Antitumor Potential and Other Emerging Medicinal Properties of Natural Compounds Evandro Fei Fang · Tzi Bun Ng Editors

Antitumor Potential and Other Emerging Medicinal Properties of Natural Compounds Evandro Fei Fang · Tzi Bun Ng Editors Antitumor Potential and Other Emerging Medicinal Properties of Natural Compounds 1 3 Editors Evandro Fei Fang Tzi Bun Ng Laboratory of Molecular Gerontology School of Biomedical Sciences National Institute on Aging, NIH The Chinese University of Hong Kong Baltimore, MD Hong Kong USA Hong Kong SAR ISBN 978-94-007-6213-8 ISBN 978-94-007-6214-5 (eBook) DOI 10.1007/978-94-007-6214-5 Springer Dordrecht Heidelberg New York London Library of Congress Control Number: 2013932335 © Springer Science+Business Media Dordrecht 2013 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. Exempted from this legal reservation are brief excerpts in connection with reviews or scholarly analysis or material supplied specifically for the purpose of being entered and executed on a computer system, for exclusive use by the purchaser of the work. Duplication of this publication or parts thereof is permitted only under the provisions of the Copyright Law of the Publisher's location, in its current version, and permission for use must always be obtained from Springer. Permissions for use may be obtained through RightsLink at the Copyright Clearance Center. Violations are liable to prosecution under the respective Copyright Law. 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. While the advice and information in this book are believed to be true and accurate at the date of publication, neither the authors nor the editors nor the publisher can accept any legal responsibility for any errors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to the material contained herein. Printed on acid-free paper Springer is part of Springer Science+Business Media (www.springer.com) Foreword by Joseph J. Y. Sung The new millennium is characterized by high-tech gadgets such as Facebook, iPad, TV games, but also as an era of genomic medicine. However, residents in our global village are still harried by different incurable and new diseases that threaten human life. Are there any solutions? One way to circumvent the problem is to return to Mother Nature since it is still a main source of drug leads. According to a recent comprehensive review, from around the 1940s to 2010, a total of 175 small compounds with antitumor activity were approved by FDA and similar organi- zations. Among them, 74.8 % were other than synthetic compounds and 48.6 % were natural products and their derivatives [2]. However, good reference books in this field are scarce. Therefore, the book ‘Health Cornucopia: The Emerging Medicinal Properties of Natural Compounds’ arrives at the most opportune moment. This repertoire of promising medicinal components encompasses a variety of molecules ranging from large proteins to small compounds. Molecules on this list appear sequentially as lectins, ribonucleases, ribosome inactivating proteins, pro- tease inhibitors, and a vast diversity of small compounds (such as triterpenoids). In order to enlighten readers on the medicinal efficacies of the components at the cellular and molecular levels, the chapters in each part of this book not only place a focus on the stirring history of discovery of the components, but also present a detailed description of the molecular mechanisms and clinical research studies wherever possible. Examples include MAP30, BBIC, acetaldehyde, rapamy- cin, and others. The book also contains information on some new hot research areas which are related but not limited to cancer research, such as the strategy of exploiting autophagy for neurodegenerative diseases, the crosstalk between apop- tosis and autophagy, and the prolongation of life span by employing natural compounds. Moreover, the book does not restrict the origin of natural compounds to plants, but extends it to bacteria, fungi, and animals. For instance, there are chapters on animal lectins, lectins of marine organisms, and plant lectins, which render the library of drug candidates more vivid. Ethnomedicine is emerging as a new trend globally. Though a dominant con- tribution to human health in the old times, it was displaced by modern medicine and has faded away for many years. However, it is now enjoying a revival as many diseases can be alleviated by ‘complementary medicine’. Traditional Chinese v vi Foreword by Joseph J. Y. Sung medicine (TCM), which constitutes an important part of ethnomedicine, has been credited with some efficacy during its long history of practice. Eminent examples comprise arsenic trioxide (a therapy for human acute promyelocytic leukaemia), artemisinin from Artemisia annua (exhibiting anti-malaria