Table Of ContentQuality Control and Evaluation of Herbal Drugs
Quality Control and
Evaluation of Herbal Drugs
Evaluating Natural Products and
Traditional Medicine
Pulok K. Mukherjee
Elsevier
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Preface
The spectacular growth in the market for herbal medicinal products is one of the most interesting aspects of healthcare
throughout the world. The rediscovery of natural substances with therapeutic potential has raised questions of quality,
safety, and efficacy on the part of the consumer and also from health professionals. The majority of natural substances used
in this way consist of plant parts or simple extracts. Such materials have been used in medical practices in most parts of the
world for millennia, and this has resulted in a long and rich heritage in many cultures, which is now being shared worldwide
as a part of globalization.
The development of herbal drugs requires integration in various fields of science and technology with a major emphasis
on quality control and standardization. Medicinal plants and extracts have been utilized in the ancient practices of tradi-
tional medicine in many countries, including China (TCM), India (Ayurveda, Siddha, Unani, Homeopathy), Korea, Japan,
Tibet, South America, the Middle East, and Russia, among others. These codified traditional medicines and uncodified folk
medicine practices have immense importance in healthcare worldwide for the prevention and treatment of various acute
and chronic ailments.
The standardization and quality control of herbal drugs are crucial for the production, evaluation, regulation, and safety
surveillance of plant-made pharmaceuticals. This book intends to bring together current thinking and practices in these ar-
eas and also to highlight several facets of the research, which will facilitate improvement in the topics under consideration.
In the light of increasing legislation to enforce better standards for herbal products and the public demand for assurance
of their safe and effective use, this publication seeks to provide state-of-the-art reviews that present information and guid-
ance for the promotion and development of natural products.
This book elucidates various challenges and opportunities for quality evaluation and quantitative analysis of herbal
drugs, including marker analysis and stability testing. Some of the topics highlighted include traditional systems of medi-
cine, harmonization, ethnopharmacology- and ethnomedicine-inspired drug development, morphological and microscopic
evaluations, and bioactive phytocomponents and their analysis. Dedicated chapters cover classical pharmacognosy along
with other topics such as DNA bar-coding and chemometric methods for identification involving HPLC, TLC, HPTLC,
and LC-MS/MS.
This comprehensive volume has specific chapters on the methods for screening pharmacological activities, on safety,
and on anti-microbiological and antiviral activities along with the mechanisms of action useful for the evaluation of herbal
medicines. Plant metabolomics and the safety-related quality issues of phytopharmaceuticals and nutraceuticals also find
detailed discussion in this book.
I hope it will be a very useful treatise, which will not only serve as a handy tool for students and researchers in this
area but will also be useful to technocrats in industry and to legislators who want to know more about the methodologies
developed for the quality evaluation of herbal drugs in metabolomics, chromatographic studies, and the evaluation of safety
and efficacy.
In issues of emerging interest, this book covers the regulatory harmonization of nutraceuticals and traditional medicine,
as well as the role of ethnopharmacology in global healthcare generally. This volume also covers the trends in quality assur-
ance and good practices in agriculture, collection, manufacturing, and clinical aspects, which are very crucial for the quality
standardization of herbal drugs. This book provides articulate enumeration of various aspects of the quality assurance of
herbal medicines, which will help chemists and manufacturers to know more about the validation strategies for evaluating
traditional medicines, particularly for their safety and efficacy.
The main aim of this book is to elevate the level of understanding of the quality evaluation of natural products so that
they can be practiced with improved quality, raising a scientifically sound evidence base for herbal medicine. The text is
intended to present both the technical and theoretical backgrounds of different aspects of the evaluation of herbal medicinal
products. It will also be an imperative essential reference for students and professionals, and for those involved in the fields
of herbal medicine, traditional remedies, pharmaceutical sciences, and natural product research.
xix
xx Preface
I hope this book, aimed at a global readership, will provide updated guidance on the required structured approach for
quality control and evaluation of herbal drugs to all the interested stakeholders in this field.
Pulok K. Mukherjee, PhD, FRSC, FNASc
Director
School of Natural Product Studies
Department of Pharmaceutical Technology
Jadavpur University
Kolkata, India
Foreword
GOOD AFFORDABLE EVIDENCE-BASED (HERBAL) MEDICINES FOR EVERYONE
The past century was the era of drug development based on synthesis of organic molecules, often based on natural products
as a model. This resulted in a wide range of medicines mostly for the symptomatic treatment of diseases, although only
a few medicines really cure the patient. It has been said that “The vast majority of drugs—more than 90%—only work in
30% or 50% of the people” (Allen Roses, vice-president of genetics at GlaxoSmithKline). These are just some of the fac-
tors that have led to the abandoning of drug development based on the “single compound–single target” approach. Instead,
a more systemic approach is imminent. Twenty-first century science has introduced systems biology as a novel approach,
in which observing the whole system is the key. This approach dates back to our ancestors who found all medicinal plants
without any of the present-day tools: curare, opium, Artemisia, and many others—no pharmacology, no pharmacognosy, no
medicinal chemistry; they were possibly found by just trial and error. This means that observation-based approaches have
led to the discovery of approximately 30,000–70,000 plant species for various medical uses.
