all over), polypropylene top is cut at the level of the substrate totally exposing the top side and proper conditions for fruiting or pinning (temperature 28  C, 1500 ppm CO2, 800 lux light and 90–95% RH) are provided. Once the pins have grown up enough to form the cap which is indicated by the flattening of the whitish top of the pinhead, humidity is reduced to 80% and more fresh air is introduced to reduce the CO2 concentration (1000 ppm CO2). Once the cap is fully formed, which is indicated

23

Cultivation Technology of the Fungus Ganoderma lucidum (Curtis) P. Karst

605

by yellowing of the cap margin (which is otherwise white), temperature is lowered to 25  C and relative humidity is also reduced to 60% for thickening of cap, reddening and maturation of the fruit bodies. Reddish brown color of cap and spores shedding on the top of the cap indicates full maturity of G. lucidum fruit bodies. (e) Harvesting For harvesting Ganoderma fruit bodies hold the root with one hand and tightly pluck up with another. Some people also use scissors and knives for harvesting but no residual bud should be left after harvesting. One cycle of the growth takes 10–15 days. After the first flush is harvested, conditions for pinning initiation are again maintained (i.e., 28  C, 95% RH, 1500 ppm CO2, 800 lux light) for starting the second flush. Depending upon the conditions, 2–3 flushes appear and a total 25% biological efficiency can be achieved (250 g fresh mushroom from one kg dry substrate). For one crop to take place about 4 months duration is required. After harvesting mushrooms are washed with water and are dried at a temperature of around 50  C in the cabinet driers, preferably at 35  C in the dehumidifying cabinet driers. Freeze drying is, considered best for Ganoderma. The mushroom has very high dry matter 45% (i.e., 450 g dry matter from 1 kg fresh fruit bodies).

23.3

Marketing Strategy

Reishi is used as medicine and not as food because of its bitter taste and hard corky fruit bodies. Anyone who is growing reishi mushroom has to find the market which is basically herbal medicine and food supplement (nutraceuticals) sector. Manufacturers of herbal medicines and food supplements can process, pack and trade it in various forms like tablets, capsules, or liquid extracts. Products of Ganoderma have attracted a great deal of attention during the last decade in, Europe, North America, Malaysia, and Singapore. Main producers and suppliers of Ganoderma-based products are China, Japan and Korea. In 1995, the total world market for Ganodermabased natural health care products was 1628 million US dollars (Chang and Buswell 1999). In 2004, worldwide production of G. lucidum was approximately 5000–6000 MT and more than half of it was produced by China (Rai 2003). However, there are some problems which have been reported with Ganodermabased products because of low reproducibility and poor quality control. Various reasons such as seasonal variations, different soil conditions and stage of fruit body development contribute toward product quality. Products of Ganoderma are divided into three types; developmental products based on Ganoderma fruiting bodies (Wasser 2011), mycelia (He 2000), and spore powder (Xie et al. 2002). Large number of Ganoderma products have been commercialized and it is estimated that at least 100 brands and over 780 products are sold in the world markets (Lai et al. 2004). Largest market for Ganoderma and related products is known to be in USA.

606

23.4

S. Jandaik and S. K. Gupta

Conclusion and Future Trends

There are number of challenges which need to be addressed regarding Ganoderma production technology. The systematics and taxonomy of Ganoderma species needs to be studied and confirmed. Lack of good quality value-added products, homogeneity of products, poor quality and high prices are also major challenges to be considered (Li et al. 2016). The quality standard and management of Ganoderma products must be improved with proper identification and control of the bioactive components. Breeding of new Ganoderma strains will enhance the development of new high yielding strains with greater resistance to diseases, this in turn will increase productivity and reduce the use of chemicals for management of diseases and pests. The accessibility and prices for standard Ganoderma products will also be controlled with proper use of DNA markers.

References Azizi M, Tavana M, Farsi M, Oroojalian F (2012) Yield performance of lingzhi or reishi medicinal mushroom, Ganoderma lucidum (W.Curt.:Fr.) P. Karst. (Higher basidiomycetes), using different waste materials as substrates. Int J Med Mushrooms 14:521–527. https://doi.org/10.1615/ IntJMedMushr.v14.i5.110 Bernabé-Gonzalez T, Cayetano-Catarino M, Bernabé Villanueva G, Romero-Flores A, Ángel-Ríos MD, Pérez-Salgado J (2015) Cultivation of Ganoderma lucidum on agricultural by-products in Mexico. Micol Aplicada Int 27(2):25–30 Berovic M, Habijanic J, Zore I, Wraber B, Hodzar D, Boh B, Pohleven F (2003) Submerged cultivation of Ganoderma lucidum biomass and immunostimulatory effects of fungal polysaccharides. J Biotechnol 103(1):77–86. https://doi.org/10.1016/s0168-1656(03)00069 Boh B, Berovic M, Zhang J, Zhi-Bin L (2007) Ganoderma lucidum and its pharmaceutically active compounds. Biotechnol Annu Rev 13:265–301. https://doi.org/10.1016/S1387-2656(07) 13010-6 Chang ST, Buswell JA (1999) Ganoderma lucidum (Curt Fr) P Karst (Aphyllophoromycetideae)—a mushrooming medicinal mushroom. Int J Med Mushrooms 1(2):139–146. https:// doi.org/10.1615/IntJMedMushrooms.v1.i2.30 Chen AW (1999) Cultivation of the medicinal mushroom Ganoderma lucidum (Curt:Fr) P Karst (Reishi) in North America. Int J Med Mushrooms 1(3):263–282. https://doi.org/10.1615/ IntJMedMushr.v1.i3.90 Chen AW (2001) Cultivation of Lentinula edodes on synthetic logs. Mushroom Growers’ Newslett 10(4):3–9 Chen AW (2002) Natural log cultivation of the medicinal mushroom, Ganoderma lucidum (Reishi). Mushroom Growers’s Newslett 3(9):2–6 Chen KL, Chao DM (1997) Ling Zhi (Ganoderma species). In: Hsu KT (ed) Chinese medicinal mycology. United Press of Beijing Medical University and Chinese United Medical University, Beijing, pp 496–517 Chen HZ, Chen JW (2004) A preliminary report on solid-state fermentation of Ganoderma lucidum with Radix Astragali containing medium. Chin J Integr Med 2(3):216–218. https://doi.org/10. 3736/jcim20040320

23

Cultivation Technology of the Fungus Ganoderma lucidum (Curtis) P. Karst

607

Cilerdzic JL, Vukojevic JB, Klaus AS, Ivanovic ZS, Blagojevic JD, Stajic MM (2018) Wheat straw—a promissing substrate for Ganoderma lucidum cultivation. Acta Sci Pol Hortorum Cultus 17(1):13–22. https://doi.org/10.24326/asphc201812 De Silva DD, Rapior S, Hyde KD, Bahkali AH (2012) Medicinal mushrooms in prevention and control of diabetes mellitus. Fungal Divers 56:1–29. https://doi.org/10.1007/s13225-0120187-4 Denisova NP (2001) Traditions of using medicinal mushrooms in different nations. Int J Med Mushrooms 3(4):409–415. https://doi.org/10.1615/IntJMedMushr.v3.i4.110 Escribano MC, Pihlava JM, Miina J, Veteli P, Linnakoski R, Vanhanen H (2020) Effect of strain, wood substrate and cold treatment on the yield and β-glucan content of Ganoderma lucidum fruiting bodies. Molecules 25:4732. https://doi.org/10.3390/molecules25204732 González-Matute R, Figlas D, Devalis R, Delmastro S, Curvetto N (2002) Sunflower seed hulls as a main nutrient source for cultivating Ganoderma lucidum. Micol Aplicada Int 14(2):19–24 He H (2000) Research advances and prospect on submerged fermentation technology of Ganoderma lucidum primary. JCMA 14:48–49 Kamra A, Bhatt AB (2013) First attempt of an organic cultivation of red Ganoderma lucidum under subtropical habitat and its economics. Int J Pharm Pharm 5(4):94–98 Karsten PA (1881) Enumeralio boletinearum et polypore arum fennicarum, systemate novo dispositarum. Revue de Mycol 3:16–19 Khajuria R, Batra P (2014) Supplementation of nitrogen source in wheat straw for improving cellulolytic potential of Ganoderma lucidum. Int J Pharm Bio Sci 5:90–99 Kwon H, Kim BS (2004) Mushroom growers’ handbook 1; bag cultivation. In: Oyster mushroom cultivation. Mush World, Republic of Korea, pp 144–159 Lai T, Gao Y, Zhou SF (2004) Global marketing of medicinal Ling Zhi mushroom Ganoderma lucidum (WCurt:Fr) Lloyd (Aphyllophoromycetideae) products and safety concerns. Int J Med Mushrooms 6(2):189–194. https://doi.org/10.1615/IntJMedMushr.v6.i2.100 Li S, Dong C, Wen HA, Liu X (2016) Development of Ling-zhi industry in China—emanated from the artificial cultivation in the Institute of Microbiology, Chinese Academy of Sciences (IMCAS). Mycology 7(2):74–80. https://doi.org/10.1080/2150120320161171805 Lin ZB (2009) Lingzhi: from mystery to science. Peking University Medical Press, Beijing, p 1 Magday JC Jr, Bungihan ME, Dulay RMR (2014) Optimization of mycelial growth and cultivation of fruiting body of Philippine wild strain of Ganoderma lucidum. Curr Res Environ 4(2): 62–172. https://doi.org/10.5943/cream/4/2/4 Mayzumi F, Okamoto H, Mizuno T (1997) Cultivation of Reishi (Ganoderma lucidum). Food Rev 13(3):365–370. https://doi.org/10.1080/87559129709541118 Mckenna D, Jones K, Hughes K, Tyler V (2002) Botanical medicines. In: The desk reference for major herbal supplements. Routledge, New York. https://doi.org/10.4324/9780203048368 McMeekin D (2004) The perception of Ganoderma lucidum in Chinese and Western culture. Mycologist 18(4):165–169. https://doi.org/10.1017/S0269-915X(04)00406-9 Mehta S, Jandaik S, Gupta D (2014) Effect of cost-effective substrates on growth cycle and yield of lingzhi or reishi medicinal mushroom, Ganoderma lucidum (higher Basidiomycetes) from Northwestern Himalaya (India). Int J Med Mushrooms 16(6):585–591. https://doi.org/10. 1615/intjmedmushrooms.v1.6i.680 Meunick J (2015) Basic illustrated edible and medicinal mushrooms. Rowman & Littlefield, Montana Moncalvo JM, Ryvarden L (1997) A nomenclatural study of the Ganodermataceae Donk. Synopsis Fungorum 10:1–114 Paterson RRM (2006) Ganoderma a therapeutic fungal bio factory. Phytochemistry 67:1985–2001. https://doi.org/10.1016/jphytochem.2006.07.004 Pegler DN (2002) Useful fungi of the world: the Ling-zhi—the mushroom of immortality. Mycologist 16(3):100–101. https://doi.org/10.1017/S0269915X0200304X

608

S. Jandaik and S. K. Gupta

Peksen A, Yakupoglu G (2009) Tea waste as a supplement for the cultivation of Ganoderma lucidum. World J Microbiol Biotechnol 25(4):611–618. https://doi.org/10.1007/s11274-0089931-z Perumal K (2009) Indigenous technology on organic cultivation of Reishi. AMM Murugappa Chettiar Research Centre, pp 1–12 Pilotti CA (2005) Stem rots of oil palm caused by Ganoderma boninense: pathogen biology and epidemiology. Mycopathologia 159(1):129–137. https://doi.org/10.1007/s11046-004-4435-3 Pilotti CA, Sanderson FR, Aitken AB, Armstrong W (2004) Morphological variation and host range of two Ganoderma species from Papua New Guinea. Mycopathologia 158:251–265. https://doi. org/10.1023/b:myco.0000041833.410856f Rai RD (2003) Successful cultivation of the medicinal mushroom Reishi, Ganoderma lucidum in India. Mushroom Res 12:87–91 Rawat S (2018) Isolation and evaluation of Ganoderma lucidum from Uttarakhand. Int J Curr Microbiol App Sci 7(03):472–479. https://doi.org/10.20546/ijcmas2018703057 Regori A, Pohleven A (2014) Cultivation of three medicinal mushroom species on olive oil press cakes containing substrates. Acta Agric Slov 103:49–54. https://doi.org/10.14720/ aas2014103105 Riu H, Roig G, Sancho J (1997) Production of carpophores of Lentinus edodes and Ganoderma lucidum grown on cork residues. Microbiologia 13(2):185–192. PMID: 9253758 Roy S, Jahan MAA, Das KK, Munshi SK, Noor R (2015) Artificial cultivation of Ganoderma lucidum (Reishi medicinal mushroom) using different sawdusts as substrates. AJBIO 3(5): 178–182. https://doi.org/10.11648/jajbio2015030513 Sanodiya BS, Thakur GS, Baghel RK, Prasad GB, Bisen PS (2009) Ganoderma lucidum: a potent pharmacologicalmacrofungus. Curr Pharm Biotechnol 10:717–742. https://doi.org/10.2174/ 138920109789978757 Sliva D (2006) Ganoderma lucidum in cancer research. Leuk Res 30:767–768. https://doi.org/10. 1016/jleukres200512015 Smith BJ, Sivasithamparam K (2000) Internal transcribed spacer ribosomal DNA sequence of five species of Ganoderma from Australia. Mycol Res 104:943–951. https://doi.org/10.1017/ S0953756200002458 Stamets P (2000) Growing gourmet and medicinal mushrooms, 3rd edn. Ten Speed Press, Berkeley Thakur R, Sharma BM (2015) Deployment of indigenous wild Ganoderma lucidum for better yield ondifferent substrates. Afr J Agric Res 10(33):3338–3341. https://doi.org/10.5897/AJAR2015. 9866 Turner PD (1981) Oil palm diseases and disorders. Oxford University Press, Oxford, pp 88–110 Ueitele ISE, Kadhila MNP, Matundu N (2014) Evaluating the production of Ganoderma mushroom on corn cobs. Afr J Biotechnol 13:2215–2219. https://doi.org/10.5897/AJB2014.13650 Veena SS, Pandey M (2010) Effect of spawn substrate and spawn rate on cultivation of Ganoderma lucidum. J Mycol Plant Pathol l40(1):158–161 Veena SS, Pandey M (2011) Paddy straw as a substrate for the cultivation of lingzhi or reishi medicinal mushroom in India. Int J Med Mushrooms 13(4):397–400. https://doi.org/10.1615/ IntJMedMushr.v13.i4.100 Wasser SP (2005) Reishi or Ling Zhi (Ganoderma lucidum). In: Coates PM, Blackman MR, Cragg GM, Levine M, Moss J, White JD (eds) Encyclopedia of dietary supplements. Marcel Dekker, New York, pp 603–622 Wasser SP (2011) Current findings, future trends, and unsolved problems in studies of medicinal mushrooms. Appl Microbiol Biotechnol 89:1323–1332. https://doi.org/10.1007/s00253-0103067-4 Wasser SP, Weis AL (1999) General description of the most important medicinal higher Basidiomycetesmushrooms. Int J Med Mushrooms 1:351–370. https://doi.org/10.1615/ IntJMedMushr.v1.i4.80

23

Cultivation Technology of the Fungus Ganoderma lucidum (Curtis) P. Karst

609

Xie YZ, Zhang Z, Li SZ, Li C (2002) Recent advances in the development and processing works of the Lingzhi fungus. J Microbiol 22:43–45 Yang FC, Liau CB (1998) Effect of cultivating conditions on the mycelial growth of Ganoderma lucidum in submerged flask cultures. Bioprocess Eng 19:233–236. https://doi.org/10.1007/ PL00009014 Yu YN, Shen MZ (2003) The history of Lingzhi (Ganoderma spp) cultivation. Mycosystema 22:3– 9 Zhou X (2017) Cultivation of Ganoderma lucidum. In: Diego CZ, Pardo-Giménez A (eds) Edible and medicinal mushrooms: technology and applications, pp 385–413

Chapter 24

Problems of Fungal Contaminants and Cultivation Strategies of Certain Medicinal Mushrooms Rashmi Mishra

Abstract Mushrooms are crucial elements of youngster forest produce, that develop at the maximum plentiful biomolecule of this biosphere, that is, cellulose. Presently mushrooms are basically macro-fungi with an extraordinary fruiting structure, which may be epigeous or hypogeous and massive enough to be visible with the bare eyes and can be picked by means of hand. Only fruiting frame of the mushroom may be visible while the relaxation of the mushroom stays underground as mycelium. Mushrooms are rich source of protein and have vitamins and tocopherol which acts as antiaging chemical Vitamin E. Mushrooms like Tuber, Morchella and Boletus are delicious. Mushrooms have peculiar flavour and taste. Hundreds of scent molecules waft off from truffles. These are hypogean and have ectomycorrhizal association with the roots of forest trees. Most of the saprophytic mushrooms are commercially cultivated on large scale. These mushrooms utilize straw of cereals or synthetic logs of saw dust. Various fungal contaminants and nematodes and insect may cause hindrance in cultivation protocol. Few strategies available to cultivate certain medicinal mushrooms are discussed. Keywords Cultivation · Medicinal mushroom · Contaminants · Volvariella volvacea · Agaricus bisporus · Tremella fuciformis · Flammulina velutipes

24.1

Introduction

The word mushroom means different things to different people living in different countries. In some Western countries, mushroom refers only to the “button” or “white” mushroom (Agaricus bisporus (J. E. Lange) Imbach and A. bitorquis (Quel.) Sacc.), whereas all other cultivated species are referred to as “speciality”, “exotic” or alternative mushrooms. A mushroom is basically a macrofungus with a distinctive fruiting body belonging to Asco or Basidiomycetes. Only fruiting frame

R. Mishra (*) Biotechnology, Noida Institute of Technology, Greater Noida, Uttar Pradesh, India Swadeshi Science Movement of India, Delhi, India © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_24

611

612

R. Mishra

of the mushroom may be visible while the extended vegetative body of the mushroom stays underground as mycelium or as ectomycorrhiza. As evidenced from the fossil records of the cretaceous period. Anthropologically speaking, there’s each opportunity that ancestral human beings used the mushrooms as meals. Mushrooms provide remarkable packages as they may be used as meals and drugs except their key ecological roles. They constitute as one of the world’s best untapped sources of vitamins and palatable meals of the future. Mushrooms had been determined effective in management of cancer (Wong et al. 2020), ldl cholesterol reduction, stress, insomnia, asthma, hypersensitive reactions and diabetes etc. Due to the presence of high protein contents, they may be used to bridge the protein malnutrition gap. Due to low starch content material and low cholesterol, they in shape diabetic and coronary heart patients. Their polysaccharide content is used as an anticancer drug (Chang et al. 2010). Even, they had been used to fight HIV effectively (Nanba 1993; King 1993). Biologically active compounds from the mushrooms have antifungal, antibacterial, antioxidant and antiviral properties (Lindequist et al. 2010). As a result, cultivation of few species of mushrooms is gaining importance. Mushroom farming is practiced in more than 100 countries and production is increasing at an annual rate of 6–7% which has led to significant impacts on livelihoods and poverty eradication (Gupta et al. 2018). The Button Mushroom (Agaricus bisporus) has umbrella shaped structure with furfuraceous to scaly pileus, and is normally cultivated extensively in different parts of the world. This species is grown on composted horse manure and straw as substrate. The carpophores are agaricoid to pluteiod in habit with bivaozngrocarpous-isocarpous to hymenocarpous development (Saini et al. 2018). The Shiitakes (Lentinula edodes (Berk.) Pegler), the wood ear (Auricularia polytricha (Mont.) Sacc.) and the Enoke, (Flammulina velutipes (Curtis) Singer) to call a few, are normally grown on woody substrates or on logs. Paddy straw mushroom is grown in fields along the mixed cropping of maize and pulses. Mushroom Biotechnology is an interdisciplinary branch between Mushroom Science, fermentation technology and bioprocessing (Fig. 24.1) to use bioactive compounds of mushrooms. According to Das (2014) a Professor of Economics in Assam, although mushroom is a good source of protein its commercial cultivation is hampered because of four things. Scarcity of trained manpower and extension support, no processing facilities, long gestation period and problems of contamination are major drawbacks. In the states like Punjab, Himachal Pradesh, Haryana, etc., where the extension services are very efficient, their pace of progress is also seen to be quite impressive. It has a long gestation period and bank loans are not provided due the existing land tenure system particularly in the tribal belts. There are problems of processing and contamination during harvesting. Cultivation of certain species both from Western and Eastern cultures will be discussed. A variety of organic wastes, composted organic material, cut logs, sterilized sawdust in polypropylene bags (heat resistant plastic bags), may be used. Mycelium used to inoculate bags is called spawn. There is an urgent need to increase the level of investment in research front.

