Thảo dược nhìn dưới góc độ sinh học phân tử và ứng dụng lâm sàng

© 2011 by Taylor & Francis Group, LLC


© 2011 by Taylor & Francis Group, LLC


OXIDATIVE STRESS AND DISEASE
Series Editors

Lester Packer, Ph.D.
Enrique Cadenas, M.D., Ph.D.
University of Southern California School of Pharmacy
Los Angeles, California

1. Oxidative Stress in Cancer, AIDS, and Neurodegenerative
Diseases, edited by Luc Montagnier, René Olivier, and Catherine
Pasquier
2. Understanding the Process of Aging: The Roles of Mitochondria,
Free Radicals, and Antioxidants, edited by Enrique Cadenas
and Lester Packer
3. Redox Regulation of Cell Signaling and Its Clinical Application,
edited by Lester Packer and Junji Yodoi
4. Antioxidants in Diabetes Management, edited by Lester Packer,
Peter Rösen, Hans J. Tritschler, George L. King, and Angelo Azzi
5. Free Radicals in Brain Pathophysiology, edited by Giuseppe
Poli, Enrique Cadenas, and Lester Packer
6. Nutraceuticals in Health and Disease Prevention, edited by
Klaus Krämer, Peter-Paul Hoppe, and Lester Packer
7. Environmental Stressors in Health and Disease, edited by
Jürgen Fuchs and Lester Packer
8. Handbook of Antioxidants: Second Edition, Revised and

Expanded, edited by Enrique Cadenas and Lester Packer
9. Flavonoids in Health and Disease: Second Edition, Revised and
Expanded, edited by Catherine A. Rice-Evans and Lester Packer
10. Redox–Genome Interactions in Health and Disease, edited by
Jürgen Fuchs, Maurizio Podda, and Lester Packer
11. Thiamine: Catalytic Mechanisms in Normal and Disease States,
edited by Frank Jordan and Mulchand S. Patel
12. Phytochemicals in Health and Disease, edited by Yongping Bao
and Roger Fenwick
13. Carotenoids in Health and Disease, edited by Norman I. Krinsky,
Susan T. Mayne, and Helmut Sies
14. Herbal and Traditional Medicine: Molecular Aspects of Health,
edited by Lester Packer, Choon Nam Ong, and Barry Halliwell

© 2011 by Taylor & Francis Group, LLC


15. Nutrients and Cell Signaling, edited by Janos Zempleni
and Krishnamurti Dakshinamurti
16. Mitochondria in Health and Disease, edited by Carolyn D. Berdanier
17. Nutrigenomics, edited by Gerald Rimbach, Jürgen Fuchs,
and Lester Packer
18. Oxidative Stress, Inflammation, and Health, edited by
Young-Joon Surh and Lester Packer
19. Nitric Oxide, Cell Signaling, and Gene Expression, edited by
Santiago Lamas and Enrique Cadenas
20. Resveratrol in Health and Disease, edited by Bharat B. Aggarwal
and Shishir Shishodia
21. Oxidative Stress and Age-Related Neurodegeneration, edited by
Yuan Luo and Lester Packer

22. Molecular Interventions in Lifestyle-Related Diseases, edited by
Midori Hiramatsu, Toshikazu Yoshikawa, and Lester Packer
23. Oxidative Stress and Inflammatory Mechanisms in Obesity,
Diabetes, and the Metabolic Syndrome, edited by Lester Packer
and Helmut Sies
24. Lipoic Acid: Energy Production, Antioxidant Activity and Health
Effects, edited by Mulchand S. Patel and Lester Packer
25. Dietary Modulation of Cell Signaling Pathways, edited by
Young-Joon Surh, Zigang Dong, Enrique Cadenas,
and Lester Packer
26. Micronutrients and Brain Health, edited by Lester Packer,
Helmut Sies, Manfred Eggersdorfer, and Enrique Cadenas
27. Adipose Tissue and Inflammation, edited by Atif B. Awad
and Peter G. Bradford

© 2011 by Taylor & Francis Group, LLC



© 2011 by Taylor & Francis Group, LLC


CRC Press
Taylor & Francis Group
6000 Broken Sound Parkway NW, Suite 300
Boca Raton, FL 33487-2742
© 2011 by Taylor and Francis Group, LLC
CRC Press is an imprint of Taylor & Francis Group, an Informa business
No claim to original U.S. Government works
Printed in the United States of America on acid-free paper

