Nutraceuticals and Natural Product Derivatives Nutraceuticals and Natural Product Derivatives: Disease Prevention & Drug Discovery Edited by Mohammad Fahad Ullah Aamir Ahmad This edition first published 2019 © 2019 John Wiley & Sons, Inc. All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form or by any means, electronic, mechanical, photocopying, recording or otherwise, except as permitted by law. Advice on how to obtain permission to reuse material from this title is available at http://www.wiley.com/go/permissions. The right of Mohammad Fahad Ullah and Aamir Ahmad to be identified as the authors of the editorial material in this work has been asserted in accordance with law. 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Neither the publisher nor authors shall be liable for any loss of profit or any other commercial damages, including but not limited to special, incidental, consequential, or other damages. Library of Congress Cataloging‐in‐Publication Data Names: Ullah, Mohammad Fahad, editor. | Ahmad, Aamir, editor. Title: Nutraceuticals and natural product derivatives : disease prevention & drug discovery / edited by Mohammad Fahad Ullah, Aamir Ahmad. Description: Hoboken, NJ : John Wiley & Sons, Inc, 2018. | Includes bibliographical references and index. | Identifiers: LCCN 2018026810 (print) | LCCN 2018027967 (ebook) | ISBN 9781119436690 (Adobe PDF) | ISBN 9781119436737 (ePub) | ISBN 9781119436676 (hardcover) Subjects: | MESH: Dietary Supplements | Drug Discovery | Biological Products–pharmacology Classification: LCC RS420 (ebook) | LCC RS420 (print) | NLM QU 145.5 | DDC 615.1/9–dc23 LC record available at https://lccn.loc.gov/2018026810 Cover Design: Wiley Cover Image: © Creative Crop/Getty Images; © MirageC/Getty Images Set in 10/12pt WarnockPro by SPi Global, Chennai, India 10 9 8 7 6 5 4 3 2 1 v Contents Editor Biographies xv List of Contributors xvii Foreword xxi Preface xxv About the Book xxix Expert Commentary xxxi 1 Natural Food Sources for the Control of Glycemia and the Prevention of Diabetic Complications 1 Carlo Pesce, Carla Iacobini, and Stefano Menini 1.1 Introduction: Obesity, Metabolic Syndrome, and Type 2 Diabetes Epidemics: The Role of Nutrition 1 1.2 Phytochemicals of Nutraceutical Importance and Functional Foods of Plant Origin 3 1.2.1 Dietary Oils 3 1.2.2 Vegetables and Fruits 4 1.3 Nutraceuticals and Functional Foods of Animal Origin 8 1.3.1 The Case of Carnosine 8 1.4 Nutraceuticals of Both Plant and Animal Origin 9 1.5 Probiotics, Prebiotics, and Symbiotics 12 1.6 Conclusion 15 References 17 2 Anti‐Aging Effects of Sulfur‐Containing Amino Acids and Nutraceuticals 25 Geetika Garg, Abhishek Kumar Singh, Sandeep Singh, and Syed Ibrahim Rizvi 2.1 Aging and Nutrition 25 2.2 Natural Antioxidants 26 2.2.1 Sulfur‐Containing Amino Acids and Their Role as Antioxidants 26 2.2.2 Anti‐Aging Effects of L‐Cysteine 27 vi Contents 2.3 N‐Acetyl‐L‐Cysteine 28 2.3.1 Neuroprotective Effects of N‐Acetyl‐L‐Cysteine 29 2.3.2 N‐Acetyl‐L‐Cysteine in Combination with Other Antioxidants 29 2.4 Methionine 30 2.4.1 Methionine Restriction 30 2.5 Sulfur‐Containing Nutraceuticals and Foods Rich in Sulfur‐Containing Amino Acids 31 2.5.1 Whey Protein 32 2.5.2 Anti‐Aging Effects of Whey Protein 32 2.6 Conclusion 33 Acknowledgments 33 Conflict of Interest 33 References 33 3 Garcinia Fruits: Their Potential to Combat Metabolic Syndrome 39 Oliver D. John, Lindsay Brown, and Sunil K. Panchal 3.1 Introduction 39 3.2 Overview of Compounds in Garcinia Species 40 3.2.1 Garcinia mangostana 44 3.2.1.1 Chemical Properties 45 3.2.1.2 Biological Activities of G. mangostana 45 3.2.1.3 Toxicity 49 3.2.2 