Prime Ayurvedic Plant Drugs [2 ed.] 3031220749, 9783031220746

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Sukh Dev

Prime Ayurvedic Plant Drugs Second Edition

Prime Ayurvedic Plant Drugs

Sukh Dev

Prime Ayurvedic Plant Drugs Second Edition

Sukh Dev Professor (Retd.), Indian Institute of Technology Delhi New Delhi, India

ISBN 978-3-031-22075-3 (eBook) ISBN 978-3-031-22074-6 https://doi.org/10.1007/978-3-031-22075-3 © The Author(s) 2023 Jointly published with Ane Books Pvt. Ltd. In addition to this printed edition, there is a local printed edition of this work available via Ane Books in South Asia (India, Pakistan, Sri Lanka, Bangladesh, Nepal and Bhutan) and Africa (all countries in the African subcontinent). ISBN of the Co-Publisher’s edition: 978-93-8061-818-0 1st edition: © Author 2016 This work is subject to copyright. All rights are solely and exclusively licensed by the Publisher, whether the whole or part of the material is concerned, specifically the rights of reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publishers, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publishers nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publishers remain neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland

Dedicated to 

the Rishies and Acharyas of Yore

O Man, I, the physician bring here for you all those unique herbs wherein the practitioners have discovered healing power. Let the herbaceous plants with flowers,with buds, with fruits, and without fruits bestow their health reviving quality for the perfect health of man, like the mother to her children. I deliver you, O man, from the pain in the five cognitive organs, from the pain in the teen organs, from the shackles of all-bonding death and from all the pains and troubles arising from disobedience to the laws of Nature. Atharva Veda–7/26—28  (Second millennium B.C.)



“The science of Life shall never attain finality. Hence, humility and relentless effort should characterize your endeavour and your approach to knowledge... The entire world consists of teachers for the wise and enemies for the fools... Therefore knowledge conducive to health, longevity, fame and excellence, coming even from an unfamiliar source, should be received, assimilated and utilized with earnestness...” Punarvasu Atreya 

(First millennium B.C.)

Foreword to the First Edition

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: NCEs) of the modern system of medicine. Many of the drugs thus discovered are still used in the modern 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 modern 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 paclitaxel; cardiovascular agents like forshkolin; anti-HIV agent like calanolid and the latest to add to this list is gugulsterone, the active constituent of Guglip, a hypolipidemic drug, which has been shown to act through inhibition of farnesoyl 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 fulfil this requirement admirably. ix

x  Prime Ayurvedic Plant Drugs 

Ayurvedic drugs are also attracting much attention of diseases with no or inadequate drugs for treatment in modern medicine, such as for metabolic and degenerative disorders. Most of these diseases have multifactorial 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 more 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 modern stream of scientific investigation and expose it to modern scientific developments. This is close to the fast emerging SystemsBiology perspective, which looks at the living systems as multi-component with interconnected molecular networks. This ‘wholistic’ view of SystemsBiology is very close to the ‘holistic’ view of Ayurveda. In modern medicine the “wholistic” perspective of ‘Systems-Biology’ is fast emerging as a very useful approach to understand biological systems, including to understand 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 Ayurveda 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 modern medicine, and how best the two could complement each other. This will bring out the essence of ancientmodern 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 Dev, an authority on natural product chemistry, with special emphasis on medicinal plants used in Ayurveda, has done in this book. The book in Section I 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

  Prime Ayurvedic Plant Drugs xi

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 useful by all those interested in important plants of Ayurveda and would serve as a useful standard reference book.

Nitya Anand

Former Director  Central Drug Research Institute  Lucknow, India

Preface to the Second Edition 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 modern 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 agroclimatic 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 modern 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.

Sukh Dev

June 2023

xiii

Preface to the First Edition 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, plantbased 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—15% annually. Traditional Ayurvedic therapeutic formulations draw on an impressive array of plants, many of which have been scrutinized by modern 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 1950s. 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, antiobesity, and antiageing 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 presentday 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 modern scrutiny. A few entries with little modern 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 xv

xvi  Prime Ayurvedic Plant Drugs 

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 in Ayurveda 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.

Sukh Dev January 2006



Explanatory Notes 1. References are invariably given to reviews, books, rather than to original papers in order to avoid voluminous citations. Reference to an original publication is only done, when it is not covered in the cited review/ book, or for further details. 2. To avoid repetitive references to an Annexure on Ayurvedic terms, translation of these words is usually included in the translation of the Sanskrit shloka, and an Annexure on Ayurvedic terms has been dispensed with. 3. Invariably, total yield of an appropriate solvent extract of the relevant part of the plant has been entered for each Monograph under ‘Chemical Constituents’. Wherever the extraction is with methanol and no reference number is given, the cited data have been obtained in the Author’s laboratory. In other cases, appropriate reference is cited. 4. While composing ‘Chemical Constituents’ occurrence of usual amino acids, fatty acids, usual colouring matters, vitamins, and minerals has been left out, unless there is something specific to a discussion. 5. Structures of only compounds with pharmacological/therapeutic action, as mentioned under ‘Modern Scientific Validation’, are given. Structures have also been shown to emphasise a certain biological effect, even though no work on the subject has been carried out on the Monograph plant (e.g., Eugenia jambolana). 6. A certain % alcohol (methanol/ethanol) implies that rest is water, e.g., 70% methanol denotes methanol containing 30% water (v/v). 7. In connection with the pharmacological and related data, it may be noted that x quantity/kg implies x quantity/kg of body weight. 8. In the structural formulae of organic compounds, a β-hydrogen at the ring junction is shown by a bold dot.

xvii

Abbreviations Language Beng. Burm. Chin. Eng. Fr. Ger. Guj. Hin. Indones. Ital. Jap. Kan.

: : : : : : : : : : : :

Bengali Burmese Chinese English French German Gujarati Hindi Indonesian Italian Japanese Kannad

Mal. Malay. Mar. Nep. Punj. Russ. Sing. Sinhal. Span. Tam. Tel. Tibe. Thai. Viet.

: : : : : : : : : : : : : :

Malayalam Malaysian Marathi Nepali Punjabi Russian Singapuri Sinhalese Spanish Tamil Telugu Tibetan Thailand Vietnam

Technical AAP ABTS ACE ADP Akt AMP AMPA AP 2BS cells BALB/3T3 cell Bax Bcl-2

: 2,2′-azobis (2-amidinopropane). : 2,2′-azinobis-3-ethylbenzothiazoline-6-sulphonic acid. : angiotensin converting enzyme. : adenosine diphosphate. : also known as protein kinase B (PKB), is an important molecule in mammalian cellular signalling. : adenoside monophosphate. : α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid. : alkaline phosphatase. : human diploid fibroblast. : a mouse embryo cell line. : a pro-apoptotic Bcl-2 protein. : B-cell lymphoma/leukaemia-2. xix

xx  Prime Ayurvedic Plant Drugs 

BHT bid bw CAT CCK CD50 CNS COX Da dB dia. DMSO DNA DPPH EC50

: : : : : : : : : : : : : :

ECG EPS

: :

ER ERK GABA GC GI50 Glc GLUT 4 GSH GSSG GPT GPx HDL HeLa

: : : : : : : : : : : :

HEK HepG2 HER2

: : :

:

:

butylated hydroxytoluene. bis in die, twice daily. biweekly. catalase. cholecystokinin. 50% cell death. central nervous system. cyclooxygenase. daltons. decibel. diameter. dimethylsulphoxide. deoxyribonucleic acid. 1,1-diphenyl-2-picrylhydrazyl. effective concentration causing 50% reduction in parasite growth. electrocardiogram. extra pyramidal symptoms, side effects resulting from certain anti-anxiety medication. estrogen receptor. extracellular signal-regulated kinases. γ-aminobutyric acid. gas chromatography. growth inhibition by 50%. β-D-glucopyranosyl. glucose transporter isoform 4. reduced glutathione. glutathione disulphide. glutamate pyruvate transaminase. glutathione peroxidase. high density lipids. cells of the first continuously cultured (human cervical) carcinoma strain. human embryonic kidney. human hepatocellular carcinoma cell line. is a signalling protein of the epidermal growth factor receptor family, and is notable for its role

  Prime Ayurvedic Plant Drugs xxi

hERG HI HIV HL-60 HPLC HPTLC HSDB HT-29 icv Ig i.g. i.m. IFN-γ iNOS INS-1 i.p. i.v. IC50 ID50 IL JNK K562 KB

: : : : : : : : : : : : : : : : : : : : : : :

LC LD50

: :

LDL LDLR 5-LOX LPS M MAPK MDA-MB-231 MEK MIC

: : : : : : : : :

in the pathogenesis of breast. human Ether-à-go-go related gene. haemagglutination inhibition. human immunodeficiency virus. a leukaemia cell line. high performance liquid chromatography. high performance thin layer chromatography. hazardous substances database. human colonic adenocarcinoma cell line. intracerebroventricular. immunoglobulin. intragastric. intramuscular. interferon-gamma. inducible nitric oxide synthase. pancreatic islet derived insulinoma cells. intraperitoneal. intravenous. 50% inhibitory concentration. 50% inhibitory dose. interleukin. c-Jun NH2-terminal kinase. a human myelogenous leukaemia cell line. a cell strain derived from human epidermoid carcinoma. liquid chromatography. a dose which is lethal to 50% of the experimental animals. low density lipids. low density lipoprotein receptor. 5-lipoxygenase. lipopolysaccharide. mole. mitogen-activated protein kinase. human breast adenocarcinoma. a phosphorylating kinase. minimum inhibitory concentration.

xxii  Prime Ayurvedic Plant Drugs 

mol. wt. mRNA

MS MTD MTT NADH NADPH NF NF-AT NF-κB NFATc1 NIDDM NK NMDA NMR NO NOD NOS OVCAR-3 PAD PAF PDGF PG pJAK2 PKC p.o. PPAR P selectin pSTAT3 RANTES

: molecular weight. : messenger RNA. Ribonucleic acid that mediates the genetic information from DNA in the cell nucleus to ribosomes sites for protein synthesis in the cell. : mass spectrometry. : maximum tolerated dose. : 3-(4,5-dimethylthiazol-2-ly)-2,5-diphenyl-tetrazoliun bromide. : nicotinamide adenine dinucleotide (reduced form). : nicotinamide adenine dinucleotide phosphate (reduced form). : nuclear factor. : nuclear factor in activated T cells. : is a protein complex that acts as a transcription factor, and is found in all cell types. : nuclear factor of activated T-cells. : non-insulin dependent diabetes mellitus. : natural killer. : N-methyl-D-aspartate. : nuclear magnetic resonance. : nitric oxide. : non-obese diabetic. : nitric oxide synthase. : human ovarian adenocarcinoma. : pulsed amperometric detection. : platelet activating factor. : platelet derived growth factor. : prostaglandin. : phosphorylated Janus kinase 2. : protein kinase C. : per os (by mouth). : peroxisome proliferator-activated receptor. : a cell adhesion molecule present in granules in endothelial cells. : a member of STAT ( signal transducer & activator of transcription) family of transcription factors. : is a protein encoded by chemokine ligand 5 gene

  Prime Ayurvedic Plant Drugs xxiii

RANKL RBC RNA s.c. SC50

: : : : :

SGOT SGPT SMAD

: : :

SOD SRB STZ Syn. TBARS Th2

: : : : : :

tid. Tert TGF TLC TNF VEGF VLDL WBC Wnt

: : : : : : : : :

in humans. receptor activator for NF-κB ligand. red blood corpuscles. ribonucleic acid. subcutaneous. (scavenging) concentration required for 50% reduction of 40 µM DPPH radicals. serum glutamic oxaloacetic transaminase. serum glutamic pyruvate transaminase. are proteins that modulate the activity of TGFβ ligands. superoxide dismutase. Sulforhodamine B (protein staining assay). streptozotocin. synonym. thiobarbituric acid reactive substances. T helper cells; play an important role in immune system. ter in die, three times a day. tertiary. transforming growth factor. thin layer chromatography. tumour necrosis factor. vascular endothelial growth factor. very low density lipids. white blood corpuscles. Wingless-type–a family of secreted signalling proteins.

Literature References BOOKS (Classical Ayurvedic Texts) Bhavaprakasha:

Bhavaprakasha Nighantu. [i] D.N. SenGupta and U.N. SenGupta, C.K. Sen & Co., Calcutta, India (1931). [ii] V.N.D. Shastri, Motilal Banarsidass, Delhi, India (1998). [iii] K.R.S. Murthy, Krishnadas Academy, Varanasi (2001).

Charaka:

Charaka Samhitaa. [i] P.M. Mehta (ed), Vols. I—VI, Shri Gulabkunverba Ayurvedic Society, Jamnagar, India (1949). [ii] P. Ray and H.N. Gupta, (A Scientific Synopsis), National Institute of Sciences of India (now Indian National Science Academy), New Delhi, India (1965). [iii] P.V. Sharma,  Vols. I—IV, Chaukhambha Orientalia, Varanasi, India (2003).

Dhanvantari:

Dhanvantari Nighantu. [i] Anandashram, Pune, India (1925). [ii] S.D. Kamat, Chaukhamba Sanskrit Pratishthan, Delhi, India (2002).

Raajanighantu:

Raaja Nighantu, See Dhanvantri [ii].

Sushruta:

Sushruta Samhitaa. [i] A.K. Shastri (ed), Chaukhambha Sanskrit Sansthan, Varanasi, India (1979). [ii] P. Ray, H.N. Gupta, and M. Roy, (A Scientific Synopsis), Indian National Science Academy, New Delhi, India (1980).

Todaraananda:

B. Dash and L. Kashyap, Materia Medica of Ayurveda based on Ayurveda Saukhyam of Todaraananda. Concept Publishing Co., New Delhi, India (1980). xxv

xxvi  Prime Ayurvedic Plant Drugs 

BOOKS and REPORTS Asolkar, Kakkar & Chakre: L.V. Asolkar, K.K. Kakkar, and O.J. Chakre, Second Supplement to Glossary of Indian Medicinal Plants with Active Principles, Part-I (A—K: 1965—1981). Publication and Information Directorate, CSIR, New Delhi, India (1992). Atal & Kapur: C.K. Atal and B.M. Kapur (eds), Cultivation & Utilization of Medicinal Plants. Regional Research Laboratory, Council of Scientific & Industrial Research, Jammu-Tawi, India (1982). Bisset:

N.G. Bisset (ed), Herbal Drugs and Phytopharmaceuticals. CRC Press, Boca Raton, U.S.A. (1993).

Chang & But: H.M. Chang and P.P.H. But (eds), Pharmacology and Applications of Chinese Materia Medica, Vol 1 (1986), Vol 2 (1987). World Scientific, Singapore. Chatterjee & Pakrashi: A. Chatterjee and S.C. Pakrashi (eds), The Treatise on Indian Medicinal Plants, Vol 1 (1991), Vol 2 (1992), Vol 3 (1994), Vol 4 (1995), Vol 5 (1997). Publication & Information Directorate, New Delhi, India. Dahanukar & Thatte: S.A. Dahanukar and U.M. Thatte, Ayurveda Revisited. Popular Prakashan, Bombay, India (1989). Database Med Plants: P.C. Sharma, M.B. Yelne, T.J. Dennis (eds), Database on Medicinal Plants used in Ayurveda, Vol 1 (2000); Vol 2 (2001); Vol 3 (2001); Vol 4 (2002); Vol 5 (2002); Vol 6 (2003). Central Council for Research in Ayurveda and Siddha, New Delhi, India. Dict Org Compds: J. Buckingham (Exec ed), Dictionary of Organic Compounds (fifth edition), Vols 1—5 (1982); Supplements 1—5 (1983—1987); Supplements 6—9 (1988—1991). Chapman and Hall, London, England.

  Prime Ayurvedic Plant Drugs xxvii

Fieser & Fieser: Garg:

L. Fieser and M. Fieser, Steroids. Reinhold Publishing Corporation, New York, U.S.A. (1959). D.S. Garg (editor-in-chief), Dhanvantri–Banaushdhi Vishesh Ank, Vol 1 (1961); Vol 2 (1963); Vol 3 (1965); Vol 4 (1967); Vol 5 (1969); Vol 6 (1971). Dhanvantri Karyalaya, Vijaygarh, Aligarh, India.

Gross, Hemingway & Yoshida: G.G. Gross, R.W. Hemingway, T. Yoshida (eds), Plant Polyphenols 2: Chemistry, Biology, Pharmacology, Ecology. Kluwer Academic, New York, U.S.A. (1999). Gunapaatha: Gunapaatha. Bharathavilasom Press, Trichur, India (1098 ME). Gupta,Tandon & Sharma: A.K. Gupta, N. Tandon and M. Sharma (Editors), Quality Standards of Indian Medicinal Plants, Vol 1 (2003); Vol 2 (2005); Vol 3 (2005); Vol 4 (2006). Indian Council of Medical Research, New Delhi, India. Handa & Kaul: S.S. Handa and M.K. Kaul (eds), Supplement to Cultivation & Utilization of Medicinal Plants. Regional Research Laboratory, Council of Scientific & Industrial Research, Jammu-Tawi, India (1996). Karrer:

W. Karrer, Konstitution und vorkommen der orgaischen Pflanzenstoffe, original Vol (1976); Supplement 1 (1977); Supplement 2 (Part 1, 1981; Part 2, 1985). Birkhauser, Basel, Switzerland.

Kleemann & Engel: A. Kleemann, J. Engel, B. Kutscher and D. Reichert, Pharmaceutical Substances, Vol (A—M), Vol (N—Z). Thieme, Stuttgart, Germany (2001). Koman:

Extracts from Dr. M.C. Koman’s Report on the Investigation of Indigenous Drugs. Government of Madras (1921) [Reprinted: Ministry of Health, Government of India, New Delhi, India, 1965.]

xxviii  Prime Ayurvedic Plant Drugs 

Krishnanand: Gavoin mein Aushth Rattan, Vol 1 (1974). Krishngopal Ayurved Bhavan, Ajmer, India. Mahanand: Mahanand, Rahnamayai Seyat. Seva Book Depot, New Delhi, India, 16th Reprint (1949). Malhotra & Sharma: S.C. Malhotra and D.P. Sharma (eds), Pharmacological Investigations of Certain Medicinal Plants and Compound Preparations used in Ayurveda and Siddha. CCR in Ayurveda and Siddha, New Delhi, India (1996). Merck Index: The Merck Index, Eleventh Edition. Merck & Co., Rahway, U. S. A. (1989). Merck Manual: The Merck Manual of Medical Information, Second Home Edition. Merck Research Laboratories, Whitehouse Station, U.S.A. (2003). Mooss:

V.N.S. Mooss, Ayurvedic Flora Medica. Vaidyasarathy Press, Kottyam, India (1978).