24

Problems of Fungal Contaminants and Cultivation Strategies of Certain. . .

Identification

613

Biology Bioprospecting

Cultivation Collection

n entatio

Ferm

tate Solid s on tati n e rm e F y hnolog

Bio Processing

Mushroom Biotechnology

Transfor mation

Tec

Fig. 24.1 Mushroom Biotechnology involves interaction between Mushroom Science, fermentation technology and bioprocessing to use bioactive compounds from these fruiting bodies and mycelium

24.2

Mushrooms as a Source of Food and Medicine

Man has been looking for the wild mushrooms since antiquity. Thousands of years ago, fructifications of better fungi had been used as a supply of food (Mattila et al. 2001) because of their chemical composition that’s appealing from the vitamins factor of view. During the early days of civilization, mushrooms had been consumed regularly for their palatability and unique flavours. This is particularly true, when the drugs from mushrooms were used in an ancient culture's religious rituals. In such typically performed covertly practices, a passage of the Egyptian Book of the Dead (Budge 1969; Berlant 2005) makes a clear mention that such details should be kept secret. Moreover, these practices were common in the ancient times. However, for palaeobotanists, evidences from this region, is remarkably rare (Merlin 2003). Mushrooms have been consumed since earliest history; ancient Greeks believed that mushrooms content and type of biologically active substances may vary considerably in edible mushrooms; their concentrations of these substances are affected by differences in strain, substrate, cultivation, developmental stage, age, storage conditions, processing, and cooking practices. According to the National Audubon Society Field Guide to Mushrooms, “Mushrooms are among the most mysterious life forms”. In Greek mythology, mushrooms were said to come from Zeus’s lighting because they appeared after rain storms. In Roman times, mushrooms were famous as a gourmet delicacy for royalty and were called the food of the gods, having supernatural powers. Recipes for their use have been found in ancient Greek and

614

R. Mishra

Roman writings (Mackenzie 2009). The Caesar’s mushroom that is popular in Europe has some look alike in North America that are poisonous. In describing the edibility of wild mushrooms, my books use the word “caution”. Due to the awareness, shortcomings and dangers in chemotherapy interest in the use of complementary medicines, especially herbal medicines for the prevention and treatment of various diseases growing very fast. Mushrooms from nutritional point of view have a distinct place in human diet. Besides the attributes which make mushrooms “the ultimate health food”, recent investigations have proved the imperial observations of the oriental herbalists that certain mushrooms possess many useful medicinal attributes. Among them Lentinula edodes commonly known as “shiitake”, Ganoderma lucidum (Reishi mushroom) or mushroom of longevity. Many active substances (polysaccharides, proteins, triterpenoides, steroids and organic geranium) showing immune-modulating effects have been isolated from G. lucidum. Ganoderma nutraceuticals have exhibited promising antiviral effects like anti HIV (Paterson 2006). L. edodes is a valuable mushroom used to stimulate the immune system against cancerous tumours, viral infections and chronic fatigue symptoms, immuno regulating compounds as polysaccharides and β-glucans. The chemical structure of polysaccharides and its connection to antitumor activity, including possible ways of chemical modification, experimental testing, and clinical use of antitumor or immune-stimulating polysaccharides, as well as possible mechanisms of their biological action, According to Wasser (2010) there are 700 mushrooms with such bioactive compounds. Present use of mushrooms is completely distinctive from their conventional use because, a lot of researchers have helped to find out their chemical composition and uses in regular diet or to combat the diseases. Numerous bioactive polysaccharides or polysaccharide protein complexes from medicinal mushrooms appear to enhance innate and cell-mediated immune responses and exhibit antitumor activities in animals and humans. A wide range of these mushroom polymers have been reported previously to have immunotherapeutic properties by facilitating growth inhibition and destruction of tumour cells. Several of the mushroom polysaccharide compounds have proceeded through clinical trials and are used extensively and successfully in Asia to treat various cancers and other diseases. A total of 126 medicinal functions are thought to be produced by selected mushrooms The excess of free radicals may damage cellular lipids, proteins and DNA, affecting normal function and leading to various diseases. In aerobic organisms, the free radicals are constantly produced during the normal cellular metabolism, mainly in the form of Reactive Oxygen Species (ROS) and Reactive Nitrogen Species (RNS). Exposition of the organism to free radicals has led to the development of endogenous defence mechanisms to eliminate them. These defences were the response of evolution to the inevitability of ROS production in aerobic conditions. Natural products with antioxidant activity may help the endogenous defence system (Ferreira et al. 2009).

24

Problems of Fungal Contaminants and Cultivation Strategies of Certain. . .

24.3

615

Improvement of New Strains

This expansion in the mushroom market is ever increasing. The economic importance can be explained as a result of scientific advances such as new molecular biology tools for the indirect identification of species; and development of largescale production techniques through high yielding strains. However, there is still space for advances, emphasizing the discovery and identification of new species. Genetic Improvement or development of newer strains of mushrooms through breeding has remained integral part of all research and developmental activities aimed at improving the cultivation technology of mushrooms. In the beginning, the process of strain improvement was based on identification and selection of a suitable strain. However, with the release of two hybrids Ui & Us by the conventional techniques of crossing homokaryons and selection of high yielding hybrids (Fritsche 1991), the mushroom breeding programmes all over the world took a big leap and newer techniques supporting the breeding programme were brought in light (Loftus 1995). The newer techniques, like protoplasting, have also improved the methodology as well as frequency of homokaryons isolation having utility in hybrid formation. The distinct features of different mushroom species like existence or non-existence of clamp connections in heterokaryons, variations in number of nuclei per cell and also in basidiospore per basidium have created confusion and forced to adopt different breeding strategies for each species. Though the conventional method of mushroom breeding like introduction and selection has remained the main tool in the mushroom improvement programmes but other techniques like mutations, single spore culture, multispore culture and hybridization have also been tried with different levels of success. The multispore culture technique is said to be useful in rejuvenation of the degenerated cultures while single spore culture and hybridization techniques have generated some of the commercially popular strains all over the world. The best example of hybridization is the development of Ui and U3 hybrids of A. bisporus (Fritsche 1991) in Holland. Similarly, some of the single spore isolates from Volvariella spp. (Kalra and Phutela 1991) were reported to have higher yield potential than their parents.

24.4

Cultivation Strategies for Certain Mushrooms

Although mushrooms have long been appreciated for their flavour and texture Chang (1993) warned that they should be collected from nature and should be consumed only if they have been identified with precision. Cultivation is needed to meet the increasing demand. According to Dehariya and Vyas (2013) it was observed that among the non-conventional test substrates, Bamboo leaves (BL) required lesser time for spawn run (17 days) of oyster mushroom. The pin head appeared in 21 days but average yield was 521.7 g kg
1. On the other hand domestic waste (DW) was found to be best substrate because of higher yield (718.4 g kg
1) and BE (71.8%)

616

R. Mishra

obtained. Besides DW, used tea leaves (UTL) produced good yield (655.0 g kg
1). Saw dust (SD) was found as poor substrate because it not only require more time for spawn run (31.7 days) and pin head appearance (34.7 days) but also produced lowest yield (321.7 g kg
1) with 32.1% BE. In newspaper (NP) also more time (30.7 days) for spawn run and pin head appearance (34.7 days) was observed, but maximum stipe length (2.7) cm and cap diameter (6.2) cm measured with 558.4 g kg
1 yield and 55.8% BE. The B.E. was calculated as follows: B:E:ð%Þ ¼

Fresh weight of mushroom  100 Dry weight of substrate

The moisture content of mushroom was calculated by the following formula: Moisture content sample ð%Þ ¼

Weight of fresh sample
weight of dry  100 Weight of fresh sample

The ability of mushrooms to colonize solid substrates is related to their capacity of synthesizing enzymes in an environment of low water activity. Considering that the substrates for Solid state fermentation (SSF) are usually lignocellulosic, proteic, or starchy residues, most of the enzymes produced by mushrooms in SSF include cellulases, xylanases, laccases, proteases, and amylases. The production of lipases, pectinases, and phytases can also be significantly explored. These enzymes are usually produced during the early stages of mycelial growth (Letti et al. 2018). Methods to cultivate Pleurotus were first tried in Germany as a subsistence measure during World War I (Flack 1917) and is now grown commercially around the world for food. One of the easily grown mushroom is Oyster, it can be cultivated on pasteurized straw and other substrates. Pleurotus is primary decomposer of hardwood trees and is found worldwide. The Pleurotus cultivation was standardized by Bano and Srivastava (1962) utilizing P. flabellatus and the first domesticated species was P. ostreatus. Later, P. sajor-caju became popular. The typical morel (Morchella) mycelium differs from many mushroomproducing fungi in Basidiomycota. Hyphal cells of morels are multikaryotic or multinucleated, it belongs to Ascomycota. They have either multiple copies of the same haploid nuclei, as observed in many Ascomycetes, or many different haploid nuclei co-exist unpaired in a typical morel mycelium. A heterokaryotic mycelium is produced sexually when haploid hyphae of sexually reproducing fungi anastomose with other hyphae containing different haploid nuclei. Heterokaryosis allows morels to adapt to a broader range of environmental conditions and may be protective against deleterious mutations because it is more likely that a good copy of the gene exists if the mycelium is heterokaryotic than it was dikaryotic. Some Morchella spp. produces asexual conidia released by simple hyphal structures clonal propagation (Stamets 2000). Occurrence of 18 species of Morchella are reported from 28 countries, of these 14 are reported to be edible (Negi 2006).According to Eliuzand Goksen the mycelia of Ascomycetous fungi morels, form a variety of other structures, including

24

Problems of Fungal Contaminants and Cultivation Strategies of Certain. . .

617

sclerotia, mycorrhiza, mycelial muffs, and sporocarps. The mycelia have a critical role in the rapid formation of fruiting bodies. Changes in soil pH, temperature, moisture and chemistry, microbial diversity, tree death (with or without fire), and other disturbances have also been associated with fruiting morels (Longley et al. 2019). These have mycorrhizal associations hence difficult to grow and are collected from nature. Masaphy (2010) has developed the technique to grow them in lab. Production of extracellular ligninolytic enzymes from wild Auricularia polytricha, Helvella sp. and Morchella sp. is studied by Thakur et al. (2017). Production of extracellular ligninolytic enzymes were observed in all three species in different pattern. The results of the present study allow us to conclude that Morchella sp. and Helvella sp. were good for production of ligninolytic enzymes in comparison to A. polytricha. MnP was thought to play a crucial role during the primary attack on lignin, because it generates highly reactive Mn3+ which acts as a low molecular mass redox mediator and forms water soluble lignin fragments. Moreover, there are indications that MnP is even capable of mineralizing lignin up to carbon dioxide (Hatakka 2001). Usually mushroom strains prefer high temperatures and low pH values. The majority of the strains screened showed higher growth rates at 30  C, but only Lentinus edodes kept maximum rates at low pH (pH 4.0), and temperature, followed by Stropharia rugosoannulata and Pleurotus ostreatus, that grew rapidly at pH 5.0. According to Tokimoto and Komatsu (1978), the initial pH of the medium did not affect mycelial growth of L. edodes (strain 5). For other strains, growth rate increased with pH. Only strain 5 has an optimal growth rate at low pH (pH 4.0). pH 5.0 was optimum for growth of strains 1 and 4 and higher rates of growth at this pH value were attained by strain 1. Maximum error for these experiments was 10%. Other than Agaricus require light for the initiation of fruiting and for their normal development. Conversely, we observed that the presence of light negatively influenced mycelial growth of all the strains tested. In this case, maximum error between replicates was 12.5%. In conclusion, the incubation of all the strains in medium WDA, in the absence of light promoted higher growth rates. Except for F. velutipes and Kuehneromyces mutabilis, the strains showed higher growth rates at 30  C, allowing their cultivation in tropical countries.

24.4.1 Cultivation of Agaricus bisporus Agaricus bisporus is generally known as the button mushroom. The cultivation of this species started out round 1650, in Paris France, in regions wherein mushrooms had been regularly amassed on used compost from melon crops. For about 160 years, A. bisporus turned into grown in open fields. At a few point, it turned into found out that mycelium, or what's known as the spawn of the mushroom, turned into what gave upward push to the mushroom and can be applied just like the seed of flora to grow the mushrooms. Another good sized discovery was use of culture rooms with humidity control for fruiting of A. bisporus, which replaced the herbal caves, quarries or excavated tunnels. The gain of cultivating A. bisporus in caves turned

618

R. Mishra

into the cool, moist, uniform environment. It is likewise the maximum cultivated mushroom with inside the world, however in Western culture, it turned into additionally the most effective species to be had till across the past during 1970s. According to Chang (1993) cultivation of button mushroom was first recorded in 1600. It is believed that the white button mushroom variety was generated through spontaneous mutation during artificial cultivation (Genders 1969). In 1910, mushroom homes were established in France, however caves were nevertheless the favoured developing systems for the cultivation. Cultivation of A. bisporus sooner or later unfolded to England, and by the end of 1865, it had reached to America. At first, spawn for the mushroom was imported from England, however due to the long time taken in shipping, the mushroom spawn could not be grown into fruiting stage. Until 1903, when the scientists of United States Department of Agriculture could advance their own spawn, and then it was grown. Louis F. Lambert, a French mycologist, commenced the American Spawn Company of St. Paul Minnesota, the primary manufacturer of natural mushroom spawn within side the United States. His product turned into offered throughout the USA as “Lambert’s Pure Culture Spawn”. This spawn acquired a silver medal on the Universal Exposition in St. Louis in 1904. A degree of Lambert’s achievement turned into that English spawn turned into quickly being offered below the name “English Pure Culture Spawn”. By the 1914, 4–5 million kilos of mushrooms had been grown in USA. Uddin et al. (2012) grew button mushroom in wheat: paddy (1:1) straw compost, paddy straw compost and decomposed cow dung. When data of BE were statistically analysed following Completely Randomized Design (CRD) the highest yield was in wheat + paddy substrate and lowest in degraded cow dung. In Asia, rice straw is widely used as the substrate for cultivating Oyster mushroom (Thomas et al. 1998) and is also considered the best substrate for yield and high protein content. Wheat straw is commonly used as a substrate in Europe and sawdust is commonly used as a substrate in Southeast Asian countries for the cultivation of Oyster mushrooms. Hitherto, the button mushroom was the only mushroom cultivated on a large scale, using composted wheat straw as the substrate. The production and marketing potential of the milky white mushroom in Bangladesh is promising, because of the high local demand. According to Rózsa et al. (2017) the compost quality can be substantially improved by adding a protein supplement to the composition of the compost. Protein with 3% wheat bran provides a mean production increase of 6.9% for synthetic compost and 10.9% for mixed compost. The addition of 3% honey flour has significant effects on the level of production compared to the compost variant without additional protein supplementation. The preparation of composting is done in two phases. Phase I—First soaking of substrate (anaerobic phase) was carried out for 5–6 days. Considering that the experimental composting plant has a capacity of 1 m3 for an experimental variant, on day 6 the compost temperature rose to 60  C to trigger the anaerobic fermentation process of the compost. At the start of aerobic composting, the filtered air was introduced into each composting trough, thus on

24

Problems of Fungal Contaminants and Cultivation Strategies of Certain. . .

619

day 7 it began with 25 m3 of air/tonne/h, then on day 11 it was reduced to 10 m3 air/tonne/h, and from day 15 only 5 m3 of air/tonne/h was provided. Phase II—In this phase of compost preparation, heat treatment, or pasteurization, was done by raising the compost temperature to 60  C for a period of 8–12 h, then the compost temperature was lowered to 50  C with fresh air mixing and then cooling continued up to room temperature. The temperature of 45  C was maintained until the NH3 content of the compost fell below 0.05% and the pH stabilized in the range of 7.3–7.5, then it was used for spawning (Rózsa et al. 2017).

24.4.2 Cultivation of Enoki (Flammulina velutipes) The Enoki is a small, sensitive mushroom. Doshi and Sharma (1997) reported occurrence of F. velutipes (Curt. ex Fr.) Singer from the dead trunk of Populus and Prunus spp. from Udaipur and Mount Abu (Doshi et al. 2012). The species is whitish-yellow, with a cap no longer extra than 1–2 cm. The stalk is about 3–400 length and thin. It is cultivated on sawdust substrate in large, urn-fashioned containers. It could appear to be a not going candidate for cultivation due to its small size, however is typically available within supermarkets of USA. The beginning of cultivation of this species was assumed to be in Japan, however its records is even extra difficult to understand than different species, which we’ve got discussed. Mushroom cultivation is a complicated business. It involves a number of different operations including the selection of an acceptable fruiting culture of the mushroom, preparation of spawn and compost or substrate, inoculation of the substrate, crop care, harvesting, preservation of the mushrooms and marketing. Each of these operations consists of many sequential steps which are equally important if success is to be achieved in the mushroom business. It requires cold temperature 15  C and dim light. Ambient light or a fluorescent light positioned 3 m away will do just fine. Do not expose your kit to direct sunlight or wind to avoid drying. Enoki will develop elongated stem and a white colour in an environment high in carbon dioxide and deprived of light. Fruiting Temperature: 13–16  C; mycelium dies over 38  C. Relative Humidity: 90% Instructions: If the air is very dry, spray the walls of the container. To avoid moulds, do not spray directly the fruiting bodies or culture block. Harvest the mushrooms before they fully expand and release their spores.

24.4.3 Cultivation of Silver Ear (Tremella fuciformis) This silver ear fungus or jelly mushroom species produces a white, lobed, irregularly fashioned fruiting bodies. It is a species that has been lengthy applied as a "herbal remedy” for many ailments. It belongs to family Tramellaceae and is indexed as a people’s treatment in antique pharmacological, Chinese books, and is stated to be a

620

R. Mishra

treatment for tuberculosis, excessive blood pressure, and to increase existence expectancy. Polysaccharide TFPS are bioactive compounds. However, it's also taken into consideration a delicacy and, previous to its cultivation, turned into inexpensive best for the tables of the rich. For many years, it is believed that this species turned into a timber decomposer as is the Shiitake and ear fungus (Auricularia). However, it's far now regarded to be a parasite on species of Ascomycota which can be normally discovered developing closed by at the log as T. fuciformis. A fungus this is parasitic on some other fungus is stated to be a mycoparasite. Thus, on the way to develop this species, the host fungus ought to first be inoculated into the substrate and allowed to develop for a time frame and the T. fuciformis is later inoculated and could derive its vitamins at the host fungus and now no longer from the woody material. The fungus A. auricula was reported as mycoparasite on Schizopora paradoxa (De 1999). T. fuciformis Berk was reported from tree trunks in Udaipur. T. aurantia has been found to contain a polysaccharideTramellastin, which decreases glucose level in blood (Doshi et al. 2012).

24.4.4 Cultivation of Volvariella volvacea (Paddy Straw Mushroom) Volvariella volvacea (Bull.) Singer is the probably one that you've got and fed on when you have ever dined in a Chinese restaurant. Many recipes name for this precise species of mushrooms. The mushroom is large. The cap, if allowed to mature, frequently exceeding 500 in diameter, and is mild to darkish grey. When young, the mushroom is absolutely enclosed in a white, egg-like shape known as the volva. As the mushroom develops, the stalk will elongate and push the cap upward, thereby rupturing the volva, leaving best a cup-like shape at the bottom of the stalk. However, it may be frequently picked for ingesting even as slightly beginning from its volva. This species was first cultivated in China during 1700 Yuen (1822). The cultivation extended from subtropical to tropical areas of China or in Southeast Asia, wherein Chinese have migrated. Its cultivation in Hawaii reached through Chinese migrants. The paddy straw mushroom, may also be cultivated on different plant substrate like fabrics. In Hawaii, its cultivation is practised on compost piles made up of sugar cane bagasse or wooden mulch. In Singapore, paddy straw is once more used, however cotton waste, banana leaves also are used (Chang 1993). Thus, for a protracted time, this species turned into now no longer very worthwhile as a business mushroom. It turned into now no longer till 1970, whilst cotton waste turned into added as a substrate that there has been a widespread benefit in yield, and via way of means of 1973, cotton waste had absolutely changed paddy straw, in cultivation of this species in Hong Kong (Chang 1974). This subsequently brought about the Paddy Straw Mushroom turning into semi-industrialized in Hong Kong, Thailand, Taiwan and Indonesia. The cultivation approach of this species is

24

Problems of Fungal Contaminants and Cultivation Strategies of Certain. . .