10 9 8 7 6 5 4 3 2 1
International Standard Book Number: 978-1-4398-0713-2 (Hardback)
This book contains information obtained from authentic and highly regarded sources. Reasonable efforts have been made to
publish reliable data and information, but the author and publisher cannot assume responsibility for the validity of all materials
or the consequences of their use. The authors and publishers have attempted to trace the copyright holders of all material repro duced in this publication and apologize to copyright holders if permission to publish in this form has not been obtained. If any
copyright material has not been acknowledged please write and let us know so we may rectify in any future reprint.
Except as permitted under U.S. Copyright Law, no part of this book may be reprinted, reproduced, transmitted, or utilized in any
form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microfilming,
and recording, or in any information storage or retrieval system, without written permission from the publishers.
For permission to photocopy or use material electronically from this work, please access www.copyright.com ( or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400.
CCC is a not-for-profit organization that provides licenses and registration for a variety of users. For organizations that have been
granted a photocopy license by the CCC, a separate system of payment has been arranged.
Trademark Notice: Product or corporate names may be trademarks or registered trademarks, and are used only for identification and explanation without intent to infringe.
Library of Congress Cataloging-in-Publication Data
Herbal medicine : biomolecular and clinical aspects / editors, Iris F.F. Benzie and Sissi Wachtel-Galor. -- 2nd
ed.
p. ; cm. -- (Oxidative stress and disease ; 28)
Rev. ed. of: Herbal and traditional medicine / edited by Lester Packer, Choon Nam Ong, Barry Halliwell.
c2004.
Includes bibliographical references and index.
Summary: “Responding to the increased popularity of herbal medicines and other forms of
complementary or alternative medicine in countries around the world, this reference reviews and evaluates
various safety, toxicity, and quality-control issues related to the use of traditional and herbal products for
health maintenance and disease prevention and treatment. With over 3,550 current references, the book
highlights the role of herbal medicine in national health care while providing case studies of widely used
herbal remedies and their effects on human health and wellness and the need for the design and performance
of methodologically sound clinical trials for the plethora of herbal medicines”--Provided by publisher.
ISBN 978-1-4398-0713-2 (hardcover : alk. paper)
1. Herbs--Therapeutic use. 2. Herbs --Molecular aspects. 3. Traditional medicine. I. Benzie, Iris F. F. II.
Wachtel-Galor, Sissi. III. Herbal and traditional medicine. IV. Series: Oxidative stress and disease ; 28.

[DNLM: 1. Phytotherapy. 2. Plants, Medicinal. W1 OX626 v.28 2010 / WB 925]
RM666.H33H458 2010
615’.321--dc22
Visit the Taylor & Francis Web site at

and the CRC Press Web site at


© 2011 by Taylor & Francis Group, LLC

2010042248


Contents
Series Preface.....................................................................................................................................ix
Foreword............................................................................................................................................xi
Preface............................................................................................................................................ xiii
Editors............................................................................................................................................... xv
Contributors....................................................................................................................................xvii

Chapter 1 Herbal Medicine: An Introduction to Its History, Usage,
Regulation, Current Trends, and Research Needs........................................................1
Sissi Wachtel-Galor and Iris F. F. Benzie
Chapter 2 Antioxidants in Herbs and Spices: Roles in Oxidative Stress
and Redox Signaling................................................................................................... 11
Ingvild Paur, Monica H. Carlsen, Bente Lise Halvorsen, and Rune Blomhoff
Chapter 3 Evaluation of the Nutritional and Metabolic Effects of Aloe vera.............................. 37
Meika Foster, Duncan Hunter, and Samir Samman
Chapter 4 Bilberry (Vaccinium myrtillus L.)............................................................................... 55
Wing-kwan Chu, Sabrina C. M. Cheung, Roxanna A. W. Lau, and Iris F. F. Benzie

Chapter 5 Cordyceps as an Herbal Drug..................................................................................... 73
Bao-qin Lin and Shao-ping Li
Chapter 6 Cranberry.................................................................................................................. 107
Catherine C. Neto and Joe A. Vinson
Chapter 7 The Amazing and Mighty Ginger............................................................................. 131
Ann M. Bode and Zigang Dong
Chapter 8 Biological Activities of Ginseng and Its Application to Human Health................... 157
Jae Joon Wee, Kyeong Mee Park, and An-Sik Chung
Chapter 9 Ganoderma lucidum (Lingzhi or Reishi): A Medicinal Mushroom......................... 175
Sissi Wachtel-Galor, John Yuen, John A. Buswell, and Iris F. F. Benzie
Chapter 10 Pomegranate Ellagitannins....................................................................................... 201
David Heber
vii
© 2011 by Taylor & Francis Group, LLC


viii

Contents

Chapter 11 Medical Attributes of St. John’s Wort (Hypericum perforatum)............................... 211
Kenneth M. Klemow, Andrew Bartlow, Justin Crawford,
Neil Kocher, Jay Shah, and Michael Ritsick
Chapter 12 Health Benefits of Tea............................................................................................... 239
Mauro Serafini, Daniele Del Rio, Yao Denis N’Dri,
Saverio Bettuzzi, and Ilaria Peluso
Chapter 13 Turmeric, the Golden Spice: From Traditional Medicine to Modern Medicine....... 263
Sahdeo Prasad and Bharat B. Aggarwal
Chapter 14 Biomolecular and Clinical Aspects of Chinese Wolfberry...................................... 289
Peter Bucheli, Qiutao Gao, Robert Redgwell, Karine Vidal,