Nig. Ratna.: Nighantu Ratnaakar. [i] in Shaaligram Nighantu Bhooshnam, first published in 1896 [Now printed by Khemraj Shrikrishn Das, Mumbai, India (2002)]. Oliver & Rolf: Oliver von Bohlen und Halbach and Rolf Dermietzel, Neurotransmitters and Neuromodulators. Wiley–VCH, Weinheim, Germany (2002). Raghunathan & Mitra:

K. Raghunathan and R. Mitra (eds), Pharmacognosy of Indigenous Drugs, Vol I (1982); Vol II (1982); Vol III (O.P. Gupta, ed, 1999). CCR in Ayurveda and Siddha, New Delhi, India.

  Prime Ayurvedic Plant Drugs xxix

Rastogi & Mehrotra: R.P. Rastogi and B.N. Mehrotra, Compendium of Indian Medicinal Plants, Vol 1, period 1960—1969 (1990); Vol 2, period 1970—1979 (1991); Vol 3, period 1980—1984 (1993); Vol 4, period 1985—1989 (1995); Vol 5, period 1990—1994 (1998). Central Drug Research Institute, Lucknow, and National Institute of Science Communication, New Delhi, India. Rowe: Sarin:

J.W. Rowe (ed), Natural Products of Woody Plants, Vol I (1989); Vol II (1989). Springer-Verlag, Berlin, Germany. Y.K. Sarin, Illustrated Manual of Herbal Drugs used in Ayurveda. Council of Scientific and Industrial Research, New Delhi, India (1996).

Satyavati: G.V. Satyavati (ed), Medicinal Plants of India, Vol. 1 (1976); Vol. 2 (1987). Indian Council of Medical Research, New Delhi, India. Shaaligram: Shaaligram Nighantu Bhooshnam, first published in 1896 [Now printed by Khemraj Shrikrishn Das, Mumbai, India (2002)]. Sharma: P.V. Sharma, Dravyaguna-vijnana, Vol. II. Chaukhambha Bharti Academy, Varanasi, India (1986). Southon & Buckingham: I.W. Southon and J. Buckingham (eds), Dictionary of Alkaloids. Chapman & Hall, London, U.K. (1989). Sukh Dev (Report): Report of the INSA Professorship work carried out at I.I.T. Delhi (1989—1993) in collaboration with Takasago Research Institute (I. Kawada), Japan (Unpublished). Sukh Dev, Gupta & Patwardhan: Sukh Dev, A.S. Gupta, S.A. Patwardhan, Handbook of Terpenoids: Triterpenoids, Vol II. CRC Press, Boca Raton, U.S.A. (1989).

xxx  Prime Ayurvedic Plant Drugs 

Sukh Dev & Misra: Sukh Dev and R. Misra, Handbook of Terpenoids: Diterpenoids, Vol. I (1985); Vol. II (1985); Vol. III (1986); Vol. IV (1986). CRC Press, Boca Raton, U.S.A. Sukh Dev & Misra (Report): Report of the INSA Professorship work carried out at I.I.T. Delhi (1989—1993) in collaboration with N.I.H. (R. Misra), U.S.A. (Unpublished). Sukh Dev & Nagasampagi: Sukh Dev, B.A. Nagasampagi, Handbook of Terpenoids: Triterpenoids, Vol I (1989). CRC Press, Boca Raton, U.S.A. Sukh Dev, Narula & Yadav: Sukh Dev, A.P.S. Narula and J.S. Yadav, Handbook of Terpenoids: Monoterpenoids, Vol II (1982). CRC Press, Boca Raton, U.S.A. Tang & Eisenbrand: W. Tang and G. Eisenbrand, Chinese Drugs of Plant Origin. Springer-Verlag, Berlin, Germany (1992). Varier’s:

Watt:

P.S. Varier’s Indian Medicinal Plants, Vol 1 (1994); Vol 2 (1994); Vol 3 (1995); Vol 4 (1995); Vol 5 (1996). Orient Longman, New Delhi, India. G. Watt, A Dictionary of the Economic Products of India, Vol. I (1889); Vol. II (1889); Vol. III (1889); Vol IV (1890); Vol. V (1890); Vol. VI (1892—1893). Government of India, Calcutta, India.

Wlth India: The Wealth of India (Raw Materials), many volumes. Publication and Information Directorate, CSIR, New Delhi, India [Dates of publications in the citation]. Zs-Nagy, Harman, & Kitani: I. Zs-Nagy, D. Harman, K. Kitani, Pharmacology of Aging Processes: Methods of Assessment and Potential Interventions. The New York Academy of Sciences,New York, U.S.A. (1994).

Contents Section I: General Introduction  Section II: Monographs  1. Abies spectabilis   2. Acacia catechu 3. Achyranthes aspera 4. Acorus calamus 5. Adhatoda zeylanica 6. Aegle marmelos 7. Aloe vera 8. Alpinia galanga 9. Alstonia scholaris 10. Andrographis paniculata 11. Argyreia nervosa 12. Asparagus adscendens 13. Asparagus racemosus 14. Azadirachta indica 15. Bacopa monnieri 16. Barleria prionitis 17. Benincasa hispida 18. Berberis aristata 19. Bergenia ciliata 20. Boerhavia diffusa 21. Bombax ceiba 22. Boswellia serrata 23. Butea monosperma 24. Caesalpinia bonduc 25. Calotropis procera 26. Cannabis sativa

1 47 49 53 59 64 70 75 83 92 98 103 111 116 120 126 136 142 146 151 157 162 169 174 181 188 194 202 xxxi

xxxii  Prime Ayurvedic Plant Drugs 

27. Carum carvi 28. Cassia absus 29. Cassia angustifolia 30. Cassia fistula 31. Cassia tora 32. Cedrus deodara 33. Celastrus paniculatus 34. Centella asiatica 35. Cissus quadrangularis 36. Clitoria ternatea 37. Coccinia grandis 38. Commiphora wightii 39. Convolvulus microphyllus 40. Costus speciosus 41. Crataeva nurvala 42. Crocus sativus 43. Cuminum cyminum 44. Curculigo orchioides 45. Curcuma longa 46. Curcuma zedoaria 47. Cyperus rotundus 48. Desmodium gangeticum 49. Eclipta alba 50. Embelia ribes 51. Emblica officinalis 52. Eugenia jambolana 53. Ficus bengalensis 54. Fumaria indica 55. Garcinia morella 56. Glycyrrhiza glabra 57. Gymnema sylvestre 58. Hedychium spicatum 59. Hemidesmus indicus 60. Holarrhena antidysenterica 61. Hygrophila auriculata

212 218 221 226 232 238 243 249 259 264 269 275 284 290 296 301 310 316 322 335 340 346 352 358 364 375 382 387 393 398 411 417 423 429 434

  Prime Ayurvedic Plant Drugs xxxiii

62. Inula racemosa 63. Lawsonia inermis 64. Leptadenia reticulata 65. Leucas aspera 66. Litsea glutinosa 67. Mallotus philippensis 68. Mangifera indica 69. Momordica charantia 70. Moringa oleifera 71. Mucuna pruriens 72. Nardostachys jatamansi 73. Nelumbo nucifera 74. Nigella sativa 75. Ocimum sanctum 76. Phyllanthus fraternus 77. Picrorhiza kurroa 78. Piper longum 79. Pluchea lanceolata 80. Plumbago zeylanica 81. Psoralea corylifolia 82. Pterocarpus marsupium 83. Pueraria tuberosa 84. Punica granatum 85. Rauvolfia serpentina 86. Rubia cordifolia 87. Salacia prinoides 88. Santalum album 89. Saussurea lappa 90. Semecarpus anacardium 91. Sida cordifolia 92. Swertia chirayita 93. Terminalia arjuna 94. Terminalia bellirica 95. Terminalia chebula 96. Tinospora cordifolia

440 445 450 454 459 465 470 479 488 497 503 508 516 526 537 545 551 560 564 571 582 588 595 606 612 620 626 631 639 646 652 661 670 677 687

xxxiv  Prime Ayurvedic Plant Drugs 

97. Tribulus terrestris 98. Trigonella foenum-gracecum 99. Valeriana jatamansi 100. Vitex negundo 101. Withania somnifera 102. Zingiber officinale 103. Zingiber zerumbet

696 704 713 719 727 742 757

Section III: Annexures  

763

Annexure 1. Glossary of Botanical Terms Annexure 2. Glossary of Medical and Biochemical Terms Annexure 3. Activity-wise Plant Listing Annexure 4. Plant-wise Activities Index  1.  Botanical  Names Index  2.  Ayurvedic  Plant  Names

765 768 779 804 823 825

Section-I GENERAL INTRODUCTION

GENERAL INTRODUCTION

I

n 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),1–3 which is fully devoted to the concepts and practice of Ayurveda. Its hallmark is internal medicine and © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 S. Dev, Prime Ayurvedic Plant Drugs, https://doi.org/10.1007/978-3-031-22075-3_1

3

4 Prime Ayurvedic Plant Drugs

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),4–7 which has special emphasis on surgery. It has six sections covering 186 chapters. Sushruta, lived and practised 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 are 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 Ayurvedic 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 Ayurveda. 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).10 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.

General Introduction 5

Table 1. Eight Branches of Ayurveda No.

Sanskrit designation

Modern rendering

1.

Kayachikitsa

Internal medicine and therapeutics

2.

Shalakyatantra

Diseases of eyes, ears, nose, tongue, oral cavity, throat

3.

Shalyatantra

Surgery

4.

Kaumarabhritya

Paediatrics, gynaecology

5.

Agadatantra

Toxicology

6.

Bhutavidya

Psychiatry

7.

Rasaayana

Antiageing

8.

Vajikarana

Virility

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, aetiology, pathology, effect of age, sex and season. There are also detailed renderings of diagnosis and treatment of diseases covering 200 disease entities.2, 5 Table 2. Eight Sections of Charaka Samhitaa No.

Sanskrit designation

Modern rendering

1.

Sutrasthaana philosophy

General principles and

2

Sharirasthaana

Anatomy and embryology

3.

Indriyasthaana

Prognosis

4.

Vimanasthaana

Drug administration (factors in)

5.

Nidhanasthaana

Causes of diseases

6.

Chikitsasthaana

Diagnosis and treatment of diseases

7.

Kalpasthaana

Pharmacy

8.

Siddhisthaana

Cure of diseases

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

6 Prime Ayurvedic Plant Drugs

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, 16 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 neighbouring 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.17–20 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.21 According to one estimate, the number of registered Ayurvedic practitioners in India is well over 250,000.22

1.2 Concepts Ayurveda has evolved its own theoretical base. Though, much of this may be difficult to comprehend in terms of current scientific knowledge, it is necessary to explain some of these terms and concepts, as they repeatedly appear in the traditional therapeutic claims of the medicinal plants discussed later in this book.

Tridosha23 The most basic concept of Ayurveda is that all living beings (including vegetable kingdom) derive their subsistence from three essential factors (tridoshas, i.e., three doshas) namely, vaata, pitta and kapha, which operate in unison.24 All human beings, right from the time of conception, have varying preponderance of one or the other of the three doshas, but still in equilibrium specific to that individual. This equilibrium shifts with age, and even seasons tend to redefine the equilibrium state. Thus, we have individuals with different prakrities (constitutions), that is people are vaatapradhaan (vaata dominated) or pittapradhaan (pitta dominated) or kaphapradhaan (kapha dominated) in varying degrees, which is reflected in their metabolic outcome (parinaamaapadya). As a result of these differences, these individuals are considered to differ in susceptibility to diseases, and react differently to different foods, drugs, seasons, exercise, emotions, etc. Disease arises when this equilibrium gets deranged, due to

General Introduction 7

physical (both external or intrinsic) or mental causes. Ayurvedic physician’s first job is to determine the doshic type of the person, and find out which dosha(s) is/are aggravated. This he does by examining the pulse, and noting its intensity and mode of pulsating. He then formulates a strategy to re-establish the doshic equilibrium with the help of drugs, diet or any other suitable means [shades of pharmacogenomics! 25]. These three doshas are not theoretical concepts, but are tangible entities, and are considered to have specific functions: (i) Vaata (Vaayu): This dosha controls all phenomenon connected with movement in the body, that is the motor and sensory phenomenon, the entire functioning of the central and autonomic nervous systems. (ii) Pitta: This pertains to metabolism and production of energy. It is responsible for digestion, assimilation, enzyme induction, endocrine functions, etc. (iii) Kapha (Shleshma): It is responsible for structural integrity of the system and storage and regulation of energy. According to Ayurveda, the three doshas have distinct sites in the body. Vaata is located in the pelvis, pitta in the gut, and kapha in the stomach, chest and head. It has been suggested that these doshas may correspond to three receptor families located across the body, which on activation by suitable ligands (endogenous/exogenous) generate appropriate cellular signals.26 In the Ayurvedic literature, diseases arising from vitiation of these doshas have been enumerated, and diets and drugs in terms of their effects on the three doshas have been described in much detail. In a book, the author has listed highly interesting questionnaires 27 in number meant for the general readers to determine the dosha prakriti of a person.

Drug Action28 Keeping in mind the era in which the Ayurvedic classics were written, it is remarkable that a workable edifice was created by evaluating the effect of drugs, diet by the only analytical means available then, namely the sensory perceptions. Five qualities, namely taste (rasa), post-digestive taste (vipaaka), potency (veerya, therapeutic efficacy), physical characteristics (guna), and specific influence (prabhava), have been considered as determining the therapeutic outcome. The first four of these have been linked to the tridosha, while the prabhava has been considered to arise by some unknown pathway, having no relationship with taste. Taste has been given much importance, and six tastes have been enumerated

8 Prime Ayurvedic Plant Drugs

and their effect on the modulation of doshas described (Table 3). Postdigested tastes are only three, viz., sweet, sour and pungent. Effect of taste on various physiological parameters has been described in much detail. Potency is either cold (sheetaveerya) that is it subdues pitta or hot (ushnaveerya) when it excites pitta. Thus, drugs (diets) having sheetaveerya quality, generally taste sweet, bitter or astringent, and slow down certain metabolic processes, inhibit haemorrhage, and increase vigour and vitality. On the other hand, materials with ushnaveerya character have usually salty, sour or pungent taste, and stimulate digestion, diaphoresis and thirst. Table 3. Taste-dosha Interplay No.

Taste

1.

Sweet (Madhura)

2.

Sour (Amla)

3.

Salty (Lavana)

4.

Bitter (Tikta)

5.

Pungent (Katu)

6.

Astringent (Kasya)

Dosha Vaata

Pitaa

Kapha

These concepts based on taste are difficult to comprehend, but the modern Ayurveda physicians still utilize these generalizations, when prescribing diets for patients.

1.3 Diseases When we talk about ancient-modern concordance in the context of traditional medicinal plants, it is necessary to ascertain that we are talking about the same disease entity. Both in Charaka29 and Sushruta Samhitaas,30 detailed accounts of diseases and their classification have been described. For example, in Charaka Samhitaa, over 200 diseases and around 110 pathological conditions and congenital defects have been described. A complete listing of these with their modern equivalents is available.2 Certain diseases unknown in those times, are described in the later Ayurvedic texts. For example, syphilis (phiranga) makes its first appearance in Bhavaprakasha. Though, in most cases, identity of diseases in terms of modern parlance has been carried out, some explanatory notes and comments appear to be in order for certain terms and disorders in the context of subject matter of the book.

General Introduction 9

Gulma (Gaseous lumps in the abdomen) Variously described as phantom tumour or gaseous lumps in the abdomen, and characterized by its distension due to obstruction to the passage of intestinal gas and faeces.29, 30

Hrdroga (Heart diseases) Both in Charaka Samhitaa and Sushruta Samhitaa, there are descriptions of heart disorders, which have been correlated with the conditions now described as cardiac arrhythmias, ischaemic heart disease, and infective endocarditis.29–31

Jvara (Fever) Fevers have been described in much detail, and a good account of these from a modern perspective will be found in Ref. 29. It will suffice to mention here that malaria (vishama jvara) was one of the well-recognized maladies, and was classified into four types depending on its periodicity.

Krimi (Parasites) The term krimi has been used to denote both invisible (microorganisms?) and gross parasites (worms) responsible for infections and infestations (krimi roga). However, the major emphasis is on worms, maggots and insects.30, 32

Kustha (Skin diseases including leprosy) In classical Ayurvedic texts, the term kustha has been use in a generic sense to denote refractory skin diseases. In Sushruta, 18 types falling in two main divisions (major and minor) have been described. The major (mahaakustha) category covers mostly lepromatous leprosy with varying severity.30

Medoroga (Lipid disorders) In Sushruta Samhitaa, the description of medoroga (diseases arising from improper metabolism of medas, that is fat) is quite reminiscent of the modern concepts of the pathogenesis of atherosclerosis, and a vivid graphical comparison has been made.33

Meha/Prameha (Obstinate urinary disorders) These terms are used to denote obstinate urinary disorders. Three types, further subdivided into several subtypes including diabetes have been described. Specific term madhu meha is used for diabetes. These diseases have been discussed at length in both Charaka and Sushruta Samhitaas.29, 30

10 Prime Ayurvedic Plant Drugs

Rakta pitta (Haemorrhagic disorders) This refers primarily to gastrointestinal bleeding which comes out from both outlets of alimentary canal. Bleeding through the urinary and rectal passages, mouth, nose, ears and eyes are covered under rakta pitta.29, 30

Visarpa (Cellulitis) In Ayurvedic texts, visarpa has been described as a rapidly spreading elongated patches of dermatitis over extensive areas of skin, involving also the tissues beneath the skin, as well as the blood. Several types have been described. Visarpa has been equated with cellulitis/erysipelas.29, 30, 34

1.4 Medicinal Plants Ayurveda has an extensive materia medica based on products of plant, animal and mineral kingdoms. For example, in Sushruta Samhitaa 395 medicinal plants, 57 drugs of animal origin, and 64 minerals and metals have been described as therapeutic agents. However, medicinal plants constitute the dominant part of the drug substances. There are some 1,250 Ayurvedic medicinal plants35 which go into formulating therapeutic preparations as per Ayurvedic or other traditional systems. If we add to these the folklore medicinal herbs, the total number of plants with medicinal applications used throughout India will exceed 2,000. Plant and other products were recognized as of medicinal value by interaction with wandering tribes of forests, by keenly observing the behaviour of normal, sick and wounded animals, and on the basis of extensive experience of long usage in both healthy and sick patients. In the classical texts, much emphasis has been laid on the identification, collection and storage of medicinal plants. It has been stated that the medicinal potency of the plant varies depending on its habitat (soil and climate of the area in which it has grown), the degree of maturity of the plant, the season of collection, and even time of collection. Different seasons are mentioned for the collection of different parts of the plant. For example, leaves and stems are best collected during the rainy season, while bark, rhizomes, roots are to be harvested in the winter. As far as possible, freshly collected plant materials are to be employed in the preparation of medications, except in certain special materials such as pippalee (Piper longum) and vidanga (Embelia ribes) which are best used after storage for certain periods. However, when a plant material must be stored, as in the case of seasonal products, these must be utilized within a year.16, 36

Classification of Medicinal Plants In classical Ayurvedic texts, plants have been classified in terms of their

General Introduction 11

therapeutic actions. Descriptions given in both Charaka and Sushruta Samhitaas will serve to elaborate this feature. According to Charaka3, 26, 36 drugs basically fall into two categories: one type is promoter of vigour in the healthy, while the other is destructive of disease in the ailing. Thus, the first group is aimed at positive health, whereas the second category is curative of different diseases. In a further sophistication, Charaka classified drugs into 10 main categories (mahaakasaaya), consisting of varying number of subgroups, but each consisting of 10 plants on the basis of physiological/pharmacological actions of their decoctions (kasaaya). Thus, there are a total number of 50 groups of 10 drugs each, classified on the basis of these activities (Table 4). In addition, plant groups with pharmacological activities not covered in Table 4 are also listed at appropriate places. Examples are plant drugs with antidiarrhoeal, anticonvulsant, antiulcer, hepatoprotective, aphrodisiac activities. In these groupings, some plants appear in more than one group/subgroup, indicating that these plants have more than one biological activity. Table 4. Classification of Plant Drugs (Charaka Samhitaa) Main category

I

II

III

Sub-groups 1. 2. 3. 4. 5. 6.