621

greater corresponding to that of Agaricus bisporus in that each grown on compost. The Paddy Straw Mushroom differs, however, with inside the fabric this is used for composting. In the case of cotton waste, the subsequent percentage of substrates is used: Cotton waste with 4% rice or wheat straw and 4–6% floor agricultural limestone are combined and allowed to ferment for 2–3 days. The composting pile is pasteurized with steam. Mishra (2012) reported cultivation of paddy straw mushroom by women mushroom growers in Odisha to increase their living standards.

24.5

Problems of Fungal Contaminants

A grower has to face the complexity of metabolic behaviour, environmental and ecological requirements of different mushrooms, having relatively long growth cycle and the challenge of innumerable predator, parasitic, and competitor organisms like bacteria, fungi, insects, etc. In the beginning of the nineteenth century, breakthroughs in microbiology and industrial machinery took fungiculture to new levels of controlled productivity on small and commercial scale. This allowed isolation of pure cultures of mushrooms, the selection of new and high yielding strains and breeding of compatible ones to survive in varied climatic zones (Siniscalco et al. 2013). Different spawns are used for the production of oyster mushrooms. Cereal grains (wheat, barley and oats), millets like jowar (Sorghum vulgare) and bajra (Pennisetum typhoides) are used. It is said that spawn produced from jowar or bajra gives greater yield for the simple reason, for the same weight are more grains and therefore more points of contact. The prepared spawn if contaminated by bacteria or fungal contaminants should not be used in cultivation. Common fungal contaminants include Aspergillus niger, Rhizopus stolonifer and Trichoderma spp. The grain spawn in bags is filled with gypsum and calcium carbonate. The gypsum prevents the sticking of grains together and the calcium carbonate helps in maintaining the pH. The freshly prepared spawn is preferred. For longer use it can be stored in a refrigerator. The insect pests like cecid fly, sciarid fly (Sandhu 1995), and staphylinid beetle were observed on oyster mushroom bags (Majumder et al. 2005). Use of margosabased insecticide (Achook-azadirachtin 0.15% EC at 0.3%) and an organophosphate insecticide (Melathion 50EC at 0.05%) were suggested. Nisha (2011) reported occurrence of Aspergillus flavus Link, A. niger van Tiegh. (Fig. 24.2a, d), Trichoderma viride Pers. (Fig. 24.2g), Chaetomium sp. and Rhizopus stolonifer (Fig. 24.2b, c), Trichoderma causes dark coloured green colonies in spawn and substrate, and their presence delays the formation of fruiting bodies. Singh et al. (2012) studied the cultivation of two oyster mushrooms Pleurotus flabelattus and P. florida, they observed 3–5% incidence of black mould (Aspergillus niger), 11–13% green mould caused by Penicillium and 14–16% occurrence of Trichoderma. In a few cases presence of Alternaria alternata (Fig. 24.2e) and Chaetomium sp. was observed. It is very essential that proper pasteurization of straw is done. Addition of supplements like wheat bran or gram flour increases the

622

R. Mishra

Fig. 24.2 Fungal contaminants of spawn and substrate; (a) and (d) Aspergillus flavus, (f) Conidial heads of Penicillium (b) Parithecium and ascospores of Chaetomium (c) Aplanosporangia of Rhizopus; (e) Muriform conidia of Alternaria alternata; (g) Conidia and phialides of Trichoderma. (Source of microscopic pics—Dr. Arun Arya)

24

Problems of Fungal Contaminants and Cultivation Strategies of Certain. . .

623

chances of contamination. The fruiting was reduced or infected bags failed to produce the mushrooms. Singh et al. (2012) suggested use of neem cake powder 5% or Bavistin a carbendazim based fungicide may help to solve the problem. Among weed fungi the prevalence of Trichoderma spp. was 14–16% (Singh et al. 2012). Anandh et al. (1999) showed a loss in yield to the extent of 17.23–77.27%, 8.50–10.91% and 11.77–74.01%, respectively due to Aspergillus flavus, A. niger and T. harzianum, respectively. The contaminants and higher temperature may reduce the yield of oyster mushroom, if proper treatment of paddy straw is not done by heating or chemical disinfection with formalin, there are chances of appearance of another weed mushroom Coprinus sp. Tiwari (2005) working with Agaricus bisporus recorded presence of Chaetomium globosum, Epicoccum nigrum and two spp. of Trichoderma harzianum and T. longibrachiatum on compost and casing of mushroom beds in Agaricus. Use of Carbendazim at 500 ppm was suggested, which increased the biological efficiency 20% (Tiwari 2005). Use of Achook and Nimbecidine two margosa based fungicides were tried (Majumder et al. 2005). Pre-treatment of compost was suggested with 50 ppm formalin and 1000 ppm carbendazim (Tiwari 2005). During composting the dominant fungi in primary phase were Penicilliuma and Fusarium acuminatum. To enhance the composting process use of two thermophilic fungi Scytalidium thermophilum and Humicola insulens was made by Vijay et al. (2002). In composting process the pH was 7.3–7.5, moisture percentage was between 73 and 57 and C/N ratio which was 30 in the beginning reached to 23 after composting. The thiophanate-methyl or carbendazim may be added to spawn grain before autoclaving at 0.15%w/w in order to manage fungal contaminants like Trichoderma and A. flavus (Mazumder and Rathaiah 2001). Bacterial contamination can be checked by mixing streptomycin sulphate after autoclaving (Ahlawat et al. 1997; Mazumder and Rathaiah 2001). Sharma and Vijay (1996) reported incidence of cobweb disease (Dactylium dendroides) in Northern India causing 66.6% losses in button mushroom. This mycoparasite can be controlled by the use of carbendazim and prochloraz manganese. Fungicides were added at the time of spawning and casing (Kaur and Sodhi 2001). Wet bubble (Mycogone perniciosa) and dry bubble (Laecanicillium fungicola) are the two most devastating fungal diseases in white button mushroom. Primary source of infection is casing soil for the former and pest flies for the latter one. Both the organisms infect the reproductive hyphae only. Application of carbendazim, benomyl, and chlorothalonil in casing soil can control the disease (Sharma and Jandaik 2003; Sharma and Kumar 2012).

24.6

Regulation of Other Growing Conditions

Temperature, relative humidity and light are the parameters to be controlled for mushroom growth. Low cost poly houses are used to cultivate mushrooms. The use of exhaust fan, sprinkling of water and sand beds are used. For paddy straw the temperature required is 20–30  C.

624

R. Mishra

V. volvacea grows naturally and commercially on substrates whose nitrogen appears in complex organic forms (Torres-Lopez and Hepperly 1988). It grew best in substrates whose C: N ratios were 60:1 or greater. Ratios of 30:1 have a negative effect on growth, and 15:1 ratios may inhibit it totally. As in Asian strains of V. volvacea, the strain grew better on substrates with nitrogen of organic origin. Growth was inhibited by inorganic nitrogen. Chang-Ho (1980) indicated that high levels of nitrogen can be toxic. Seven different nitrogenous substances were used for cultivation of oyster mushroom (Singh et al. 2012).

24.7

Conclusion

Mushroom cultivation is needed to meet the market demands. It can be used to reduce the organic agro waste and pollution can be minimized. At present only a small fraction of useful mushrooms can be cultivated with current technology. For most species, the complex nutritional composition of substrates, subtle environmental requirements, as well as complex ecological interactions are difficult to mimic under artificial conditions. The popularity among tribal is not high as it has a long gestation period and bank loans are not provided due the existing land tenure system particularly in the tribal belts. There are problems of processing and contamination during cultivation, harvesting and preservation. The chapter discusses the details of contaminants of mushroom culture along with new cultivation techniques of few mushrooms. There is an urgent need to increase the level of investment on research front and develop eco-friendly methods to control the contaminants.

References Ahlawat OP, Rai RD, Verma RN (1997) Management of bacterial contamination of spawn by physico-chemical methods. Mushroom Res 6:15–20 Anandh K, Ramanujam K, Prakasham V (1999) Esrimation of yield loss of Pleurotus eous caused by contaminants. Indian J Mycol Plant Pathol 29:333–335 Bano Z, Srivastava HC (1962) Studies on the cultivation of Pleurotus species on paddy straw. Food Sci 11:36–38 Berlant SR (2005) The entheoniycological origin of Egyptian crowns and the esoteric underpinnings of Egyptian religion. J Ethnopharmacol 102:275–288 Budge EAW (1969) The papyrus of Ani, sheet 2. In: Budge EAW (ed) The gods of the Egyptians or studies in Egyptian mythology, 2. Dover Publications, New York, p 153ff Chang ST (1974) Production of straw mushroom (Volvariella volvaceae) from cotton wastes. Mushroom J 21:348–354 Chang ST (1993) Mushrooms and mushroom biology. In: Chang ST, bushwell JA, Miles PG (eds) Genetics and breeding of edible mushrooms. Gordon and Breach Science Publishers, Philadelphia, pp 1–13

24

Problems of Fungal Contaminants and Cultivation Strategies of Certain. . .

625

Chang H-H, Hsieh K-Y, Yeh C-H, Tu Y-P, Sheu F (2010) Oral administration of an Enoki mushroom protein FVE activates innate and adaptive immunity and induces anti-tumor activity against murine hepatocellular carcinoma. Int Immunopharmacol 20:239–246 Chang-Ho Y (1980) Some factors affecting cellulose utilization by Volvariella volvacea Sing. Presented at the Mycological Workshop at the York University, Toronto, Ontario. January 26, 1980 Das D (2014) Commercial utilization of mushroom cultivation: the case of Assam. J IJMR 2(12): 9 pp De AB (1999) Auricularia auricula as a parasite on Schizopora paradoxa. Mycopathol Res 37:47– 48 Dehariya P, Vyas D (2013) Effect of different agro-waste substrates and their combinations on the yield and biological efficiency of Pleurotus sajor-caju. IOSR J Pharmacy Biol Sci IOSR-JPBS 8(3):60–64. e-ISSN: 2278-3008, p-ISSN:2319-7676 Doshi A, Sharma SS (1997) Wild mushrooms of Rajasthan. In: Rai RD, Dhar BL, Verma RN (eds) Advances in mushroom biology and production. Mushroom Society of India, Solan, pp 193–203 Doshi A, Sharma SS, Ratnoo RS (2012) Evaluation of bio-Industrial waste as casing material in Agaricus bisporus cultivation in Rajasthan. J Mycol Plant Pathol 42(2):234 Ferreira ICFRA, Barros L, Abreu RMV (2009) Antioxidants in wild mushrooms. Curr Med Chem 16(12):1543–1560. https://doi.org/10.2174/092986709787909587 Flack R (1917) Uber dle walkulter des austernpilzes (Agaricus ostreatus) out laubholzstubben. Z forst-sagdwes 49:159–165 Fritsche G (1991) A personal view on mushroom breeding from 1957–1991. In: Genetics and breeding of Agaricus. Pudoc, Wageningen, p 3 Genders R (1969) Mushroom growing for everyone. Faber, London Gupta S, Summuna B, Gupta M, Annepu SK (2018) Edible mushrooms: cultivation, bioactive molecules, and health benefits. In: Mérillon K, Ramawat G (eds) Bioactive molecules in food, reference series in phytochemistry. https://doi.org/10.1007/978-3-319-54528-8_86-1 Hatakka A (2001) Biodegradation of lignin. In: Hofrichter M, Steinbüchel A (eds) Lignin, humic substances and coal, vol 1. Wiley, Weinheim, pp 129–180 Kalra R, Phutela RP (1991) Strain selection and development in Volvariella. Indian Mushroom Sci 1:145–149 Kaur G, Sodhi HS (2001) In vitro control of cobweb (Dactylium dendroides) disease of Agaricus bisporus. Mushroom Res 10(2):85–90 King TA (1993) Mushrooms, the ultimate health food but little research in U. S to prove it. Mushroom News 41:29–46 Letti LAJ, Vítola FMD, Pereira GVDM, Karp SG, Medeiros ABP, Da Costa ESF, Bissoqui L, Soccol CR (2018) Solid-state fermentation for the production of mushrooms. In: Current developments in biotechnology and bioengineering. Elsevier, pp 285–318. https://doi.org/10. 1016/B978-0-444-63990-5.00014-1 Lindequist U, Rausch R, Füssel A, Hanssen HP (2010) Höhere Pilze in der traditionellen Heilkunde und Medizin [Higher fungi in traditional and modern medicine]. Med Monatsschr Pharm 33(2): 40–48. German. PMID: 20184262 Loftus M (1995) Breeding new strains of mushrooms. Mushroom News 43:6 Longley R, Benucci GMN, Mills G, Bonito G (2019) Fungal and bacterial community dynamics in substrates during the cultivation of morels (Morchella rufobrunnea) indoors. FEMS Microbiol Lett 366(17):fnz215. https://doi.org/10.1093/femsle/fnz215. PMID: 31603508; PMCID: PMC6836762 Mackenzie K (2009) The humongous fungus. The Concord Insider. https://www.theconcordinsider. com/2009/12/01/the-humongous-fungus/ Majumder N, Dutta SK, Gogoi R (2005) Evaluation of pesticideal formulation against Scaphisoma tetrasticum in oyster mushroom. Mushroom Res 14(2):76–79

626

R. Mishra

Masaphy S (2010) Biotechnology of morel mushrooms: Successful fruiting body formation and development in a soilless system. Biotechnol Lett 32(10):1523–1527. https://doi.org/10.1007/ s10529-010-0328-3 Mattila P, Karoliina K, Merja E, Juha-Matti P, Jouni A, Liisa V, Veli H, Jorma K, Meli V, Vieno P (2001) Contents of vitamins, mineral elements, and some phenolic compounds in cultivated mushrooms. J Agric Food Chem 49:2343–2348. https://doi.org/10.1021/jf001525d Mazumder N, Rathaiah Y (2001) Management of fungal and bacterial contaminations of oyster mushroom spawn. Mushroom Res 10(2):113–115 Merlin M (2003) Psychoactive plant use in the old world. Econ Bot 57(3):295–323 Mishra S (2012) Mushroom in livelihood system of rural women. Mushroom Res 21:157–163 Nanba H (1993) Maitake mushroom the king mushroom. Mushroom News 41:22–25 Negi CS (2006) Morels (Morchella spp.) in Kumaun Himalaya. Nat Products Radiance 5(4): 306–310 Nisha (2011) Conversion of waste into edible protein, B.Sc. dissertation. The MS University of Baroda, p 101 Paterson RRM (2006) Ganoderma—a therapeutic fungal biofactory. Phytochemistry 67(18): 1985–2001 Rózsa S, MăniuŃiu D, Gocan TM, Sima R, Andreica I, Rózsa M (2017) Agaricus blazei Murrill mushroom compost study anaerobic and aerobic phase. Curr Trends Nat Sci 6(12):75–82 Saini MK, Kaur H, Malik NH (2018) The genus (Agaricus, Agaricales) from India—a check list. Kavaka 51:49–58 Sandhu GS (1995) Management of mushroom insect pest. In: Advances in horticulture mushroom, vol 13, pp 239–260 Sharma VP, Jandaik CL (2003) Management of bubble diseases through chemicals. Indian J Mush 21:21–24 Sharma VP, Kumar S (2012) Comparative efficacy of carbendazim and prochloraz manganese against dry bubble, wet bubble and cobweb disease of button mushroom. Mushroom Res 21 (2):145–149 Sharma SR, Vijay B (1996) Prevalence and interaction of competitor and parasitic moulds in Agaricus bisporus. Mushroom Res 5:13–18 Singh SP, Bhagwati R, Chandra A (2012) Effect of organic amendments on yield of Pleurotus spp. in Arunachal Pradesh. Mushroom Res 21(2):176–176 Siniscalco C, Doveri F, Bellato G et al (2013) History of Italian mycology and first contribution to the correct nomenclature of fungi. In: ISPRA, handbooks and guidelines, Rome Stamets P (2000) Growing gourmet and medicinal mushrooms, 3rd edn. Ten Speed Press, Berkeley/ Olympia, WA. 574 pp Thakur N, Tripathi A, Sagar S, Kumar P et al (2017) Estimation of extracellular lignolytic enzymes from wild Auricularia polytricha, Helvella sp. and Morchella sp. Int J Adv Res 5:968–974. https://doi.org/10.21474/IJAR01/5612 Thomas GV, Prabhu SR, Reeny MZ, Bopaiah BM (1998) Evaluation of lignocellulosic biomass from coconut palm as substrate for cultivation of Pleurotus sajor-caju. (Fr.) Singer. World J Microbiol Biotechnol 14:879–882 Tiwari AK (2005) Pre-treatment of compost and casing with fungicide for the management of Agaricus bisporus moulds. Mushroom Res 14(2):72–75 Tokimoto K, Komatsu M (1978) Biological nature of Lentinus edodes. In: Chang ST, Hayes WA (eds) The biology and cultivation of edible mushrooms. Academic Press, New York, pp 445–459 Torres-Lopez RI, Hepperly PR (1988) Nutritional influences on Volvariella volvacea (Bull. ex. Fr.) Sing, growth in Puerto Rico. I. Carbon and nitrogen. J Agric Univ PR 72(1):19–29 Uddin MJ, Haque S, Haque ME, Bilkis S, Biswas AK (2012) Effect of different substrate on growth and yield of button mushroom. J Environ Sci Nat Resour 5(2):177–180

24

Problems of Fungal Contaminants and Cultivation Strategies of Certain. . .

627

Vijay B, Sharma SR, Lakhanpal TN (2002) Role of thrmophilic fungi in compost production for Agaricus bisporus. J Mycol Pl Pathol 32:204–210 Wasser SP (2010) Medicinal mushroom science: history, current status, future trends, and unsolved problems. Int J Med Mushrooms 12(1):1–16 Wong JH, Ng TB, Chan HHL, Liu Q, Man GCW et al (2020) Mushroom extracts and compounds with suppressive action on breast cancer: evidence from studies using cultured cancer cells, tumor-bearing animals, and clinical trials. Appl Microbiol Biotechnol 104(11):4675–4703. https://doi.org/10.1007/s00253-020-10476-4 Yuen Y(1822) Kuangtung Tung Chin, China

Chapter 25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus florida on Cellulosic Waste of Cotton and Paper Nisha, Aesha Chhatbar, Harsiddhi Chhatbar, and Arun Arya

Abstract Mushrooms have been an integral part of ancient food consumed by man as mentioned in Vedas. Like other vegetables, the mushrooms contain about 90% moisture and are basically included among low calorie food. Mushrooms are rich in fiber, quality protein containing lysine and tryptophan and rich in lenolic acid. Cholesterol is absent and in its place ergosterol is present which can be converted into vitamin D by the human body. These are good source of vitamin B complex especially rich in thiamine, riboflavin and niacin, folic acid and vitamin B12 which are absent in most of the vegetables. Most of the compounds present in mushrooms are classified as host defensive potentiators (HDP); these compounds include polysaccharides, peptides, nucleosides, triterpenoids, alkaloids, complex structures, and other metabolites produced by mushrooms. It is suggested that regular consumption of different varieties of mushrooms not only protects human beings from heart trouble but also had medicinal potential for certain ailments. Different agro-wastes like paddy straw, wheat straw, sugarcane bagasse, cassava bagasse, coffee waste, leaf litter of forest trees have been used to produce a variety of Pleurotus spp. Various supplements like gram flour, maize meal, and soybean powder are used to enhance the biological efficiency. An experiment was conducted to find out best possible use of organic office waste. A large amount of paper, threads, jute string, card board, etc. are commonly presented as office waste. Of these paper and cotton (cellulose) was used in combination with paddy straw. The results are indicative of better biological efficiency (B.E.) at 50% proportions of cotton and paddy. However, the B.E. was more than 90% in paddy straw mixed with 25% of the waste paper substrate. A large number of smaller basidiocarps were produced in the repeated trials. This chapter describes role of enzymes in substrate utilization. The technology can be effectively used to manage the huge agro as well as biodegradable municipal solid waste. The mushroom cultivation is an important component of

Nisha (*) · H. Chhatbar · A. Arya Department of Environmental Studies, Faculty of Science, The Maharaja Sayajirao University of Baroda, Vadodara, India A. Chhatbar Parul Institute of Applied Science, Parul University, Waghodia, Gujarat, India © The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7_25

629

630

Nisha et al.

circular economy as after cultivation the spent mass can be used in a variety of ways. It can serve as an effective tool to reduce the air pollution caused by stubble burning and deter climate change. Keywords Cultivation · Pleurotus florida · Cellulose · Cotton · Paper · Biological efficiency (B.E.)

