Prime Ayurvedic Plant Drugs (A Modern Scientific Appraisal)

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In the early development of modern medicine, biologically active compounds from higher plants played a vital role in providing medicines to combat pain and disease, and most of these were culled from plants traditionally used for that purpose in one culture or another. Even now, search for bioactive molecules from nature (plants, animals, micro flora) continues to play an important role in fashioning new therapeutic agents. Besides, in the last three decades or so, a new trend in the preparation and marketing of drugs based on medicinal plants has become increasingly important in several European countries. These preparations, labeled herbal drugs or phytomedicines are carefully standardized, and their efficacy and safety foray specific application demonstrated, and are dispensed just like the allopathic preparations.

Additionally, in several countries traditional medicine is still in vogue, and in fact, has been gaining more acceptability for treatment of chronic ailments. This is especially true for countries like India and China, which have a long tradition of fairly well-organized traditional therapy.

With this background, it is not surprising to see a renascence in the exploration of medicinal plants by more incisive modern techniques of chemical and biological sciences, available now. Traditional Ayurvedic therapeutic formulations draw on an impressive array of plants, and several of these had attracted the attention of investigators from mid-1950s, and highly significant amount of research results have been published in various peer-reviewed international journals. Though, several books on Ayurvedic plant drugs have been published, there was not a single cogent one, aimed primarily at evaluation of therapeutic claims in the present-day context. This void motivated the present author to write and get published ‘Prime Ayurvedic Plant Drugs’in 2006. Since then, highly meaningful new research results covering these and a few additional Ayurvedic medicinal plants have been published. This necessitated the publication of an updated Second Edition of this book.

In this revised and enlarged edition, not only highlights of new medicinally valuable information that emerged since 2005, has been incorporated, but 14 new prime Ayurvedic plant drugs, which attracted the attention of research workers, have also been included. Besides updating other sections, including the General Introduction, another Annexure (no. 4) covering Plant-wise Activities has been added. Both Annexure 3 and 4 depict medicinal therapeutic activities confirmed by modern scientific methods, and in both of these, clinical confirmation has been highlighted (green print).

Sukh Dev is an organic chemist who worked for his Ph.D. and D.Sc. degrees at the Indian Institute of Science (I. I. Sc.), Bangalore. He served as a lecturer at the I. I. Sc., and later for one year as Research Associate at the University of Illinois, Urbana (USA), before taking over as Head of the Division of Organic Chemistry (Natural Products) at the National Chemical Laboratory, Pune in 1960. In 1974 he shifted to the newly created Malti-Chem Research Centre, Nandesari, Vadodara, as its Research Director. In 1989 he moved to the Indian Institute of Technology (lIT), New Delhi as INSA Research Professor, from where he retired in 1994. He has been a visiting Professor at the Steven Institute of Technology, Hoboken, New Jersey, at the University of Georgia, Athens, and at the University of Oklahoma, Norman. After his retirement from lIT, he has been a visiting Professor (until 2010) at the Centre for Biomedical Research, University of Delhi. He has been an invited speaker at several international conferences, symposia, and universities and research institutes all over the world. He is the recipient of several national awards including the S.S. Bhatnagar Memorial Award, the American Chemical Society’s Ernest Guenther Award, and the Third World Academy of Sciences Award in Chemistry. He was elected President of the Indian Chemical Society (1978—79), and in 1987 President of the Organic Chemistry Division of the International Union of Pure and Applied Chemistry for the term 1987—89.

His research interests include natural products chemistry, especially biologically active compounds, organic synthesis, and new technology development. He has over 450 publications including 55 patents. He has authored 10 books, and has contributed chapters to several other books.

The knowledge of the medicinal plants used in the drugs of the traditional systems of medicine (TSMs) has been of great value especially as leads for the discovery of new single molecular medicines (New Chemical Entities: NCE5) of the modem system of medicine. Many of the drugs thus discovered are still used in the modem system, and many more carry the structural imprint of the parent molecular prototype which had led to their discovery. However, the recent widening of the horizons of drug discovery and development research, resulting from the dramatic advances in instrumentation and computational methods, has greatly widened the perspective of the use of this knowledge resource in drug development research and of benefiting the society. Looking at the situation in India a large segment of the population still depends on Ayurvedic drugs for their health-care needs, and the situation will continue to be so for many more years to come. The first and foremost consideration, therefore, is to put the materia medica of Ayurveda on a modem scientific footing to provide drugs of proper standard quality. Standardization of herbal drugs, which are multi-component, is a daunting task. But the recent advances in separation techniques and analytical methods offer unprecedented opportunities for identification of correct plants and characterization of athe right cultivars such as by DNA fingerprinting: analysis of multi-component mixtures with finger-print of major components, including by LC-MS-MS spectrum, if necessary, would help in development of effective quality control standards of drugs. This is the first major task that needs to be undertaken in R&D on Ayurvedic drugs, so that patients get drugs of standard quality.