Promoter of longevity (jivaniya) Bulk promoting, anabolic (brmhaniya) Scarifying, antiobesity (lekhaniya) Promoting excretion (bhedaniya) Promoting union of fractures (sandhaaniya) Appetite enhancing (dipaniya)

1. 2. 3. 4.

Promoting strength (balya) Improving complexion (varnya) Improving voice (kanthya) Cardiac tonic (hrdya)

1. 2. 3.

6.

Counters satiety (trptighna) Antihaemorrhagic (arsaghna) Curative of obstinate skin diseases (kushthaghna) Curative of itching (kandughna) Counters infection, worm infestation (krmighna) Antidote of poisoning (visaghna)

1. 2. 3. 4.

Galactogogue (stanyajanana) Galactodepurant (stanyashodhana) Spermatopoietic (shukrajanana) Semen depurant (shukrashodhana)

4. 5.

IV

12 Prime Ayurvedic Plant Drugs

V

1. 2. 3. 4. 5. 6. 7.

VI

VII

VIII

1. 2. 3.

Antiemetic (chardinigrahana) Quenches morbid thirst (trsnaanigrahana) Antihiccup (hikkaanigrahana)

1. 2. 3. 4. 5.

Renders faeces consistent (purisasamgrahaniya) Removes faecal pigment (purisavirajaniya) Antidiuretic (mutrasamgrahaniya) Decolours urine (mutravirajaniya) Diuretic (mutravirechaniya)

1. 2. 3. 4. 5.

Antitussive (kasahara) Antidyspnoeic (shwaasahara) Antiinflammatory (svayathuhara) Antipyretic (jvarahara) Relieves fatigue (shramahara)

1.

5.

Curative of burning sensation (daahaprashamana) Curative of sensation of cold (sheetaprashamana) Curative of urticaria (udardaprashmana) Relieves bodyache (angamardaprashamana) Relieves colic (shulaprashmana)

1. 2. 3. 4. 5.

Haemostatic (sonitasthaapana) Analgesic (vedanaashaapana) Resuscitative (samjnaashaapana) Promoting foetal growth (prajaasthaapana) Antiageing (vayahsthaapana)

2. IX

X

Adjunct emollient (snehopaga) Adjunt diaphoretic (svedopaga) Adjunct to emesis (vamanopaga) Adjunct to purgation (virechanopaga) Useful in lubricant enemas (arusthaapanopaga) Useful in lubricant enemas (anuvasanopaga) Useful in nasal evacuation (shirovirechanopaga)

3. 4.

In Sushruta Samhitaa also, plants have been divided on the basis of their therapeutic value. There are, in all, 37 groups named chiefly after the most prominent plant in the group. In each group, plants have been arranged in order of their therapeutic potency. However, some groups are named after the number of roots or fruits they consist of. Since in Sushruta Samhitaa

General Introduction 13

the main stress is on surgery, a number of plants have been listed for cleaning and healing of wounds.7, 16 Special mention should be made of the rasaayana drugs, which according to Ayurveda retard ageing, improve memory and learning, protect one from diseases, and in general promote vigour in the healthy, and thus extend lifespan without senile decay.37

2. Modern Evaluation of Ayurvedic Plant Drugs The above, necessarily brief, foray into Ayurveda should convince even the most sceptic that Ayurvedic medicinal plants provide a fertile ground for exploration using modern scientific tools. In fact, these plants have been investigated since the early decades of the last century, but there has been a spurt of activity in this area over the past two decades or so.22, 35 The Monographs section of this book summarizes these investigations carried out on a selection of Ayurvedic plant drugs. Mostly those plants have been selected which are considered important in Ayurveda, and have received at least some modern scrutiny. These researches have generated sufficient data from which, one can conclude that in a highly significant number of cases there is broad corroboration of some of the the main claims of these plants as per their traditional usage. Though, this aspect is the main thrust of the book, it appears worthwhile to elaborate on some of the findings, as an example, in a consolidated manner in order to bring out the scientific, commercial and social potential of such investigations. In the following, salient features of researches on a few Ayurvedic curative plants and on one group of plants recommended for positive health, have been summarized.

2.1 Curative Plant Drugs Psoralea corylifolia Linn. (Baakuchi) Seed powder of this plant is highly valued in Ayurveda for the treatment of vitiligo, infective and inflammatory diseases of the skin. Chemical and pharmacological investigations led to the isolation of the active principle, psoralen, in the mid-1930s. Psoralen has been shown to stimulate the formation of melanin on exposure of the skin to light.38 Psoralen is being used in the treatment of vitiligo.

14 Prime Ayurvedic Plant Drugs

O

O Psoralen

O

HO Bakuchiol

More recent investigations led to the isolation of the meroterpene bakuchiol and other related compounds.39 Bakuchiol has been shown to be a potent antimicrobial agent against a range of oral microorganisms (Table 5), and is being evaluated for its use in food additives and mouthwash preparations, and for preventing and treating dental caries.40 Table 5. Antimicrobial Activity of Bakuchiol Microorganism Streptococcus mutans JCM 5175

MIC (µg/ml)

Sterilising conc. (µg/ml)

1.0

20.0

Streptococcus sobrinus 6715

1.6

10.0

Porphyromonas gingivalis ATCC 33277

4.0

20.0

Enterococcus faecium IFO 3826

2.0

10.0

Lactobacillus acidophilus AKU 1122

1.0

10.0

Lactobacillus plantarum AKU 1130

1.0

5.0

Streptococcus sanguis 179-3

ND

10.0

Streptococcus salivarius 70-2

ND

5.0

Actinomyces viscosus 19246

ND

5.0

Lactobacillus plantarum 8016

ND

20.0

Lactobacillus casei 4646

ND

5.0

ND: Not determined

Bakuchiol has been found to display a range of other biological activities: antioxidant, immunostimulant, antiinflammatory, antihypoglycaemic, and inhibitor of DNA polymerase and topoisomerase II (anticancer).41

Rauvolfia serpentina Benth. ex Kurz (Sarpagandhaa) Rauvolfia serpentina is a famous Ayurvedic plant, as it represents the earliest (~1950) contribution of Ayurveda to modern drug development. This plant received international attention and, in a way rekindled the interest of researchers in exploring higher plants for innovative leads. Roots of this plant are valued in Ayurveda for the treatment of hypertension, insomnia and insanity. As a matter of fact, this plant in local parlance (Hindi speaking areas) is called pagle ki booti (plant for the insane). Significant

General Introduction 15

pharmacological and clinical, and chemical work on the plant carried out in India,42 attracted the attention of the CIBA group in Switzerland, which finally succeeded (1952) in isolating the sedative principle, named reserpine (3), a minor alkaloidal constituent. Reserpine was introduced in the market in 1953, and was heralded as a revolutionary event in the treatment of hypertension, as it had the twin effect of lowering high blood pressure and acting as a tranquillizer.43 Since then, several other alkaloid constituents of R. serpentina have been shown to possess antihypertensive action, and special mention may be made of ajmaline, ajmalicine and deserpidine.41 Ajmaline, which is the major alkaloid of R. serpentina, has also significant antiarrhythmic activity and is being used clinically for the treatment of haemodynamically stable ventricular tachycardia.44

N

N H

R

H OMe

H MeOOC

OMe

OOC OMe

OMe

Reserpine: R = OMe Deserpidine: R = H H N H

HO

N H

MeOOC Ajmalicine

N

N O

H OH

Me H Ajmaline

Cedrus Deodara (Roxb. ex Lamb.) G. Don (Devadaaru) Wood of the Himalayan cedar (Cedrus deodara) has several medicinal attributes, and preparations based on this are considered useful for the treatment of cough, bronchitis, inflammation, and skin diseases among others.41 Himachalol, one of the constituents of the essential oil has been shown to possess potent spasmolytic activity.45 An oil obtained from the wood is used in villages for treating insect infestation on animals, and there is sufficient experimental support for this.46 Activityguided fractionation led to the identification of himachalenes as the anti-

16 Prime Ayurvedic Plant Drugs

mange compounds. A commercial preparation (Flematic®) based on this finding is being marketed in India as a broad spectrum agent against various types of ectoparasites commonly affecting animals.41 H

H

OH

H

H

H

α-Himachalene

β-Himachalene

Himachalol

Commiphora wightii (Arnott.) Bhandari (Guggulu) Guggulu, the gum-resin from the tree Commiphora wightii, is highly prized in Ayurveda for treatment of several disorders such as rheumatoid arthritis, obesity and skin diseases. Forty-four Ayurvedic compound preparations contain this gum-resin as an important component. 47 Some of these claims appeared to be supported by the results of certain pharmacological screening48–53 carried out during the period 1960–1969 on the crude drug. Sushruta’s description of the aetiology and pathogenesis of medoroga (lipid disorders) is highly reminiscent of the modern concepts of atherosclerosis and its complications.33

O

O

O

O E-Guggulsterone

Z-Guggulsterone

Bioassay-guided fractionation of gum-resin eventually led, in 1971, to the isolation and characterization of two antihyperlipoproteinemic compounds, Z-guggulsterone and E-guggulsterone. Both compounds have similar activity which was comparable to that of clofibrate, a synthetic hypolipaemic drug which had been launched in the market (US) a few years earlier. For reasons which have been discussed later under phytopharmaceuticals, further development of the product (collecting pharmacological, biochemical, toxicological, teratogenic and mutagenic, and clinical data) was carried out on a standardized ethyl acetate extract, code-named Gugulipid, containing at least 4% guggulsterones. Gugulipid exhibits a dose-dependent lowering of serum cholesterol and triglycerides in normal and hyperlipidaemic rats, rabbits and monkeys (Table 6). A study of lipoprotein profile in rabbits

General Introduction 17

showed a significant enhancement in the level of the desired high-density lipoproteins and reduction in the unwanted low-density lipids. It also caused regression of atheromatous lesions induced in rabbits by a fat-rich diet. Gugulipid has a multifocal action: it inhibits cholesterol biosynthesis, mobilizes fat from tissues, and increases secretion of bile acids. Though, guggulsterones are pregnane derivatives, they are completely devoid of any estrogenic or antiestrogenic or progestational activity. Gugulipid was cleared for registration in India in 1986, and the drug has been manufactured and marketed in India since 1987.35, 54, 55 More recent work has led to further refinement of the mechanism of hypocholesterolaemic action of guggulsterones. Two groups independently showed that guggulsterone acts as an antagonist to the bile acid receptor (BAR), and this is partly responsible for its cholesterol lowering action.41 Table 6. Lipid Lowering Activity of Gugulipid Test system Animal

Per cent change in serum lipoproteins Dose

LDL

VLDL

HDL

Hyperlipaemic rabbits

50 mg/kg, p.o. 90 days

– 25

– 27

+29

Normal monkeys

60 mg/kg, p.o. 90 days

– 50

– 30

—

2.2 Health Supporting Plant Drugs Antiageing (Vayahsthaapana) Drugs In Ayurveda several plants have been listed as antiageing (vayahsthaapana) drugs. How does one evaluate these? A practical approach would be to look at the current understanding/theories of ageing, and see if a suitable factor can be identified as an indicative tool.

Ageing Ageing is inborn for all living creatures: plants, animals and humans. Though, senescence is believed to be programmed and controlled by genetic factors, the course of events in a multicellular organism can be upset by snapping of cellular signalling due to extracellular factors. Thus, the rate of senescence appears to be subject to external pressure. It appears, the rate of human ageing is governed by several factors, principally by genetic defects, lifestyle (quality, and type of food intake, physical activity) and stress (mental, physical and environmental). Antiageing is distinct from longevity. Antiageing intervention is aimed at slowing down the ageing process so as to extend the functional life of a person and not merely the lifespan. This, in turn, implies that all physiological processes of specialised tissues are able to function in an integrated fashion.

18 Prime Ayurvedic Plant Drugs

It is generally agreed that this is made possible by three systems of extracellular communication, namely nervous, endocrine and immune systems. As a matter of fact, these systems themselves are integrated, and there is no sharp difference between the endocrine and nervous systems, and the immune system is subject to endocrine and neural control.56 Thus, any therapeutic or any other intervention is aimed at preserving, as far as possible, neuroendocrine immune modulation. Longevity is expected as a consequence of slower ageing, but the reverse may not be true.

Oxidative Stress and Ageing It is generally agreed that an important factor triggering ageing is the accumulation of random damage to DNA, membranes, enzymes, etc., in spite of the presence of cellular maintenance and repair mechanisms. Tissues of muscle, brain, nerve and kidney among others contain many non-dividing cells, which must last a lifetime. In these cells damage to their DNA would result in the loss of their function, and with age more and more of such cells would be affected resulting in functional compromise.57 Also, even dividing cells do not go on dividing indefinitely, as cell’s telomeres (protective caps on the end of chromosomes) shorten each time the cell divides, and once they reach a certain length, the cell stops dividing.58 Furthermore, about 5% of neurons in the hippocampus disappear with each decade after 50 years of age, and though the brain tries to compensate for this by further growth of the neurites, several factors may be aiding or opposing this. 59 All this means that ageing is a by-product of normal metabolism, and is intrinsic, but the rate of senescence should be controllable. However, there is little consensus on what are all the factors responsible for this accumulating damage. One of the theories, namely the free radical and oxidative damage theory, has received much attention and appears to be at least one of the important contributing factors.60 This viewpoint appears to be supported by recent epidemiological studies60[ii] which suggest that diets rich in antioxidants, such as phenolic compounds, are associated with a longer life expectancy. The energy needed for normal functioning of cells arises mainly from aerobic metabolic reactions, and is trapped and stored (as adenosine triphosphate, ATP). However, during this process roughly 1–5% of molecular oxygen gets oxidized to superoxide radicals and other reactive oxygen derivatives such as hydrogen peroxide. These in turn generate hydroxyl and peroxyl radicals. These species, being highly reactive, attack virtually all cellular components: proteins, lipids, DNA. However, in the normal course these species are countered both by enzymatic (superoxide dismutase, glutathione peroxidase, catalase) and non-enzymatic (antioxidants such as reduced glutathione, vitamin E, ascorbic acid) reactions. The accumulation

General Introduction 19

of net damage due to oxidative stress over a period of time is considered responsible for the age-related diseases and decline, leading eventually to death. Variations in rate of ageing and lifespan in different species and among members of the same species are attributed to the level of this oxidative stress. Biochemical investigations on cellular and subcellular components have revealed that with age the concentrations of oxidatively damaged proteins, lipids and DNA molecules increase. For example, 8hydroxydeoxyguanosine, a specific product of oxidative damage to DNA molecules, increased in all tissues during the ageing process. Antiageing gene in fruit flies (Drosophila melanogaster) that regulates the production of superoxide dismutase has been isolated, and it was further demonstrated that activity of this gene governs the lifespan of fruit flies.61 Free radical and other oxidative damage has been implicated in several medical conditions, and the possibility of incidence of such diseases increases with advancing age. These so-called ‘oxidative stress diseases’ include senile dementia, Alzheimer’s disease, immunity related problems, inflammation, carcinogenesis and cardiovascular problems.62 [Studies, mostly on mice and yeast, have highlighted that dietary restriction without malnutrition is one of the most OH powerful ways to delay ageing. It has been found that caloric restriction activates SIRT 1 expression. SIRT 1, HO a functional protein, is a key regulator OH of cell defences and survival in Resveratrol response to stress, and the underlying mechanism has been investigated. It was also demonstrated that the antioxidant compound resveratrol activated this pathway, and thus extended the lifespan of yeast, human cells, and fruit flies that were nourished with a normal amount of diet63, 64]. It is in this realm that it would be interesting to re-examine the antiageing (vayahsthaapana) drugs listed in Charaka Samhitaa (Table 7). Of these, seven (shown in bold) are also to be found under the plants used in rasaayana (rejuvenation) therapy. It is gratifying to note that modern scientific investigations have revealed that all these 10 plants possess highly significant antioxidant activity, which is briefly reviewed in the following Table 7.

Asparagus racemosus Willd. (Shataavari) Its aqueous extract has been examined in vitro (mitochondrial rat liver membranes exposed to free radical damage generated during γ-radiation). Results were comparable to the actions of glutathione and ascorbic acid.

20 Prime Ayurvedic Plant Drugs

Table 7. Antiageing Plants in Charaka Samhitaa No.

Plant

1.

Tinospora cordifolia (Willd.) Hook. f. and Thoms.

2.

Terminalia chebula Retz.

3.

Emblica officinalis Gaertn.

4.

Pluchea lanceolata Clarke.

5.

Clitoria ternatea Linn.

6.

Leptadenia reticulata (Retz.) Wt. and Arn.

7.

Asparagus racemosus Willd.

8.