25.1

Introduction: Fungi and Mushrooms as Nutraceuticals

Fungi constitute an important part of human diet along with vegetables for their aroma, taste and texture. Making bread, cheese and wine with the use of yeast (Saccharomyces cereviceae) and Penicillium is well known. Edible mushrooms have been cultivated for a wide range of essential nutrients such as protein, carbohydrate, fiber, minerals, vitamins (Papaspyridi et al. 2010; Atri et al. 2013; Fernandes et al. 2015). Stamets (2000) proposed that fungal mycelium helps in managing ecosystems, it acts as natural internet of neural network of communicating cells. Petrovska (2001) showed a high nutritive value of mushroom protein. They have a high proportion of albumins and globulins and are low in prolamines and glutelins by comparison with other food products. These are preferred for better nutritional value, and production of a wide variety of bioactive molecules. These compounds affect the maintenance of biological homoeostasis and reestablishment of the balance and natural defense system of an organism. Gunde-Cimerman and Cimerman (1995) recorded production of lovastatin in P. sajor-caju, which lowers cholesterol in body. Among fungi mushroom fungus is more prominent due to its distinctive fruiting body which can be hypogeous or epigeous, large enough to be seen with the naked eye and to be picked by hand (Chang and Miles 1992). Mushrooms includes 14,000–22,000 species while the real number may be much higher associated with the un-description of species and the non-differentiation associated with overlapping morphological characters (Hawksworth 2001). There are about 2000 species of mushrooms in edible; and 700 exhibiting therapeutic activity (Cheng et al. 2008). After button (Agaricus) and Shiitake (Lentinula) the oyster (Pleurotus spp.) is nowadays ranked the third most cultivated mushroom. Species popular in Eastern Asia include also Auriclaria auricular judae (wood ear mushroom/Uchina), Flammulina velutipes (winter mushroom) and Volvariella volvacea (straw mushroom) (Aida et al. 2009). Due to the presence of medicinal compounds, these are used in medical field either in crude or purified compound form. It is known that different species of oyster mushroom scientifically termed as Pleurotus synthesize bioactive compound β glucans, such as pleuran, an insoluble b-(1,3/1,6)-D-glucan (Paulík et al. 1996), which is a potential candidate for the development of nutraceuticals (Giavasis and Biliaderis 2006). Species of Ganoderma is a very prominent member of white rot aphyllophore fungi, which is characterized by the laccate surface of pileus and formation of double-walled, echinulate basidiospores

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

631

with truncate base is recognized as an important source of traditional Chinese medicine (Zhang et al. 2002). Bioactive fungal polysaccharides are often described as “Biological Response Modifiers” (BRMs), due to their ability to trigger a nonspecific response against tumor cells, viral and bacterial infections, inflammations, and also to provoke an increased synthesis of hormones and cells of the host immune system. In addition, their ability to lower cholesterol and blood sugar levels, acting as antioxidants and free-radical scavengers, as well as hepatoprotective and detoxifying molecules (Giavasis and Biliaderis 2006; Mizuno and Nishitani 2013; Ohnon Miura et al. 2001). Apart from mushrooms polysaccharides, other food-grade fungal biopolymers have been used or proposed for use in functional food and nutraceuticals. For instance, pullulan, a common food additive produced by Aureobasidium (syn. Pullularia) pullulans. It is a soluble homopolysaccharide consisted of maltotriose units with alternating a-(1,4) and a-(1,6) linkages and has an average molecular weight of 360,000–480,000 Da. Pullulan is only partly degraded by human amylases and has been used as a dietary fiber or prebiotic substance (Giavasis 2013). Saccharomyces cerevisiae, the common food-grade brewer’s and baker’s yeast is also known for the production of immno-potentiating glucans found in the cell wall. The highly branched glucans are insoluble in water, but after enzymatic hydrolysis, chemical oxidation or derivatization (sulfation of the biopolymer) soluble glucans with a low content of glucosyl branches can be produced, which facilitates their use in foods or pharmaceuticals. Commercialized Brewer’s yeast glucan is termed as BYG (Thammakiti et al. 2004). PGG (also known as Betafectin) is a similar bioactive glucan from baker’s yeast composed of (1,6)-bD-glucopyranosyl-(1,3)-bD-glucopyranose groups with a Degree of branching of 0.5 (one branch in every two molecules of the main chain) (Giavasis and Biliaderis 2006; Kim et al. 2006). S. cerevisiae is also the industrial producer of zymosan, an immunomodulating cell wall proteoglucan with long (1,3)-glucosyl and (1,6)-glucosyl groups, as well as mannan, protein, and nucleic acid groups. The presence of double or triple helix, the degree of branching and of course the type and composition of sugar or protein complexes, or sulfate groups alter the medicinal properties of these macromolecules (Giavasis 2013; Ohnon Miura et al. 2001). Based on their wide range of bioactive metabolites from different groups like polysaccharides, proteins, phenolics, and many other low molecular weight compounds, Lion’s mane (Hericium erinaceus) mushrooms can be enjoyed raw, cooked, dried or steeped as a tea. The extracts is often used in over-the-counter health supplements. It contain bioactive substances that have beneficial effects on the body, especially the brain, heart and gut. The glucans and proteoglucans from mushrooms have been reported to be very effective in the treatment of different types of sarcomas and carcinomas in mice, or in increasing the excretion of interferon (IFN-g) in serum. It is also known for the suppression of several allergic reactions and has been proposed as an antiallergic immunomodulator (Mizuno and Nishitani 2013).

632

Nisha et al.

25.1.1 Soma for Better Health and Longevity The indigenous system of medicine is cost effective and easy to practice. For example to get relief from cough and infection due to Corona virus, it is advised to take tea with basil leaves, black pepper, ginger, and honey. A few doses of herbal tea taken regularly can enhance our immunity and prevent from COVID infection. For good health and longevity consumption of drink soma is mentioned in The Rigveda (8.48.3): ápāma sómam amŕtā abhūma, áganma jyótir ávidāma devā́n kíṃ nūnám asmā́n krṇavad árātiḥ, kím u dhūrtír amrta mártiyasya

Jamison (2015) translated this as: We have drunk the soma; we have become immortal; We have gone to the light; we have found the gods. What can hostility do to us now, and what the malice of a mortal, o immortal one?

Maharishi Swami Dayanand Saraswati explained this as: Good fruit containing food not any intoxicating drink, we drink you, You are elixir of life, achieve physical strength or light of god, achieve control over senses; In this situation, what our enemy can do to me? God what even violent people can do to me?

Wasson and botanist Roger Heim collected and identified various members of family Strophariaceae (notably the genera Pholiota, Psilocybe, Hebeloma, Galerina, Gymnopilus, Agrocybe, and Stropharia) and genus Psilocybe. Swiss chemist Albert Hofmann (1959) identified the chemical structure of the active compounds, psilocybin and psilocin. The unwanted attention completely altered the social dynamics of the Mazatec community and threatened to terminate the traditional Mazatec customs. The community blamed Sabina, and she was ostracized in the community and had her house burned down. Sabina felt sorry to introduce the local practice, but Wasson contended that his only intention was to contribute to the sum of human knowledge (Wasson 1957, 1980). Wasson’s next major contribution was a study of the ancient Vedic intoxicant Soma, which he hypothesized was based on the psychoactive fly agaric (Amanita muscaria) mushroom. This hypothesis was published in 1967 under the title Soma: Divine Mushroom of Immortality (Wasson 1968). His attention then turned to the Eleusinian Mysteries, the initiation ceremony of the ancient Greek cult of Demeter and Persephone. In The Road to Eleusis: Unveiling the Secret of the Mysteries (1978), co-authored with Albert Hofmann and Carl A. P. Ruck, it was proposed that the special potion “kykeon,” a pivotal component of the ceremony, contained psychoactive ergoline alkaloids from the fungus Ergot (Claviceps spp.). Several of his books were self-published with illustrations, and printed in Italy, that have never been reprinted, with one exception. His last completed work, The Wondrous Mushroom, initially part of the selfpublished works, was republished by City Lights Publishers in 2014. The doubt still continues as it may be a mushroom, or a plant like Ephedra or Cannabis but

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

633

certainly not an alcoholic beverage. Yearout (1977) in his book The Power of Plants mentioned that occurrence of A. muscaria was common in North Europe and Siberia. This magic mushroom was important to the religions of the Nordic and Russian tribes, it was worshipped by Greek gods as well which was bestowing powers and prophecy and visions on those who ate it, according to Yearout (1977) “Even elements of Christianity might have grown from it-notably the eating of the body of the god, the god being the mushroom itself.”

25.1.2 Oyster Mushroom: Therapeutic Uses Medicinal properties of fungal polysaccharides and their immune stimulating and antitumor effects are well known. Pleuron showed a positive response on rat colon cancerous lesions (Bobek et al. 2001). The b-glucans extracts of Pleurotus tuber regium, mushrooms were shown to be active against several human cancer cell lines (Wasser 2002). The increase in mitogenic activity of soluble glucan molecules a specific stimulation of natural killer (NK) cells, T-cells, dendritic cells, neutrophiles, and monocytes, an increased expression of immunoglobulins and cytokines was observed (Kim et al. 2010; Gentles et al. 2015; Wculek et al. 2019). Pleurotus can improve the antioxidant status during ageing , which resulted in reducing the age related disorders like stroke, Parkinson’s disease, atherosclerosis etc. (Patel et al. 2012). The extracts of P. abolonus elevated the levels of vitamin C and E, increased the activities of catalase, glutathione peroxidase and superoxide dismutase in aged rats (Shashoua and Adams 2004). Five percent powder of P. salmoneostramineus reduced the total lipid, phospholipids, and LDL/HDL ratio by 29.67%, 16.61%, and 65.31%, respectively (Yoon et al. 2012).

25.2

Commercial Cultivation of Mushrooms

Out of the 3000 macrocytes reported in different places of world 700 are medicinally used and 20 are grown on commercial scale for edible purposes. Oyster (Pleurotus) is at third place in production scenario, common button mushroom at first (32%) and Shiitake in Japanese and Xianggu in Chinese (Lentinus edodes) with 25% at second position. Some other popular mushrooms cultivated include winter mushroom (Flammulina velutipes) and paddy straw mushroom (Volvariella volvacea). Latin word “Auricula” means ear, Jew’s ear or rat ear fungus called Uchina in Manipuri is named after Judas Iscariot, who hanged himself on an Elder tree in shame after betraying Jesus Christ. Reddish translucent jelly like lobed bodies 3–10 cm in size with smooth inner surface (Auricularia auricula-judae) was the first mushroom whose commercial cultivation was practiced on dried Elder trees during Tung dynasty (618–907 A.D.) (Arya 2020).The world production of mushrooms in 2009 was 6.4 million tones. In that the share of Asian countries was 75% (4.8 million

634

Nisha et al.

tonnes) (FAOSTAT 2005). China tops the cultivation followed by USA and Netherlands (Sánchez 2010). In Poland production of P. ostreatus is 20,000 tones. Shiitake is less common there. In Poland the consumption does not exceed 1 kg per capita a year (Stachowiak and Regula 2012). Consumption of wild mushrooms are much more popular (Podymniak 2005). In India consumption of A. bisporus is more that P. sajor-caju. But considering the availability of agro-substrate and climatically it is easy to cultivate the oyster mushroom for most part of the year. The vitamin C content of Pleurotus species ranged from 51.3 to 70.3 mg per 100 g with a mean value of 61.4 mg per 100 g on dry weight basis. The neem cake produced highest amount of vitamin C (68.5 mg/100) in Pleurotus species and it was followed by gram flour. The P. florida was having more protein, tryptophan and phosphorus content on dry weight basis, while P. sajor-caju was superior to P. florida in respect to crude fat content, carbohydrate and energy (Patil et al. 2014). It is estimated that in nature, there are approximately 700 species of mushrooms exhibiting therapeutic properties (Cheng et al. 2008; Rajewska and Bałasińska 2004).The popular medicinal mushrooms include the species like, Lentinus edodes—shiitake, Hericium erinaceus (Lion’s Mane Mushroom, Bearded Tooth Mushroom, Hedgehog Mushroom, Bearded Hedgehog Mushroom and Pom Pom Mushroom), Pholiota nameko (Nameko), Gandoderma lucidum (Lingzhi or Reishi Mushroom), ABM—Agaricus blazei Murill, Cordyceps sinensis (Dong Chong Xia Cao), Auricularia auricula (Wood Ear) and Coriolus versicolor (Turkey Tail, or Yun Zhi) etc.

25.3

Waste Management Through Mushroom Cultivation

The increasing food and energy prices in the recent times have forced us for waste recycling as an alternate energy source. This will also help in preventing health hazards. In India, the total amount of agricultural by-products or wastes, which are cellulosic in nature, account for nearly 25 million tones in a year (Ghose and Ghosh 1978). These materials constitute the perennial source of raw material for mushroom cultivation. The waste is this category includes different cereal straws. This Mushroom is commonly grown for food in the orient due to its excellent flavor and certain valuable nutrients as compared to any other mushroom. Basidomycetes play an important role in nature by recycling carbohydrates through lignin degradation by the white—rot Basidomycetes is achieved through lignolytic enzymes such as laccase, lignin, peroxidase, and magnesium peroxidase. Producing mushrooms using agricultural wastes and residues such as rice straw, coco peat, rice bran, coconut husk and banana leaf litters can be considered as economically suitable solution for utilization of agricultural wastes by most efficient biological processes of recycle and reuse these wastes and by-products (Dehariya and Vyas 2013). Poppe (2000) reported that there are about 200 types of waste in which edible mushrooms can be grown.

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

635

All medicinal mushrooms are lignocellulose degraders and can use wood as substrate for the mycelial growth and for the fruit body production. The logs of hardwood trees are still practiced mainly in Asia. This process occurs over several years and yields two crops of mushrooms each year and continues until the log physically collapses due to wood degradation. In this outdoor process, various quality mushrooms are produced, but is not economically viable for production (Stamets 2000). The entire growing process being carried out with paddy straw under controlled environmental conditions over a reduced time scale (1–3 months). Almost all edible medicinal mushroom fruit bodies are now produced worldwide by modifications of this method (Stamets 2000). Different substrates tried for oyster mushroom cultivation are listed in Table 25.1. Billions of tons of agricultural waste are generated each year in the developing and developed countries. Agricultural residue includes all leaves, straw and husks left in the field after harvest, hulls and shells removed during processing of crop at the mills, as well as animal dung. The types of crop residue which play a significant role as biomass fuels are relatively few. The single largest category of crops is cereals, with global production of 1800 Tg in 1985 (Food and Agriculture Organization 1986). Wheat, rice, maize, barley, and millet and sorghum account for 28%, 25%, 27%, 10%, and 6%, respectively, of these crops. According to Yevich and Logan (2003) 400 Tg of crop residues are burned in the fields, with the fraction of available residue burned in 1985 ranging from 1% in China, 16–30% in the Middle East and India, to about 70% in Indonesia; in Africa about 1% residue is burned in the fields of the northern drylands, but up to 50% in the humid tropics. The waste products which are the main contributors to biomass burning are wheat residue, rice straw and hulls, barley residue, maize stalks and leaves, and millet and sorghum stalks. Sugarcane (0.95 gigatons) provides the next sizeable residue with two major crop wastes: barbojo, or the leaves and stalk, and bagasse, the crop processing residue. Crop residue produced in Africa accounts for about 10% of the total agricultural residue in the developing world. The other countries of Southeast Asia have rice and sugar cane as dominant crops. The fate of these residues in the five agro-climatic regions was described by McIntire et al. (1992). About 80% of wheat and barley is grown in the rain fed drylands of the northern coast, while a similar fraction of millet and sorghum is grown in the sub-Saharan semi-arid Zone. Egypt, Madagascar, and Nigeria provide 62% of the rice residues in Africa. Cotton is another produce available there. Maize is grown for the most part (about 75%) in the eastern countries of Africa, Egypt and South Africa. Most of the minor agro-industrial crop waste of palm (95%), coffee (56%), groundnut (50%), and coconut (40%) is produced in the tropical sub humid and humid zones. Sugar cane residue is burned over 90–99% of the sugar cane crop area of Brazil before harvest. Usually 50% of tobacco wastes are burned in the field as pest-control measures throughout Central and South America (Hall et al. 1993). In other countries of South and Central America, farmers burn the cotton stalks in the field. Wheat residue is burned in northern Mexico. Agroindustrial biomass waste is used mainly as fuel for the processing industry, and is rarely transported any distance from the mills for other purposes (Openshaw 1986).

636

Nisha et al.

Table 25.1 Different substrates tried by mycologists to cultivate some species of Pleurotus S. no. 1.

Mushroom Pleurotus sp.

2.

Pleurotus citrinopileatus

3.

P. djamor

4. 5.

P. flabellatus P. florida

6.

P. platypus

7.

Pleurotus spp.

8.

Pleurotus sajorcaju P. pulmonarius

9. 10.

P. pulmonarius Pleurotus sajorcaju

Substrate used Tree leaves Corn waste Textile industry waste Cotton seed hull Coir pith+ cassava bagasse Oak saw dust Safflower hay Bean straw Sunflower head residue Paddy straw Non-retted coir pith Retted coir pith Paddy straw, coco peat, and rice bran Coconut bunch waste Coconut leaf lets Bagasse + rice straw Mycoinoculated mulberry and castor biomass Eicchornia crassipes (leaf with petiole) Wheat Paddy Finger millet Poplar leaves Paddy straw Non-retted coir pith Retted coir pith Coconut coir pith Oil palm fiber waste Banana Pulses Sugarcane trashes Coco peat Cocoa leaf waste Millet waste Pinus + Sugarcane bagasse Wheat straw Cotton stalk Sorghum straw Soya hulls NaOH pretreated sugarcane Baggasse

Reference Upadhyay and Verma (2000) Khan and Chaudhary (1989) Khan and Siddiqui (1989) Sun and Yu (1989) Pothiraj and Eyini (2008) Atila (2017) Atila (2017)

Ouseph et al. (2001)

Zurbano et al. (2017) Thomas and Rajagopal (2003) Thomas and Rajagopal (2003) Pani et al. (1998) Sharma et al. (2001) Nisha (2011) Tiwari et al. (2019)

Ouseph et al. (2001)

Thiradimani and Marimuthu (1992) Thiribhuvanamala et al. (2013)

Gaitan-Hernandez (2001) Nisal et al. (2003)

Chandrashekar et al. (2001) (continued)

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

637

Table 25.1 (continued) S. no.

Mushroom

11.

P. ostreatus

12.

P. ostreatus (white strain)

13. 14.

P. tuber regium Pleurotus eryngii P. flabellatus P. florida P. ostreatus P. sajor-caju Pleurotus citrinopileatus P. flabellatus P. florida P. ostreatus P. pulmonarious P. sajor-caju

15.

Substrate used Paddy straw Non-retted coir pith Retted Coir pith Cotton + wheat+ soybean Soybean straw Coconut coir pith Coconut bunch waste + leaflets Coconut leaflets Cotton Paddy Cotton + paddy Paddy straw Ragi straw

Reference Ouseph et al. (2001)

Patil and Jadhav (1999) Dehariya and Vyas (2013) Thomas et al. (1998), Thomas and Rajagopal (2003) Solunke (2013)

Jandaik and Kapoor (1974) Jandaik and Kapoor (1974), Bano et al. (1979) Atila (2017) Velazquez-Cedeno et al. (2002) Ali et al. (2018) Khan et al. (2014)

Poplar saw dust + wheat straw Coffee pulp Oil Palm fronds Cotton waste Paddy straw Wheat straw Wheat straw + sugar cane lvs Wheat straw

Doshi and Sharma (2001) Ram et al. (2013)

Oil palm waste

Kochu and Nair (1991)

Geographical distribution of crop residue is skewed by large crop productions in India and China (FAO 1986). The other countries of Southeast Asia have rice and sugar cane as dominant crops. In the Middle East, the crop mixture is more diverse with more cereals and less rice and sugar cane. In the dry lands of the Near East and Mediterranean northern Africa, wheat and barley predominate. In the sub-Saharan Sahel in Africa, millet and sorghum are the main crops. However, residue is burned in the fields in India; for example, in Punjab (Jenkins et al. 1992). Rice straw in the central region around Hyderabad is also burnt in the fields.