activity), bitter melon (Momordica charantia), and Cordyceps sinensis which manifests many exploita- ble pharmacological activities. Two chapters in this book are focused on the recent progress of research on medicinal compounds in the bitter melon. There is also a chapter on high-throughput screening for discovery of TCM-based drugs which may provide a guideline for future drug evaluation. The research accomplishments alluded to in these chapters as well as elsewhere furnish a scientific basis for the application of TCM and other ethnomedicine. The editors of this book are Prof. T. B. Ng who is a professor at the Chinese University of Hong Kong and Dr. Evandro Fei Fang who is a brilliant young sci- entist in the field. I am confident that this book will provide comprehensive and useful information to researchers in the fields of cancer research, pharmacognosy, drug discovery, preventive medicine, plant nutrition, and others. For undergradu- ate and graduate students with a curiosity about natural products with medicinal activity, I recommend you this book as a valuable guide to the fascinating, rapidly evolving, and rewarding scientific genre. Joseph J. Y. Sung MD, Ph.D. Mok Hing Yiu Professor of Medicine President and Vice Chancellor The Chinese University of Hong Kong Shatin, Hong Kong Foreword by Rob Verpoorte The most important human heritage: our knowledge of the use of plants as a resource for drug development The most important human heritage is the knowledge of nature, allowing us to survive in a hostile environment. The use of plants is probably the most important of this heritage. The knowledge of plants that serve us as food, fuel, shelter, medicines, dyes, fibers, etc., is the basis of our life! At present we use some 30 species for our staple food, about 100 for their fruits and also about 100 as veg- etables. It is estimated that some 30,000–70,000 species are used for medicinal purposes [1], of which at present some 100 are used for the production of pure compounds used in western medicine. Much of the latter group originate from the Mediterranean/Middle East area and were already described in old Egyptian, Persian, Greek, Roman, and Arab manuscripts. In the nineteenth and twentieth centuries these medicines were further developed leading to the use of pure compounds and later even to derivatives or synthetic analogues with improved pharmacological properties. Despite the high score of active compounds from studies of a limited number of medicinal plants, so far most medicinal plants have hardly been studied in-depth for potential novel medicines. This untapped reservoir of traditional knowledge is a very promising resource for drug development and our major challenge is to develop efficient ways to tap this human heritage for the benefit of humanity. The statistics on the novel drugs developed in the past three decades show clearly the importance of nature as a source for drug development, almost half of all novel small-molecule drugs are natural products or natural products derived compounds [2]. In the last three decades drug development has followed two major strategies. One is rational drug design and is based on the knowledge of targets. This means receptors or enzymes involved in diseases. In this approach, computational meth- ods were developed to design medicines based on the knowledge of stereochemis- try of targets. The limitation of this approach is that no novel modes of action are found, only when novel targets are discovered novel drugs can be developed. The other approach is high throughput screening (HTS), in which large numbers of compounds are measured in fast micro/nano scale bioassays, allowing thousands vii viii Foreword by Rob Verpoorte of compounds to be tested per day. Again this approach is based on the knowledge of targets, and thus has the same limitation of the other approach, one may find novel active structures, but still for the same target. Both approaches are based on the “single target-single compound” paradigm. However, drug development is stalling using these approaches, only novel targets may lead to novel first-in-class medicines. Moreover, except for infectious and parasitic diseases, where an exogenous organism has to be eliminated, most diseases are multifactorial and concern endogenous processes, e.g., cancer and chronic inflammatory diseases. Chances that a single target drug will cure such diseases are small. The success in treating HIV-infected patients is due to the use of multidrug treatments. But if developing a single molecule drug is difficult, two- or even multi-component medicines are exponentially more difficult. At least it seems time for a paradigm shift to develop the next generation of medicines.

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