Junkuan Wang, and Weiguo Zhang
Chapter 15 Botanical Phenolics and Neurodegeneration............................................................ 315
Albert Y. Sun, Qun Wang, Agnes Simonyi, and Grace Y. Sun
Chapter 16 Cardiovascular Disease............................................................................................. 333
Richard Walden and Brian Tomlinson
Chapter 17 Herbs and Spices in Cancer Prevention and Treatment............................................ 361
Christine M. Kaefer and John A. Milner
Chapter 18 Herbal Treatment for Dermatologic Disorders......................................................... 383
Philip D. Shenefelt
Chapter 19 Diabetes and Herbal (Botanical) Medicine...............................................................405
William T. Cefalu, Jaqueline M. Stephens, and David M. Ribnicky
Chapter 20 Bioactive Components in Herbal Medicine: Experimental Approaches.................. 419
Foo-tim Chau, Kwok-pui Fung, Chi-man Koon, Kit-man Lau, Shui-yin
Wei, and Ping-chung Leung
Chapter 21 Ethics of Using Herbal Medicine as Primary or Adjunct Treatment
and Issues of Drug–Herb Interaction........................................................................ 439
Lauren Girard and Sunita Vohra
Chapter 22 Integration of Herbal Medicine into Evidence-Based Clinical Practice:
Current Status and Issues.......................................................................................... 453
Anthony Lin Zhang, Charlie Changli Xue, and Harry H. S. Fong

© 2011 by Taylor & Francis Group, LLC


Series Preface
During evolution, oxygen—itself a free radical—was chosen as the terminal electron acceptor
for respiration; hence, the formation of oxygen-derived free radicals is a consequence of aerobic
­metabolism. These oxygen-derived radicals are involved in oxidative damage to cell components
inherent in several pathophysiological situations. Conversely, cells convene antioxidant mechanisms to counteract the effects of oxidants in either a highly specific manner (e.g., by superoxide
dismutases) or a less-specific manner (e.g., through small molecules such as glutathione, vitamin E,

and ­vitamin C). Oxidative stress, as defined classically, entails an imbalance between oxidants and
antioxidants. However, the same free radicals that are generated during oxidative stress are produced during ­normal metabolism and, as a corollary, are involved in both human health and disease
by virtue of their involvement in the regulation of signal transduction and gene expression, activation of receptors and nuclear transcription factors, antimicrobial and cytotoxic actions of immune
system cells, and aging and age-related degenerative diseases.
In recent years, research disciplines focusing on oxidative stress have increased our knowledge
of the importance of the cell redox status and the recognition of oxidative stress as a process with
implications for many pathophysiological states. From this multi- and interdisciplinary interest in
oxidative stress emerges a concept that attests the vast consequences of the complex and dynamic
interplay of oxidants and antioxidants in cellular and tissue settings. Consequently, our view of
­oxidative stress is both growing in scope and following new directions. Likewise, the term “reactive
oxygen species,” adopted at some stage to highlight nonradical/radical oxidants, now fails to reflect
the rich variety of other species in free-radical biology and medicine, encompassing nitrogen-,
sulfur-, oxygen-, and carbon-centered radicals. These reactive species are involved in the redox
regulation of cell functions and, as a corollary, oxidative stress is increasingly viewed as a major
upstream component in cell-signaling cascades involved in inflammatory responses, stimulation of
cell ­adhesion molecules, and chemoattractant production and as an early component of age-­related
neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s diseases, and
­amyotrophic lateral sclerosis. Hydrogen peroxide is probably the most important redox-signaling
molecule that, among others, can activate nuclear factor κB (NF-κB), NF-E2 related factor 2 (Nrf2),
and other universal transcription factors, and that is involved in the redox regulation of insulin and
mitogen-activated protein kinase (MAPK) signaling. These pleiotropic effects of hydrogen peroxide
are largely accounted for by changes in the thiol/disulfide status of a cell, an important determinant of the cell’s redox status with clear involvement in adaptation, proliferation, differentiation,
­apoptosis, and necrosis.
The identification of oxidants in the regulation of redox cell signaling and gene expression is a
significant breakthrough in the field of oxidative stress. The classical definition of oxidative stress
as an imbalance between the production of oxidants and the occurrence of antioxidant defenses now
seems to provide a limited depiction of oxidative stress, although it emphasizes the significance
of cell redox status. Because individual signaling and control events occur through discrete redox
pathways rather than through global balances, a new definition of oxidative stress was advanced
by Dean P. Jones as a disruption of redox signaling and control that recognizes the occurrence of

­compartmentalized cellular redox circuits. These concepts are anticipated to serve as platforms
for the development of tissue-specific therapeutics tailored to discrete, compartmentalized redox
­circuits. This, in essence, dictates the principles of drug development–guided knowledge of the
mechanisms of oxidative stress. Hence, successful interventions will take advantage of new knowledge of compartmentalized redox control and free-radical scavenging.

ix
© 2011 by Taylor & Francis Group, LLC


x

Series Preface

Virtually all diseases examined thus far involve free radicals. Although in most cases free ­radicals
are secondary to the disease process, in some instances causality is established for free radicals.
Thus, there is a delicate balance between oxidants and antioxidants in health, and disease clearly
associates with and in at least some cases is caused by loss of such balance. Their proper balance
is essential for ensuring healthy aging. Compelling support for the involvement of free radicals in
disease development originates from epidemiological studies showing that enhanced antioxidant
status is associated with reduced risk of several diseases. Of great significance is the role played by
micronutrients in modulation of cell signaling. This establishes a strong linking of diet, health, and
disease centered on the abilities of micronutrients to regulate redox cell signaling and modify gene
expression.
Oxidative stress is an underlying factor in health and disease. In this series of books, the importance of oxidative stress and diseases associated with organ systems is highlighted by exploring the
scientific evidence and clinical applications of this knowledge. This series is intended for researchers in basic biomedical sciences and for clinicians. The potential of such knowledge in facilitating
healthy aging and disease prevention warrants further knowledge about how oxidants and anti­
oxidants modulate cell and tissue functions.
Lester Packer
Enrique Cadenas