638

Nisha et al.

25.3.1 Different Substrates Used: Effect on Biological Efficiency Higher yield, N, P, and K contents were noted in rice straw (RS):coco peat (CP):rice bran (RB) combination. This substrate influenced the biological efficiency of P. djamor (Zurbano et al. 2017). Moyin-Jesu et al. (2012) also reported that there was a gradual increase in average and total yield of mushroom as the nutrient concentration increases. However, they also stated that increasing it further could increase chances for other fungi to compete with the mushroom spore for available nutrient thereby could create a suitable environment for contamination. Furthermore, Custodio and Christopher (2004) found that cellulose and lignin contents were important components of any substrate since the lignocellulytic enzymes of oyster mushrooms convert them into carbohydrates which serve as the energy source. Cellulose-rich substrates give better yield and helps in enzyme production, which is correlated with higher yield (Arisha and El-Hady 2010). Same results were obtained in our trials at Vadodara. Coconut peat contains 53.5% lignin and 35.99% cellulose (Israel et al. 2011) which was relatively higher than the lignin and cellulose of good lumber sawdust (35–45% and 20–25%) (Sjostrom 1993); coconut husk (45–55% and 25–50%) and banana leaves (13.3% and 37.3%) (Mohapatra et al. 2010). Coconut sawdust has higher cellulose content (54.78%) than coconut peat, it has lower lignin content (28.47%) than the latter. Likewise, rice straw contains 32% cellulose and 22.3% lignin (Xiao et al. 2001). Their lignin and cellulose components were much higher than the other substrates combined with rice straw, hence, the higher yield was obtained. Various hypothesis have been proposed that how the wood or organic matter with a C: ratio of 300–500: 1 N supports the growth of fungal mycelium. Preferential utilization or recycling of nitrogen may take place by autolysis and reuse or by the action of diazotrophs (Cowling and Merrill 1966). Balaji et al. (1999) reported presence of Azotobacter chroococcum in the straw which provided the nitrogen for the growing fungi. Just like helper bacteria help in mycorrhizal formation, few bacteria are involved in initiation of basidiocarp in certain mushrooms (Rainey 1989). Sharma et al. (2001) evaluated the potential of mycorrhiza inoculated castor (Ricinus communis) and mulberry (Morus alba) biomass, and found these as better substrates. The presence of greater amounts of nutrients and altered chemical constituents in highly mycorrhizal biomass and low C:N ratio (castor 45.2 and mulberry 43) as compared to wheat (63.62) and Paddy straw (68.9) may have influenced more growth. Presence of fatty acids in castor was another cause of improved mushroom yield (Sharma et al. 2001).

25.3.2 Treated Substrates for Better Mushroom Yield Arya and Arya (2003) found better results of the growth of P. sajor-caju using forest tree leaves after acid hydrolysis. Popular polythene bag technique was replaced by

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

639

earthen pot method, in which first harvest was obtained from top surface and then whole substrate was taken out of earthen pots and mushrooms were obtained in second flush from the three sides (Arya and Arya 2001). Studies on the effect of vinyl mulching on Pleurotus cultivation were reported by Oh et al. (2003). Tiwari et al. (2019) reported delayed fruiting when poplar leaves were used as substrate. Lignocellulosic degradation of three oyster mushroom was observed by (Ouseph et al. 2001). They observed better mushroom growth in retted coir as compared to normal coir. Presence of more nitrogen in retted coir was observed. Soaking of sugarcane bagasse in different concentration of NaOH was tried for 12 h (Chandrashekar et al. 2001). Better growth of P. sajor-caju was obtained in 2% NaOH treated milled bagasse.

25.4

Role of Supplements in Mushroom Production

Different Pleurotus species gave significantly higher yield with chicken manure, gram powder, maize meal and wheat bran as compared to their respective controls. Gupta and Raina (2008) working with P. sajor-caju found that chicken manure and gram powder increased the formation of sporophores, while soybean, mustard oil cake and rice bran. In P. eous the yield was more in chicken manure followed by wheat bran and maize meal. An enhanced yield response was recorded with supplements like wheat and rice bran (Bahukhandi 1990). Srivastava and Singh (1999) reported increase in yield due to maize meal. Mustard oil cake supplementation resulted in reduced yield of Pleurotus (Vijay and Upadhyay 1989). Patil et al. (2014) tried wheat, rice bran, gram flour, neem cake, urea, cellulose powder and KH2PO4 for oyster formation. The gram flour and fertilizer treatment enhanced the biological efficiency of P. florida and P. sajor-caju.The optimum C/N ratio for P ostreatus (Heltay and Latkoczky 1960), as well as P. sajor-caju (Poppe 2000) was 45–55/1 and for P. flabellatus it was 45–60/1 (Chang et al. 2000).

25.5

Mushroom Production: Role Of Enzymes

Oyster mushroom grows on a variety of substrates. Scientists have found Pleurotus as white rot causing fungi. Both lignin and cellulose are consumed by fungi as a source of carbon and wood turns white. It is interesting to note that human being across the world use about a million tons of paper every single day. Only a fraction of it is recycled paper. Most of the trash is burnt or degraded by microbes present in soil. The fungal enzymes play a definite role in degradation of cellulose present in it. Maximum activity of enzymes Cellulase (Cx) and Polygalacuronase transeliminase (PGTE) was observed at 10 days in blue oyster (Hypsizygus ulmarius) (Jatav et al. 2012). During a study, Nakazawa et al. (1974) investigated the cellulolytic enzyme activity in various edible and nonedible fungi and concluded

640

Nisha et al.

that it was higher in culture medium than the fruit bodies. Role of Cx enzymes may be in substrate colonization while polygalacturonase and PGTE may be in the primordial formation. Subsequently the role of polymethyl galacturonase and pectin transeliminase may be in the multiplication and enlargement of tissues. Cellulolytic activities of the widely consumed edible mushroom Pleurotus ostreatus from Egypt has been reported by Daba et al. (2011), in which promising endo and exoglucanase activities were shown. Laccases (p-diphenol: oxygen oxidoreductases, EC 1.10.3.2) are glycoproteins belonging to the group of polyphenol oxidases. These enzymes catalyze the oxidation of phenolic compounds, reducing one oxygen molecule to water and generating a phenoxy radical (Baldrian 2006). These are produced by most white rot fungi, insects, and some bacteria (Thurston 1994). In white rot fungi, laccase production helps in delignification of wood, water and soil bioremediation, beverage clarification, and degradation of dyes discharged in effluent etc. (Baldrian 2006). Pleurotus eryngii (Wang and Ng 2004), and have been suggested to be candidates for industrial uses. Fungal laccases are produced in submerged cultures in stirred tank reactors (STRs). Stirring is one of the process parameters that affect mycelial cultures, due to its influence over oxygen transfer to the medium and, thus, over energy dissipation by the impellers. Energy release causes cell wall damage by exercising hydrodynamic stress (Rocha-Valadez et al. 2005). It altered the fungal growth and productivity of mushroom. According to Pothiraj and Eyini (2008) the mixed substrate of coir pith and cassava bagasse had 27.2% lignin and 28.5% cellulose and 6% hemicellulose. The fungus P. citrinopileatus showed a low potential for producing ligninase and APPL in pure coir, while it reduced 41% lignin and 74% cellulose when used with cassava bagasse. Pleurotus spp. are reported to be efficient colonizers and degraders of lignocelluloses. Commercially P. ostreatus Jacq. ex Fr. grows on dead logs or stumps. In Turkey it is termed as “Kavak mantarı” or “Kayın mantarı” and “İstiridye mantarı.” Although cultivation of this mushroom has significantly increased since last 5 years (Eren and Pekşen 2016), there are very few producers growing it on commercial scale. The substrates used in each region depend on the locally available agricultural wastes for Pleurotus spp. The EDCF (kW/m3s) is the product of specific energy dissipation in the impeller sweeping volume (P/kD3) and particulate circulation frequency (1/tc) in that volume. Tinoco-Valencia et al. (2014) studied the effect of initial EDCF (0.9–5.9 kW/ m3s) and aeration rate (0.1–0.5 vvm) on the laccase production of Pleurotus ostreatus CP50. The study revealed that both the initial EDCF and the aeration rate stimulated the fungal growth but reduced the production of the enzymes. The aim of this study was to independently evaluate the effect of hydrodynamic stress and dissolved oxygen tension on the growth, production and expression of genes encoding laccases from P. ostreatus in submerged cultures with mechanical agitation. The findings of Fernandes et al. (2015) suggested that the positive effect of EDCF on the specific laccase production is not exercised at the transcriptional level, while the effect of oxygen is. The oxygen might be involved in the fungal response to oxidative stress. This response causes the activation of an alternative respiratory pathway, decreasing reactive oxygen species(ROS) production. The presence of

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

641

ROS has been shown to induce the expression of genes coding for ligninolytic enzymes (Zhao et al. 2009). The expression of the pox3 gene, another laccaseencoding gene, was also analyzed, and under the conditions, its relative expression was 100 times lower than poxc; however, neither DOT nor EDCF affected its expression. In short, EDCF had a positive effect on specific laccase production and defined the size of the pellets; however, EDCF did not affect the fungal growth rate or laccase-encoding gene expression. This suggests that the increase in the specific production of the enzyme is due to mechanical stresses. NADP-GDH occurs at high activity in the basidiome pileus, but is absent from the stipe and parental mycelium. This enzyme can be specifically detected in histological preparations of living tissues using a tetrazolium staining procedure (Elhiti et al. 1979). Application of this technique has shown that an overall increase in enzyme activity in the pileus does not occur through a uniform increase in each constituent cell. Rather, at early stages a scattering of cells show high activity, and it is the proportion of cells showing the enzyme activity which increases as the tissues mature. These scattered cells first appear in narrow stripes across the gill and as the tissues mature the stripes become wider until eventually all the hymenial cells show activity of this enzyme (Elhiti et al. 1979). Evidently, there is a channel for lateral communication, but the relationships between adjacent cells are known in only the vaguest way and evidence for the existence of chemical growth factors or hormones is confused and inconclusive (Novak Frazer 1996).

25.6

Genes Working for Lignocellulose Degradation

More than 100 genomes are sequenced from wood decay fungi. For edible mushrooms of the Pleurotus species, three North American, eight European, and five Asian inter-sterility groups have been found (Bao et al. 2004). In Schizophyllum commune the development of a fruit body inducing substance is genetically controlled (Leslie and Leonard 1980). In Polyporus species, there are fi+ genes (fruiting initiation) (Esser 1989). The force of gravity determines that the yearly hymenial layers in the bracket-like, perennial fruit bodies of Fomes fomentarius also point to the earth center if the host tree is lying on the ground (Schmidt 2006). Plant cell walls (PCW) consists of organic carbon in form of complex polymer of lignin along with cellulose and hemicelluloses. Mushroom forming fungi degrade all woody cell wall components including lignin and called white rot species, while only cellulose is degraded by brown rot fungi (Martinez et al. 2009). The traditional saprophytes may be white or brown rot fungi (Nagy et al. 2015). These Agaricomycetes are the most effective microorganisms in degrading both components of cell walls. Certain fungi produce white rot symptoms but lackclass II peroxidases(PODs), which are classified as Auxiliary Activity Family 2 (AA2) (Riley et al. 2014). In addition to AA2, lignin degradation by white rot fungi involves several other enzyme families, such as AA1 (multicopper oxidases, MCO) and heme-thiolate peroxidases (HTP) (Hofrichter 2002). In addition to

642

Nisha et al.

AA2, white rot fungi have other enzymes such as AA1 (Multicopper oxidase, MCO) and dye decolorizing peroxidases (DyP) and HTP (Rytioja et al. 2014). The degradation of cellulose takes place by cellobio-hydrolases (GH6 and GH7) and lytic polysaccharide monooxygenases AA9 LPMOs, (Morgenstern et al. 2008). A number of other carbohydrate-active enzyme families’ help in degradation of carbohydrate (Rytioja et al. 2014). Compared to white rot fungi the ectomycorrhizal organisms and brown rot fungi have reduced complements of the gene-encoding enzymes that decompose lignin, PCW polysaccharide, or both (Kohler et al. 2015).

25.7

Oyster Mushroom Cultivation: Use of Organic Cellulose Waste

Nutritional requirements and the limits of the physical environment needed for mycelial growth and formation of fruiting bodies have been investigated for many Pleurotus spp. The Shiitake mushroom is grown on wood waste. Recent studies have indicated that cellulosic materials like waste paper and cotton can be also used as a substrate for the cultivation of oyster mushroom. Paddy straw is easily available abundantly in different villages in the country. Its proper utilization is needed as its extensive burning in Punjab and nearby areas is causing a serious environmental pollution issue in capital city of Delhi every year during November and December. In this study waste paper from offices and cotton from laboratories of Science Faculty, The M.S. University of Baroda were used as along with paddy straw to access the biological efficiency of P. florida.

25.7.1 Organism Used and Culture Conditions The culture of Basidomycetous fungus Pleurotus florida was obtained from National Center for Mushroom Research and Training (NCMRT), Solan. It was maintained on 2% Agar slants consisting of PDA.

25.7.2 Cultivation Method: Use of Waste Paper and Cotton Waste Fresh, good quality paddy straw bits (4–5cm) were soaked in water for 18–24 h and dried. Paddy straw was packed into polypropylene bags and autoclaved at 15 lb psi for 45 min. Autoclaved paddy straw was filled in fresh polypropylene bags of the size of 45 cm height. A layer of spawn was added after 10 cm above paddy straw layer. The procedure was repeated until 3/4th height of polypropylene bag was filled

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

643

up. Then the holes were made throughout the bag to allow aeration, excess water was drained. The filled bags were incubated at 21  2  C in dark or with poor light for 21 days. The materials taken were cotton waste (250 g), paddy straw (750 g). The waste materials were then thoroughly mixed with water until adequate moisture content was maintained. After mixing, the substrate was packed in small polypropylene bags (1 kg), tied with rubber bands, and sterilized. After sterilization, the bags were allowed to cool in the laboratory and each bag was inoculated with 200 g spawn (5% total weight). Other combinations were tried as mentioned in Table 25.2. The inoculated substrate bags with waste cotton and paper were placed on the laboratory bench and covered with dark polythene sheet for incubation. After full colonization of mycelium, the bags were exposed in the growth room by removing the rubber bands and opening of the bags. Watering was adequately done to increase the relative humidity of the environment to enhance sporophore emergence. Results obtained are mentioned in Table 25.2.

25.7.3 Cultivation: Results and Discussion The results showed that the spawn running was completed in the bags within 21 days (Fig. 25.2a, c) and pinheads appeared on 26th day (Fig. 25.2d, e). The Pinheads turned into fully grown basidiocarps (Figs. 25.2f and 25.3b–d) on 31st day and the results of first harvest are presented in Table 25.2 and Fig. 25.1. The table shows results of four harvests. The second harvest was after 5 or 6 days of first harvest. In order to find out the Biological efficiency (BE) observations of the total mushroom harvested was calculated and the results were recorded and calculated on the basis of total dry substrate used (Fig. 25.1) The growth of Pleurotus florida in cotton waste mixed with wheat straw (50:50) produced higher yield (74.35 g) than Paddy straw and paper (51.38 g) at same ratio. The incubation period to the emergence of basidiocarps was longer for cotton waste Table 25.2 The different proportion of substrates was used in bags with waste cotton and paper and the weight of mushroom obtained and BE of P. florida was calculated

S. no 1. 2. 3. 4. 5. 6. 7.

Treatments Paddy straw 100% Straw + paper (25:75) Straw + paper (50:50) Straw + paper (75:25) Straw + cotton (25:75) Straw + cotton (50:50) Straw + cotton (75:25)

Wt. of mushroom in different harvests (in g) 1st 2nd 3rd 4th 320 280 85 70 278 182 70 – 84 410 141 35 311 350 180 103 100 92 40 – 320 291 57 70 415 65 94 –

Data based on average of three replicates

Total wt. (in g)

B.E. %

755 530 670 944 232 738 674

75.5 53 67 94.4 23.2 73.8 67.4

644

Nisha et al.

B.E. % 100 80 60 40

B.E. %

20 0 Paddy straw Straw + (100) paper (25:75)

Straw + paper (50:50)

Straw + paper (75:25)

Straw + co on (25:75)

Straw + co on (50:50)

Straw + co on (75:25)

Fig. 25.1 The B.E. of P. florida in different concentration of waste substrates

mixed with wheat straw (5 weeks) compared to that for the Paddy straw and paper (4 weeks). Adding only 25% paper enhanced the BE of P. florida, large number of fruiting bodies were observed than P sajor-caju (Fig. 25.3c). The main substrate material alone sometimes cannot provide enough nitrogen required for optimal growth of mushrooms. Additives such as rice or wheat bran provide a nitrogen source (Choi 2004). Amounts of supplements that should be added varies with the substrate chosen. Oei (2003) suggested a range of 5–10% wheat bran. Choi (2004) also reported that if cotton waste is chosen as the main substrate material for Oyster mushroom cultivation, a nitrogen source such as rice bran should be supplemented. Nitrogen is converted to ammonia nitrogen and Beyer and Wilkinson (2002) found a direct correlation between substrate ammonia content and subsequent growth of mushrooms. Atila (2017) suggested different substrates for the cultivation of oyster mushrooms i.e. 1. Cotton seed hull 95%, gypsum 2%, lime 1%, and calcium superphosphate 2%. 2. Rice straw 80%, cotton waste 18%, gypsum 1%, and lime 1%. 3. Water hyacinth 80%, cereal straw 17%, gypsum 2%, and lime 1%. Large pieces of cotton waste were torn into small parts or the straw and water hyacinth was cut into small segments. This was then be mixed with 2% (w/w) lime and sufficient water to get moisture content of about 60–65%. Pasteurization was done at a temperature of 70–80  C for at least 8 h. The substrate was filled in polythene bags, and left to stand at around 24  2  C, preferably in the dark. When the mycelium had completely covered the substrate after 3 weeks, the plastic wrapping was removed and dim light was provided. Watering was needed to keep the surface moist Figs. 25.2 and 25.3 show different treatments and production of mushrooms. In around 6 days white primordia had started to appear over the whole surface. After another three to 4 days, the mushrooms were ready for picking. During the incubation period of substrate watering was very essential three to four flushes to appear.

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

645

Fig. 25.2 (a) Substrate of paddy straw and waste paper and (b) only paddy straw used for Pleurotus florida cultivation, (c) substrate filled in polypropylene bags, (d) bags showing pin head like out growths when polypropylene is cut open, (e and f) enlargement of mushroom primordia after 7 days of incubation. (Source: author)

Mushroom fruit bodies are complex structures, both morphologically and physiologically with undoubted variations in chemical composition from batch to batch. The basic substrate and supplementary ingredients affect the chemical composition of any mushroom. Although the basic raw materials are lignocellulosics from plants. The variation in size and age which will, undoubtedly, influence specific biochemical composition (Wasser et al. 2002). These are of concern when standardization of the extracted products (nutraceuticals/pharmaceuticals) is done without extensive and costly purification. There is an increasing dependency on pure culture cultivation strategies for the

646

Nisha et al.

Fig. 25.3 (a) A bag of substrate showing white colored mycelial growth of Pleurotus florida, (b) and (d) showing complete growth of basidiocarps of P. florida, (c) growth of basidiocarps of P. sajor caju. The number of fruiting bodies were more where paper was mixed with paddy straw as substrate. (Source: author)

growth with major reduction in production time, optimisation of medium composition and physicochemical conditions to allow regulation of mushroom metabolism, improved yield of specific products and designed variation of product types. Fruit body development occurs due to exogenous factors like humidity, temperature, light, nutrition, gravity, air quality, and interaction with other organisms (Albert 2003). According to Schmidt (2006) endogenous factors include phenol oxidases, cyclic adenosine monophosphate (AMP) and genes. Temperature increase promotes fruit primordial initiation. Pleurotus has fleshy consistency, which lose when drying.

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

647

Short wavelength (UV blue) light may influence fruit body formation (Sánchez 2010). The oyster fungus (P. ostreatus) fruits below 16  C and the less tasty P. ostreatus fsp. florida at a higher temperature (Schmidt 2006).