Now we have all kind of tools to measure (observe) things that our ancestors could not observe. These new tools help
us study the whole system using “omics” and physiological and pharmacological tools. By analyzing these results using
novel algorithms, new hypotheses can be generated and subsequently be tested in the classical hypothesis-driven science.
This will provide evidence for the safe use of traditional medicines and will also be a source of novel leads for drug de-
velopment. In particular the polypharmacy aspects of traditional medicines, including synergy, will be of great interest for
developing novel therapies. Obviously, these techniques will also result in the identification of a number of plants whose
risk–benefit ratio does not favor any further medical applications. A major driver in this process of changing paradigms
of drug development is the increasing interest in the well-documented Asian medical systems. With thousands of years of
written information, there is a wealth of knowledge that may be turned into evidence-based traditional uses, and may even
result in new leads for drug development. The 2015 Medicine and Physiology Nobel Prize for the discovery of artemisinin
and an antibiotic against river blindness is a recognition of biodiversity and traditional knowledge as important resources
for drug development. Interestingly this recognition comes from western medical sciences, which “traditionally” were quite
reluctant to accept traditional medicine as an alternative to global medicine, possibly owing to the lack of awareness that
the roots of all medical systems lie in the knowledge of our ancestors.
The changing global economy is a further driver for studying traditional medicinal (herbal) treatments. The exponential
growth in the quality and quantity of the research in this field is now setting the scene for studies of medicinal plants. The
present book deals with all these historical aspects, in which the same problems have to be solved to assess and learn from
all the different traditional medical practices. It brings together current thinking and practices in the area of quality control
and standardization of herbal drugs. The major problem is to develop evidence-based traditional medicines whose toxicity
is known and efficacy is proven. Once this problem has been overcome, the next step is to ascertain the production and dis-
tribution of good quality traditional medicines. With proven activity, at least the chemical profiles of the extract and/or plant
needs to be correlated with activity to ensure proper quality management and quality control. This is a major challenge, as
crude extracts might be contaminated with many things like adulterants, substituents, wrongly identified plants, mycotox-
ins, agrochemicals, and heavy metals. The methods for ensuring quality are many, and the costs for quality control can be
enormous, which could become a major bottleneck in the development of evidence-based traditional medicines. Quality
management, which refers to the identification of the critical steps in the chain from seed to plant, could contribute to keep
these costs low, that is, the introduction of good practices in the whole chain from seed to patient. It requires quality control
using simple techniques that do not necessarily depend on expensive advanced equipment. The equipment will be useful to
define quality, but should eventually lead to the development of simple methods for quality control.
xxi
xxii Foreword
This book provides an overview of all these aspects of quality control for herbal medicinal plants (right from simple
physicochemical tests, morphology, phytochemical tests to chemo-profiling and marker analysis for quality evaluation
of herbal drugs, HPTLC, HPLC, LC-MS/MS to high-end hyphenated techniques such as chemometrics for validation of
traditional medicines), presents avenues for traditional medicine-inspired drug discovery, and will be an important guide
for further studies on evidence-based traditional medicines. I appreciate the work done by Prof. Pulok Kumar Mukherjee,
a prolific author in this field and a major contributor in the area of ethnopharmacology and ethnomedicine, which will help
students understand the complete picture of all the pharmaceutical aspects of developing herbal medicines. This book will
also be helpful for experts to learn from other experts about the multidisciplinary approach required to achieve the final goal
of “Good affordable evidence-based medicines for everyone.”
Prof. Dr. Rob Verpoorte
Natural Products Laboratory, IBL, Leiden University
Sylvius Laboratory, Sylviusweg 72, 2333BE Leiden
Leiden, The Netherlands
Acknowledgments
The resurgence of interest in herbal medicine has augmented its role in global healthcare. There has been an enormous
growth in herbal medicinal products worldwide, creating a paradigm shift in healthcare. The quality of herbal medicine,
including its safety, efficacy, validation, and regulation, can be best explored through interdisciplinary sciences.
The main aim of this book is to describe and discuss different approaches and techniques for evaluating the quality and
efficacy of herbal medicines, particularly methods to assess their activity and to understand the metabolomic aspects and
their underlying mechanisms of action.
My entire research group at the School of Natural Product Studies, Department of Pharmaceutical Technology, Jadavpur
University, Kolkata, India owe a special thanks for their enthusiasm, creativity, and efforts toward this book. I gratefully
acknowledge the support rendered by my research scholars, particularly Mr. Subhadip Banerjee, Mr. Amit Kar, Mr. Shiv
Bahadur, Mr. Joydeb Chanda, Mr. Debayan Goswami, Mr. Sayan Biswas, Mr. Bhaskar Das, Ms. Akanksha Sharma,
Mrs. Kasturi Basu, Ms. Seha Singha, Mr. Shibu Narayan Jana, Mr. Milan Ahmed, and Mr. Prasanta Kumar Maitra, and
others for their active cooperation and assistance.