© 2011 by Taylor & Francis Group, LLC


Foreword
This book, Herbal Medicine: Biomolecular and Clinical Aspects, Second Edition, edited by Iris
F.  F. Benzie and Sissi Wachtel-Galor, reports updated information on some of the most widely
investigated traditional and herbal medicines, and establishes continuity with a previous book in
this series, Herbal and Traditional Medicine: Molecular Aspects of Health, edited by Lester Packer,
Choon Nam Ong, and Barry Halliwell. This new edition is timely because there is unprecedented
interest in understanding the molecular basis of the biological activity of traditional remedies—many
of which are derived from plants and herbs (phytomedicines) or from products that are available
as herbal supplements—and because such herbal supplements enjoy much popularity throughout
the world. This popularity is the result of the recognition of alternative and complementary forms
of medicine by governmental and nongovernmental changes; for example, the U.S. Public Health
Service and the National Institutes of Health established the Office of Dietary Supplement and the
National Center for Complementary and Alternative Medicine (NCCAM), which seek to verify
health claims. Western and traditional medicines hold great promise once research and medical
practice are appropriately coordinated.
The number of herbal remedies recognized to date is staggering, and an extensive literature has
documented their existence and reported on their beneficial effects toward health and well-being,
disease prevention, and disease treatment. Herbal Medicine: Biomolecular and Clinical Aspects,
Second Edition selects some of the best-case scenarios and widely used and known herbal remedies
to report on their effects on health in light of the current knowledge concerning their basic biological mechanisms of action. Coeditors Iris F. F. Benzie and Sissi Wachtel-Galor must be ­congratulated
for their excellent effort.
Lester Packer
Enrique Cadenas

xi
© 2011 by Taylor & Francis Group, LLC

Preface
Herbal medicine has been used throughout history and within every culture to prevent and treat
diseases. In any individual culture, the materials used were those that were available within the
geographical location and addressed local health concerns. With immigration and trade, cultural
traditions were exposed and often overwhelmed by modern scientific concepts and medical practices. However, the mix and movement of cultures that began only fairly recently, along with modern transportation, storage, and communication tools, brought an enormous increase in the general
availability of herbs from different cultures and geographical areas. In a different culture, an herb
would often be used for its appearance, coloring, or taste rather than for any perceived health benefits. Indeed, some of the herbs discussed in this book, such as curcumin, garlic, and cumin, are often
referred to as “spices,” or regarded as simple, if somewhat exotic, ingredients of foods from faraway
lands. Nonetheless, the long history and powerful reputation of many types of herbs, spices, and
fungi are impressive. In this time of increasing need for effective, affordable health ­promotion and
treatment strategies for our aging populations and growing problems posed by new and antibioticresistant microbes, the history and reputation of herbal medicines must be examined in a rigorous
and scientific way so that their biomolecular effects, if confirmed, can be translated into clinical benefit. Because of the strong associations among oxidative stress, aging, and disease, there is
increasing interest in the biomolecular effects of herbs, which may be related to antioxidant action.
By biomolecular effects, we mean the measurable or observable changes (biomarkers) that occur
in cells, animals, and human subjects, healthy or otherwise, under controlled conditions of treatment with an herb. Biomarkers reflect organ, cell, and organelle function or damage, and homeostatic control mechanisms. These are not limited to the genomic level, although this is a level on
which interest and insight are growing, but include a wide range and variety of biochemical and
“metabolomic” biomarkers, such as hemoglobin A1c (HbA1c) for glycemic control, plasma highsensitivity C-reactive protein (hsCRP) for inflammation, the number and function of immune cells,
plasma cholesterol and triglycerides for lipid balance, and biomarkers of liver and renal function. In
addition, herbs contain many compounds with powerful antioxidant properties, and herb-induced
changes in biomarkers that assess antioxidant status and oxidative stress, such as plasma ascorbic
acid and lipid peroxides, antioxidant enzyme activity/induction, and oxidation-induced damage to
DNA, are of interest in relation to the mechanisms of herbal protection. In cell-culture studies,
direct cytotoxicity and protection, gene expression, protein synthesis, and transport mechanisms
can be measured, and the morphology and growth of cells can be assessed. In animal studies, tumor
occurrence and size can be examined. By clinical effects, we mean the outcome of the biomolecular
effects in terms of human health preservation and restoration.
This book focuses on presenting the current scientific evidence of biomolecular effects of selected
herbs in relation to clinical outcomes and therapy for promotion of human health. Although the