25.8

Conclusion

Mushrooms are relatively fast growing organisms, thus, mushroom cultivation as a short return agricultural business can be of immediate benefit to the community. While land availability is usually a limiting factor in most types of primary production, mushroom cultivation requires relatively little space; they can be stacked using shelf-like culture systems. It is, therefore, hoped that the avocation of mushroom farming will become a very important cottage industry in integrated rural development programs. This will lead to the economic betterment of not only small-holder farmers but also of landless labourers and other weak sections of communities. Furthermore, mushroom cultivation can be a part time agro-industrial activity, thus can help generate extra income and employment, particularly for women and youth in developing countries. Use of waste paper and cotton has resulted in better BE and can thus be adopted along with a variety of lignin and cellulosic wastes. It has a definite role in circular economy. The spent mass can be utilized as feed to cattle and then used as compost for better crop yield.

References Aida FMNA, Shuhaimia M, Yazidb M, Maaruf AG (2009) Mushroom as a potential source of probiotics: a review. Trends Food Sci Technol 20:567–575 Albert G (2003) Trichoderma. Konkurrent, Parasit und Nützling. Champignon 431:6–9 Ali N, Khairudina H, Mohamedb M, Hassana O (2018) Cultivation of Pleurotus ostreatus on oil palm fronds mixed with rubber tree sawdust. Chem Eng Trans 63:547–552 Arisha MH, El-Hady M (2010) Optimum medium for oyster mushroom production. Unpublished Master’s Thesis, Zagazig University. www.academia.edu/9849562/OPTIMUM_MEDIUM_ FOR_OYSTER_MUSHROOM_PRODUCTION Arya A (2020) Beauty, diversity and utility of mushrooms. Kahar, Lucknow, India 7(1–2):35–40 Arya C, Arya A (2001) A simple technique for cultivation of oyster mushroom. J MS Univ Baroda 48(3):67–70 Arya C, Arya A (2003) Effect of acid hydrolysis of substrates and the yield of oyster mushroom Pleurotus sajor caju (fr.). Singer Mushroom Res 12(1):35–38 Atila F (2017) Evaluation of suitability of various agro-waste for productivity of Pleurotus djamor, Pleurotus citrinopileatus and Pleurotus eryngii mushrooms. J Exp Agric Int 17(5):1–11 Atri N, Sharma SK, Joshi R, Gulati A, Gulati A (2013) Nutritional and nutraceutical composition of five culinary-medicinal species of genus Pleurotus (higher Basidiomycetes) from northwest India. Int J Med Mushrooms 15:49–56 Bahukhandi D (1990) Effect of various treatments on paddy straw on yield of some cultivated species of Pleurotus. Indian Phytopathol 43(3):471–472

648

Nisha et al.

Balaji S, Sujatha A, Kalyansundaram I (1999) Natural enhancement of nitrogen content of the oyster mushroom substrate by Azotobacter. Mushroom Res 8(1):31–36 Baldrian P (2006) Fungal laccases occurrence and properties. FEMS Microbiol Rev 30:215–242 Bano Z, Rajarathnam S, Nagaraja N (1979) Some aspects on the cultivation of Pleurotus flabellatus in India. Mushroom Sci 10(2):567–608 Bao D, Kinugasa S, Kitamoto Y (2004) The biological species of the oyster mushrooms (Pleurotus spp.) from Asia based on mating compatibility tests. J Wood Sci 50:162–168 Bobek P, Nosalova V, Cerna S (2001) Effect of pleuran (beta-glucan from Pleurotus ostreatus) in diet or drinking fluid on colitis in rats. Nahrung 45:360–363 Chandrashekar BS, Savalgi V, Kukarni JH (2001) Cultivation trials of Pleurotus sajor-caju(Fr.) Singer on sodium hydroxide pretreated sugarcane by-products. Mushroom Res 10(1):27–30 Chang ST, Miles PG (1992) Mushroom biology—a new discipline. Mycologist 6:64–65 Chang H, Moon R, Park B et al (2000) Simulation of sequential batch reactor (SBR) operation for simultaneous removal of nitrogen and phosphorus. Bioprocess Eng 23:513–521. https://doi.org/ 10.1007/s004499900188 Cheng JJ, Lin CY, Lur HS, Chen HP, Lu MK (2008) Properties and biological functions of polysaccharides and ethanolic extracts isolated from medicinal fungus, Fomitopsis pinicola. Process Biochem 43:829–834 Choi KW (2004) Shelf cultivation of oyster mushrooms. http://www.mushworld.com:1508/service/ handbook/2004/chapter-7-2.pdf Cowling EB, Merrill W (1966) Nitrogen in wood and its role in wood deterioration. Can J Bot 44: 1539–1554 Custodio D, Christopher J (2004) Oyster mushrooms substrates. Mushroom growers handbook. Mushworld. www.mushworld.com/home Daba AS, Youssef GA, Kabeil SS, Hafez EE (2011) Production of recombinant cellulase enzyme from Pleurotus ostreatus (Jacq.) P. Kumm. (type NRRL-0366). Afr J Microbiol Res 5: 1197–1202 Dehariya P, Vyas D (2013) Effect of different agro-waste substrates and their combinations on the yield and biological efficiency of Pleurotus sajor-caju. IOSR J Pharm Biol Sci IOSR-JPBS 8(3): 60–64 Doshi A, Sharma SS (2001) Production of edible tubers and fruit bodies of Pleurotus tuber regium (Fr.) Sing. in Rajasthan, India. Mushroom Res 10(1):31–35 Elhiti MMY, Butler RD, Moore D (1979) Cytochemical localization of glutamate dehydrogenase during carpophore development in Coprinus cinereus. New Phytol 82:153–157 Eren E, Pekşen A (2016) Türkiye’de kültür mantarı sektörünün durumu ve geleceğine bakış. Turkish J Agric Food Sci Tecnol 4(3):189–196 Esser K (1989) Anwendung von Methoden der klassischen und molekularen Genetik bei der Zuchtung von Nutzpflanzen. Mushroom Sci 11(1):1–23 FAOSTAT (2005) United Nations, Food and Agriculture Organization. http://faostat.fao.org/site/2 91/default.aspx Fernandes A, Barros L, Martins A, Herbert P, Ferreira ICFR (2015) Nutritional characterisation of Pleurotus ostreatus (Jacq. ex Fr.) P. Kumm. produced using paper scraps as substrate. Food Chem 169:396–400 Food and Agriculture Organization (1986) Production yearbook 1985, Rome Gaitan-Hernandez R (2001) Use of brown rot fungus degraded substrate for the cultivation of Lentinula spp. and Pleurotus spp. Mushroom Res 1(1):13–21 Gentles AJ, Newman AM, Liu CL, Bratman SV, Feng W, Kim D, Nair VS, Xu Y, Khuong A, Hoang CD (2015) The prognostic landscape of genes and infiltrating immune cells across human cancers. Nat Med 21:938–945 Ghose TK, Ghosh P (1978) Bioconversion of cellulosic substance. J Appl Chem Biotechnol 28: 309–320 Giavasis I (2013) Productionofmicrobial polysaccharides for use in food. In: McNeil B, Archer D, Giavasis I, Harvey L (eds) Microbial production of food ingredients, enzymes and nutraceuticals. Wood Head Publishing, pp 413–468

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

649

Giavasis I, Biliaderis C (2006) Microbialpolysaccharides. In: Biliaderis C, Izydorczyk M (eds) Functional food carbohydrates. CRC Press, pp 167–214 Gunde-Cimerman N, Cimerman A (1995) Pleurotus fruiting bodies contain the inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A reductase-lovastatin. Exp Mycol 19:1–6 Gupta A, Raina PK (2008) Effect of supplements on the yield of some high adaptive Pleurotus species in sub-tropics of Jammu. Mushroom Res 17(1):13–17 Hall DO, Rosillo-Calle F, Williams RH, Woods J (1993) Biomass for energy: supply prospects (Chap. 14). In: Kelly H, Reddy AKN, Williams RH (eds) Renewable energy: sources for fuels and electricity. Island, Washington, DC, pp 593–651 Hawksworth D (2001) The magnitude of fungal diversity: the 1.5 million species estimate revised. Mycol Res 105(12):1422–1432. https://doi.org/10.1017/S0953756201004725 Heltay I, Latkoczky UA (1960) Investigations to elucidate the “degeneration” problem of the cultivated mushroom (Psalliota bispora (Lge.) Möll.-Schäff.) varieties. Mushroom Sci 4:52–85 Hofmann A (1959) Psilocybin und Psilocin, zwei psychotrope Wirkstoffe aus mexikanischen Rauschpilzen. Helvetica Chemica Acta 42:1557–1572 Hofrichter M (2002) Review: lignin conversion by manganese peroxidase (MnP). Enzym Microb Technol 30:454–466 Israel AU, Ogali RE, Akaranta OO, Obot IB (2011) Extraction and characterization of coconut (Cocos nucifera L.) coir dust. Songklanakarin J Sci Technol 33(6):717–724 Jamison S (2015) The Rigveda—earliest religious poetry of India. Oxford University Press, p 1129 Jandaik CL, Kapoor JN (1974) Artificial cultivation of Pleurotus sajor caju (Fr.) Singer. Mushroom J 22:405 Jatav RS, Gupta AK, Doshi A, Meena MK, Meena VR (2012) Effect of different temperature and growth stages of blue oyster mushroom on the activity of enzymes. J Plant Dev Sci 4(3): 407–410 Jenkins BS, Turn Q, Williams RB (1992) Atmospheric emissions from agricultural burning in California: determination of burn fractions, distribution factors, and crop-specific contributions. Agric Ecosyst Environ 38:313–330 Khan SM, Chaudhary IA (1989) Some studies on oyster mushroom (Pleurotus spp.) on the waste material of corn industry in Pakistan. Mushroom Sci 12:23–29 Khan S, Siddiqui M (1989) Some studies on cultivation of oyster mushrooms on ligno-cellulosic by products of textile industry. Mushroom Sci 12(2):121–128 Khan NA, Khaliq N, Haq MIU, Javed N, Gondal AS, Bhatty N (2014) Carbohydrate and mineral contents of three strains of oyster mushroom (Jacq.Fr.) cultivated on different agricultural wastes. Mushroom Res 23(1):31–35 Kim SY, Song HJ, Lee YY, Cho KH, Roh YK (2006) Biomedical issues of medicinal propertiesof Pleurotus species (oyster mushroom): a review. J Korean Med Sci 21:781–789 Kim SK, Son CG, Yun CH, Han SH (2010) Hericium erinaceum induces maturation of dendritic cells derived from human peripheral blood monocytes. Phytother Res 24:14–19 Kochu BM, Nair R (1991) Performance of six species of Leslie JF, Leonard TJ1979 three independent genetic systems that control initiation of a fungal fruiting body. Mol Gen Genet 171:257–260 Kohler A, Kuo A, Nagy LG et al (2015) Convergent losses of decay mechanisms and rapid turnover of symbiosis genes in mycorrhizal mutualists. Nat Genet 47:410–415 Leslie JF, Leonard TJ (1980) Monokaryotic fruiting in Schizophyllum commune: survey of a population from Wisconsin. Am Midl Nat 103:367–374 Martinez D, Challacombe J, Morgenstern I et al (2009) Genome, transcriptome, and secretome analysis of wood decay fungus Postia placenta supports unique mechanisms of lignocellulose conversion. Proc Natl Acad Sci U S A 106:1954–1959 McIntire JD, Bourzat P, Crop P (1992) Livestock interaction in Sub-Saharan Africa. World Bank, Washington, DC, p 246 Mizuno M, Nishitani Y (2013) Immuno-modulating compounds in Basidiomycetes. J Clin Biochem Nutr 52:202–207

650

Nisha et al.

Mohapatra D, Mishra S, Sutar N (2010) Banana and its by-product utilization: an overview. J Sci Ind Res 69:323–329 Morgenstern I, Klopman S, Hibbett DS (2008) Molecular evolution and diversity of lignin degrading heme peroxidases in the Agaricomycetes. J Mol Evol 66:243–257 Moyin-Jesu E, Ibukonoluwa ICS, Akinola MO (2012) Comparative evaluation of different organic media on soil chemical composition, growth, and yield of mushroom (Pleurotus tubergium L.). Mushroom Res 9(1):35–38. ISRN Agronomy, Article ID 152737. https://doi.org/10.5402/2012/ 152737 Nagy LG, Riley R, Tritt A et al (2015) Comparative genomics of early-diverging mushroomforming fungi provides insights into the origins of lignocellulose decay capabilities. Mol Biol Evol 33:959–970 Nakazawa K, Jinguji I, Akiyama H, Akiyama R, Akiyama I, Kato A (1974) Studies on cellulolytic enzymes in higher fungi. Mushroom Sci 9:859–865 Nisal PR, Badve VC, Pimplaskar MS, Danay O (2003) Studies on performance of Pleurotus sp. From Israel on local substrates under rural Indian conditions. In: Upadhyay RC et al (eds) Current vistas in mushroom biology and production. Mushroom Society of India, pp 108–114 Nisha (2011) Conversion of waste into edible protein. B.Sc. dissertation, The MS University of Baroda, p 101 Novak Frazer L (1996) Control of growth and patterning in the fungal fruiting structure. A case for the involvement of hormones. In: Chiu SW, Moore D (eds) Patterns in fungal development. Cambridge University Press, Cambridge, pp 156–181 Oei P (2003) Mushroom cultivation-appropriate technology for mushroom growers, 3rd edn. Backhuys Publishers, Leiden Oh SJ, Park JS, Lee DC, Shin PG (2003) Studies on the effect of vinyl mulching on Pleurotus cultivation-control of mushroom diseases on Pleurotus ostreatus (Π). Mycobiology 31(1): 50–53 Ohnon Miura T, Miura NN, Adachi Y, Yadomae T (2001) Structure and biological activities of hypochlorite oxidize dzymosan. Carbohydr Polym 44:339–349 Openshaw KO (1986) Concepts and methods for collecting and compiling statistics on biomass used as energy, report, U.N. Stat. Off., New York Ouseph A, Geetha D, Suharban M (2001) Lignocellulose degradation by oyster mushroom. Mushroom Res 10(1):37–40 Pani BK, Panda SN, Das SR (1998) Bioconversion of sugar cane crop wastes into food by oyster mushroom, Pleurotus sajor-caju. Crop Res 15:297–299 Papaspyridi LM, Katapodis P, Gonou-Zagou Z, Kapsanaki-Gotsi E, Christakopoulos P (2010) Optimization of biomass production with enhanced glucan and dietary fibres content by Pleurotus ostreatus ATHUM 4438 under submerged culture. Biochem Eng J 50:131–138. https://doi.org/10.1016/j.bej.04.008 Patel Y, Naraian R, Singh VK (2012) Medicinal properties of Pleurotus species (Oyster Mushroom): a review. World J Fungal Plant Biol 3(1):01–12. https://doi.org/10.5829/idosi.wjfpb.3. 1.303 Patil MB, Jadhav VT (1999) Studies on production of oyster mushroom on different agro-waste under marathwada condition. J Maharashtra Agric Univ 24(2):162–163 Patil KK, Gaikwad VR, Gupta DN (2014) Influence of supplements on productivity, proximate principles, vitamin C and tryptophan content of oyster mushroom. Mushroom Res 23(1):37–45 Paulík S, Svrcek MJ, Durove A, Benísek Z, Húska M (1996) The immunomodulatory effect of the soluble fungal glucan (Pleurotus ostreatus) on delayed hypersensitivity and phagocytic ability of blood leucocytes in mice. Zentralbl Veterinarmed B 43:129–135 Petrovska BB (2001) Protein fraction in edible Macedonian mushrooms. Eur Food Res Technol 212:469–472 Podymniak M (2005) On common agaric and other cultivated mushrooms. Hasło Ogrod 6:11–12 Poppe J (2000) Use of agricultural waste materials in the cultivation of mushrooms. Mushroom Sci 15:3–23

25

Biochemical Aspects and Cultivation of Medicinal Mushroom Pleurotus. . .

651

Pothiraj C, Eyini M (2008) Biodegradation potential of mushroom fungi in urea or cassava bagasse supplemented coir pith. Mushroom Res 1791:9–12 Rainey PB (1989) The involvement of in sporophore initiation of the cultivated mushroom, Ph.D. Thesis. University of Canterbury, Christchurch Rajewska J, Bałasińska B (2004) Biologically active compounds of edible mushrooms and their beneficial impact on health. Postepy Hig Med Dosw 58:352–357 Ram RC, Pandey VN, Singh HB (2013) Comparison of growth behavior and yield potential of Pleurotus spp. Mushroom Res 22(2):101–104 Riley R, Salamov AA, Brown DW et al (2014) Extensive sampling of basidiomycete genomes demonstrates inadequacy of the white-rot/brown-rot paradigm for wood decay fungi. Proc Natl Acad Sci U S A 111:9923–9928 Rocha-Valadez JA, Hassan M, Corkidi G, Flores C, Galindo E, Serrano-Carreón L (2005) 6-pentyl-α-pyrone production by Trichoderma harzianum: the influence of energy dissipation rate and its implications on fungal physiology. Biotechnol Bioeng 91:54–61 Rytioja J, Hildén K, Yuzon J, Hatakka A, de Vries RP, Mäkelä MR (2014) Plant-polysaccharidedegrading enzymes from Basidiomycetes. Microbiol Mol Biol Rev 78(4):614–649. https://doi. org/10.1128/MMBR.00035-14 Sánchez C (2010) Cultivation of Pleurotus ostreatus and other edible mushrooms. Appl Microbiol Biotechnol 85:1321–1337. https://doi.org/10.1007/s00253-009-2343-7 Schmidt O (2006) Wood and tree fungi: Biology, damage, protection, and use. Springer, Berlin, Heidelberg, p 334 Sharma S, Kashyap S, Singh A, Chowdhary PN, Vasudevan P (2001) Yield of Pleurotus and Agaricus on mycorrhiza-inoculated castor and mulberry biomass. Mushroom Res 10(2):73–79 Shashoua VE, Adams DS (2004) New synthetic peptides can enhance gene expression of key antioxidant defense enzymes in vitro and in vivo. Brain Res 1024:34–43. https://doi.org/10. 1016/j.brainres.2004.06.086 Sjostrom E (1993) Wood chemistry: fundamentals and applications, 2nd edn. Elsevier Inc., San Diego Solunke A (2013) Utilization of some agricutral by-products for cultivation of Pleurotus sajor caju. https://doi.org/10.13140/RG.2.2.12846.10563 Srivastava DK, Singh SP (1999) Effects of different supplements in paddy straw on yield of Pleurotus citrinopileatus(Fr.) Singer. Mushroom Res 8:47–48 Stachowiak B, Regula J (2012) Health promoting potential of edible macromycetes under special consideration of polysaccharides: a review. Eur Food Res Tehnol 234:369–380 Stamets P (2000) Growing gourmet and medicinal mushrooms, 3rd edn. Ten Speed Press, Berkeley/ Olympia, WA, p 574 Sun P, Yu J (1989) The cultivation of Pleurotus mushrooms on sterilized substrate in the field. Mush Sci 12(2):219–228 Thammakiti S, Suphantharika M, Phaesuwan T, Verduyn C (2004) Preparation of spent brewer’s yeast β-glucans for potential applications in the food industry. Int J Food Sci Technol 39:21–29 Thiradimani M, Marimuthu T (1992) Utilization of Pleurotus spp. for decomposing coconut coir pith. Mushroom Res 1:49–51 Thiribhuvanamala G, Prakasam V, Kalaiselvi G, Ragupathi N (2013) Ligninolytic enzyme production by Pleurotus pulmonarius in different agro wastes under solid state fermentation. Mushroom Res 22(2):89–96 Thomas GV, Rajagopal V (2003) Oyster mushroom cultivation for recycling of lignocellulosic biomass from coconut palm. In: Upadhyay RC et al (eds) Current vistas in mushroom biology and production. Mushroom Society of India, pp 100–107 Thomas GV, Prabhu SR, Reeny MZ, Bopaiah BM (1998) Cultivation of oyster in coconut coir pith substrate. World J Microbiol Biotechnol 14:879–882 Thurston CF (1994) The structure and function of fungal laccases. Microbiology 140:19–26 Tinoco-Valencia R, Gómez-Cruz C, Galindo E, Serrano-Carreón L (2014) Toward an understanding of the effects of agitation and aeration on growth and laccases production by Pleurotus ostreatus. J Biotechnol 177:67–73

652

Nisha et al.