Structural novelty and new modes of action are common features of plant drugs. This has been shown by anticancer agents like vinblasting, vincristine and palliate; cardiovascular agents like forthcoming; anti-HIV agent like caracoled and the latest to add to this list is guguisterone, the active constituent of Guglip, a hypolipidemic drug, which has been shown to act through inhibition of foresail nuclear receptors, causing an increase of bile acid excretion and thus, increasing the metabolism and mobilization of cholesterol in the liver. One of the important current emphasis in new drug discovery research is to get products with new modes of action, and plant drugs most often fulfill this requirement admirably.

Avurvedic drugs are also attracting much attention of diseases with no or inadequate drugs for treatment in modem medicine, such as for metabolic and degenerative disorders. Most of these diseases have multifactor causation, and there is a growing realization that in such conditions combination of drugs, acting at a number of targets simultaneously, is likely to be rare effective than drugs acting at one target; one-target-one drug paradigm is not likely to be satisfactory in such cases. Ayurveda drugs which are most often multi-component have a special relevance for such detailed study to get proof of concept, but these are the opportunities offered.

Connected with this multi-target approach is also the study of the doctrinaire base of Ayurveda, which takes a “holistic” view of the human system. This, in therapeutic terms, implies that the treatment of a disease should not be directed to a single tissue or organ but to the body system as a whole, taking into consideration the interconnectivity of the different body organs and their mutual dependence. It is most creditable that the founders of the Science of Ayurveda could conceive of these doctrines and concepts when other branches of science were so little developed, and built the whole edifice of Ayurvedic System of Medicine. However, due to varied reasons Ayurveda has not been much exposed to modern scientific developments. Investigation of the biological activity of multi-component Ayurvedic drugs will also bring Ayurveda into modem stream of scientific investigation and expose it to modem scientific developments. This is close to the fast emerging Systems-Biology perspective, which looks at the living systems as multi-component with interconnected molecular networks. This ‘holistic’ view of Systems-Biology is very close to the ‘holistic’ view of Ayurveda. In modem medicine the “holistic” perspective of ‘Systems-Biology’ is fast emerging as a very useful approach to understand biological systems, including understanding drug action and for drug discovery. The time is just ripe for Ayurveda to be brought into this perspective of Systems-Biology which will provide an experimental basis to the ‘holistic ‘concept of Aurveda and move the doctrinaire base of Ayurveda towards a modernized scientific perspective. Encouraging research and development studies of this kind will help to develop a much needed interface between Ayurveda and modem medicine, and how best the two could complement each other. This will bring out the essence of ancient-modern concordance of the two medical systems.

Central to these studies is the selection of plants, on which enough studies have been carried out to provide a validated background of their therapeutic potential. This is precisely what Dr. Sukh Dcv, an authority on natural product chemistry, with special emphasis on medicinal plants used in Ayurveda, has done in this book. The book in Section 1 presents a brief introduction to Ayurveda, highlighting clearly that Ayurveda is not merely a formulary of medicaments, but a comprehensive system of medicine, with a theoretical basis and a doctrinaire base of its own. This is followed by very up-to-date monographs describing the chemo- pharmaco-therapeutic studies carried out on important plants used in Ayurvedic medicine. The book ends with three useful Annexures; Annexure 3 lists the plants reviewed on the basis of their activity, making it easy to locate plants with a specific activity. The book would be found very useflul by aX those interested in important plants of Ayurveda and would serve as a useful standard reference book.

The book ‘Prime Ayurvedic Plant Drugs: Ancient Modern Concordance’ was published in 2006. Since then however, most of these plants have been the focus of additional modem scientific scrutiny in several countries of the world, and this activity has generated quite significant new findings. While in the earlier book, emphasis was on garnering modern scientific support in favour (or otherwise) of the Ayurvedic therapeutic claims (and hence the subtitle ‘Ancient Modern Concordance’), the new information has uncovered additional plant medicinal attributes. In view of this. The subtitle has been changed to: ‘A Modern Scientific Appraisal’.

It is well-established that a given plant’s secondary metabolites content and composition is highly dependent on its maturity, and on the agro climatic conditions in the area of its cultivation, and hence, preparations based on a particular plant have to be standardized in terms of the known active principle(s). To assist the workers in this area, references to the estimation of the important constituents of the plant by modern analytical tools have been incorporated.

Fourteen new plant drugs, important in Ayurveda, and which have also received significant modem scientific scrutiny, have been included in the edition. A new Annexure (no. 4) depicting plant-wise activities has also been added. In both Annexures, 3 and 4, clinical information has been highlighted.