Garcinia cambogia 50 3.2.2.1 Chemical Properties 50 3.2.2.2 Biological Activities 51 3.2.2.3 Toxicity 53 3.2.2.4 Future Research 53 3.2.3 Garcinia humilis 53 3.2.3.1 Chemical Properties 53 3.2.3.2 Biological Activities 54 3.2.4 Garcinia dulcis 55 3.2.4.1 Chemical Properties 55 3.2.4.2 Biological Properties 55 3.2.4.3 Potential Research 56 3.3 Limitations 63 3.4 Conclusion 64 References 64 4 Pro‐Angiogenic and Anti‐Angiogenic Effects of Small Molecules from Natural Products 81 Jingyi Ma and Xuelin Zhou 4.1 Biological Mechanisms of Angiogenesis 81 4.2 Pharmacological Models for Angiogenesis Study 82 Contents vii 4.3 Pro‐Angiogenic Effects of Small Molecules from Natural Products 83 4.3.1 Natural Products as Sources for Screening Pro‐Angiogenic Stimulators 83 4.3.2 Flavonoids 84 4.3.3 Saponins 84 4.3.4 Salvianolic Acids 85 4.3.5 Other Small Molecules 85 4.3.5.1 Ferulic Acid 85 4.3.5.2 Aloe vera–Derived Compounds 85 4.3.6 Summary 86 4.4 Anti‐Angiogenic Effects of Small Molecules from Natural Products 86 4.4.1 Natural Products as Sources for Screening Angiogenic Inhibitors 87 4.4.2 Flavonoids 87 4.4.3 Diterpenoids 89 4.4.4 Polyphenol 90 4.4.5 Saponins 92 4.4.6 Alkaloids 93 4.4.7 Chalcone 93 4.4.8 Anthraquinone 93 4.4.9 Carotenoids 94 4.4.10 Other Small Molecules 94 4.4.10.1 Cucurbitacin B 94 4.4.10.2 Honokiol 95 4.4.10.3 Shikonin 95 4.4.10.4 Hyperforin 95 4.4.10.5 Glyceollins 95 4.4.10.6 Sulforaphane 99 4.4.11 Summary 99 4.5 Conclusion 99 Acknowledgment 99 Conflict of Interest 99 References 100 5 Nutraceuticals and Natural Product Derivatives in the Premises of Disease Prevention 111 Mohammad Fahad Ullah, Showket Hussain Bhat, and Faisel M. Abu‐Duhier 5.1 Introduction: How Significant Is the Role of Natural Molecules in Disease Prevention? 111 5.2 Natural Products in Cancer Chemoprevention 113 5.3 Natural Products in the Management of Diabetes 117 5.4 Natural Products as Therapeutic Agents against Gout Disease 122 viii Contents 5.5 Herbal Derivatives in Prevention of Alzheimer’s Disease 124 5.6 Conclusion 127 Acknowledgments 127 References 127 6 Honey‑ and Propolis‐Mediated Regulation of Protein Networks in Cancer Cells 137 Ammad Ahmad Farooqi, Mirna Azalea Romero, Aliye Aras, Muhammad Zahid Qureshi, and Lara Hanna Wakim 6.1 Introduction 137 6.2 Honey‐Mediated Targeting of Signal Transducer and Activator of Transcription (STAT) Proteins 138 6.3 Reactive Oxygen Species (ROS) Production in Cancer Cells 138 6.4 Apoptosis 139 6.5 Regulation of DNA Damage 139 6.6 Combinatorial Strategies: It Takes Two to Tango 139 6.7 Bioactive Propolis Chemicals as Tumor Necrosis Factor (TNF)‐ Related Apoptosis‐Inducing Ligand (TRAIL) Sensitizers 141 6.8 Bioactive Chemicals of Propolis Target Different Proteins of Cell‐Signaling Pathways 142 6.9 Conclusion 142 References 142 7 Antiproliferative Effects and Mechanism of Action of Phytosterols Derived from Bioactive Plant Extracts 145 Gabriel López‐García, Amparo Alegría, Reyes Barberá, and Antonio Cilla 7.1 Introduction 145 7.2 Mechanisms of the Anticancer Actions of Phytosterols 146 7.3 Anticancer Effects of Phytosterols 147 7.3.1 Plant Extracts Containing Phytosterols 148 7.3.2 Isolated Phytosterols from Plant Extracts 155 7.4 Conclusions 161 Acknowledgments 162 References 162 8 Yerba Mate (Ilex paraguariensis A. St. Hil.): A Promising Adjuvant in the Treatment of Diabetes, Obesity, and Metabolic Syndrome 167 Vanesa Gesser Correa, Rúbia Carvalho Gomes Corrêa, Tatiane Francielli Vieira, Eloá Angélica Koehnlein, Adelar Bracht, and Rosane Marina Peralta 8.1 Introduction 167 8.2 Nutritional Composition of Ilex paraguariensis 169 8.3 Composition in Bioactive Compounds 170