terms “herb” and “herbal medicine” in traditional medicine are sometimes used in relation to animal or insect parts, our use of the term is limited to plants and fungi. Also, whereas many herbal
medicines are made by mixing different herbs, the focus in this book is on single herbs. The herbs
selected cover a wide range and include flowering herbs, leaves, and leaf exudate (St. John’s wort,
tea, aloe vera), fruits and berries (pomegranate, cranberry, wolfberry, bilberry), roots and rhizomes
(ginseng, ginger, and turmeric), and fungi (lingzhi and cordyceps). There is a chapter that focuses
on the antioxidant properties and effects of herbs (Chapter 2), and other chapters shift the focus
into the clinical arena and the use of herbs in relation to cardiovascular disease, cancer, diabetes,
skin disorders, and neurodegenerative disease. The ethics of using herbal medicine and its integration into modern, evidence-based medicine are also discussed. Finally, the use of new technologies
xiii
© 2011 by Taylor & Francis Group, LLC


xiv

Preface

of mass spectrometry and chemometric fingerprinting in the authentication of herbs is presented.
These technologies will bring a previously unknown level of quality control to the production of
herbal extracts. Currently, many commercially available herbal products are uncharacterized and
of questionable quality or content. The composition of natural products such as herbs can vary
greatly with season, growing conditions, preparation, and storage. However, there is also adulteration, contamination, and misidentification of herbs and herbal products. Improved quality control
techniques and processes for the identification of herbs and the establishment of characteristic
chemical “fingerprints” for herbs and herbal medicines are badly needed.
For well-designed clinical trials to be performed and for them to generate valid findings, herbs
that are safe and of consistent quality and composition are needed. For findings to be valid in terms
of human health and disease, a wide and diverse range of biomarkers needs to be investigated in
controlled human trials. To translate the positive findings of science-based studies and clinical trials
into action for health promotion, consumers need to be supplied with the same herbal products as
the ones shown to have these effects. Quality, consistency, and control are needed across all aspects
of production, testing, and promotion of herbal medicines; further, at the heart of ethically acceptable and responsible use of herbal medicines in modern health care, there must be science-based

evidence of biomolecular and clinical effects.
In closing, we would like to express our sincere thanks to the authors who contributed their
expertise and time to the production of this volume. Individually the authors are leaders in their
field. Collectively they embody a truly international collection of wisdom and experience in the
biomolecular and clinical aspects of herbal medicine. We are honored to be in their company.
MATLAB® is a registered trademark of The MathWorks, Inc. For product information, please contact:
The MathWorks, Inc.
3 Apple Hill Drive
Natick, MA 01760-2098 USA
Tel: 508 647 7000
Fax: 508 647 7001
E-mail:
Web: www.mathworks.com

© 2011 by Taylor & Francis Group, LLC


Editors
Dr. Iris F. F. Benzie is a chair professor of biomedical science in
the Department of Health Technology and Informatics at the Hong
Kong Polytechnic University, Hong Kong SAR, People’s Republic
of China ( She has a doctorate in biomedical science from the University of Ulster, United Kingdom,
and a master’s degree in clinical and pathological science from the
Chinese University of Hong Kong. She is a fellow of the Institute of
Biomedical Science in the United Kingdom, a fellow of the Hong
Kong Society of Clinical Chemistry, an accredited clinical biochemist, a chartered biologist, and a chartered scientist. Originally from
Scotland, she has lived and worked in Hong Kong for many years.
Her research interest is in the area of dietary antioxidants, herbs, and
functional foods, and the role of antioxidants and oxidative stress in aging and chronic degenerative
disease using a biomarker approach. She has published over 100 scientific papers and book chapters,

and she developed the patented ferric reducing ability of plasma (FRAP) assay, a widely used test
for measuring the total antioxidant/reducing power of foods, herbs, drugs, and biological fluids.
Dr. Sissi Wachtel-Galor is a research fellow in the Department of
Health Technology and Informatics at the Hong Kong Polytechnic
University, Hong Kong SAR, People’s Republic of China. She has
a bachelor’s degree in industrial engineering and a master’s degree
in biotechnology from the Technion–Israel Institutes of Technology,
Haifa, Israel. Dr. Wachtel-Galor received her PhD in biomedical sciences from the Hong Kong Polytechnic University, Hong Kong, where
she was awarded the first distinguished thesis prize for her outstanding
achievements. Dr. Wachtel-Galor was born in Italy, grew up in Israel,
and has traveled and lived in the United States and in Asia. During her
travels, she was introduced to different types of traditional and herbal
medicine, which sparked her interest in her present research areas.
Her research interests include herbal medicine with a focus on Chinese medicine, vegetarian diets,
endogenous antioxidants, and antioxidants from dietary sources and their effects on inflammatory
mechanisms. Her approach is to use biomarkers in the assessment of antioxidant status and oxidative
stress, and she has extensive experience in both animal and human supplementation studies.

xv
© 2011 by Taylor & Francis Group, LLC



Contributors
Bharat B. Aggarwal
Cytokine Research Laboratory
Department of Experimental Therapeutics
The University of Texas
and
Anderson Cancer Center

Houston, Texas
Andrew Bartlow
Department of Biology
Wilkes University
Wilkes-Barre, Pennsylvania
Iris F. F. Benzie
Department of Health Technology and
Informatics
The Hong Kong Polytechnic University
Kowloon, Hong Kong, People’s Republic of
China
Saverio Bettuzzi
Division of Biochemistry
Department of Experimental Medicine
University of Parma
Parma, Italy
Rune Blomhoff
Department of Nutrition
Institute of Basic Medical Sciences
Faculty of Medicine
University of Oslo
Oslo, Norway
Ann M. Bode
The Hormel Institute
University of Minnesota
Austin, Minnesota
Peter Bucheli
Manufacturing Support Department
Nestlé Product Technology Centre
Konolfingen, Switzerland