Centella asiatica (Linn.) Urban.

9.

Desmodium gangeticum (Linn.) DC.

10.

Boerhavia diffusa Linn.

An active fraction consisting mainly of polysaccharides, and which was effective even at 10 µg/ml, has been identified.65 In another investigation, the extract was shown to possess potent reducing action on ferric ion. Me HO This extract was evaluated against Me kainic acid induced hippocampal and O OH striatal neuronal damage in MeO anaesthetised mice. The extract Racemofuran supplemented mice showed reduced lipid peroxidation and increase in glutathione peroxidase and glutathione contents, thus demonstrating its antioxidant activity.66 Racemofuran, a novel constituent of the roots of the plant, has been demonstrated to exhibit significant antioxidant action against DPPH (IC50, 130 µM; BHT, which was used as a positive control, exhibited IC50, 87 µM).41

Boerhavia diffusa Linn. (Punarnavaa) Methanolic extract of the plant roots has been demonstrated to possess significant antioxidant activity. The extract reduced, in a concentration dependent manner, the formation of free radicals in an ESR assay, and inhibited lipid peroxidation in a TBARS assay. Boeravinones are considered to be the active agents of which boeravinone G appeared to be the most potent.41 Besides, plant contains ursolic acid which has been shown to be a free radical quencher.67

General Introduction 21

OMe HO

O

COOH

O OH

HO

O

Boeravinone G

H HO

H Ursolic acid

Centella asiatica (Linn.) Urban. (Mandookaparni) This plant has received highly significant modern scientific attention, especially for its memory and intellect promoting properties. Mechanism of action has been COOH HO investigated and it was inferred H that an antioxidant action is HO involved. Triterpenoids occurring HO H Asiatic acid in the plant have been shown to be the active agents. Asiatic acid, the principal triterpenoid constituent of C. asiatica has been demonstrated to reduce hydrogen peroxide-induced cell death and lower intracellular free radical concentration. 68 Asiatic acid has been patented (Hoechst Aktiengesellschaft) as a therapeutic agent for the treatment of dementia, and this compound as well as some related synthetic analogues have been shown to protect cultured cortical neurons from glutamate-induced excitotoxicity.69

Clitoria ternatea Linn. (Apraajitaa) Aqueous and alcoholic extracts of flowers have been demonstrated to possess significant activity (DPPH radical scavenging activity) with IC50 values of 1 µg/ml, and 4 µg/ml respectively. It may be pointed out that the plant flowers are a rich source of flavonoid glycosides based on kaempferol, quercetin and myricetin.41

Desmodium gangeticum (Linn.) DC. (Shaalparni) Aqueous ethanolic (50%) extract of the aerial parts of the plant exhibited potent antioxidant activity in several in vitro systems (DPPH, ferryl-bipyridyl, lipid peroxidation). Reactive oxygen species, among others, have been implicated as mediators of inflammation, and it was considered worthwhile

22 Prime Ayurvedic Plant Drugs

to evaluate the antioxidant status of caffeic and chlorogenic acids, isolated from the plant and shown to possess antiinflammatory activity (vide supra). When adjuvant-induced arthritic rats were administered these compounds (separately, 10 mg/kg/day, 6 weeks, oral), it was found that the treatment greatly enhanced the antioxidant defence system (SOD, CAT, glutathione) of the animals close to that in the control normal rats. Caffeic acid and chlorogenic acid, constituents of the extract, have been identified as the compounds mostly responsible for the antioxidative activity.41

Emblica officinalis Gaertn. (Aamalaki) At one time, E. officinalis fruit was considered to be a potent source of vitamin C (0.6–0.7% in fruit pulp). More recent studies, using HPTLC diode array detection, show that presence of ascorbic acid in the E. officinalis fruit is highly variable. However, the plant contains emblicaninA and -B, which have the core sugar acid structure similar to that of

General Introduction 23

ascorbic acid.70 Emblicanin-A and -B enriched fraction from the fresh juice of the fruits has been shown to increase both frontal cortical and striatal (rat brain) concentrations of free radical scavenging enzymes (superoxide dismutase, catalase, etc.) with concomitant decrease in lipid peroxidation in these brain areas. Results have been compared with a well-documented therapeutic antioxidant deprenyl.71 Besides these compounds, pyrogallol, gallic acid, ellagic acid and quercetin occurring in the fruit are also potent antioxidants. In another study, DPPH scavenging activity of compounds isolated from the fruit was investigated and it was concluded that the free radical scavenging activity of these compounds was in the order emblicanin B > emblicanin A > gallic acid > ellagic acid > ascorbic acid. For example, scavenging activity of emblicanin B was 11.2 times that of ascorbic acid.41

Leptadenia reticulata (Retz.) Wt. and Arn. (Jeevanti) Though no investigations on antioxidant activities, which are relevant to the plant’s traditional claim of being antiageing, appear to have been reported, stigmasterol, an important constituent of this plant, does display antioxidant activity: for example, stigmasterol (5 mg/kg) has been shown to inhibit hepatic lipid peroxidation, and enhance activities of catalase, SOD, and glutathione in experimental animals (mice). Also, the various flavonoid constituents of the plant possess potent antioxidant activity.41

Pluchea lanceolata (DC.) Clarke (Raasnaa) P. lanceolata plant extract (solvent ?) OH has been demonstrated to possess O HO significant antioxidant activity in vivo. OR In experimental animals (male Wistar rats) ingestion of ferric nitrilotriacetate OH (9 mg Fe/kg, i.p.) induced oxidative O OH stress as evidenced by enhanced renal Quercetin: R=H lipid peroxidation and generation of free Isorhamnetin: R = Me hydrogen peroxide, and curtailment of body’s antioxidant defence (glutathione reductase, catalase, etc.). However, when the animals were pretreated with the extract (100, 200 mg/kg), there was highly significant antioxidant defence against the chemically induced oxidative stress.8 Authors suggest that the antioxidant action of the extract is due to the presence of flavonoids (quercetin, isorhamnetin), which are constituents of the extract, and are known antioxidants.41

24 Prime Ayurvedic Plant Drugs

Terminalia chebula Retz. (Haritaki) Aqueous extract of fruits was evaluated for its antioxidant activity by studying inhibition of radiation induced lipid peroxidation in rat liver microsomes at different radiation doses. The action was evaluated in terms of ascorbate equivalents by different methods. Extract showed potent antioxidant action and was found to restore enzyme superoxide dismutase from radiation damage.72 Four compounds responsible for this activity have been isolated (box), and it was found that each of these compounds has a different pathway for its action.73 HOH2C Galloyl

OH2C OH

OH O

Galloyl

O O

Galloyl

O

O

OH

OC

OH 1,6-Di-O-galloylglucose

HOOC

O H H

HO

CO OH

O

O

OH

Chebulanin

OH

Galloyl

HO

OH2C

Galloyl

HO O C

HO HO HO

CO

Galloyl

H

O

H

O

O

C

C

C

C

C

CH2

HO

H

O

H

H

O

C

O

O

O O

C

O

O OC

OH

HO

HOOC HO

HO Casuarinin

HO

OH

OH

Galloyl

O H H

CO OH

O OH O Chebulinic acid

Tinospora cordifolia (Willd.) Hook. f. and Thoms. (Guduchi) Aqueous extract of the drug was shown to inhibit lipid peroxidation and quench superoxide and hydroxyl radicals in in vitro experiments. Oral

General Introduction 25

administration of 2.5 gm and 5.0 gm/kg body weight of the aqueous extract led to significant reduction in thiobarbituric acid reactive substances and increase in reduced glutathione, catalase and superoxide dismutase in alloxan diabetic rats.74 An arabinogalactan polysaccharide has been identified as the active constituent.75

Conclusion It is remarkable to see from the above exercise that the traditional antiageing drugs, which have received some measure of modern scientific scrutiny, do indeed possess significant free radical quenching and other antioxidant attributes in consonance with the presently held views. The conclusion, that these plants indeed can be classified as antiageing as was done several centuries ago, gets further reinforced when one looks at their action on some of the disorders typical of senescence (Table 8). Additionally, one of these plants (Terminalia chebula) has been found to significantly inhibit age-dependent shortening of telomeric DNA length (HEK-NF cells). Since shortening of telomeres (protective caps on the end of chromosomes) is indicative of progressive senescence, this finding supports the traditional claims for the drug being antiageing.41 Table 8. Ayurvedic antiageing plant drugs and some typical old age disorders Plant

Protection against Dementia

Arthritis

Diabetes

Cardiac

Cancer

Asparagus racemosus Boerhavia diffusa

– –

– –

+ +

– +

+ +

Centella asiatica

+

+

–

+

+

Clitoria ternatea Desmodium gangeticum

+ +

– –

– +

+ +

+ +

Emblica officinalis

+

+

+

+

+

Leptadenia reticulata Pluchea lanceolata

– –

– –

– –

+ –

+ +

Terminalia chebula

–

+

+

+

+

Tinospora cordifolia

–

+

+

+

+

+ : Available findings support this activity. – : No research on this debility appears to have been carried out.

Thus, there are strong indicators in support of the antiageing claims of the drugs listed in Charaka Samhitaa under the category Vayahsthaapana. However, there is still an urgent need for further investigations on modern scientific lines to reinforce the above conclusions.

26 Prime Ayurvedic Plant Drugs

3. Ethnotherapeutics and Modern Drug Development What is the relevance of the above storehouse of information available in Ayurvedic materia medica to modern therapeutics? To evaluate this, one must first analyse the contributions of higher plant natural products to what has come to be known as modern medicine. In this context, the part played by ethnotherapeutics will be highlighted and its potential for useful contributions will be touched upon with special reference to plants described in Ayurvedic literature. Molecular medicine and phytopharmaceuticals will be discussed separately.

3.1 Molecular Drugs Till quite recently, modern medication was essentially based on single molecular entities as specific agents against a targeted disorder, and even now the game is to discover and invent therapeutically valuable molecules. Several approaches to this end are being exploited,22, 76 but a discussion on these is outside the purview of the present work, except to evaluate the role played and that being played by compounds elaborated by higher plants towards this goal.

Higher Plant Drugs and the Role of Ethnotherapeutics One of the important routes to new drug discovery is accessibility to libraries of compounds and well-directed biological screens, and the game is how to reduce the numbers to be screened before a hit is made. It is in this context, that the potential of molecular diversity engineered by nature in the plants will be examined. Nature has no parallel in constructing simple or complex molecules in unimaginable modes and shapes, as is evident from our current knowledge of the so-called secondary metabolites. Classically, higher plants have played a dominant role in the introduction of new therapeutic agents.77 Even now, contrary to common belief, drugs from higher plants continue to occupy an important niche in modern medicine. On a global basis, at least 130 drugs, all single chemical entities extracted from higher plants, or modified further synthetically, are currently in use, though some of these are now being made synthetically for economic reasons. However, the number of new chemical entities (NCE) emerging as therapeutic agents from higher plants or leads therefrom, has been rather low, after the so-called classical period of plant drug discovery. Thus,

General Introduction 27 O R2

NH

OH

O

R1O

O

OH

O HO

OBz

H

O OAc

Paclitaxel: R1 = Ac, R2 = Ph t Docetaxel: R1 = H, R2 = O – Bu R2

R1

O

R3

O

N

O

N R1

HO R2

Camptothecin: H

H

Irenotecan:

Et

H

Tpootecan:

H

CH2NMe2

R3 O O

C

H N

N

OH

the period 1950–70 saw the introduction of approximately 100 basic new drugs in the US market, but this list contained no more than five drugs (reserpine, deserpidine, rescinnamine, vinblastine and vincristine) derived from higher plants.78, 79 Again, during the next 20 years (1971–90) period, over 600 NCEs were launched worldwide, but the number of plantbased drugs including those fashioned after plant-based lead structures (teniposide, etoposide, ∆9-tetrahydrocannabinol, nabilone, lentinan, artemisinin, sofalcone, plaunotol) was just over 1% of the total.79, 80 More recently the decade 1995–2004 saw the introduction of 309 NCEs globally, and in this the number of introductions based on higher plant leads amounted to 2.6% (irinotecan, docetaxel, nalmefene, topotecan, arglabin, colforsin, artether, egualen sodium).81 Thus, the contribution (in terms of numbers) from this route to modern drug development has been anything but significant, and the possible reasons for this situation have been discussed elsewhere. 22 However, there is another facet to these contributions which adds significance to these efforts, and this is elaborated in the following. Plants have turned out to be a good resource for compounds effective in treating certain neoplastic diseases. Some of the important chemotherapeutic agents, currently in use for the treatment of certain types of cancer are plant-based: vinblastine (Eli Lilly, 1961) and vincristine (Eli Lilly, 1963), both

28 Prime Ayurvedic Plant Drugs

isolated from Catharanthus roseus G. Don., for the treatment of Hodgkin’s disease, lymphosarcoma, and leukaemia in children;79, 82, 83 teniposide (Sandoz, 1970) and etoposide (Sandoz,1971), developed from the antineoplastic lignan podophyllotoxin, a constituent of Podophyllum spp., are currently being used against testicular cancer, small cell lung cancer, and lymphomas;84–87 paclitaxel (Bristol-Myers Squibb, 1993), previously known in the scientific literature as taxol, a diterpenoid constituent of several Taxus spp., is effective in the treatment of metastatic ovarian cancer, and has potential uses in the treatment of lung cancer, metastatic breast cancer and malignant melanoma;88–90 irenotecan (Yakult Honsha, 1994), analogue of the quinoline alkaloid camptothecin, first isolated from the Chinese tree Camptotheca acuminata, but now obtained mostly from the Indian tree Nothapodytes nimmoniana Mabberley syn. Mappia foetida Miers,91, 92 is being used in Japan for the treatment of lung, ovarian and cervical cancers.93, 94 As a matter of fact, development of new antineoplastic therapeutic agents based on natural product leads is proving to be a fertile area of activity.95, 96 Already, another molecule, docetaxel (Rhone-Poulenc Rorer, 1995) fashioned after paclitaxel has been marketed for the treatment of ovarian, breast and non-small cell lung cancers.97 Likewise, topotecan (SmithKline Beecham, 1996), a water soluble derivative of camptothecin with decreased toxicity, has been launched as a second-line treatment of ovarian cancer.98 Another contribution from such studies on natural products has been the opening up of new and novel vistas of their mode of action, which in turn has facilitated mechanism-based drug development. In the anticancer area, for example, podophyllotoxin-based compounds act by inhibiting topoisomerase II, while camptothecin-derived compounds inhibit the enzyme topoisomerase I; topoisomerases are involved in DNA replication. On the other hand, both vincristine-type compounds and taxol are antimitotic agents, but whereas vincristine class compounds act by preventing microtubules assembly, taxol is unique in that it promotes assembly of microtubules and inhibits their disassembly process.99–101 Some of the biologically active natural products have proved useful as tools in biological and biochemical research, which has a bearing on drug discovery. A relatively recent example would be forskolin, a diterpene from the roots of the Indian plant Coleus forkohlii Briq. syn. C. barbatus Benth., which is being used in purification of adenylate cyclase, and in receptor binding assays.102

Role of Ethnotherapeutics From the above, it is clear that higher plants continue to play a useful role in the development of modern therapeutic agents. It should be possible to optimize this role by diligent planning.

General Introduction 29

Table 9. Ethnotherapeutics and traditional modern drugs Drug

Basis of investigation

Codeine, morphine

Opium, the latex of Papaver somniferum used by ancient Sumerians, Egyptians and Greeks for treatment of headaches, arthritis, and for inducing sleep.105, 106

Atropine, hyoscyamine

Atropa belladonna, Hyoscyamus niger, etc., were important drugs in Babylonium folklore.107

Ephedrine

Crude drug, Ma-huang (astringent yellow), derived from Ephedra sinica had been used by the Chinese for respirotory ailments since 2700 BC.107

Quinine, etc.

Cinchona spp. were used by Peruvian Indians for the treatment of fevers.105, 107

Emetine

Brazilian, Indians and several other South American tribes used roots and rhizomes of ipecacuanha (Cephaelis spp.) to induce vomiting and cure dysentery.105, 107

Colchicine

Use of Colchicum in the treatment of gout has been known in Europe since 78 AD.107

Digoxin, etc.

Digitalis leaves were being used in heart therapy in Europe during the 18th Century.105

If one looks at how the traditional plant drugs, referred to above, came to be utilized in modern medicine, one will find that invariably, the starting point has been some reference to the use of that plant material as an indigenous cure in a folklore or traditional system of medicine of one culture or another. Table 9 illustrates this point convincingly.103 Even after this classical plant drug discovery era, most of the important plant drugs were discovered by investigating the so-called medicinal plants of one country or another. Reserpine, the discovery of which had its origin in Ayurveda has been referred to earlier. The discovery of two anticancer dimeric indole alkaloids, vinblastine and vincristine from the periwinkle plant (Catharanthus roseus), discussed above, is again the result of a folklore remedy investigation, though in a different way. Work on this plant was taken up for its alleged hypoglycaemic activity as per Jamaican folklore. Podophyllum resin, the source of podophyllotoxin, has been used by American Indians for treatment of cancer.104 Camptothecin is a constituent of the Chinese tree Camptotheca acuminata DC., used in Chinese medicine for the treatment of cancer. Of course, taxol (paclitaxel) was discovered as a result of random screening of plant extracts for antineoplastic activity.