In the preparation of the new edition some of the plant photos have been replaced. I am again grateful to Prof. S.R. Yadav for placing at my disposal his collection of plant photos for my selection and use. I am also thankful to Dr. K.K. Bhutani for similar help. I also wish to thankfully acknowledge the help I received from Dr. Vibha Tandon and Dr. Urmila for collecting several literature reference articles, I needed.

Finally, I have pleasure in acknowledging the moral support and understanding of my ardhangani, Shashi Prabha, which made this undertaking possible.

It has been estimated that 75—80% of world population depends on crude plant drug preparations to tackle their health problems, though this may be mostly because of economic considerations. However, in countries like India, China, and other countries with well-founded traditional systems of medicine, plant-based therapeutic agents occupy an important niche in health management. The last three decades or so are a witness to a new development. The economically developed countries, for whatever reasons, are seeing an ever-growing interest in natural remedies, which have come to be known as herbal drugs or phytomedicines. These preparations are invariably single plant extracts, or fractions thereof, as distinct from pure chemical entities which may be called molecular drugs. This new breed of plant- derived products are carefully standardized, and their efficacy and safety, for a specific application, fairly demonstrated. It has been estimated that the present global market for these products may be of the order of 20 billion US dollars, and is growing at the rate of 10—i 5% annually.

Traditional Ayurvedic therapeutic formulations draw on an impressive array of plants, many of which have been scrutinized by modem scientific methods. The first Ayurvedic herb which attracted international attention was Rauvolfia serpentina, when it was found that its constituent alkaloid, reserpine, had the twin effect of lowering high blood pressure and acting as a tranquillizer. In its traditional usage, it has been employed to treat insanity. This was in the 195 Os. Currently, Curcuma longa (turmeric), another Ayurvedic crude drug, is being evaluated for several therapeutic applications. In the classical Ayurveda literature several plants with therapeutic claims as immunomodulators, memory enhancers, neuroprotectives, ant obesity, and ant ageing agents, etc., have been described, and which have now received some modern scientific attention. Though, several books on Indian medicinal plants have been published in recent years, there is not a single cogent one, aimed primarily at evaluation of these claims in the present-day context. The present volume is the result of such an endeavour. Mostly those plants have been selected which are considered important in Ayurveda, and have also received at least some modem scrutiny. A few entries with little modem evaluation have also been included keeping in mind their potential. To put the Ayurvedic therapeutic claims in a proper time frame, I have opted for citing the relevant original Sanskrit descriptions (with translation). Most of these quotations are from Bhavaprakasha, a 16th Century compilation, highly esteemed by the present-day Ayurveda practitioners. A few, of course, have been culled from other texts.

It is my hope that if this book can spur greater research and development activity in this area to fashion useful phytomedicines or obtain newer lead compounds, or assist traditional Ayurveda pharmacies in standardizing their products, my efforts would have been worthwhile.

I wish to gratefully acknowledge the help of following institutes/persons for placing at my disposal their collections of plant photographs, from which I could select for inclusion in the book: Central Council for Research inAyurveda and Siddha (New Delhi), Prof. S.R. Yadav (Delhi University), and Dr. Y.K. Sarin (Dehradun). I would also like to thank my wife, Shashi Prabha, for her understanding and patience.

In order to place the work covered in this book in a proper perspective, it would be desirable to present a brief introduction to Ayurveda as its medicinal plants comprise the main thrust of the present work. Also, a brief commentary on the scope of possible leads from these medicinal plants in the development of both the molecular drugs and phytopharmaceuticals has been included in the hope that such an account may provide an impetus to those unfamiliar with the terrain, to delve deeper for scientific curiosity or for possible commercial outcome.

1. Ayurveda

1.1 Introduction

The word Ayurveda is derived from Ayus (r), meaning life, and Veda, meaning knowledge, thus, Ayurveda literally means science of life. It is the ancient Indian system of healthcare and longevity. Ayurveda takes a holistic view of man, his health and illness. It aims at positive health, which has been defined as a well-balanced metabolism coupled with a healthy state of being. Disease, according to Ayurveda, can arise from body and/or mind due to external factors or intrinsic causes. Ayurvedic treatment is aimed at the patient as an organic whole, and treatment consists of salubrious use of drugs, diets and certain practices.

The origin of Ayurveda is lost in prehistoric antiquity, but its characteristic concepts appear to have matured between 2500—500 BC. In ancient India, Ayurveda has a vast literature in Sanskrit and various Indian languages, but it would be feasible to present here only a fleeting account of this.

Earliest references to drugs and diseases are to be found in the Rig Veda and Atharva Veda, dating back to second millennium BC. In fact, of the 6,599 hymns and around 700 prose lines which comprise Atharva Veda, a substantial part relates to human body, its disorders and possible cures which included recitation of prayers and magical invocations.