John A. Buswell
Institute of Edible Fungi
Shanghai Academy of Agricultural Sciences
Shanghai, People’s Republic of China
Monica H. Carlsen
Department of Nutrition
Institute of Basic Medical Sciences
Faculty of Medicine
University of Oslo
Oslo, Norway
William T. Cefalu
The Botanical Research Center
Pennington Biomedical Research Center
Louisiana State University System
Baton Rouge, Louisiana
and
Biotech Center
Rutgers University
New Brunswick, New Jersey
Foo-tim Chau
Department of Applied Biology and
Chemical Technology
The Hong Kong Polytechnic University
Kowloon, Hong Kong, People’s Republic
of China
Sabrina C. M. Cheung
Department of Health Technology and
Informatics
The Hong Kong Polytechnic University

Kowloon, Hong Kong, People’s Republic
of China
Wing-kwan Chu
Department of Health Technology and
Informatics
The Hong Kong Polytechnic University
Kowloon, Hong Kong, People’s Republic
of China
xvii

© 2011 by Taylor & Francis Group, LLC


xviii

An-Sik Chung
Department of Biological Sciences
Korea Advanced Institute of Science and
Technology
Daejeon, Korea
Justin Crawford
Department of Biology
Wilkes University
Wilkes-Barre, Pennsylvania
Zigang Dong
The Hormel Institute
University of Minnesota
Austin, Minnesota
Harry H. S. Fong
University of Illinois at Chicago

Chicago, Illinois
and

Contributors

David Heber
Department of Medicine
UCLA Center for Human Nutrition
David Geffen School of Medicine at
University of California
Los Angeles, California
Duncan Hunter
Discipline of Nutrition and Metabolism
School of Molecular Bioscience
University of Sydney
Sydney, Australia
Christine M. Kaefer
Epidemiology and Genetics Research Program
Division of Cancer Control and Populations
Sciences
National Cancer Institute
Rockville, Maryland

The Royal Melbourne Institute of
Technology (RMIT)
Melbourne, Australia

Kenneth M. Klemow
Department of Biology
Wilkes University

Wilkes-Barre, Pennsylvania

Meika Foster
Discipline of Nutrition and Metabolism
School of Molecular Bioscience
University of Sydney
Sydney, Australia

Neil Kocher
Department of Biology
Wilkes University
Wilkes-Barre, Pennsylvania

Kwok-pui Fung
Institute of Chinese Medicine
The Chinese University of Hong Kong
Shatin, Hong Kong, People’s Republic of China
Qiutao Gao
Nestlé Research Centre
Nestlé R&D Centre Beijing Ltd.
Beijing, People’s Republic of China
Lauren Girard
CARE Program
Department of Pediatrics
Faculty of Medicine and Dentistry
University of Alberta
Edmonton, Alberta, Canada
Bente Lise Halvorsen
Department of Nutrition
Institute of Basic Medical Sciences

Faculty of Medicine
University of Oslo
Oslo, Norway
© 2011 by Taylor & Francis Group, LLC

Chi-man Koon
Institute of Chinese Medicine
The Chinese University of Hong Kong
Shatin, Hong Kong, People’s Republic of China
Kit-man Lau
Institute of Chinese Medicine
The Chinese University of Hong Kong
Shatin, Hong Kong, People’s Republic of China
Roxanna A. W. Lau
Department of Health Technology and
Informatics
The Hong Kong Polytechnic University
Kowloon, Hong Kong, People’s Republic
of China
Ping-chung Leung
Institute of Chinese Medicine
The Chinese University of Hong Kong
Shatin, Hong Kong, People’s Republic of China


xix

Contributors

Shao-ping Li

Institute of Chinese Medical Sciences
University of Macau
Macao, People’s Republic of China

Robert Redgwell
Food Science and Technology Department
Nestlé Research Centre
Vers-chez-les-Blanc, Lausanne, Switzerland

Bao-qin Lin
Institute of Chinese Medical Sciences
University of Macau
Macao, People’s Republic of China

David M. Ribnicky
The Botanical Research Center
Pennington Biomedical Research Center
Louisiana State University System
Baton Rouge, Louisiana

John A. Milner
Nutrional Science Research Group
Division of Cancer Prevention
National Cancer Institute
Rockville, Maryland
Yao Denis N’Dri
Human Nutrition Unit
Department of Public Health
University of Parma
Parma, Italy

Catherine C. Neto
Department of Chemistry and Biochemistry
University of Massachusetts–Dartmouth
North Dartmouth, Massachusetts
Kyeong Mee Park
Department of Oriental Medicine
Daejon University
Daejeon, South Korea
Ingvild Paur
Department of Nutrition
Institute of Basic Medical Sciences
Faculty of Medicine
University of Oslo
Oslo, Norway

and
Biotechnology Center
Rutgers University
New Brunswick, New Jersey
Daniele Del Rio
Human Nutrition Unit
Department of Public Health
University of Parma
Parma, Italy
Michael Ritsick
Department of Biology
Wilkes University
Wilkes-Barre, Pennsylvania
Samir Samman
Discipline of Nutrition and Metabolism