30 Prime Ayurvedic Plant Drugs

O

OH O O

HO

O O

HO

O

Sophoradin

Artemisinin O O

O

MeO O

MeO OH MeO

HOOC. CH2O

OMe Gomishin

O Sofalcone

CH2OH CH2OH Plaunotol

Results from modern investigations on Chinese medicinal plants still further strengthen the paradigm that the folklore or traditional medicinal plants (of different cultures) can provide a fruitful starting point in our search for molecular therapeutic agents from higher plants. Chinese medicine108, 109 (Zhong yao in Chinese, Campo in Japanese) has been practised in China, Japan and other far Eastern countries since some 2,000 years ago, and its crude drugs are mostly plant-based. For example, Chinese Pharmacopoeia (1990) lists 784 traditional Chinese drugs, of which some 630 are of plant origin.110 Chinese drugs have been the subject of intense modern scrutiny during the past three decades or so, mostly at the hands of Chinese.110– 116 Outstanding results have been obtained, essentially confirming many claims of the ancients. A few examples may be cited. The herb Artemisia annua Linn. has been used traditionally in China for treatment of fevers. It has yielded an effective antimalarial, a sesquiterpene peroxide, artemisinin (qinghaosu). The compound is active against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium

General Introduction 31

falciparum and P. vivax, and is equally effective against cerebral malaria.111 It was introduced worldwide in 1987.117 Mechanism of its action has been explored, and it appears artemisinin has a unique mode of action; it targets a critical calcium-pumping enzyme in the parasite.118 Taking a cue from artemisinin structure, a stable ozonide (OZ277) has been fashioned, and this is now in Phase I clinical trials as an oral antimalarial.119 Gomishin, a lignan from the fruits of Chinese medicinal plant Schizandra chinensis, has hepatoprotective activity112 as revealed from studies carried out in China and Japan, and is being released for treatment of chronic hepatitis.114 The Chinese plant Sophora substrata (roots) has been used in China for treatment of stomach troubles and sophoradin, a chalcone, isolated from this has shown significant anti-gastric ulcer activity. A synthetic compound, sofalcone developed after this lead is now in clinical usage.114, 115 Plaunotol, a diterpene constituent of a Thai medicinal plant plau-noi (Croton sulyrantus), has been introduced as a cytoprotective antiulcer agent (Sankyo, 1988).114, 120 The contribution of Ayurvedic medicinal plants towards modern medicine has been described earlier in some detail under the subtitle 2. In the case of anticancer screening, a comparison was made of the hits from random screening with those from screening of ethnic plants, and it was concluded that folklore-plant screening showed some three times better score.121

3.2 Phytopharmaceuticals As described earlier, plant drugs played an important role in the development of single chemical entities for therapeutic purposes. Initially these traditional remedies were inducted into the so-called allopathic medicine as extracts or tinctures in the early decades of the last century. They appear to have returned in a more sophisticated form in recent years in a big way. Over the past three decades or so, the economically developed countries, for whatever reasons, are seeing an ever-growing interest in the so-called alternative medicine, in which remedies based on herbal drugs are playing an important role. These preparations, which have come to be known as phytomedicines or phytopharmaceuticals, are usually a single plant extract, or an appropriate fraction thereof. This new trend, to a large extent, originated in Europe, especially Germany, where most of the presently leading phytopharmaceuticals were first developed. It has been estimated that the world market for these products in the year 2000 was around US $ 20 billion (Rs. 2,000 crore), and its growth rate has been assessed at around 15–20% annually.22, 122 These phytopharmaceuticals are quite distinct from the traditional herbal medicinal preparations of Ayurveda or Chinese Zhong yao or other traditional

32 Prime Ayurvedic Plant Drugs

systems of medicine. Invariably these classical medicinal formulations consist of several plants, and little is known about the active principle(s), and are quite difficult, if not impractical, to standardize. On the other hand, this new breed of plant-derived products are produced, standardized, and clinically evaluated just like the conventional pharmaceuticals. The European Scientific Co-operative on Phytotherapy (ESCOP) has listed some 150 herbal drugs as beneficial. In Germany, the Federal Ministry of Health has set up a special Commission (E), which looks after various aspects of herbal drugs, and has evaluated and published monographs on more than 300 individual herbs. These medicines are available as prescription drugs. In France also, herbal medicine is governed by similar regulations which cover over 200 medicinal plant products.123–125 However, in the US at present, most herbal products are sold as dietary supplements and no therapeutic claims are permitted. Development of new herbal products continues, as evidenced, for example, by filing of more than 50 Investigational New Drug applications for botanical medicines by industry and accepted by the US Food and Drug Administration during the period 1996–1998 alone.126 This popularity of these products raises the important question: is this trend just a fad or is there a scientific rationale for developing and using such phytomedicines? On the face of it, the standardization of herbal therapeutic agents is clearly more problematic and hence expensive. Also, why load a patient or even an healthy individual with a lot of inactive debris of the herb by administering an extract of the medicinal herb rather than the pure active principle(s). Therefore, it is important to answer the posed question. In a mixture of compounds, such as an herbal extract, the biological (or, in fact, any other) activity of a certain individual compound is subject to influences of the other constituents. If the other constituents do not possess the same activity, they may just act as diluents or may potentiate (synergism) or reduce (antagonism) the said activity. If, on the other hand, other compounds also possess the same activity, though to varying extents, then the effect could be additive or even synergistic. The same situations will arise when two or more herbal extracts are mixed. Cases have been noted where individually, compounds isolated from a herb are inactive, but their mixture is active. Synergistic action of a compound devoid of that particular activity on an active is well-known (vide infra). It must be emphasised that synergism is a well-recognized phenomenon in biology. For example, in the field of insecticides, piperonyl butoxide is a well-established synergist for natural and synthetic pyrethroides and rotenone, and has been used as an adjunct since 1950s.127 In current treatment of various cancers, different combination chemotherapy regimens are routinely employed.128 In the area of antimicrobials, efflux pump inhibitors have been demonstrated to potentiate the activity, and this is an active research area at present.129

General Introduction 33

Further discussion on herbal extracts will be continued keeping in view the additive and synergistic interactions.130

Herbs with Several Actives Several medicinal plants elaborate closely related secondary metabolites, and at least some of these may be expected to exhibit a particular activity to varying degrees. Several examples are on record. Also, different classes of compounds have been found to display the same activity. In such mixtures the potentiation may be additive or synergistic. To reinforce these points some examples are cited. Curcuma longa Linn. Methanol extract of turmeric was found to protect PC12 rat pheochromocytoma cultured cells against β-amyloid (βA) insult as a model for neuronal cells protection. This has a bearing on protection against Alzheimer’s disease. Bioassay-guided fractionation of the extract led to the isolation of highly active five compounds (box) with ED50 = 0.5–10 µg/ml. The positive control, Congo red, had ED50 = 37–39 µg/ml under the same conditions.131 Curcumin as well as neutral polysaccharides ukonan A and D, constituents of C. longa rhizomes, have been shown to possess immunopotentiating activity. These polysaccharides activate the reticuloendothelial system and have powerful phagocytic activity in mice.41 O

O R′

R

OH

HO

Curcumin: R = R′ = OMe Demethoxycurcumin: R = OMe; R′ = H Bisdemethoxycurcumin: R = R′ = H O

O

OH

HO Dihydrobisdemethoxycurcumin

OH

O MeO HO

O

OMe O

Calebin-A

34 Prime Ayurvedic Plant Drugs

Curcuma zeodory (Berg.) Rosc. Macrophage tumour necrosis factor-α (TNF-α) is an important factor in inflammatory processes. Crude methanolic extract of the rhizomes exhibited significant inhibition of release of TNF-α in activated macrophages. Activityguided fractionation led to the isolation of three active compounds, 1,7bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one, procurcumenol and epiprocurcumenol. Of these, the first one (a curcuminoid) had IC50 value of 12.3 µM in the bioassay.41 Glycyrrhiza glabra Extract of G. glabra roots has been shown to possess antiinflammatory action in several experimental models and in clinical trials. Action resembles that of phenylbutazone/hydrocortisone. Active agents have been identified as glycyrrhizinic acid as well as its aglycone glycyrrhetic acid, and the flavonoids liquiritin and its genin liquiritigenin.41 Tinospora cordifolia (Willd.) Miers ex Hook. f. & Thoms. Cordioside (a diterpenoid), cordifolioside-A and -B (diglycosides related to syringin), and cordiol (an ecdysteroid), all compounds present in T. cordifolia stems, have been shown to possess immunopotentiating activity (antibody response to sheep red blood cells in mice: enhancement of immunoglobulins IgG). Humoral and cell-mediated immunity were also enhanced in a dosedependent manner.132 An immunologically active arabinogalactan has also been identified in dried stems of the plant.133 Zingiber officinale Rosc. Ginger extract (500 mg/kg) was shown to possess significant antiulcer activity against several ulcerogenic agents including aspirin, and indomethacin in experimental animals. Several constituents of ginger have been demonstrated to have this activity; β-sesquiphellandrene, β-bisabolene, ar-curcumene, and [6]-shogoal were active in the ethanol-hydrochloric acid induced stomach ulcers in rats. A minor constituent, [6]-gingesulphonic acid, was shown to have potent antiulcer action.41 Ginger extracts have been shown to possess antiinflammatory activity. Gingerols and diarylheptanoids occurring in ginger were found to be potent inhibitors (in vitro) of cyclooxygenase (COX) and lipoxygenase. These enzymes are involved in the biosynthesis of prostaglandins and leukotrienes, which are recognized inflammation mediators.134 [8]-Paradol, another constituent of ginger, was found to be a potent inhibitor of COX-1. 135 In an in vivo investigation, aqueous extract of ginger (500 mg/kg, p.o., 4 weeks)

General Introduction 35

was shown to significantly lower PGE2 level in blood serum in rats.136 [6]Gingerol, a pungent constituent of ginger, exhibits dose-dependent inhibition of nitric oxide (NO) and significant reduction of inducible NO synthase in lipopolysaccharide stimulated J774.1 mouse macrophages; NO is also a proinflammatory mediator.137 O MeO

OMe OH

HO Gingerenone-A (a diarylheptanoid) O MeO HO

[6]-Paradol

Herbs with Synergistic Interactions of Constituents Synergistic interactions of herbal constituents, resulting in potentiation of a pharmacological or therapeutic effect, is now well-recognized, and many cases have been reported. The subject matter has been recently reviewed, and methods useful in proving synergy have been discussed.130 In the following account, some examples are cited with special reference to plants described in this book. Artemisia annua Linn. Artemisinin is the active antimalarial in this plant. However, the two cooccurring flavonoids, chrysoplenol-D and chrysoplenetin which have no antimalarial activity, potentiate the antimalarial action of artemisinin.138 OR OH O

MeO MeO

OMe OH

O

Chrysoplenol-D: R = H Chrysoplenetin: R = Me

Berberis spp. Berberine which is the characteristic alkaloid of most Berberis spp. has poor antibacterial activity. This is essentially because the microbes have

36 Prime Ayurvedic Plant Drugs

developed a mechanism by which they simply pump out the drug out of their cells. However, another constituent of B. repens, namely 5′methoxyhydnocarpin (5′-MHC), has been found to be an effective inhibitor of this pump (transmembrane proteins). And it has been demonstrated that 5′-MHC, which has no antibacterial activity effectively potentiates the antibacterial action of berberine against antibiotic resistant strains of Staphylococcus aureus.139 OH

OMe O O

HO

OH

O

O

OMe CH2OH

5′-Methoxyhydnocarpin

Cassia angustifolia Vahl. Preparations of this herb are used as purgatives. Active agents have been identified as sennosides-A and -B. Another constituent aloe-emodin dianthrone diglucoside has no such activity, but exerts a potentiating effect of about 1.3 times on the purgative activity of sennoside-A in mice, even when present to the extent of only 15% in a mixture.140 Commiphora wightii (Arnott.) Bhandari Ethyl acetate extract of the gum-resin of this tree has been shown to possess useful hypolipidaemic activity, and preparations based on this are being marketed. This extract has been extensively chemically examined,41 and consists of diterpenoids, triterpenoids, steroids, lignans, fatty tetrol esters, etc. It had been shown that the active compounds are E- and Zguggulsterones, and these compounds are present in the extract to the extent of some 4%. However, a comparison (Table 10) of activity of this product with that of pure guggulsterones showed vastly disproportionate activity for the total extract, possibly due to synergistic or additive activity of some of the components of the mixture.

General Introduction 37 Table 10. A comparison of hypolipaemic activity of guggulsterones and some gum-resin extract and cuts in rats* Per cent lowering of serum lipids

Product (100 mg/kg, oral, 30 days)

Normal rats

High fat diet fed rats

Cholesterol

Triglycerides

Cholesterol

Triglycerides

34

24

46

24

Ethyl acetate extract #

Guggulsterones

35

28

48

29

Ketonic fraction

30

26

29

20

Non-ketonic fraction

15

16

25

15

*Data provided by Dr. Nitya Nand #Mixture

of Z- and E-guggulsterone isomers (80 : 20)

Curcuma longa Linn. In an azoxymethane-induced animal (Male Sprague-Dawley rats) model of colon cancer using aberrant crypt foci as a preneoplastic marker, it was demonstrated that at 300 ppm curcumin in the C. longa extract in the diet of the rats was as effective at one-seventh the concentration of curcumin as the positive control. 141 Curcumin, demethoxycurcumin, bisdemethoxycurcumin, and cyclocurcumin, all constituents of C. longa, showed no nematocidal activity individually, but a mixture of these compounds was nematocidal.142

Herbal-Herbal Interactions and Adjuvant Therapy As already stated, classical herbal preparations of Ayurveda or other similar traditional systems of medicine are invariably complex mixtures of many herbal products. It is claimed that mixing is done to potentiate the curative effect and mitigate adverse reactions. There is now mounting evidence that certain pure compounds or extracts of some plants potentiate the therapeutic or pharmacological action of another plant extract or an active compound. This potentiation by an auxiliary, is being exploited in some situations in conventional practice to curtail the therapeutic dose, thus limiting any side reactions. It appears the adjuvant compounds operate by several mechanisms. Some target the defence system of the invading organism, others reinforce the immune system of the host, while still others increase the bioavailability of the drug by curtailing the action of the drug metabolizing enzymes. Other modes remain to be explored. Examples of all these situations are known, and some of these are cited below.

38 Prime Ayurvedic Plant Drugs

Bioavailability Enhancers The use of trikatu (the three acrids) or any one of its constituents (fruits of Piper longum, P. nigrum, and rhizomes of Zingiber officinale) is wide spread in Ayurvedic formulations. In 1929, it was demonstrated that O antiasthmatic action of leaves of N O Adhatoda vasica was potentiated by the addition of long pepper. O While trying to find a rationale for Piperine this, some workers discovered that piperine, the important constituent of both the Piper spp., has the interesting property of enhancing the plasma concentration of a number of drugs like vasicine, sulphadiazine, and tetracycline, when co-administered with the drug in experimental animals. These studies were later extended to several other drugs (rifampicin theophylline, β-lactam antibiotics, nimesulide, etc.) and to human volunteers.143–148 There is evidence to the effect that piperine inhibits the major drug-metabolizing enzyme CYP3A4 and the drug transporter P-glycoprotein.149

Disabling Infection/Disease Resistance Earlier, it has been described that 5′-MHC which co-occurs with berberine in some Berberis spp. is able to potentiate antimicrobial action of berberine by inhibiting the action of certain proteins which transport out berberine from the organisms cells. This finding has been followed up to show that two synthetic multi-drug resistance pumps (MDRs) inhibitors are able to potentiate the antimicrobial action of several plant actives against a number of pathogens. Thus, the activity of rhein, the principal antimicrobial from rhubarb, was potentiated 100- to 2,000-fold (depending on the bacterial species) by disabling the MDRs. Comparable potentiation of activity was observed with plumbagin, resveratrol, gossypol, coumesterol, and berberine.139 In another study, it was shown that curcumin enhanced the action of the antitumour drug cisplatin in experimental rats with fibrosarcoma, as revealed by rapid normalization of the cancer marker enzymes (such as aminotransferases, lactate dehydrogenase, etc., in the liver) as compared to use of cisplatin alone.150 Curcuminoids from C. longa, and especially its constituent bisdesmethoxycurcumin, have been shown to decrease human multi-drug resistance gene expression in human carcinoma cell line KB-V1, thus increasing their sensitivity to the drug vinblastine.151

General Introduction 39

Fortifying Immune Defence In Germany, preparations based on Echinacea have been reported as the best selling herbal immunostimulants as an adjuvant therapy in the treatment of reoccurring urinary tract and respiratory infections, and for the prevention and treatment of common colds and flu. It has been demonstrated that cichoric acid, alkyl amides and polysaccharides, all constituents of these herbs are responsible for the stimulation of the non-specific immune system.12 OH O HOOC

O HO

OH O

COOH O

HO Cichoric acid

In a related study, it was demonstrated that mixing Glycyrrhiza glabra root extract with that of Echinacea purpurea herb led to potentiation of the immunostimulating activity using several in vitro tests and the in vivo carbon-clearance model in mice.152 In Germany, several preparations based on Pelargonium spp. are in the market for the treatment of infections of the respiratory tract and acute tonsillitis in children. These plants are rich in tannins. From an investigation aimed at providing a scientific rationale for their therapeutic efficacy, it was concluded that these preparations stimulate the non-specific immune system, which enhances the antimicrobial activity, thus paving the way for the satisfactory therapeutic outcome observed.153

Comments Phytopharmaceuticals appear to be a preferable alternative for promoting vigour in the healthy, for the treatment of metabolic disorders, and other moderately severe infectious diseases, provided these medicines are produced, and standardized as per proper scientific norms. For this to be possible, appropriate legislation has to be in place. In the US, since no therapeutic claims are permitted there is little regulatory control, and this has resulted in the marketing of several spurious preparations containing little or none of the active principle(s).154, 155 In India, the market is flooded with products with tall claims, but with absolutely no basis. Even if the above requirements are met, for the commercial production of phytomedicines, and for that matter even for authentic classical Ayurvedic formulations, several problems inherent in the supply of raw material will

40 Prime Ayurvedic Plant Drugs

have to be addressed. These pertain to the deliberate or accidental adulteration of the plant material, contamination with insects, fungi, bacteria, heavy metals and pesticide residues. Besides, a consistent supply of plant material with the appropriate content of actives must be ensured. These problems have been discussed in several publications.156

References 1. Charaka Samhitaa is, in fact, an edited and enlarged version of an older treatise (Tantra) by Agnivesha, which was based on discussions and proceedings of a series of meetings and symposia, organized by his preceptor Atreya Punarvasu, somewhere in the Himalayas (circa 900 BC). This Charaka Samhitaa (~100 AD) was redacted and enlarged later by other scholars, most important among these being Drdhabala. Thus, there are three distinct time spans to the latest redaction. However, it may be noted that the major part even in the latest redaction of Charaka Samhitaa has been presented in the form of questions and answers between the disciple Agnivesha and his teacher Atreya. 2. P Ray, HN Gupta, Caraka Samhita (A Scientific Synopsis). National Institute of Sciences of India (now Indian National Science Academy), New Delhi, India (1965). 3. PV Sharma, Caraka Samhitaa (text with English translation), Vols 1–4. Chaukhambha Orientalia, Varanasi, India (2003). 4. Sushruta, the author of Sushruta Samhitaa, was the senior disciple of Divodasa Dhanvantari, who had developed a school in surgery (9–6 BC) in Kashi (now Varanasi). The original Sushruta Samhitaa was later revised in 2nd Century (AD) by Nagarjuna. 5. GD Singhal, in Realms of Ayurveda (ed. S Sharma), p 124. Arnold-Heinemann, New Delhi, India (1979). 6. SA Dahanukar, UM Thatte, Ayurveda Revisited. Popular Prakashan, Mumbai, India (1989). 7. P Ray, HN Gupta, M Roy, Sushruta Samhitaa (A Scientific Synopsis). Indian National Science Academy, New Delhi, India (1980). 8. PM Mehta, in Realms of Ayurveda (ed. S Sharma), p 47. Arnold-Heinemann, New Delhi, India (1979). 9. GK Garde (ed), Sartha Vagbhatta: Ashtangahridaya with Marathi translation. Aryabhushana Mudranalaya, Pune, India (1954). 10. RC Majumdar in A Concise History of Science in India (eds. DM Bose, SN Sen, BV Subbarayappa), p 222. Indian National Science Academy, New Delhi, India (1971). 11. Sarangdhara Samhitaa (edited and published by GY Dikshit), Pune, India (1908). 12. KRS Murthy, Bhavaprakasha of Bhavamishra. Krishnadas Academy, Varanasi, India (2001). 13. A Namjoshi, in Realms of Ayurveda (ed. S Sharma), p 217. Arnold-Heinemann, New Delhi, India (1979). 14. Ref 10, p 264.