I very much appreciate the interest taken by Elsevier USA in producing this book. I gratefully acknowledge the coop-
eration and support received from Susan Dennis, Kathryn Morrissey, Amy Clark, Andrae Akeh, Denny Mansingh, and the
entire team in bringing out this book. You are unrivaled!
My father, late Harihar Mukherjee, a man I intensely admire, has always inspired me in my work and he continues to
live in my heart.
I am thankful to my extended family, including my brothers Aloke, Tilok, and Amit, and my sisters, who have supported
me throughout my journey.
I thank my extraordinary wife, Dr. Kakali Mukherjee, my absolute best friend, for her love and patience during the
writing process, without whose support this book would never have been possible. I thank my mother Smt. Sudharani
Mukherjee, daughter Maria, and son Manish, for all the love they give to me always; you are the reason behind my every
success.
Pulok K. Mukherjee, PhD, FRSC, FNASc
Director
School of Natural Product Studies
Department of Pharmaceutical Technology
Jadavpur University, Kolkata, India
xxiii
Chapter 1
Traditional Systems of Medicine and
Harmonization
Chapter Outline
1.1 Traditional Medicine in Healthcare 1 1.8 Traditional Chinese Medicine 12
1.2 AYUSH Systems of Medicine 3 1.8.1 Concepts of Traditional Chinese Medicine 13
1.2.1 Traditional Knowledge Digital Library 4 1.8.2 Quality Evaluation of Chinese Herbal Medicine 14
1.3 Ayurveda 4 1.9 Japanese Traditional Medicine 14
1.3.1 Origin of Ayurveda 5 1.10 Thai Herbal Medicine 15
1.3.2 Ayurvedic Drugs and Pharmaceuticals 6 1.11 Traditional Medicine in Bangladesh 15
1.3.3 Medicinal Plants in Ayurveda 6 1.12 Iranian Traditional Medicine 16
1.3.4 Globalization of Ayurvedic Medication 6 1.13 Malaysian Traditional Medicine 18
1.3.5 Ayurvedic Treatment and Practice 7 1.14 Traditional Medicine in Australia 19
1.4 Unani 9 1.15 Nature’s Natural Product Library for New Drug Discovery 21
1.4.1 Therapy and Formulation of Unani 1.16 Drugs Derived From TM 22
Medicine 10 1.17 Harmonization of Traditional Systems and Health
1.5 Siddha 11 Practices 24
1.6 Homeopathy 11 References 26
1.7 Sowa-Rigpa 12 Further Reading 27
1.1 TRADITIONAL MEDICINE IN HEALTHCARE
Traditional medicine (TM) refers to the knowledge, skills, and practices that are nurtured from the beliefs and age-old experi-
ences of indigenous people from different cultures that are used to maintain health and to prevent and treat different ailments.
Other terms for TM are complementary, alternative, and/or nonconventional medicine. The World Health Organization
(WHO) notes that traditional and complementary medicine (T&CM) is a component of the worldwide socio-global health-
care framework. Considering its importance, WHO has prescribed legislative frameworks, which should be incorporated to
promote health and wellness. WHO also recommends the development of regulation, research, education, marketing and
training to promote health and wellness. In October 2013, WHO published the “WHO Traditional Medicine Strategy 2014–
2023” to oversee the needs, controls, and administration of traditional medicine inside their own country (WHO, 2013a, b).
Archaeological evidence reveals that the consumption of medicine has a long history (Randive, 2010). By necessity,
the drugs used in ancient civilizations were extracts of plants or animal products, with a few inorganic salts. In India, the
Ayurvedic system of medicine developed an extensive use of medicines from plants dating from at least 1000 BC. The
earliest Chinese records give descriptions of diseases but not medicines; illnesses were thought to be godly punishments
and they were treated by prayers and offerings. The earliest recorded Chinese prescription after about 500 BC shows the
beginning of the use of natural products as drugs. The first classic texts in Chinese medicine appeared in AD 25–220, and
some of their formulae remain in use today (Huang, 1984; Hikino, 1989). Similarly, the Egyptian Ebers papyrus (around
1550 BC) contains descriptions of several active ingredients (notably purgatives) that are still used today (Panda, 2010).
TM alludes to health practices, methodologies, wisdom, and principles, incorporating plant-, animal-, and mineral-
based medications, spiritual treatments, manual strategies and activities, connected independently or in combination, with
the aim to treat, analyze, and counteract ailments or to promote wellness. Nations in Africa, Asia, and Latin America utilize
TM to meet some of their essential health needs. In Africa, up to 80% of the population utilizes T&CM for essential me-
dicinal services. In industrialized nations, the practice of TM is called “Complementary” or “Alternative” Medicine (CAM).
Quality Control and Evaluation of Herbal Drugs. https://doi.org/10.1016/B978-0-12-813374-3.00001-6
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