School of Molecular Bioscience
University of Sydney
Sydney, Australia
Mauro Serafini
Area of Nutrition Sciences
Antioxidant Research Laboratory
Rome, Italy

Ilaria Peluso
Area of Nutrition Sciences
Antioxidant Research Laboratory
Rome, Italy

Jay Shah
Department of Biology
Wilkes University
Wilkes-Barre, Pennsylvania

Sahdeo Prasad
Cytokine Research Laboratory
Department of Experimental Therapeutics
The University of Texas
Austin, Texas

Philip D. Shenefelt
Department of Dermatology and
Cutaneous Surgery
College of Medicine
University of South Florida
Tampa, Florida

and
Anderson Cancer Center
Houston, Texas
© 2011 by Taylor & Francis Group, LLC


xx

Agnes Simonyi
Department of Biochemistry
University of Missouri
Columbia, Missouri
Jaqueline M. Stephens
The Botanical Research Center
Pennington Biomedical Research Center
Louisiana State University System
Baton Rouge, Louisiana
and
Biotechnology Center
Rutgers University
New Brunswick, New Jersey
Albert Y. Sun
Department of Medical Pharmacology and
Physiology and Department of Pathology and
Anatomical Sciences
University of Missouri
Columbia, Missouri
Grace Y. Sun
Department of Pathology and Anatomical

Sciences and Department of Biochemistry
University of Missouri
Columbia, Missouri
Brian Tomlinson
Department of Medicine and Therapeutics
The Chinese University of Hong Kong
Shatin, Hong Kong, People’s Republic of China
Karine Vidal
Food Immunology Department
Nestlé Research Centre
Vers-chez-les-Blanc
Lausanne, Switzerland
Joe A. Vinson
Department of Chemistry
University of Scranton
Scranton, Pennsylvania
Sunita Vohra
CARE Program
Department of Pediatrics
Faculty of Medicine and Dentistry
University of Alberta
Edmonton, Alberta, Canada
© 2011 by Taylor & Francis Group, LLC

Contributors

Sissi Wachtel-Galor
Department of Health Technology and
Informatics
The Hong Kong Polytechnic University

Kowloon, Hong Kong, People’s Republic
of China
Richard Walden
Centre for Clinical Pharmacology and
Therapeutics
Division of Medicine
University College London
Junkuan Wang
Nestlé Research Centre
Nestlé R&D Centre Beijing Ltd.
Beijing, People’s Republic of China
Qun Wang
Department of Medical Pharmacology
and Physiology
University of Missouri
Columbia, Missouri
Jae Joon Wee
KT&G Central Research Institute
Daejeon, South Korea
Shui-yin Wei
Department of Applied Biology and Chemical
Technology
The Hong Kong Polytechnic University
Kowloon, Hong Kong, People’s Republic
of China
Charlie Changli Xue
Discipline of Chinese Medicine
School of Health Sciences
RMIT University
Melbourne, Australia

John Yuen
Department of Health Technology and
Informatics
The Hong Kong Polytechnic University
Kowloon, Hong Kong, People’s Republic
of China


xxi

Contributors

Anthony Lin Zhang
Discipline of Chinese Medicine
School of Health Sciences
RMIT University
Melbourne, Australia

© 2011 by Taylor & Francis Group, LLC

Weiguo Zhang
Nestlé Research Centre
Nestlé R&D Centre Beijing Ltd.
Beijing, People’s Republic of China



Medicine
1 Herbal
An Introduction to Its History,

Usage, Regulation, Current
Trends, and Research Needs
Sissi Wachtel-Galor and Iris F. F. Benzie
CONTENTS
1.1 Herbal Medicine: A Growing Field with a Long Tradition....................................................... 1
1.2 Herbal Medicine and the Aging Population.............................................................................. 4
1.3 Herbal Medicines: Challenges and Regulations........................................................................4
1.3.1 International Diversity and National Policies................................................................ 5
1.3.2 Quality, Safety, and Scientific Evidence........................................................................ 6
1.4 Research Needs.........................................................................................................................7
1.5 Conclusions................................................................................................................................8
Acknowledgments............................................................................................................................... 9
References........................................................................................................................................... 9