General Introduction 41

15. SD Kamat, Dhanvantari Nighantu (Incorporating Raja Nighantu). Chaukhamba Sanskrit Pratishthan, Delhi, India (2002). 16. KH Krishnamurthy, Wealth of Susruta. International Institute of Ayurveda, Coimbatore, India (1991). 17. RD Lele, in Realms of Ayurveda (ed. S Sharma), p 217. Arnold-Heinemann, New Delhi, India (1979). 18. Ref. 10, pp 257–262. 19. BV Subbarayappa, in India’s Contribution to World Thought and Culture (eds. L Chandra, D Swarup, S Goel, SP Gupta), p 54. Vivekanand Rock Memorial Committee, Chennai, India (1970). 20. J Filliozat, in India’s Contribution to World Thought and Culture (eds. L Chandra, D Swarup, S Goel, SP Gupta), p 67. Vivekanand Rock Memorial Committee, Chennai, India (1970). 21. See e.g., JF Hartzell, KG Zysk, J. Alternative Complementary Medicine, 1, 297 (1995). 22. Sukh Dev, Current Science, 73, 909 (1997) [Review]. 23. For example, see [i] Ref 6, p 39. [ii] VVS Shastri, Tridosha Theory. Arya Vaidya Sala, Kottakkal, India (2002). The term dosha (Sanskrit) means fault. It is socalled, as this factor is not only capable of vitiation, but is also capable of vitiating other factors (doshas) of the body. 24. As per Ayurvedic authorities these terms, in no way, correspond to any of the four Greek humours. See e.g., S Sharma, Prog Drug Res, 15, 1 (1971). 25. See e.g., S Borman, C&EN, April 19, 59 (1999). 26. MS Valiathan, The Legacy of Caraka, p liv. Orient Longman, Chennai, India (2003). 27. D Chopra, Perfect Health, p 21. Hormony Books, New York, USA. (1991). 28. For example, see [i] Ref 6, p 97. [ii] B Dash, L. Kashyap, Materia Medica of Ayurveda based on Ayurveda Saukhyam of Todaraananda, p 2. Concept Publishing Co., New Delhi, India (1980). 29. For example, see Ref 26, pp xxiii–xlix. 30. For example, see Ref 7, pp 48–61, 255–424. 31. JN Sharma, Souvenir of The IX International Heart Congress, New Delhi, India (1978). 32. Ref. 26, p 166. 33. GV Satyavati, Indian J Med Res, 87, 327 (1988). 34. Ref. 27[ii], p 644. 35. Sukh Dev, Environ Health Perspect, 107, 783 (1999) [Review]. 36. PV Sharma, Dravyaguna-vijnana, Vol I. Chaukhambha Bharti Academy, Varanasi, India (1986). 37. See e.g., [i] HS Puri, Rasayana, Taylor & Francis, London, UK (2003). [ii] Ref 25, p lxviii, 233. 38. TF Anderson, JJ Voorhees, Ann Rev Pharmacol Toxicol, 22, 235 (1980). 39. CC Shah, VK Bhalla, Sukh Dev, J Indian Chem Soc, 74, 970 (1997). 40. H Katsura, RI Tsukiyama, A Suzuki, M Kobayashi, Antimicrob Agents Chemother, 45, 3009 (2001). 41. For references see the Monograph on the plant. 42. RJ Vakil, Br. Heart J, 11, 350 (1949).

42 Prime Ayurvedic Plant Drugs

43. RE Woodson, HW Yongken, E Schlittler, JA Schneider, Rauwolfia: Botany, Pharmacognosy, Chemistry and Pharmacology. Little, Brown, Boston, USA (1957). 44. BD Gonska, Z Kardiol, 89, 51, 57 (2000). 45. K Kar et al., J Pharm Sci, 64, 258 (1975). 46. RK Gupta, SK Saxena, B Dutt, V Mahadevan, Indian J Vet Sci, 38, 203 (1968). 47. VV Sastry, Bull Indian Inst Hist Med, 6, 102 (1976). 48. ML Gujral, K Sareen, KK Tangri, MKP Amma, AK Roy, Indian J Physiol Pharmacol, 4, 267 (1960). 49. G Santhakumari, ML Gujral, K Sareen, Indian J Physiol Pharmacol, 8, 36 (1964). 50. SN Tripathi, VVS Shastri, GV Satyavati, J Res Indian Med, 2 (2), 10 (1968). 51. VL Mehta, CL Malhotra, NS Kalrah, Indian J Physiol Pharmacol, 12, 87 (1968). 52. DS Khanna, OP Agarwal, SK Gupta, and RB Arora, Indian J Med Res, 57, 900 (1969). 53. GV Satyavati, C Dwarakanath, SN Tripathi, Indian J Med Res, 57, 1950 (1969). 54. S Nityanand, NK Kapoor, Indian J Biochem Biophys, 15, 77 (1978). 55. RC Agarwal, et al., Indian J Med Res, 84, 626 (1986). 56. William, Foster, Williams Text Book of Endocrinology, p 1. WB Saunder’s Co., Philadelphia, USA (1992). 57. M Rothstein, C&EN, August 11, 26 (1986). 58. ES Epel et al., Proc Natl Acad Sci, 101, 17312 (2004). 59. DJ Selkoe, Sci Am, 267, 135 (1992) [Review]. 60. For example see: [i] Pharmacology of Aging Processes (eds. I Zs-Nagy, D Harman, K Kitani), The New York Academy of Sciences, New York, USA (1994). [ii] MGL Hertog, Eur J Clin Nutr, 50, 63 (1996). [iii] T Finkel, NJ Holbrook, Nature, 408, 239 (2000). [iv] AK Tiwari, Curr Sci, 86, 1092 (2004) [Review]. 61. V Srinivasan, Curr. Sci, 76, 46 (1999) [Review]. 62. See e.g., E Middleton, C Kandaswamy, TC Theoharides, Pharmacol Rev, 52, 673 (2000). 63. R Sharma, Curr. Sci, 87, 1203 (2004) [Review]. 64. SL Rovner, C&EN, August 23, 30 (2004). 65. JP Kamat, KK Boloor, TP Devasagayarn, SR Venkatachalam, J Ethnopharmacol, 71, 425 (2000). 66. MS Parihar, T Hemnani, J Neural Transm, 111, 1 (2004). 67. S Balanehru, B Nagarajan, Biochem Int, 24, 981 (1991). 68. I Mook-Jung et al., J Neurosci Res, 58, 417 (1999). 69. MK Lee et al., Res Commun Mol Pathol Pharmacol, 108, 75 (2000). 70. S Ghosal, VK Tripathi, S Chauhan, Indian J Chem, 35B, 941 (1996). 71. A Bhattacharya, A Chatterjee, S Ghosal, SK Bhattacharya, Indian J Exp Biol, 37, 676 (1999). 72. GH Naik et al., Phytochemistry, 63, 97 (2003). 73. HY Cheng, TC Lin, KH Yu, CM Yang, CC Lin, Biol Pharm Bull, 26, 1331

General Introduction 43

(2003). 74. PSM Prince, VP Menon, Phytother Res, 15, 213 (2001). 75. M Subramanian, GJ Chintalwar, S Chattopadhyay, Redox Rep, 7, 137 (2002). 76. See e.g., Burger’s Medicinal Chemistry and Drug Discovery (ed. ME Wolff), Vol. 2, Wiley-Interscience, New York, USA (1995). Medicinal Chemistry for the 21st Century (ed. CG Wermuth), pp 3–60, Blackwell Scientific Publications, Oxford, UK (1992). RA Maxwell, SB Eckhardt, Drug Discovery: A Casebook and Analysis, Humana Press, Clifton, USA (1990). 77. Sukh Dev, in Plants and Society (eds. MS Swaminathan, SL Kochhar), p 267. Macmillan, London, UK (1989). 78. LA Mitscher, A Alshamma, Annu Rep Med Chem, 15, 255 (1980). 79. The Merck Index (ed. S Budavari). Merck & Co, Rahway, USA (1989). 80. This figure has been extrapolated from the data available for the period 198391: Annu Rep Med Chem, 27, 357 (1992). 81. Data culled from Annu Rep Med Chem, Vols 30–39 (1995–2004). 82. M Sitting, Pharmaceutical Manufacturing Encyclopedia. Noyes Data Corporation, Park Ridge, USA (1979). 83. The Catharanthus Alkaloids (eds. WI Taylor, NR Farnsworth). Marcel Dekker, New York, USA (1975). 84. AR Kraska, Annu Rep Med Chem, 14, 132 (1979). 85. JD Loike, Cancer Chemother. Pharmacol., 7, 103 (1982). 86. Ref, 76, pp 610, 1440. 87. Ullmann’s Encyclopedia of Industrial Chemistry (eds. W Gerhartz et al.,) Vol A5, p 21. VCH Verlag, Weinheim, Germany (1986). 88. M Suffness, Annu Rep Med Chem, 28, 305 (1993). 89. Taxol: Science and Applications (ed. M Suffness). CRC Press, Boca Raton, USA (1995). 90. Taxane Anticancer Agents: Basic Science and Current Status (GI Georg, TT Chen, I Ojima, DM Vyas). American Chemical Society, Washington DC, USA (1995). 91. ME Wall et al., J Amer Chem Soc, 88, 3888 (1966). 92. TR Govindachari, N Viswanathan, Phytochemistry, 11, 3529 (1972). 93. Camptothecins: New Anticancer Agents (eds. M Potmesil, H Pinedo). CRC Press, Boca Raton, USA (1995) 94. XM Cheng, Annu Rep Med Chem, 30, 301 (1995). 95. GR Pettit, FH Pierson, CL Herald, Anticancer Drugs from Animals, Plants and Microorganisms. John Wiley, New York, USA (1994). 96. Anticancer Drug Discovery and Development: Natural Products as Molecular Models (eds. FA Valeriote, TH Corbett, LH Baker). Kluver Academic Publishers, Norwell, USA (1994). 97. XM Cheng, Annu Rep Med Chem, 31, 341 (1996). 98. P Galatsis, Annu Rep Med Chem, 32, 320 (1997). 99. RK Johnson, RP Hertzberg, Annu Rep Med Chem, 25, 129 (1990). 100. RP Hertzberg, RK Johnson, Annu Rep Med Chem, 28, 167 (1993). 101. Compounds which bind to tubulin, interfere with the assembly of

44 Prime Ayurvedic Plant Drugs

102. 103.

104. 105. 106. 107. 108. 109. 110. 111. 112. 113. 114.

115. 116. 117. 118. 119. 120. 121. 122. 123. 124.

microtubules, resulting in mitotic block, while taxol which enhances the rate of microtubules assembly results in the formation of aberrant microtubule bundles, again leading to the arrest of mitosis (Ref. 88, p 307). KB Seamon, Annu Rep Med Chem, 19, 293 (1984). Also see: [i] SM Kupchan, in Drug Discovery, p 1, American Chemical Society, Washington, USA (1971). [ii] Economic and Medicinal Plant Research (eds. H Wagner, H Hikino, NR Farnsworth), Vol 2, Academic Press, London, UK (1989). [iii] Bioactive Compounds from Plants (eds. DJ Chadwick, J Marsh), John Wiley, Chichester, UK (1990). [iv] Human Medicinal Agents from Plants (eds. AD Kinghorn, MF Baladrin), American Chemical Society, Washington, USA (1993). [v] The Discovery of Natural Products with Therapeutic Potential (ed. VP Gullo), Butterworth-Heinemann, Boston, USA (1994). [vi] Phytomedicine of Europe, ACS Symposium Series No. 691, American Chemical Society, Washington, USA (1998). JL Hartwell, AW Schrecker, Fortsch Chem Org Naturstoffe, 15, 83 (1958). N Taylor, Plant Drugs that Changed the World. George Allen and Unwin, London, UK (1965). WH Lewis, Elvin-Lewis, Medical Botany. Wiley-Interscience, New York, USA (1977). Materials and Technology (eds. LW Codd et al.), Vol V, p 707. Longman, London, UK (1972). S Shibata, in Advances in Natural Products Chemistry (eds. S Natory, N Ikekawa, M Suzuki). p 398. Kodansha, Tokyo, Japan (1981). Herbal Medicine: Kampo, Past and Present (eds. T Takemi, M Hasegawa, A Kumagai, Y Otsuka). Tsumura Juntendo, Tokyo, Japan (1985). D Bai, Pure & Appl Chem, 65, 1103 (1993). PG Xiao, in Natural Products as Medicinal Agents (eds. JL Beal, E Reinhard), p 351. Hippokrates, Stuttgart, Germany (1981). L Huang, in Natural Products and Drug Research (eds. Krogsgaard-Larsen, SB Christensen, H Kofod), p 94. Munksgaard, Copenhagen, Denmark (1984). Advances in Chinese Medicinal Materials Research (eds. HM Chang, HW Yeung, WW Tso, A Koo). World Scientific, Singapore (1985). U Sankawa, in Proceedings of Seventh Asian Symposium on Medicinal Plants, Spices and Other Natural Products (eds. LJ Cruz, GP Concepcion, MAS Mendigo, BQ Guevara), p 143. University of the Philippines, Manila, Philippines (1992). RC Allen, Annu Rep Med Chem, 20, 323 (1985). PG Xiao, in Proceedings of Seventh Asian Symposium on Medicinal Plants, Spices and Other Natural Products (vide Ref. 113), p 151. HH Ong, RC Allen, Annu Rep Med Chem, 23, 327 (1988). U Eckstein-Ludwig et al., Nature, 424, 957 (2003). JL Vennerstrom et al., Nature, 430, 900 (2004). Ref. 116, p 340. RW Spjut, RE Perdue, Cancer Treatment Reports, 60, 979 (1976). VE Tyler, Chemtech, 27(5), 52 (1997). G Harrer, H Sommer, Phytomedicine, 1, 3, (1994). Herbal Drugs and Phytopharmaceuticals (ed. and translator of the German

General Introduction 45

125. 126. 127. 128. 129. 130. 131. 132. 133. 134. 135. 136. 137. 138. 139. 140. 141. 142. 143. 144. 145. 146. 147. 148. 149. 150. 151. 152. 153. 154. 155. 156.

edition, NG Bisset). CRC Press, Boca Raton, USA (1994). H Wagner, Environ Health Perspect, 107, 779 (1999) [Review]. P Brevoort, HerbalGram, 44, 33 (1998). See e.g., Merck Index, p 1187. Ref. 127, Misc-2. JJ Bronson, JF Barrett, Annu Rep Med Chem, 36, 93 (2001). EM Williamson, Phytomedicine, 8, 401 (2001) [Review]. SY Park, DSHL Kim, J Nat Prod, 65, 1227 (2002). A Kapil, S Sharma, J Ethnopharmacol, 58, 89 (1997). G Chintalwar et al., Phytochemistry, 52, 1089 (1999). F Kiuchi, S Iwakami, M Shibuya, F Hanaoka, U Sankawa, Chem Pharm Bull, 40, 387 (1992). EN Nurtjahja-Tjendraputra, AJ Ammit, BD Roufogalis, VH Tran, CC Duke, Throm Res, 111, 259 (2003). M Thomson et al., Postaglandins Leukot Essent Fatty Acids, 67, 475 (2002). K Ippoushi, K Azuma, H Ito, H Horie, H Higashio, Life Sci, 73, 3427 (2003). KCS Liu, SL Yang, MF Roberts, BC Elford, JD Phillipson, Plant Cell Reports, 11, 637 (1992). G Tegos, FR Stermitz, O Lomovskaya, K Lewis, Antimicrob Agents Chemother, 46, 3133 (2002). K Nakajima, K Yamauchi, S Kuwano, J Pharm Pharmacol, 37, 703 (1985). C Kirana, GH McIntosh, IR Record, GP Jones, Nutr Cancer, 45, 218 (2003). F Kiuchi et al., Chem Pharm Bull, 41, 1640 (1993). RK Johri, U Zutshi, J Ethnopharmacol, 37, 85 (1992) [Review]. CK Atal, U Zutshi, PG Rao, J Ethnopharmacol, 4, 229 (1981). G Shoba et al., Planta Med, 64, 353 (1998). AR Hiwale, JN Dhuley, SR Naik, Indian J Exp Biol, 40, 277 (2002). SK Gupta, P Bansal, RK Bhardwaj, T Velpandian, Pharmacol Res, 41, 657 (2000). V Balakrishnan, S Varma, D Chatterji, Curr Sci, 80, 1302 (2001) RK Bhardwaj et al., J Pharmacol Exp Ther, 302, 645 (2002). I Navis, P Sriganth, B Premalatha, Pharmacol Res, 39, 175 (1999). P Limtrakul, S Anuchapreeda, D Buddhasukh, BMC Cancer, 4, 13 (2004). H Wagnerm, HK Jurcic, Phytomedicine, 9, 390 (2002). H. Kolodziej, O. Kayser, KP Latte, in Plant Polyphenols 2, Chemistry, Biology, Pharmacology, Ecology (eds. GG Gross, RW Hemingway, T Yoshida), p 575. Kluwer Academic/Plenum Publishers, New York, USA (1999). HB Matthews, GW Lucier, KD Fisher, Environ Health Perspect, 107, 773 (1999) [Review]. VE Tyler, in International Seminar on Medicinal Plants—Quality Standardization (Souvenir), p 9. VHERDS, Chennai, India (2001). See e.g., (i) Ref. 124, pp 33–38. (ii) SJ Murch, KL Choffe, PK Saxena, in Development of Plant-Based Medicines: Conservation, Efficacy and Safety (ed. PK Saxena), p 107. Kluwer Academic Publishers, Dordrecht, the Netherlands (2001).

