© 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

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
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© 2011 by Taylor and Francis Group, LLC
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© 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

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,

­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




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

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.
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© 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,

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

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

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

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

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

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

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,

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