1.1  HERBAL MEDICINE: A GROWING FIELD WITH A LONG TRADITION
Traditional medicine is “the knowledge, skills and practices based on the theories, beliefs and experiences indigenous to different cultures, used in the maintenance of health and in the prevention,
diagnosis, improvement or treatment of physical and mental illness” (World Health Organization,
There are many different systems of traditional medicine, and the philosophy and practices of each are influenced by the prevailing conditions, environment, and geographic area within which it first evolved (WHO 2005), however, a
common philosophy is a holistic approach to life, equilibrium of the mind, body, and the environment, and an emphasis on health rather than on disease. Generally, the focus is on the overall
condition of the individual, rather than on the particular ailment or disease from which the patient
is suffering, and the use of herbs is a core part of all systems of traditional medicine (Engebretson
2002; Conboy et al. 2007; Rishton 2008; Schmidt et al. 2008).
Traditional Chinese medicine (TCM) is an important example of how ancient and accumulated
knowledge is applied in a holistic approach in present day health care. TCM has a history of more
than 3000 years (Xutian, Zhang, and Louise 2009). The book The Devine Farmer’s Classic of
Herbalism was compiled about 2000 years ago in China and is the oldest known herbal text in the
world, though the accumulated and methodically collected information on herbs has been developed into various herbal pharmacopoeias and many monographs on individual herbs exist.
Diagnosis and treatment are based on a holistic view of the patient and the patient’s symptoms,
expressed in terms of the balance of yin and yang. Yin represents the earth, cold, and femininity,
whereas yang represents the sky, heat, and masculinity. The actions of yin and yang influence

the interactions of the five elements composing the universe: metal, wood, water, fire, and earth.
1
© 2011 by Taylor & Francis Group, LLC


2

Herbal Medicine: Biomolecular and Clinical Aspects

TCM practitioners seek to control the yin and yang levels through 12 meridians, which bring and
channel energy (Qi) through the body. TCM is a growing practice around the world and is used
for promoting health as well as for preventing and curing diseases. TCM encompasses a range of
practices, but herbal medicine is a core part (Engebretson 2002; Nestler 2002; Schmidt et al. 2008;
Xutian, Zhang, and Louise 2009). Three of the top-selling botanical products, namely Ginkgo
biloba, Allium ­sativum (garlic), and Panax ginseng, can be traced back to origins in TCM and are
today used to treat various diseases (Li, Jiang, and Chen 2008; Xutian, Zhang, and Louise 2009).
Over the past 100 years, the development and mass production of chemically synthesized drugs
have revolutionized health care in most parts of the word. However, large sections of the population
in developing countries still rely on traditional practitioners and herbal medicines for their primary
care. In Africa up to 90% and in India 70% of the population depend on traditional medicine to
help meet their health care needs. In China, traditional medicine accounts for around 40% of all
health care delivered and more than 90% of general hospitals in China have units for traditional
medicine (WHO 2005). However, use of traditional medicine is not limited to developing countries,
and during the past two decades public interest in natural therapies has increased greatly in industrialized countries, with expanding use of ethnobotanicals. In the United States, in 2007, about
38% of adults and 12% of children were using some form of traditional medicine (Ernst, Schmidt,
and Wider 2005; Barnes, Bloom, and Nahin 2008). According to a survey by the National Center
for Complementary and Alternative Medicine (Barnes, Bloom, and Nahin 2008), herbal therapy
or the usage of natural products other than vitamins and minerals was the most commonly used
alternative medicine (18.9%) when all use of prayer was excluded. A survey conducted in Hong
Kong in 2003 reported that 40% of the subjects surveyed showed marked faith in TCM compared

with Western medicine (Chan et al. 2003). In a survey of 21,923 adults in the United States, 12.8%
took at least one herbal supplement (Harrison et al. 2004) and in another survey (Qato et al. 2008),
42% of respondents used dietary or nutritional supplements, with multivitamins and minerals most
commonly used, followed by saw palmetto, flax, garlic, and Ginkgo, at the time of the interview.
The most common reasons for using traditional medicine are that it is more affordable, more
closely corresponds to the patient’s ideology, allays concerns about the adverse effects of chemical (synthetic) medicines, satisfies a desire for more personalized health care, and allows greater
public access to health information. The major use of herbal medicines is for health promotion
and therapy for chronic, as opposed to life-threatening, conditions. However, usage of traditional
remedies increases when conventional medicine is ineffective in the treatment of disease, such as
in advanced cancer and in the face of new infectious diseases. Furthermore, traditional medicines
are widely perceived as natural and safe, that is, not toxic. This is not necessarily true, especially
when herbs are taken with prescription drugs, over-the-counter medications, or other herbs, as is
very common (Canter and Ernst 2004; Qato et al. 2008; Loya, Gonzalez-Stuart, and Rivera 2009;
Cohen and Ernst 2010).
Regardless of why an individual uses it, traditional medicine provides an important health care
service whether people have physical or financial access to allopathic medicine, and it is a flourishing global commercial enterprise (Engebretson 2002; Conboy et al. 2007; Evans et al. 2007). In
1990, expenditure associated with “alternative” therapy in the United States was estimated to be
US$13.7 billion. This had doubled by the year 1997, with herbal medicines growing faster than any
other alternative therapy (Eisenberg et al. 1998). In Australia, Canada, and the United Kingdom,
annual expenditure on traditional medicine is estimated to be US$80 million, US$1 billion, and
US$2.3 billion, respectively. These figures reflect the incorporation of herbal and other forms of
traditional medicine into many health care systems and its inclusion in the medical training of doctors in many parts of the developed world.
The total commercial value of the ethnobotanicals market cannot be ignored. For example, in
1995, the total turnover of nonprescription-bound herbal medicines in pharmacies was equal to
almost 30% of the total turnover of nonprescription-bound medicines in Germany, and in the United
States, the annual retail sales of herbal products was estimated to be US$5.1 billion. In India,
© 2011 by Taylor & Francis Group, LLC