Atharva Veda has been considered as the forerunner of Ayurveda.

The post-Vedic era, which has been called the Arsha (sages) period, saw systematic development of Ayurveda. This period witnessed the emergence of several medical compilations (Samhitaas) written and organized on more scientific basis. One of the most outstanding of these has come to be known as Charaka Samhitaa (900 BC),’3 which is fully devoted to the concepts and practice of Ayurveda. Its hallmark is internal medicine and therapeutics (Kayachikitsa). The work consists of eight sections divided into 120 chapters on specific topics. The next landmark in Ayurvedic literature is Sushruta Samhitaa (600 BC),7 which has special emphasis on surgery. It has six sections covering 186 chapters. Sushruta, lived and practiced surgery in Varanasi some 2600 years ago. The next important authority on Ayurveda, after Charaka and Sushruta, was Vagbhatta of Sind, who practised around 7th Century AD. His work, Ashtanga Hridaya, is considered unrivalled for principles and practice of medicine, and is essentially an edited compilation of complementary sections of Charaka and Sushruta works. Ashtanga Hridaya consists of six sections covering 120 chapters, and contains 7,444 verses; the entire book is in verse.8’9 Charaka, Sushruta, and Vagbhatta arc the Vrihat Traya (Powerful Triad) of Ayurveda, and their period (900 BC to 1000 AD) is considered as the golden age of Ayurveda.

The next important milestone in the development of Ayurveda is the famous work on diagnosis of diseases by Maadhavakara (800 AD). This is entitled Madhava Nidana, and consists of 1,552 verses in 69 chapters. It is a valuable clinical guide.8’ 10 Sarangdhara (14th Century), systematized Ayurvedic materia medica, and his work Sarangdhara Samhitaa consists of three parts, 32 chapters and 2,500 verses.8’ 11 The last celebrated writer on Hindu medicine was Bhava Mishra of Magadha, and his treatise Bhavaprakasha, written around 1550, is held in high esteem by the modern Ayurvcdic practitioner. It has three sections containing 10,831 verses.12 Madhava, Sarangdhara and Bhava Mishra have been referred to as the Laghu Traya (Junior Three) in the Ayurvedic literature.

Besides these monumental treatises, a rather large number (>70) of Nighantu Granthas (Pharmacy Lexicons) were written, mostly between 7th and 16th Centuries.13’ 14 These books provide valuable information about medicinal plants used in Ayurvcda. Of these texts, Madanapala Nighantu (12th Century), Dhanvantari Nighantu ( 1300), and Raja Nighantu (—1370.) by Narhari Pandita are considered masterpieces on Ayurvedic materia medica.8’ 15 All ancient texts on Ayurveda divide medical knowledge into eight branches (Ashtanga).’° The classifications given by Charaka, Sushruta and Vagabhatta are identical, though differing in order. Table 1 depicts the eight branches as enumerated in Charaka Samhitaa, and as can be seen, this is very much reminiscent of the modern division of medical science.

At this stage, it appears appropriate to digress very briefly on the main themes of Charaka and Sushruta Samhitaas, as the edifice of subsequent Ayurvedic treatises was built on these. As mentioned earlier, Charaka Samhitaa is an exhaustive compendium on therapeutics, although there are brief chapters on other seven branches. Table 2 depicts the eight sections (sthaanas) of the treatise, and this clearly delineates the thoroughness of the approach, especially when viewed in the then time background. While dealing with diseases, 10 aspects are discussed which include physiology, etiology, pathology, effect of age, sex and season. There are also detailed renderings of diagnosis and treatment of diseases covering 200 disease entities.2’

As already stated, the main emphasis in Sushruta Samhitaa is on surgery. The treatise is the world’s first comprehensive work on surgery. Surgical intervention in situations of gynaecology and obstetrics, intestinal obstructions, bladder stones, diseases of eyes, ear, nose and throat, as well as amputation of limbs, among others, have been described. Detailed descriptions of instruments and their uses have been given. It is now agreed that the origin of modern plastic surgery such as in rhinoplasty lay in Sushruta’s technique.5’7’‘

From this brief and rather cursory introduction, it must have become obvious that Ayurveda, in its prime time, was a cogent, scientifically organized discipline. This is further borne out by the fact that Ayurvedic texts were much respected in the then contemporary world of neighboring countries as evidenced from their translation into Greek (300 BC), Tibetan and Chinese (300 AD), Persian and Arabic (700 AD), and several other languages of other Asian people.’72°

In the present-day context, it can be stated that Ayurveda is a very much alive system of medicine widely practised in the Hindustan peninsula (India and the neighbouring countries) and, in recent years has been attracting much attention in the economically developed countries such as (of) Europe, US and Japan.2’ According to one estimate, the number of registered Ayurvedic practitioners in India is well over 250,000.22