Tiwari B, Ravi S, Vivekanand, Verma SK (2019) Performance of Pleurotus florida on different substrate in mid-hill Garhwal Himalaya of Uttarakhand. J Mycopathol Res 56(4):243–245 Upadhyay RC, Verma RN (2000) Non-conventional substrates for growing oyster mushroom. Mushroom Res 9(1):35–39 Velazquez-Cedeno MA, Mata G, Savoie JM (2002) Waste reducing cultivation of Pleurotus ostreatus and Peurotus pulmonarius on coffee pulp: Changes I the production of some lignocellulosic enzymes. World J Microbiol Biotechnol 18:201–207 Vijay B, Upadhyay RC (1989) Chicken manure as a new nitrogen supplement in oystermushroom cultivation. Indian J Mycol Plant Pathol 19:297–298 Wang HX, Ng TB (2004) Purification of a novel low molecular- mass laccase with HIV-1 reverse transcriptase inhibitory activity from the mushroom Tricholoma giganteum. Biochem Biophys Res Commun 315:450–454 Wasser SP (2002) Medicinal mushrooms as a source of antitumor and immune-modulating polysaccharides. Appl Microbiol Biotechnol 60:258–274 Wasser SP, Didukh M, Amazonas MA, Nevo E, Stametes P, da Eira AF (2002) Is a widely cultivated culinary medicinal mushroom indeed agaricus blazei Murill? Int J Med Mushroom 4:267–290 Wasson RG (1957) Seeking the magic mushroom. Life Magazine, 10 June 1957 Wasson RG (1968) Soma, divine mushroom of immortality. (Ethno-mycological studies no. 1), vol xiii. Harcourt, Brace and World, Inc, The Hague: Mouton/New York, p 381 Wasson RG (1980) The wondrous mushroom: mycolatry in Mesoamerica. McGraw-Hill, New York. 7.5. Wasson and Wasson, Mushrooms, Russia, and history 29 Wculek SK, Cueto FJ, Mujal AM, Melero I, Krummel MF, Sancho D (2019) Dendritic cells in cancer immunology and immunotherapy. Nat Rev Immunol 10:1038/s41577-019-0210-z Xiao BS, Xue F, Sun R (2001) Chemical, structural, and thermal characterizations of alkali— soluble lignin and hemicelluloses, and cellulose from maize stems, rye straw, and rice straw. Polym Degrad Stab 74:307–319 Yearout F (1977) The power of plants. John Murray (Pub.) Ltd, London, p 288 Yevich R, Logan J (2003) An assessment of biofuel use and burning of agricultural waste in the developing world. Global Biogeochem Cy 17:1095–1034 Yoon KN, Alam N, Shim MJ, Lee TS (2012) Hypolipidemic and anti-atherogenesis effect of culinary-medicinal pink oyster mushroom Pleurotus salmoneostramineus L. Vass. (higher Basidiomycetes), in hypercholesterolemic rats. Int J Med Mushroom 14(1):27–36 Zhang GL, Wang YH, Ni W, Teng HL, Lin ZB (2002) Hepatoprotective role of Ganoderma lucidum polysaccharide against BCG-induced immune liver injury in mice. World J Gastroenterol 8:728–733. https://doi.org/10.3748/wjg.v8.i4.72 Zhao Y, Li J, Chen Y, Hang H (2009) Response to oxidative stress of Coriolus versicolor induced by exogenous hydrogen peroxide and paraquat. Ann Microbiol 59(2):221–227 Zurbano LY, Bellere AD, Savilla LC (2017) Mycelial growth, fruiting body production and proximate composition of Pleurotus djamor on different substrate. Int J Sci Technol 2(1):20–30

Mushroom Index

A Abortiporus biennis, 125 Agaricus arvensis, 126, 260, 262, 370 Agaricus bisporus, 5, 8, 29, 37, 151, 152, 154, 155, 189, 191, 194, 215, 260, 261, 271–275, 341, 362, 363, 366, 367, 370, 411, 461, 467–469, 479, 506, 510, 513, 514, 564–567, 573, 611, 612, 615, 617–619, 621, 623, 634 Agaricus bitorquis, 36, 126, 366, 370, 461, 467, 480 Agaricus bresadolanus, 126 Agaricus campestris, 8, 126, 271, 359, 370, 461, 464, 563 Agaricus dulcidulus, 126 Agaricus fuscosuccinea brown strain, 307, 315, 317, 318, 329 Agaricus fuscosuccinea (white variety), 329 Agaricus involutus, 423 Agaricus L., 260–262 Agaricus mesenterica, 123, 127, 303, 306, 329 Agaricus ostoyae, 119, 123, 127 Agaricus subrufescens, 30, 37, 189, 192, 233 Agaricus sylvaticus, 126 Agaricus xanthodermus, 126, 277, 411 Agaricus xerampelina, 424 Agrocybe aegerita, 507, 509, 511, 518, 519 Agrocybe dura, 126 Albatrellus confluens, 126 Aleuria aurantia, 125 Aleurodiscus amorphus, 126 Amanita caesarea, 215, 277, 413, 414, 416, 417 Amanita citrine, 414, 423

Amanita muscaria, 9, 126, 272, 273, 277, 388, 392, 405, 408, 411–414, 423, 443–445, 459, 493, 563, 632, 633 Amanita phalloides, 5, 277, 408, 414, 417 Ampulloclitocybe clavipes, 127 Antrodia camphorata, 154, 372, 373 Armillaria mellea, 119, 123, 127, 211, 215, 370, 414, 415, 441, 442, 554, 555 Astreus hygrometricus, 373, 437, 447 Auricularia auricula, 303, 305, 306, 309–312, 317, 318, 320–322, 324–330, 335–337, 339, 340, 342, 344, 345, 510–513, 516, 620, 634 Auricularia auricula-judae, 37, 123, 127, 215, 303, 305–310, 315, 317, 319, 320, 324–328, 330, 335, 337–339, 342, 345, 346, 359, 364, 633 Auricularia cornea, 303, 305, 309, 315, 317, 319–321, 327–329, 343 Auricularia delicata, 303, 305–307, 310, 312, 313 Auricularia fuscosuccinea, 193, 303, 305–307, 309, 315, 317, 318, 322, 329, 345 Auricularia heimuer, 305, 306, 309 Auricularia mesenterica, 304, 306, 307 Auricularia polytricha, 36, 37, 262, 272, 303, 305–315, 317, 318, 320, 322, 327–329, 333, 335, 336, 338–341, 343–346, 359, 510–512, 516, 612, 617 Auricularia thailandica, 311, 313, 316, 317, 320, 323, 329 Auricularia villosula, 312

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7

653

654 B Bisporella citrina, 10 Bjerkandera adusta, 127, 211, 212, 479 Boletus aereus, 123, 127 Boletus aestivalis, 119, 215 Boletus edulis, 21, 30, 37, 119, 123, 127, 155, 194, 210, 212, 215, 216, 262, 263, 271, 359, 369–371, 408, 415–417, 419, 461, 464 Boletus fumosa, 127 Boletus L., 262–263 Boletus pinophilus, 119 Boletus plumbea, 128 Boletus regius, 128 Boletus reticulatus, 417 Boletus satanas, 369, 417, 423 Bovista nigrescens, 127 Bovistella utriformis, 119, 123, 128, 143 Bulgaria inquinans, 125 Butyriboletus appendiculatus, 128

C Calocera viscosa, 128 Calocybe, 10, 260, 502, 506 Calocybe gambosa, 128, 370 Calocybe indica, 10, 261, 263–264, 359, 362, 363, 504, 507, 509, 510, 512, 513, 517, 518, 567 Calvatia, 11, 119, 260, 359, 368, 429, 461 Calvatia cyathiformis, 429 Calvatia gigantea, 11, 128, 271–273, 429 Calycella, 9 Cantharellus cibarius, 119, 123, 128, 210–212, 215, 359, 411, 446, 564 Cerioporus squamosus, 128 Cerrena unicolor, 129, 367, 368 Chllorophyllum molybdites, 408 Chroogomphus rutilus, 129 Citizens, 9, 393, 435–454 Clathrus ruber, 426–428 Clavaria vermiculris, 466 Clavariadelphus truncatus, 129 Clitocybe geotropa, 129 Clitocybe illudens, 555 Clitocybe maxima, 155 Clitopilus passeckerianus, 373 Clitocybe sinopica, 129 Coprinellus, 211, 219 Coprinellus micaceus, 129, 419 Coprinellus radians, 129, 373 Coprinopsis atramentaria, 129 Coprinus atramentarius, 419

Mushroom Index Coprinus comatus, 129, 151, 189, 211–213, 217–219, 226–229, 236–238, 240, 241, 243, 359, 363, 364, 366, 419, 462, 571 Coprinus sterquilinus, 219 Cordyceps militaris, 32, 37, 155, 191, 214, 359, 363, 396, 461, 579–593 Cordyceps sinensis, 31, 32, 233, 374, 453, 580, 585, 634 Coriolus versicolor, 156, 211, 363, 541, 543, 634 Cortinarius caperatus, 129 Cortinarius cinnamomeus, 130 Cortinarius collinitus, 130 Cortinarius sanguineus, 130 Cortinarius torvus, 130 Cortinarius violaceus, 130 Craterellus cornucopioides, 10, 11, 119, 123, 130 Crinipellis rhizomaticola, 372, 373 Cyarhus striatus, 130 Cyathus, 11–12, 373 Cyathus africanus, 372, 373 Cyathus stercoreus, 130 Cyclocybe aegerita, 211 Cyclocybe cylindracea, 130

D Daedaleopsis confragosa, 36 Daedaleopsis tricolor, 130 Daldinia concentrica, 125 Datroniamollis, 36 Desarmillaria tabescens, 130 Dictyophora indusiata, 194 Dissingia leucomelaena, 125

E Entoloma clypeatum, 130 Entoloma lividoalbum, 363, 364

F Fistulina hepatica, 123, 130, 211 Flammulina velutipes, 35–37, 123, 130, 156, 195, 206, 211, 214, 265–266, 271, 272, 361, 363, 366, 368, 372, 373, 507, 509, 510, 513, 516, 519, 612, 617, 619, 630, 633 Fomes fomentarius, 119, 123, 130, 143, 189, 206, 210, 271, 359, 445, 641 Fomitiporia punctata, 131 Fomitoporia robusta, 131

Mushroom Index Fomitopsis betulina, 206, 211, 364 Fomitopsis pinicola, 131 Fuscoporia torulosa, 131, 214

G Ganoderma, 12, 29, 31–34, 37, 39, 118, 155, 156, 162–166, 168, 169, 171, 176, 214, 216–222, 224, 225, 236, 240, 242, 243, 366–368, 372, 373, 389, 459, 460, 463, 465, 466, 475–477, 499, 506, 563, 598, 599, 602, 604–606, 614, 630 Ganoderma abietinus, 217 Ganoderma adspersum, 214, 217 Ganoderma applanatum, 12, 30, 123, 131, 211, 214, 216, 217, 224, 240–242, 271, 366, 367 Ganoderma carnosum, 12, 214, 217, 236 Ganoderma lingzhi, 162, 171, 189, 217, 218, 475 Ganoderma lucidum, 5, 12, 33, 34, 37, 38, 119, 131, 152, 154, 155, 162–177, 189, 190, 192, 195, 207, 211, 214, 216–218, 221–224, 233, 234, 237, 238, 240, 242, 243, 271, 359, 361–368, 372, 373, 395, 398, 449, 450, 462, 465, 467, 474–479, 506, 507, 510, 511, 513, 520, 597–606, 614 Ganoderma pfeifferi, 33, 155, 214, 217, 224, 225, 236 Ganoderma resinaceum, 12, 123, 131, 143, 214, 217, 218, 225–226, 236, 475 Ganoderma rufescens, 131 Ganoderma spp., 154, 195, 206 Ganoderma trabeum, 131 Geastrum fimbriatum, 131 Geastrum triplex, 131, 429 Gerronema viridilucens, 551, 553 Gigantea, 392, 507, 512, 513, 521 Gloeophyllum sepiarium, 131 Gloeophyllum trabeum, 536 Gomphus clavatus, 132 Grifola, 13, 29, 30, 37, 461, 466, 506 Grifola frondosa, 13, 37, 132, 152, 155, 156, 189, 193, 194, 206, 271, 369, 466, 470, 507, 511, 518 Guepinia helvelloides, 123, 131 Gymnopilus, 488, 495, 632 Gymnopus androsaceus, 132 Gyroporus castaneus, 132

655 H Helvella lacunosa, 125 Hemileccinum impolitum, 123, 132 Hericium coralloides, 132, 220 Hericium erinaceus, 37, 155, 186, 189, 190, 206, 207, 217, 220, 221, 229, 232–233, 236, 237, 365, 369, 370, 394, 398, 461, 508, 510, 511, 519, 631, 634 Hericiume rinaceus, 156 Heterobasidion, 460 Hexagonia apiaria, 543 Hexagonia tenuis, 445, 446 Hohenbuehelia serotina, 367, 368 Hortiboletus rubellus, 132 Hydnellum concrescens, 132 Hydnellum scabrosum, 132 Hydnum repandum, 119, 123, 132, 211, 359 Hygrocybe conica, 132 Hygrophoropsis aurantiaca, 132 Hymenochaete mougeotii, 442 Hymenopellis radicata, 123, 132 Hypholoma capnoides, 132 Hypholoma fasciculare, 132, 423 Hypoxylon fragiforme, 125 Hypsizigus marmoreus, 367, 368 Hypsizygus ulmarius, 156, 189, 359, 639

I Imleria badia, 133, 370 Infundibulicybe gibba, 133 Inocutis rheades, 133 Inocybe aeruginascen Inocybe patouillardii, 420, 423 Inocybe rimosa, 133 Inonotus abaumii, 367 Inonotus cuticularis, 133 Inonotus hispidus, 133 Inonotus obliquus, 30, 34, 35, 133, 155, 233, 372, 373 Inonotus pachyphloeus, 442 Irpex lacteus, 133, 479, 536 Ischnoderma benzoinum, 36 Ischnoderma resinosum, 133

L Laccaria amethystina, 123, 422 Laccaria laccata, 133, 480 Lactarius controversus, 133

656 Lactarius deliciosus, 119, 123, 134, 215, 359, 370, 412, 417 Lactarius lignyotus, 134 Lactarius pallidus, 134 Lactarius picinus, 134 Lactarius piperatus, 215, 371 Lactarius pubescens, 134 Lactarius rufus, 134 Lactarius salmonicolor, 119, 134 Lactarius sanguifluus, 119, 134 Lactarius vellereus, 134 Lactarius volemus, 134 Lactarius zonarius, 134 Lactifluus piperatus, 134, 210 Laetiporus sulphureus, 119, 123, 134, 143, 206, 211, 213, 410, 440, 441 Lantinus subnudus, 464 Laricifomes officinalis, 36 Leccinum aurantiacum, 134, 420 Lentinellus cochleatus, 134 Lentinula edodes, 30, 35, 37, 152, 155, 189, 192, 206, 359, 462, 473–474, 479, 507, 509–514, 612, 614 Lentinula novaezelandieae, 13, 20, 514, 515, 614, 617 Lentinus arcularius, 134 Lentinus crinitus, 13 Lentinus edodes, 35, 38, 191–194, 208, 233, 242, 266, 271–274, 276, 341, 362, 365, 371, 466, 471, 567, 617, 633, 634 Lentinus mammiforme, 135 Lentinus tigrinus, 13, 135, 360 Lenzites betulina, 14, 36, 410 Lenzites stereoides, 541, 543 Lenzites warnieri, 14 Lepiota procera, 421 Lepista irina, 135 Lepista nuda, 135 Lepista sordida, 135 Leucoagaricus leucothites, 135 Lignosus rhinocerotis, 367, 368 Lycoperdon excipuliforme, 135 Lycoperdon perlatum, 267, 466 Lycoperdon perlatum Pers., 135 Lycoperdon pyriforme, 135, 215 Lycoperdon umbrinum, 135 Lyophyllum decastes, 135

M Macrocybe, 507, 512, 513, 521 Macrolepiota zeyheri, 408 Macrolepiota dolichaula, 363

Mushroom Index Macrolepiota excoriata, 135 Macrolepiota procera, 135, 215 Marasmiellus confluens, 135 Marasmiellus ramealis, 135 Marasmius oreades, 5, 119, 123, 136, 451, 466 Megacollybia platyphylla, 123, 136 Mensularia radiata, 136 Meripilus giganteus, 136, 143, 211, 212 Microporus xanthopus, 156, 445, 446 Morchella angusticeps, 14 Morchella crassipes, 14, 123, 125, 267 Morchella deliciosa, 14, 21, 359, 371 Morchella elata, 119, 125 Morchella esculenta, 14, 21, 119, 123, 125, 267, 271, 359, 361, 365, 417, 439, 461 Morchella importuna, 363, 365 Mucidula mucida, 123, 136 Mycena asterina, 550, 551 Mycena chlorophos, 554 Mycena discobasis, 551 Mycena fera, 551 Mycena galericulata, 136, 555 Mycena haematopus, 14, 136 Mycena leaiana var. australis, 15 Mycena leaina, 15 Mycena lucentipes, 551, 553 Mycena singeri, 551 Mycetinis scorodonius, 136 Mycna citricolor, 553, 554 Mycoleptodonoides aitchisonii, 189

N Neoboletus erythropus, 136 Neobulgaria pura, 125 Neofavolus alveolaris, 136 Neolentinus adhaerens, 136

O Omphalotus japonicus, 554 Omphalotus olearius, 136, 190, 553, 554 Ophalalotus olearius, 555 Ophiocordyceps sinensis, 189, 359, 461, 580

P Panellu stipticus, 553, 554 Panus conchatus, 136 Panus styticus, 555 Panus tigrinus, 211 Paxillus involutus, 136, 277, 422, 423 Peziza citrina, 9

Mushroom Index Phaeolepiota aurea, 137 Phaeolus schweinitzii, 137 Phaeotremella foliacea, 137 Phallus impudicus, 137 Phallus indusiatus, 194, 452 Phanerochaete chrysosporium, 479, 536 Phellinus, 15, 17, 155, 465, 466 Phellinus baumii, 195 Phellinus hartigii, 137 Phellinus igniarius, 15, 137, 156, 214, 215 Phellinus linteus, 365, 368, 453 Phellinus nilgheriensis, 15 Phellinus rimosus, 137 Phellinus tremulae, 137 Phlebia tremellosa, 137 Phoiota squarrosa, 137 Pholiota adiposa, 137 Pholiota aurivella, 137 Pholiota highlandensis, 137 Pholiota mutablitis, 423 Pholiota nameko, 507, 511, 519, 634 Pholiota populnea, 137 Pholiota squarrosa, 367 Phylloporia ribis, 123, 137 Pisolithus arhizus, 137 Pleurocybella porrigens, 211, 212 Pleurotus citrinopileatus, 15, 359, 515, 636, 637, 640 Pleurotus cornucopiae, 137, 366 Pleurotus cystidiosus, 37, 268 Pleurotus djamor, 238, 359, 363, 365, 636, 638 Pleurotus eous, 367, 480, 510, 515, 639 Pleurotus eryngii, 17, 37, 137, 151, 194, 241, 359, 364, 373, 509, 510, 515, 637, 640 Pleurotus eryngii var. ferulae, 17 Pleurotus flabellatus, 37, 268, 636, 637, 639 Pleurotus florida, 16, 37, 268, 461, 510, 515, 567, 621, 629–647 Pleurotus ostreatus, 15, 17, 36, 119, 123, 138, 143, 151, 154, 155, 189, 191, 192, 194, 207, 208, 211, 215, 217, 219, 226–229, 233, 234, 237, 238, 240–243, 268, 274, 276, 359, 366, 461, 467, 479, 509, 512, 513, 515, 572, 616, 634, 637, 640, 647 Pleurotus platypus, 515, 636 Pleurotus pulmonarious, 637 Pleurotus pulmonarius, 138, 155, 219, 268, 466, 467, 479, 636 Pleurotus sajor-caju, 21, 37, 268, 272, 276, 359, 368, 509, 515 Pleurotus tuber regium, 637 Polyporus palustris, 536 Polyporus umbellatus, 138

657 Poria cocos, 154 Psathyrella candolleana, 138 Pseudoclitocybe cyathiformis, 138 Pseudohydnum gelatinosum, 138 Psilocybe cubensis, 495 Psilocybe yungensis, 488 Psilocybe zapotecorum, 459 Pycnoporellus fulgens, 447 Pycnoporus cinnabarinus, 138 Pycnoporus sanguineus, 156