Section-II Monographs

bies spectabilis (D. Don) Spach. [syn. A. webbiana Lindl.] (Fam.: Pinaceae)

Ayurveda (Sanskrit):  TAALISHA Regional names: Beng. - Talispatra*; Guj. - Talispatro; Hin. - Talispatra; Kan. - Taleshpatre; Mal. - Taleshpatre; Mar. Talispatra; Punj. - Chilrow; Tam. - Talispatri; Tel. - Talispatri Nep.:  Talis patra Eng.:  Indian silver-fir Indian trade names:  Bengali birmi, Taalispatri

It is a stout, evergreen tree up to 60 m tall and 9—10 m in girth, with a broad conical crown, and horizontally spreading branches. It is found growing wild in the Himalayas from Kashmir to Assam at altitudes of 1,800—4,500 m. It is also grown as an ornamental tree.

A

Plant

Bark is dark grey, rough, scaly and fissured. Buds are large, globose and resinous. Leaves are leathery, dark green, glossy, with two broad stomata bands beneath, variable in length, flat, out 2 mm broad, and densely set in 2—4 ranks on stout branchlets. * patra = leaves © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 S. Dev, Prime Ayurvedic Plant Drugs, https://doi.org/10.1007/978-3-031-22075-3_2

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50  Prime Ayurvedic Plant Drugs 

Female cones cylindrical, 14—20 cm long and about 4—6 cm thick, violet-purple when young and later brown, with broad fan-shaped scales. Male catkins 1.3—1.8 cm long, ellipsoid. Seeds are around 8 mm long, angular, oblong-obovate, with notched wings. Cones mature around October—November. Tree exudes a resin, which does not appear to have been investigated. Medicinally valuable part: leaves. Odour: characteristic, pleasant. Taste: astringent.

Chemical Constituents

[Methanol extract (leaf): yield ~14%] Needles (leaves) of the plant yield an essential oil, in which monoterpenoids (~40%) have been identified as camphene (9%); limonene, α-pinene (10%); β-pinene, bornyl acetate (15.5%); and carvone (< 1%. CH2OH OO OAc

RO

HO HO

OH

HO (–)-Bornyl acetate

Betuloside: R=H Methyl betuloside: R = Me

Secondary metabolites, somewhat characteristic of this plant, are the phenylbutanol glycosides, betuloside (= rhododendrin) and its methyl ether, methyl betuloside.2 Other compounds isolated from the leaves so far are: α-bisflavonoid (abiesin), n-triacontanol, and the ubiquitous β-sitosterol.1

Estimation A report on the GC/MS analysis of the essential oil of the A. spectabilis needles has been published.1

Therapeutic Uses In Charaka, taalishapatra has been considered to be valuable in the treatment of cough, anaemia, digestive disorders and colic pain. Its therapeutic

Abies spectabilis (D. Don) Spach. 51

uses, as summarized in Bhavaprakasha, are ctd (box).

Taalisapatra is easily digestible (laghu), is sharp (teekshna) and hot. It mitigates asthma (svaasa), cough (kaasa), kapha, anila (vaata), anorexia (aruchi), gulma (gaseous lumps in the stomach), aama (a product of improper digestion), loss of appetite (maandhya), and consumption (ksaya). Bhavaprakasha: Karpuradivarga,

(Shloka 115)

In addition, modern Ayurveda practitioners consider it as antipyretic, analgesic, antiinflammatory, and useful in the treatment of dysuria.3

Modern Scientific Validation Methanol extract of plant leaves has been evaluated as an antitussive agent in a cough model induced by sulphur dioxide in mice. An oral dose of 400 mg/kg suppressed coughing frequency by ~72%, a value considered by the authors to be comparable in effect to that of codeine phosphate.4 In animal experiments (carrageenan-induced paw oedema in rats), methanol extract of leaves (400 mg/kg, p.o.) exhibited antiinflammatory activity, which was considered to be superior to that produced by the prescription drug diclofenac sodium (150 mg/kg, p.o.).5 In this connection, it may be noted that bornyl acetate, the major monoterpene component of the essential oil of the leaves has been demonstrated to show antiinflammatory activity.6 Furthermore, it may be mentioned that compounds closely related to betuloside (= rhododendrin), have been shown to suppress NO production by activated macrophages in vivo. As we know, NO is a critical mediator in the aetiology of inflammation.7 [Though, no further pertinent investigations on the other traditional claims appear to have been carried out, the following remarks have a bearing on the subject]. Bornyl acetate, the main monoterpenoid constituent of the leaf essential oil, has been shown to possess potent analgesic activity in pain models (hot plate and writhing reactions in mice).6, 8

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New Findings Methanol extract of plant leaves (at 100, 150 and 200 mg/kg, i.p.) has been found to exhibit significant synergistic effect on the hypnotic activity of standard sedatives, pentobarbitone sodium (50 mg/kg) and diazepam (6 mg/kg), in mice. The extract alone had no hypnotic action at these concentrations.5 In the context of these findings it may be noted that bornyl acetate, a chemical constituent of the leaves, has a positive modulating effect on GABA action at human GABAA receptors leading to inhibition of anxiety responses.9 Methanol extract of leaves showed significant anticancer activity (in vitro, anticellogram assay, cell line HL-60, MIC 20 ppm).10

Toxicity5 Methanol extract:

LD50, 986 mg/kg (Swiss albino mice, p.o.).

Petroleum ether extract:

LD50, 3200 mg/kg (Swiss albino mice, p..).

References 1. Rastogi & Mehrotra: Vol. 3, p 2; Vol. 4, p 1; Vol. 5, p 1. 2. SK Sarkar, G Poddar, SB Mahato, Planta Med., 53, 219 (1987). 3. Sharma: p 244. 4. SS. Nayak, AK Ghosh, K Srikanth, B Debnath, T Jha, Phytother Res, 17, 930 (2003). 5. SS Nayak, AK Ghosh, B Debnath, SP Vishnoi, T Jha, J Ethnopharmacol, 93, 397 (2004). 6. X Wu et al., Zhong Yao Cai, 27, 438 (2004). 7. S Fushiya, Y Kabe, Y Ikegaya, F Takano, Planta Med, 64, 598 (1998). 8. X Wu, F Xiao, Z Zhang, X Li, Z Xu, Zhong Yao Cai, 28, 505 (2005). 9. RE Granger, EL CAmpbell, GA Johnston, Biochem Pharmacol, 69, 1101 (2005). 10. Sukh Dev (Report).

Acacia catechu Willd. (Fam.: Mimosaceae)

Ayurveda (Sanskrit): KHADIRA Regional names: Beng. - Khayar; Guj. - Khario; Hin. - Khair; Kan. - Kaggali; Mal. - Khadiram; Mar. - Khair; Punj. - Khair; Tam. - Kadiram; Tel. - Kadiramu Chin.:  Pegu catechu; Nep.:  Khayer Eng.:  Cutch tree Indian trade name:  Khair

Plant1 It is a medium-sized (up to 3—4 m high), deciduous tree with a light feathery crown, distributed throughout the the sub-Himalayan region up to an altitude of 1,200 m, and further occurring in the drier parts of rest of India. It is being cultivated in several states of India. Tree bark is rough, 1—1.5 cm thick, exfoliating in narrow strips, and dark greyish brown in colour; sapwood is yellowish white, while heartwood is reddish and darkens with age. Leaves are pinnate, 10—15 cm long with a pair of small, hooked thorns at the base of rachis; leaflets are small, 60—100, ligulate. Flowers are small, white or pale yellow in cylindrical spikes; pods are thin, 5—8 cm long, glabrous, oblong, and dark brown. Trees flower in rainy season, and fruit in winter. Medicinally most important product from this tree is the dried aqueous © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 S. Dev, Prime Ayurvedic Plant Drugs, https://doi.org/10.1007/978-3-031-22075-3_3

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54  Prime Ayurvedic Plant Drugs 

extract of the heartwood, known in trade as katthaa (catechu) [and is manufactured in large quantities for applications other than medicinal2], and only the yellowish brown variety is used for therapeutic purposes. Odour: sharp, characteristic (katthaa). Taste: bitter, astringent (katthaa).

Chemical Constituents

[Acetone extract (heartwood): yield ~15%]3 Heartwood of A. catechu is a rich source of flavonoids (~90% of acetone extract), the chief constituent (> 70%) being (—)-epicatechin; presence of gallocatechins, and tetramers of catechin have also been demonstrated.4 Other related compounds isolated from the heartwood include quercetin, taxifolin (dihydroquercetin), isorhamnetin, kaempferol (its C3 rhamnoside: afzelchin), dihydrokaempferol, and dimers such as procyanidin B-4.3 Leaves have been shown to contain significant quantities of epicatechin3-O-gallate (~2%) and epigallocatechin-3-O-gallate (~1%).5 Very old trees often contain a white product (khairsaar) deposited in the trunk cavities, and this has been shown to consist essentially of catechin.2

[Medicinal grade catechu (katthaa) consists mostly of (+)-catechin and (+)-catechin. Catechu is manufactured by concentrating the water extract of heartwood, and it is very likely that during this process, epimerization and racemization of (—)-epicatechin to (+)-catechin and (+)-catechin takes place]. Wood also yields a gum polysaccharide, structure of which has been investigated.6

Estimation A method, based on high-performance liquid chromatography coupled with electrospray ionization mass spectrometry, has been described for quantitative estimation of main constituents of heartwood and leaves of this tree. An accuracy range of 1.1 to 11.8% is claimed.5

Therapeutic Uses Khadira in Sanskrit means one that destroys diseases and stabilizes metabolism. No wonder its use is recommended in treating various diseases (box). In Sushruta Samhitaa, it has been classified as a Saalsaaradi drug, a group with therapeutic efficacy in diseases of skin, urinary tract, lipid

Acacia catechu Willd. 55

metabolism and anaemia. As per Sushruta, khadira prolonslifespan.

Khadira is cooling (in potency), good for teeth (danta), and cures itching (kandu), cough (kaasa), anorexia (aruchi). It is bitter (tikta), astringent (kasaaya), reduces fat (medas), destroys worms (krimi), and cures meha (obstinate urinary disorders including diabetes), fever, ulcers (vrana), vitiligo, oedema (shotha), aama (a product of improper digestion and metabolism), pittaasra (bleeding from different parts of the body), anaemia (paandu), obstinate skin diseases, and diseases arising from imbalance of kapha. Bhavaprakasha: Vataadivarga

(Shloka 31, 32)

It is also considered valuable for the treatment of diarrhoea, dysentery, splenic disorders, piles, ulcers of oral cavity, fistula-in-ano, cuts and wounds.1, 7

Modern Scientific Validation [Much of the data pertaining to (—)-epicatechin, (+)-catechin, their oligomers (procyanidins), and other flavonoids (described below) were collected while investigating plants other than A. catechu, mostly tea and cocoa. However, these findings are equally relevant to our present discussion because of the occurrence of these compounds in A. catechu]. Free radical damage during normal mammalian metabolism is considered as one of the important ageing factors, and antioxidants which quench free radicals are being recommended as antiageing agents.8 There is considerable evidence to show that (—)-epicatechin, (+)-catechin, and their oligomers, and other flavonoids (e.g., quercetin, taxifolin) are powerful antioxidants and protect cell integrity by inhibiting oxidative damage to the lipid layer of the membrane.9,10 (+)-Catechin has also been shown to protect murine microglia against oxidative (tertbutylhydroperoxide) stress-induced DNA damage.11 These compounds have also been shown to have antioxidant synergy and regeneration effect (in vitro) on biological antioxidant α-tocopherol12; in a in vivo study, rats (Sprague-Dawley) consuming (+)-catechin had a 2.5—3.5 times enhance-

56  Prime Ayurvedic Plant Drugs 

ment of plasma, liver and lung α-tocopherol concentrations.13 Since atherosclerosis of arteries (and consequently coronary heart disease) appears to involve oxidation of LDL in the sub-endothelial space, catechin and related compounds have been found to have antiatherogenic effect in humans (clinical) and apolipoprotein E-deficient mice.14 It may be further noted that atherosclerosis involves endothelial dysfunction characterized by a decreased bioactivity of NO, and impaired flow-mediated vasodilation. In another clinical study (healthy male adults), it was demonstrated that oral ingestion of (—)-epicatechin led to acute enhancement of circulating NO species, and improved vascular function.15 Catechin oligomers have moderate antibacterial (against Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumoniae, etc.); and antifungal (against Candida albicans) activities (broth microdilution method: MIC, 500—2000 µg/ml). However, (+)-catechin and proanthocyanidins also show moderate immunostimulatory effect (in different cellular test systems), thus possibly amplifying the antimicrobial action in infectious conditions.16, 17 Catechins, quercetin and related compounds are recognized haemostatic agents.18 These compounds have also a strong astringent action, justifying the use of katthaa in dental hygiene. In this connection, it may also be noted that in a randomized clinical trial with 30 healthy human volunteers, use of tea extract (which contains catechins and related derivatives) as a mouth wash was found to be a potent agent for reducing units of colony forming bacteria.19 Catechins (from tea) have been shown to stimulate lipid catabolism in the liver, and thus produce beneficial effects on diet-induced obesity (in C 57BL/6 J mice). 20

New Findings (+)-Catechin and (—)-epicatechin have cancer preventive activity: feeding of (+)-catechin along with nutritionally complete amino acid-based diet to transgenic mice significantly delayed tumour onset.21 Epigallocatechin3-O-gallate, a minor component of Acacia catechu heartwood (though, it is the main antioxidant present in green tea) has been demonstrated to be a potent cancer preventive agent.22 [In a clinical study, green tea catechins (three capsules of 300 mg each; oral, one year) have been shown to possess remarkable cancer preventive action against prostate cancer23]. Epicatechin and catechin have been shown to be neuroprotective. For

Acacia catechu Willd. 57

example, these compounds have been demonstrated to prevent amyloid β-protein-induced neuronal cell death in in vitro experiments.24 Keeping in view other published studies (on green tea catechins), it appears that these compounds should prove therapeutically valuable in neurodegenerative diseases such as Parkinson’s disease and Alzheimer’s disease.25 (+)-Catechin, (—)-epicatechin, and their derivatives, produce a potentiation of the contractile response and inhibition of the vasorelaxant response (in rat thoracic aorta with endothelium), possibly via inactivation of endothelium derived nitric oxide.26

Toxicity Considered generally safe. Aq. alcoholic (50%) extract: i.p.).27

Maximum tolerated dose: 100 mg/kg (mice,

Quercetin: A dietary admixture of 3000 mg/kg/day given to Swiss mice for 25 days, did not cause any adverse reaction, and biochemical parameters wre not affected.20

References 1. Sharma: p 159. 2. Wlth India: Vol 1A (1985), p 24. 3. VH Deshpande, AD Patil, Indian J Chem, 20B, 628 (1981). 4. R Murari, S Rangaswami, TR Seshadri, Indian J Chem, 14B, 661 (1976). 5. D Shen et al., J Agric Food Chem, 54, 3219 (2006). 6. A Agarwal, P Soni, Indian J Chem, 27B, 55 (1988). 7. Garg: Vol 2, p 364. 8. See e.g.: Zs-Nagy, Harman & Kitani: pp 1, 68, 166. 9. SV Verstraeten, CL Keen, HH Schmitz, CG Fraga, PI Oteiza, Free Radic Biol Med, 34, 84 (2003). 10. T Lapidot, MD Walker, J Kanner, J Agric Food Chem, 50, 7220 (2002). 11. Q Huang et al., J Pharmacol Sci, 98, 16 (2005). 12. P Pedrielli, LH Skibsted, J Agric Food Chem, 50, 7138 (2002). 13. J Frank et al., J Nutr, 133, 3195 (2003). 14. Gross, Hemingway, Yoshida: p 471. 15. H Schroeter et al., Proc Natl Acad Sci USA, 103, 1024 (2006). 16. Gross, Hemingway, Yoshida: p 575. 17. Also see: H Arakawa, M Maeda, S Okubo, T Shimamura, Biol Pharm Bull, 27, 277 (2004). 18. Rowe: Vol II, p 1059. 19. CO Esimone, MU Adikwu, SV Nwafor, CO Okolo, J Altern Complement Med, 7, 523 (2001).

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20. T Murase, A Nagasawa, J Suzuki, T Hase, I Tokimitsu, Int J Obes Relat Metab Disord, 26, 1459 (2002). 21. SE Ebeler et al., Am J Clin Nutr, 76, 865 (2002). 22. See e.g.: HK Na, YJ Surh, Mol Nutr Food Res., 50, 152 (2006) [Review]. 23. S Bettuzzi et al., Cancer Res, 66, 1234 (2006). 24. HJ Heo, CY Lee, J Agric Food Chem, 53, 1445 (2005). 25. See e.g.: NT Zaveri, Life Sci, 78, 2073 (2006) [Review]. 26. F Sanae, Y Miyaichi, H Kizu, H Hayashi, Life Sci, 71, 2553 (2002). 27. ML Dhar, MM Dhar, BN Dhawan, BN Mehrotra, C Ray, Indian J Exp Biol, 6, 232 (1968). 28. MJ Ruiz et al., J Agric Food Chem, 57, 3180 (2009).

chyranthes aspera Linn. (Fam.: Amarnthaceae)

Ayurveda (Sanskrit): apaamaarga Regional names: Beng. - Apang; Guj. - Adhero; Hin. - Chirchira; Kan. - Uttarani; Mal. - Valiya-katalati; Mar. - Aghara; Punj. - Kutri; Tam. - Nayuruvi; Tel. - Apaamaargamu Chin.:  Niuxi; Nep.:  Apamarga; Viet.:  Co xuoc Eng.:  Prickly-chaff flower Indian trade name:  Chirchira

It is an annual weed distributed throughout India in locations up to 915 m high. The plants come up during the rainy season, and attain full growth and flower by end of winter, and gradually wither after seeding during the summer months.

A

Plant

It is an erect shrub, 0.3—1 m high, with ascending branches. The stem is slightly woody at the base, is furrowed, not much branched, and often tinged with reddish colour. Branches are quadrangular and thickened above the nodes. Leaves are opposite, ovate-elliptic or obovate, thick and hairy, and variable in size. Flowers are small, greenish white, and borne in long spikes reaching as much as 60 cm in length. Seeds are very small, about 2.5 mm long, and brown in colour. Freshly dried plant is greyish in colour, which slowly changes to pale brown during storage at ambient temperatures. All parts of the plant including seeds are used for medicinal preparations.