R Ramaria botrytis, 138 Ramaria formosa, 138, 367, 368 Rariorum plantarum historia, 11 Rhizopogon roseolus, 138, 360 Rigidoporus ulmarius, 138 Roridomyces phyllostachydis, 547 Rubroboletus satanas, 138 Russela capensis, 408 Russula alutacea, 139 Russula aurea, 139 Russula cyanoxantha, 17, 139 Russula delica, 139 Russula emetica, 17, 139 Russula foetens, 139 Russula grata, 139 Russula integra, 139 Russula lepida, 17, 368 Russula nigricans, 139 Russula queletii, 139 Russula rosea, 139 Russula sanguinea, 139 Russula sororia, 139 Russula vesca, 139 Russula virescens, 17, 139 Russula xerampelina, 424, 425 Rusulla paludosa, 17

S Sarcodon imbricatus, 139, 214 Sarcodon leucopus, 139 Schizophyllum commune, 37, 139, 152, 156, 189, 192, 206, 207, 217, 219, 228–230, 233, 234, 236, 238, 241, 360, 362, 437, 438, 462, 465, 468, 569, 641 Scleroderma areolatum, 140 Scleroderma bovista, 140 Scleroderma citrinum, 140 Scleroderma polyrhizum, 140 Scleroderma verrucosum, 140

658 Serpula lacrymans, 140 Sparassis latifolia, 189, 366, 367 Stereum hirsutum, 140, 211, 212, 373 Stereum subtomentosum, 211, 212 Strobilomyces strobilaceus, 140 Stropharia rugosoannulata, 617 Suillellus luridus, 140 Suillus bovinus, 140

T Tapinella atrotomentosa, 140 Tephrocybe anthracophila, 141 Terfezia boudieri, 289, 292, 293 Termitomyces clypeatus, 18, 367 Termitomyces microporus, 18 Termitomyces titanicus, 18 Tirmania, 286, 289 Tirmania nivea, 289, 291–294 Trametes gibbosa, 36, 141, 465, 466 Trametes hirsuta, 141 Trametes lactinea, 465 Trametes pini, 535–544 Trametes pubescens, 141, 220 Trametes suaveolens, 141 Trametes trogii, 141 Trametes versicolor, 17, 30, 36, 37, 119, 141, 143, 154, 192, 206, 207, 211–214, 217, 220, 229–232, 236, 238, 240, 242, 439, 462, 467, 470, 471, 473, 479, 506, 507, 511, 520–521, 537 Tremella aurantialba, 18 Tremella fuciformis, 18, 188, 189, 193, 233, 508, 510, 511, 519, 619–620 Tremella mesenterica, 18, 141 Trichaptum abietinum, 141 Trichaptum albobrunneum, 141 Trichaptum caligatum, 141 Trichaptum equestre, 141 Trichaptum fuscoviolaceum, 141 Trichaptum imbricatum, 141 Trichaptum portentosum, 141 Trichaptum sejunctum, 141 Trichaptum sulphureum, 141 Trichaptum ustale, 141

Mushroom Index Trichaptum vaccinum, 141 Trichaptum virgatum, 141 Tricholoma acerbum, 141 Tricholoma crassum, 562 Tricholoma giganteum, 37 Tricholoma mangolica, 426 Tricholoma matsutake, 20, 194, 427 Tuber aestivum, 21, 234, 243, 269, 287, 288, 291, 292, 297, 564 Tuber borchii, 288, 289, 469 Tuber brumale, 234, 243, 269, 287, 289, 297 Tuber driophilum, 289 Tuber gibbosum, 288, 289 Tuber himalayas, 289 Tuber indicum, 289, 291, 292, 297 Tuber magnatum, 234, 243, 269, 287–290, 292, 295, 461, 469 Tuber melanosporum, 234, 243, 269, 287–289, 291, 292, 295, 296 Tuber oregonense, 289 Tuber puberulum, 289 Tulostoma brumale, 142, 234, 243, 269, 289 Tylopilus felleus, 142, 423

V Vanderbylia fraxinea, 142 Verpa bohemica, 125 Volvariella bombycina, 142 Volvariella volvacea, 189, 193, 272, 275, 281, 461, 467, 468, 507, 510, 512, 513, 516, 517, 567, 569, 570, 620–621, 624, 630, 633

W Wolfiporia cocos, 154

X Xerocomus subtomentosus, 142, 421 Xeromphalina campanella, 142 Xylaria, 47–110, 555 Xylaria carpophila, 61, 90, 108, 125 Xylobolus frustulatus, 142

Subject Index

A Acetylcholinesterase enzyme (AChE), 69–72, 98–100, 102, 203–243, 388 Activated B cells, 365 Activator protein, 374 Agaricus, 8, 9, 29, 30, 155, 156, 260, 277, 309, 362, 369, 370, 460, 466, 469, 479, 499, 506, 507, 562, 567, 617, 623, 630, 634 Alkaloids, 79, 100, 150, 156, 162, 165, 173, 206, 221, 224, 227, 228, 232, 392, 409, 467, 632 Amanita muscaria (A. muscaria), 9, 126, 272, 273, 277, 388, 392, 405, 408, 411–414, 423, 443–445, 459, 493, 563, 632, 633 Amino acids, 20, 150, 151, 162, 165, 166, 169, 170, 193, 194, 274, 281, 289, 291, 293, 294, 314, 317–318, 339, 346, 392, 411, 463, 467, 499, 521, 556 Antiaging, 21, 321, 507 Anti-cancer, 31, 290–292, 294, 346, 362, 585, 588 Antioxidants, 12–14, 19, 71, 76, 100, 101, 105, 118, 123, 125–142, 144, 151–154, 156, 192, 206–243, 290, 291, 321–329, 340, 344, 346, 358, 363–365, 369–371, 373, 374, 388, 395, 396, 466, 507, 585, 591, 612, 614, 631, 633 Antiviral activity, 96, 173–175, 263, 336, 368, 374, 592 Aqueous extracts, 36, 233, 323, 326, 335, 343, 344, 466, 467 Arceuthobium, 392

Atomic absorption spectrometry (AAS), 211 Auricularia, 119, 123, 260–262, 273, 301–347, 358, 361, 363, 371, 461, 465, 499, 506, 508, 515, 516, 620 Auricularia auricula-judae (A. auricula-judae), 37, 123, 127, 215, 303, 305–310, 315, 317, 319, 320, 324–328, 330, 335, 337– 339, 342, 345, 346, 359, 364, 633 Auricularia fuscosuccinea (A. fuscosuccinea), 193, 303, 305–307, 309, 315, 317, 318, 322, 329, 345 Auricularia mesenterica (A. mesenterica), 304, 306, 307

B Beauty of mushrooms, 9, 22 Beneficial, 33, 149, 153, 176, 188, 216, 227, 308, 320, 365, 397, 412, 462, 631 Bioactive compounds, 19, 21, 32, 49, 151, 156, 162, 166, 168, 169, 175–177, 290, 293, 329, 346, 360, 415, 465, 519, 566, 612– 614, 620, 630 Bioconcentration factor (BCF), 238 Biocontrol agents, 460 Biologically active metabolites, 206 Bioluminescence, 441, 547–556 Bioluminescent, 14, 21, 547–556 Biotechnology, 188, 458–480, 536, 612, 613 Black ear fungus, 306 Body weight, 187, 235, 272, 325, 338, 341, 342, 344, 395, 585, 586, 592

© The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2022 A. Arya, K. Rusevska (eds.), Biology, Cultivation and Applications of Mushrooms, https://doi.org/10.1007/978-981-16-6257-7

659

660 C Camellia sinensis (C. sinensis), 31, 32, 392, 585 Cannabis, 392, 632 Citizens, 9, 393, 435–454 Coffea arabica, 392 Coffee, 167, 392, 394, 460, 479, 509, 519, 571, 635, 637 Cognitive impairments, 169, 233, 388, 393, 396 Colombia, 459, 487–495 Commercially useful, 497–522 Consciousness, 272, 392–393 Coprinus comatus (C. comatus), 129, 151, 189, 211–213, 217–219, 226–229, 236–238, 240, 241, 243, 359, 363, 364, 366, 419, 462, 571 Cordyceps, 30–32, 233, 374, 389, 453, 580, 581, 583–586, 591, 634 Corona virus pandemic, 28 Cosmeceuticals, 168, 190, 191, 223, 228, 230, 233–234, 242, 243, 358, 460 Cosmetics, 167, 168, 177, 186–195, 224, 228, 230, 233, 234 Cultivation, 13, 17, 21, 104, 105, 118, 188, 207, 213, 214, 216, 219, 236, 243, 266, 268, 276–283, 286–297, 305, 307–314, 317, 320, 336, 346, 358, 359, 397, 398, 450, 457–481, 498–522, 554, 561–575, 580– 592, 598–606, 611–624, 633–640, 642– 647 Cultivation process, 39, 216, 308, 313, 504 Culture broth, 169, 345 Cytochrome P450 (CYPs), 190, 207

D Dietary food, 358, 374, 460 Dietary supplements, 17, 20, 29–31, 119, 162, 166, 167, 172, 207, 243, 345, 358, 387– 398, 460, 520 Distribution, 13, 87, 118–145, 189, 216, 218– 221, 295–296, 302, 306, 442, 548–550, 553, 555, 569, 637 Diversity, 4–21, 29, 48, 104, 106, 110, 118– 145, 206–243, 359, 459, 617 Dry weight (DW), 151, 153, 191, 235, 239, 275, 276, 289, 309, 314, 315, 318, 320, 476, 634

E Ear mushrooms, 302, 304, 308, 309, 313, 314, 318, 319, 321, 325, 328, 329, 461, 499, 515, 630

Subject Index Ecological aspects, 547–556 Ecology, 4, 117–145, 189, 479, 548, 550 Edibility, 210, 454, 614 Efficiencies, 31, 241, 276, 311, 312, 340, 470, 472–474, 476, 479, 514–519, 571, 572, 605, 623, 638, 639, 642, 643 Electron spin resonance spectroscopy (ESR), 211 Ephedra, 392, 563, 632 Ergothioneine, 151, 154, 226, 417 Estrogen-dependent breast cancer cell lines (MCF-7), 56–62, 66, 67, 85–90, 95, 212, 213, 290, 291, 367, 368 Ethanolic extracts, 194, 330, 337 EUNIS classification, 123 Exopolysaccharide, 364

F Fatty acids, 19, 20, 31, 152, 162, 165, 169, 170, 186, 193, 275, 314, 318–319, 339, 346, 358, 365, 374, 417, 638 First day cover (FDC), 404, 408 Food and Agriculture Organization (FAO), 458, 566, 637 Foods, 7, 12, 15, 17, 18, 20, 22, 30–33, 37, 118, 127, 149, 150, 153, 156, 165, 167, 168, 173, 176, 186, 187, 192, 206, 208, 213– 215, 227, 228, 230, 235, 238, 239, 243, 260, 273, 274, 286, 288–290, 293–295, 302–306, 308, 314, 321, 335, 340, 342, 358, 359, 375, 388–391, 394, 420, 424, 429, 458–460, 463, 465, 473, 480, 499, 501, 502, 514, 521, 522, 561–566, 571– 573, 598, 605, 613–614, 616, 630–632, 634 Forest wastes, 509 Fourier-transform infrared spectroscopy (FTIR), 211, 214, 327 Free FA (FFA), 230 Fresh weight, 235, 239, 274, 275, 282, 306 Fruiting bodies, 7, 8, 11, 12, 14, 33, 36, 118, 143, 167–169, 186, 188, 193, 194, 206, 243, 260–262, 264, 268, 305–307, 313, 319, 327, 339, 343, 360, 364, 370, 372, 405, 410, 412, 415, 424, 429, 431, 445, 447, 458, 460, 471–476, 478, 503, 515, 520, 549, 552, 561, 580–586, 598, 599, 602, 605, 611, 613, 617, 619, 621, 630, 642, 644 Functional foods, 20, 30, 38, 206, 230, 360, 375, 631 Fungal forays, 412, 572

Subject Index G Ganoderic acids, 32, 33, 169, 174, 190, 372 Ganoderma, 12, 29, 31–34, 37, 39, 118, 155, 156, 162–166, 168, 169, 171, 176, 214, 216–222, 224, 225, 236, 240, 242, 243, 366–368, 372, 373, 389, 459, 460, 463, 465, 466, 475–477, 499, 506, 563, 598, 599, 602, 604–606, 614, 630 Ganoderma lucidum (G. lucidum), 5, 12, 33, 34, 37, 38, 119, 131, 152, 154, 155, 162–177, 189, 190, 192, 195, 207, 211, 214, 216–218, 221–224, 233, 234, 237, 238, 240, 242, 243, 271, 359, 361–368, 372, 373, 395, 398, 449, 450, 462, 465, 467, 474–479, 506, 507, 510, 511, 513, 520, 597–606, 614 Ganoderma triterpenoids (GT), 169, 170 Gas chromatography with flame ionization detection (GC-FID), 211 Gases (GHG), 470, 498 Glutathione peroxidase (GP), 230, 295, 324, 364, 633 Green house, 498 Growth behaviour, 509–513

H Health benefits, 118, 152, 221, 223, 270, 285– 297, 359, 360, 364, 366, 367, 369, 373– 375, 465–466, 592 Heavy metals, 21, 143, 208, 480, 481, 548 Heimuer, 306 Hericium, 29, 216–221, 394, 407, 499, 506, 519 Hericium erinaceus residue, 232 Herpes simplex virus, 155, 175, 225, 263 High molecular weight (HMW), 206, 226–228, 362 High-performance liquid chromatography (HPLC), 19, 211, 212, 369 History of use, 34 Human brain, 390, 591 Human immunodeficiency virus (HIV), 13, 33, 37, 155, 174, 271, 336, 363, 462, 465, 563, 612, 614 Hydroxoperhydroxomercury (II) complex, 212 Hypolipidemic activity, 129, 137, 321

I Immunomodulation, 31, 125–127, 129–133, 135, 137, 138, 162, 169, 190, 221, 362, 364, 367, 368, 374, 375

661 Interleukins, 291, 340, 362, 364, 592 Internal transcribed spacer (ITS), 217, 218, 220, 221, 242, 276–283, 305, 475

L Light microscopy, 536, 538–540, 543 Lignocellulosics, 164, 424, 459, 460, 498–521, 616, 639, 645 Lingzhi, 29, 32–34, 161–177, 598, 599, 634 Low molecular weight (LMW), 38, 206, 223, 228, 362, 631 Luciferins, 441, 548, 549

M Macrofungi, 3–22, 118–120, 122–124, 143– 145, 206, 208, 234, 243, 269, 309, 317, 318, 321, 327, 328, 335, 346, 358, 388, 458, 500, 550 Malnutrition, 22, 274, 358, 375, 458, 566, 575, 612 Mandrax, 392 Manizales, 459 Medical macrofungi, 118, 120, 123–145 Medicinal mushrooms, 5, 13, 19, 20, 22, 27–39, 118, 119, 156, 162, 163, 165, 170–172, 176, 189, 193, 206–243, 259–283, 303, 359, 394, 429, 436, 449–450, 459, 460, 465–467, 480, 497–522, 580, 581, 584, 598, 611–624, 634, 635 Medicinal prospects, 346 Medicinal uses, 18, 19, 398, 463, 580–592 Medicinal values, 48, 270, 273, 302, 346, 466, 499, 506 Megabases (mb), 207 Memory mushrooms, 387–398 Methanolic extracts, 194, 195, 211, 262, 326, 328, 369, 374, 466 Minimal inhibitory concentration (MIC), 48– 56, 65, 66, 75, 77–79, 81–84, 92, 94, 105, 211, 330, 331, 334, 336, 466 Mistletoe, 392 Mitogen activated protein kinases (MAPK), 36, 365, 374, 589 Molecular identification, 218 Molecular weights, 151, 169, 325, 328, 329, 338, 345, 346, 364, 631 Monounsaturated, 233 Montagne mushroom, 306 Montenegro, 118–145, 210, 216, 217, 242 Morels, 14, 21, 260, 267, 268, 404, 422, 439, 461, 616, 617

662 Mushroom biology, viii, ix Mushroom pharmaceuticals, 358, 460 Mushroom tea, 167, 394, 451, 631 Mycelial biomass, 206, 309 Mycena, 14, 21, 551–555 Mycophilately, 404–409

N Nicotiana tabacum, 392 Normal cell lines, 87 Nutritional values, 18, 119, 144, 186, 216, 227, 273–276, 294, 308, 463, 499, 503, 516, 566–567, 569, 572, 630 Nutritious foods, 286

P Papaver somniferum, 392 Periploca, 392 Pharmacological compounds, 149–157 Phoradendron, 392 Pleurotus, 15–17, 30, 37, 156, 206, 216–221, 226, 236, 238, 241, 260, 268, 272, 273, 275, 276, 281, 282, 309, 358–360, 362, 372, 460–463, 466, 479, 480, 499, 502, 506, 507, 510, 511, 515, 555, 573, 616, 617, 621, 630, 633, 634, 636, 639–642, 646 Polycyclic aromatic hydrocarbons, 207 Polysaccharides, 18, 20, 21, 29–31, 34–38, 150–152, 154–156, 188, 191–193, 206, 232, 263, 290–293, 308, 317, 319, 324– 328, 335–346, 360–366, 374, 465–467, 479, 521, 563, 585, 586, 598, 612, 614, 620, 631, 633, 642 Polysaccharopeptides, 230 Polyunsaturated fatty acids (PUFA), 165, 170, 226, 233, 234, 258, 318, 319, 358, 374 Poppy, 392 Postage stamps, 403–431 Proximate compositions, 315, 318, 346 Psilocybe zapotecorum, 459

R Radical scavenging capacity (RSC), 214, 215 Reactive oxygen species (ROS), 187, 212, 326, 369, 395, 396, 588, 591, 614, 640 Remediation, 478–480 Rheum, 209, 392 Roridomyces phyllostachydis, 547 Rosemary, 392 Rosmarinus officinalis, 392

Subject Index S Santalaceae, 392 Sarcostemma, 392 Schizophyllan, 152, 186, 188, 192, 228, 233, 362, 466, 470 Schizophyllum commune (S. commune), 37, 139, 152, 156, 189, 192, 206, 207, 217, 219, 228–230, 233, 234, 236, 238, 241, 360, 362, 437, 438, 462, 465, 468, 569, 641 Secondary metabolites, 7, 19, 20, 106, 110, 150, 165, 176, 186, 188, 206, 223–225, 227, 231, 232, 308, 335, 369, 394, 398, 409 Selective, 83, 212, 341, 394, 395, 397, 536– 544, 555 Simultaneous delignification, 536–544 Skin, 12, 126, 150, 167, 170, 186–195, 216, 223, 230, 233, 234, 243, 419, 508 Split gill fungi, 189, 462 St George' s mushroom, 404, 462 Sugarcane bagasses, 313, 479, 509, 510, 513– 515, 517–520, 571, 636, 639 Superoxide dismutase, 295, 324, 343, 364, 396, 633 Systemic aesthetic medicine, 185–196

T Teak wood, 538, 539, 543 Tectona grandis, 311, 474, 476, 516, 520, 536, 538, 544, 571 Terminalia crenulata, 538, 544 Terminalia wood, 540, 542–544 Tobacco, 392, 635 Toll like receptor, 365 Total phenolic content, 154, 212, 326 Toxic elements, 235, 239 Trametes pini (T. pini), 535–544 Triterpenes, 33, 34, 37, 38, 48, 152, 154, 224, 372, 467, 598 Truffles, 4, 8, 14, 21, 106, 194, 234, 260, 269, 286–297, 389, 460, 461, 469, 564 Tumor necrosis factor (TNF), 340 2, 2-diphenyl-1-picrylhydrazyl, 291, 324 Tylopilus felleus (T. felleus), 142, 423

U Ultra structural, 543–544 Unsaturated FAs (UFA), 152, 156, 213, 275, 318, 319, 346 Uses of mushrooms, 388–398 Utility of mushrooms, 403–431

Subject Index V Viscum, 392 Volvariella, 37, 260, 270, 271, 275, 282–283, 366, 368, 371, 468, 469, 499, 506, 569, 615

663 W Waste management, 498–522, 634–639 Wood decay, 13, 192, 410, 415, 470, 536, 541–544, 641 World Health Organization, 29, 38, 235