© The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 S. Dev, Prime Ayurvedic Plant Drugs, https://doi.org/10.1007/978-3-031-22075-3_4

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Odour: faint. Taste: pungent and bitter. Ayurveda literature distinguishes between plants with reddish stems (Rakta Apaamargaa), and those with greenish white stems (Shweta Apaamargaa).

Chemical Constituents [Methanol extract: yield ~6%]

Several paraffins (e.g., hentriacontane) and their derivatives (alcohols, ketones) have been isolated from the stems and young shoots. A simple base, betaine, has been separated from aqueous extract of the whole plant in a yield of 0.26%1 +

Me3N CH 2COO

–

Betaine

Two saponins based on the triterpene oleanolic acid have been obtained from the seeds.2 Ecdysterone, a steroid, has been isolated from its roots in a yield of around 0.1.3 HO

OH OH

COOR′

HO OH

RO

HO Oleanolic acid: (R = R′ = H) Saponins: (R = sugars, R′ = H/sugar)

H

O Ecdysterone

Estimation Amount of oleanolic acid in the roots of this plant growing in China has been determined by dual-wavelength TLC-scanning, and found to be 0.054%.4

Therapeutic Uses In Sanskrit, Apaamargaa means rectifier of metabolic disorders (tridosha), and since Vedic times (> 2000 BC), this herb has been acclaimed as a wonder plant for treatment of a variety of ailments. A quotation (see

Achyranthes aspera Linn. 61

box) from Bhavaprakasha is illustrative of this. Sushruta recommends it as an antidote for certain poisons, for treatment of ulcers, piles, and skin diseases. In folklore,5,6 it has been described as a diuretic, hypoglycaemic, abortifacient, and has been recommended for induction of child labour, for treatment of urinary tract infections and urolithiss.

Apaamaarga is pungent and bitter in taste and sharp in action. It is laxative (sara), and stimulates digestive power (dipana). It is carminative (paachana) and appetizer (rochana). It cures chardi (vomiting), diseases caused by deranged kapha, adiposity (medas), anila (diseases caused by vaata dosha), heart diseases (hrdroga), aadhmaana (tympanites), kandu (prurites), shoola (colic pain), udara (abdominal diseases) and apachi (cervical adenitis). Bhavaprakasha: Guducyadivarga (Shloka 220)

Modern Scientific Validation Ecdysterone, one of the constituents of this plant, has shown good protein anabolic activity (dipana, paachana) (in mice) comparable to that of 4-chlorotestosterone.7 In a recent investigation,8 aqueous extract of the leaves has been demonstrated (in rats) to exhibit significant prothyroidic activity, resulting in enhanced levels of serum glucose concentration, increased bodyweight, and elevated protein anabolism in the liver. Alcoholic extract of the whole plant has been shown to possess good hypoglycaemic activity in albino rats.9 In another study, oral ingestion of 2—4 g/kg of A. aspera powder in normal and diabetic rabbits produced a significant dose-dependent hypoglycaemic effect.10 Ecdysterone, a constituent of A. aspera, has been demonstrated (in vitro, Hep G2 cell line) to enhance glucose metabolism, and the results were comparable to those obtained with the oral antidiabetic drug metformin (N,N-dimethylbiguanide).11 Ethanolic extract of the plant exhibited antiinflammatory and antiarthritic activities at dose levels of 100—200 mg/kg (p.o.) in mice and

62  Prime Ayurvedic Plant Drugs 

rats (inhibition of paw oedema induced by carrageenan and Freund’s complete adjuvant, and inhibition of accumulation of inflammatory cells in carrageenan-induced peritonitis).12 In another similar investigation on albino male rats,13 performance of the alcoholic extract of the herb was evaluated against diclofenac sodium as the reference standard drug. The saponin fraction from the seeds has shown diuretic activity9 (in albino rats, and dogs) comparable to that of acetazolamide. In a clinical investigation in China,7 four cases of urinary lithiasis were successfully treated with Achyranthes (+ Boswellia) powder. Ethanol extract (200 mg/kg) of the plant root has been demonstrated to possess pronounced antifertility and abortifacient activities in fertile female albino rats. The extract was also shown to possess estrogenic by testing its action on immature ovariectomized female albino rats, and histological studies.14 Methanolic extract of the leaves also exhibit these activities.15 Aqueous and alcoholic extracts of the roots stimulate the gravid as well as non-gravid uteri of rats, guinea pigs and rabbits.9 In Chinese clinics, a piece of fresh or dried root has been introduced directly in the cervix canal to induce labour, especially in cases of therapeutic abortions7 (for a similar Indian folklore practice, see Krishnanand 5).

New Findings A. aspera leaf extract and the non-alkaloidal fraction thereof, have shown valuable anticarcinogenic effect in the in vivo two-stage mouse skin carcinogenesis test.16

Toxicity No adverse or side effects at dosages (of powdered whole plant) up to 8 g/kg orally in rabbits (7 days acute toxicity test).10 Ecdysterone: LD50, 6.4 g/kg (mice; intraperitoneal).7 [There is one report17 on the antiandrogenic activity of 50% ethanolic extract of the roots (500 mg/kg/day/60 days, oral, gastric intubation) on male rats. The treatment suppressed the production of testosterone and enhanced its catabolism. Action is similar to that of herbicide isoproturon]

Achyranthes aspera Linn. 63

References 1. KV Kapoor, H Singh, Indian J Chem, 4, 461 (1966). 2. Rastogi & Mehrotra: Vol 3, p 10; Vol 5, p 7. 3. A Banerjee, MS Chadha, Phytochemistry, 9, 1671 (1970). 4. X Li, S Hu, Zhongguo Zhong Yao Za Zhi, 20, 459, 511 (1995). 5. Krishnanand: Vol 1, p 58. 6. Garg: Vol 1, p 171. 7. Chang and But: Vol 1, p 223. 8. P Tahiliani, A Kar, J Ethnopharmacol, 71, 527 (2000). Also see: L Dinan, Phytochemistry, 57, 325 (2001) [Review]. 9. Satyavati: Vol 1, p. 10. 10. MS Akhtar, J Iqbal, J Ethnopharmacol, 31, 49 (1991). 11. Q Chen, Y Zia, Z Qui, Life Sci, 78, 1108 (2006). 12. AB Gokhale, AS Damare, KR Kulkarni, MN Saraf, Phytomedicine, 9, 433 (2002). 13. T Vetrichelvan, M Jagadeesan, Phytother Res, 17, 77 (2003). 14. N Vasudeva, SK Sharma, J Ethnopharmacol, 107, 179 (2006). 15. W Shibeshi, E Makonnen, I Zerihun, A Debella, Afr Health Sci, 6, 108 (2006). 16. A Chakraborty et al., Cancer Lett, 177, 1 (2002). 17. K Sandhyakumary, RG Boby, M Indira, Indian J Exp Biol, 40, 1307 (2002).

Acorus calamus Linn. (Fam.: Acoraceae)

Ayurveda (Sanskrit): VACHA Regional names: Beng. - Bach; Guj. - Vaj; Hin. - Bach; Kan. - Baje; Mal. - Vayambhu; Mar. - Vekhand; Punj. - Varch; Tam. - Vasambu; Tel. - Vasa Chin.: Shuichangpu; Nep.: Bojho; Viet.: Thuy xuong bo Eng.: Sweet flag Indian trade names: Bacha, Ghorbacha

Plant It is an aromatic marsh herb with a perennial thick creeping and branching rhizome. It is found wild or cultivated throughout India and neighbouring countries. It is especially plentiful in Sikkim, Manipur and Naga Hills. Its leaves are bright green with waved margins, are 90—150 cm or more in length and 2—3 cm wide, and originate from close to the root stock. Rhizome is cylindrical or compressed, up to 20 cm long and 1.5 cm thick, marked with the withered leaf-bases; and is light brown or pinkish brown externally, and white and spongy internally. Medicinally valuable part is the rhizome, which is whole dried or peeled and cut into pieces and then dried for marketing. Odour: characteristic, strong aroma. Taste: pungent, aromatic. Ayurveda literature describes two varieties of vacha: vacha and shweta (white) vacha. However, the second variety belongs to a different Family, and has been tentatively identified as Paris polyphylla.1 © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 S. Dev, Prime Ayurvedic Plant Drugs, https://doi.org/10.1007/978-3-031-22075-3_5

64

Acorus calamus Linn. 65

Chemical Constituents [Methanol extract: yield ~20%]

Acorus calamus occurs with different degrees of ploidy (e.g., Acorus calamus var. americanus is diploid, while A. calamus var. angustatus is tetraploid), resulting in wide variation in chemical composition.2—4 Its essential oil, the content of which can vary from 2—9%, is an important chemical characteristic of the herb. The components of the essential oil also vary widely. Important constituents of the essential oil are a range of sesquiterpene hydrocarbons, alcohols and ketones (e.g., acorone, acoragermacrone, calamendiol), besides eugenol, methyl isoeugenol and the characteristic phenylpropane derivatives α- and β-asarone, the latter being the far more predominant. β-Asarone content of the essential oil can vary greatly (0—83%) depending on the source of the drug.5 Essential oil from Indian plant material contains ~80% asarones. Among the steam non-volatile components, mention may be made of fatty acids, sugars and several phenylpropane-based dimers.2 Since β-asarone is a carcinogen (vide infra), plant races with β-asarone content of the essential oil of not more than 0.5% (and with a minimum of 2% essential oil content) should be employed for therapeutic purposes.6 H

OH

O

OH

O

O Acorone

Acoragermacrone OMe MeO

Calamendiol OMe

MeO

OMe α-Asarone

OMe β-Asarone

Estimation A recent report on the GC/MS analysis of the supercritical CO2 extracted essential oil of the A. calamus rhizomes has been published.7 A quantitative high-performance TLC procedure for the determination of β-asarone content of A. calamus rhizomes has been described.8

66  Prime Ayurvedic Plant Drugs 

Therapeutic Uses In Ayurveda (e.g., see box) vacha has been acclaimed for treatment of bronchial diseases, indigestion, chronic diarrhoea, epilepsy, and as a tranquillizer; in larger doses it is a strong emetic. In Sanskrit, the word vacha means strengthening of word power, and the herb is prescribed for improving voice and intellectual capacity. Juice of the herb has been recommended in Sushruta Samhitaa for intellectual vigour and longevity, and other preparations of the rhizome for treatment of asthma, pustular eruptions and heart disease. In Charaka Samhitaa, the plant has been described as a resuscitative (Samjnshapana).

Vacha has an acute pungent smell. In taste, it is pungent and bitter. It produces heating effect, causes emesis and stimulates digestive power. It cures constipation (vibandha), tympaites (aadhmaana), colic pain (shoola), epilepsy (apasmaara), kapha (diseases caused by kapha dosha), insanity (unmaada), bhoota and jantu (affliction by various types of pathogenic organisms) and anila (diseases caused by vaat dosha). Bhavaprakasha: Haritakyadivarga hloka 103)

(

Vacha enhances digestive power, cures diarrhoea, improves voice and intellectual capacity. In large doses, it causes vomiting. Gunapatha

Modern Scientific Validation It has been recorded9 that a decoction of root stalk given to several patients suffering from ‘indigestion’ proved efficacious.

Acorus calamus Linn. 67

Aqueous and alcoholic extracts of the rhizome has been demonstrated to possess antidiarrhoeal activity against castor-oil induced diarrhoea in mice.10 In acute and chronic experiments on mice, rats, cats and rabbits, α-asarone has been shown to have significant spasmolytic action.11 Its essential oil exhibited antitussive (cats), expectorant (rats and rabbits) and antiasthmatic (guinea pigs) activity in in vivo experiments.12 In a clinical study12 involving 3,012 cases of chronic bronchitis, therapeutic effects were realized. A number of investigations11—13 have been directed at the sedative and tranquillizing activity of the drug (various extracts), its essential oil and α-asarone. Both the oil and α-asarone repressed the aggressive behaviour of mice, and in small doses α-asarone potentiated the action of reserpine and that of chlorpromazine. Several other neuropharmacological studies confirmed the tranquillizing activity of the essential oil in rats, mice, cats and dogs. α-Asarone produced prolonged calming effect on monkeys. The mode of action of α-asarone is considered to be different from that of reserpine. Its essential oil at 10 mg/ml shows various degrees of bactericidal activity against several organisms.12, 13 In a recent study, ethanol extract of the plant has been demonstrated to exhibit potent antibacterial activity (in vitro) against several bacteria including multidrug-resistant strains.14 Both α- and β-asarone exhibit good anthelmintic (nematodes) action.15 A. calamus exhibited immunomodulating activity. Methanol extract of the plant has been shown to possess significant immunopotentiating activity (in vitro anticellogram assay against cell line J-774: MIC, 20 ppm).16 While, in another study ethanolic extract displayed immunosuppressive action by inhibiting proliferation of mitogen- and antigen-stimulated human peripheral blood mononuclear cells.17 Both ethyl acetate and methanolic extracts of the plant rhizomes have been demonstrated to protect rat brain against noise stress (30 days, 100 dBA./4 hours/day). The decreased levels of CAT, GPX, GSH, protein thiols, ascorbic acid and α-tochopherol in discrete regions of the brain (such as cerebral cortex, cerebellum, hippocampus) resulting from continous exposure to loud noise, were significantly ameliorated, when the animals received the extracts before exposure to the noise. Noise stress is believed to generate oxygen free radicals, and the antioxidative property of the extracts effectively countered the deleterious action.18 In an another study, it was shown that α-asarone, a constituent

68  Prime Ayurvedic Plant Drugs 

of the rhizomes, is the active agent.19 Methanolic extract of the plant drug was found to display cholinesterase inhibitory (in vitro, Ellman colorimetric method) action at 200 µg/ml concentration.20 This has a bearing on the traditional claims for the drug as a protective against age-related dementia.

New Findings Oral administration of 50% ethanolic extract (100, 20 mg/kg) to rats showed significant hypolipidaemic activity.21 Ethanolic (50%) extract of A. calamus rhizomes has been shown to possess neuroprotective action in acrylamide-disabled rats.22

Toxicity12 Essential oil: LD50, 0.275 ml/kg (guinea pigs; i.p.)

221 mg/kg (rats; i.p.)



177 mg/kg (mice; i.p.)

α-Asarone: LD50, 300 mg/kg (guinea pigs; i.p.) β-Asarone: LD50, 122 mg/kg (rats; i.p.) β-Asarone is carcinogenic and mutageic.6

References 1. Garg: Vol 4, p 171. 2. Rastogi & Mehrotra: Vol 1, p 8; Vol 2, p 10; Vol 3, p 11; Vol 4, p 10; Vol 5, p 12. 3. Karrer: p. 95; Supplement 1, p. 44; Supplement 2, Part 1, p 425. 4. M Niwa et al., Bull Chem Soc Japan, 48, 2930 (1975); 49, 3148 (1976). 5. E Stahl, K Keller, Pharmazie, 36, 53 (1981); Planta Med, 47, 71 (1983). 6. Bisset: p 115. 7. B Marongiu, A Piras, S Porcedda, A Scorciapino, J Agric Food Chem, 53, 7939 (2005). 8. V Widmer, A Schibli, E Reich, J AOAC Int, 88, 1562 (2005). 9. Koman: p 65. 10. FG Shoba, M Thomas, J Ethnopharmacol, 76, 73 (2001). 11. LF Belova et al., Farmakol Toksikol, 48, 17 (1985). 12. Chang and But: Vol 1, p 282. 13. Satyavati: Vol 1, p 18 14. F Aqil, I Ahmad, Methods Find Exp Clin Pharmacol, 29, 79 (2007). 15. N Sugimoto et al., Biol Pharm Bull, 18, 605 (1995).

Acorus calamus Linn. 69

16. Sukh Dev (Report). 17. S Mehrotra et al., Int Immunopharmacol, 3, 53 (2003). 18. S Manikandan, R Srikumar, R Jeya, N Parthasarathy, RS Devi, Biol Pharm Bull, 28, 2327 (2005). 19. S Manikandan, RS Devi, Pharmacol Res, 52, 467 (2005). 20. MH Oh, PJ Houghton, WK Whang, JH Cho, Phytomedicine, 11, 544 (2004). 21. RS Parab, SA Mengi, Fitoterapia, 73, 451 (2002). 22. PK Shukla et al., Phytother Res, 16, 256 (2002). 23. HS Wu et al., Phytother Res, 21, 562 (2007).

Adhatoda zeylanica Medik. [syn. A. vasica Nees] (Fam.: Acanthaceae) Ayurveda (Sanskrit): vaasaa, vasaka Regional names: Beng. - Baasaka; Guj. - Arduoso; Hin. - Adusaa; Kan. - Adusoge; Mal. - Adalodakam; Mar. - Adlasa; Punj. - Baansa; Tam. - Adhatodai; Tel. - Addasaramu; Nep.: Kalo vashak Eng.: Malabar nut Indian trade names: Adussaa, Vasakapatti

Plant

It is an evergreen, dense, perennial shrub, 1–5 m in height, found throughout India up to an altitude of 1,220 m. It thrives well in a variety of soils and habitats, and often grows on waste lands and occurs as thickets. Its leaves are ovate-lanceolate or elliptic, light green above and dark green on the underside, and 10–25 cm long and 2.5–5 cm broad. Flowers are white with redbarred neck, borne in dense spikes; flowering, fruiting and seeding occur during February–May. Though the whole plant—leaves, flowers and roots are used for medicinal purposes—leaves are rated as the most useful. The commercial drug consists essentially of dried leaves and terminal branches of the plant. Odour: sharp, unpleasant. Taste: bitter. [In Kerala, another species (A. beddomei, C.B. Clarke), locally known as Cheria adalodakam is preferred by the Ayurveda practitioners]. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2023 S. Dev, Prime Ayurvedic Plant Drugs, https://doi.org/10.1007/978-3-031-22075-3_6

70

Adhatoda zeylanica Medik. 71

Chemical Constituents [Methanol extract: yield 2–3%] This drug contains1, 2 several quinazoline alkaloids, of which vasicine, vasicinone and vasicinol are important in the present context because of their pharmacological properties. Vasicine occurs in all parts of the plant, and is present in the leaves to the extent of 0.6–1.2% on dry basis; vasicinone, on the other hand, has been reported to exist only in the leaves. These compounds occur both in the levo- and racemic form in the plant. A. beddomei also contains both these alkaloids. O N

HO

N

N OH

H

(–)-Vasicine

N

H

N N

OH (–)-Vasicinone

OH

H

Vasicinol

Other chemical constituents of the drug are: betaine (leaves), essential oil (