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IJP October 06.Pmd Special Article Reverse pharmacological correlates of ayurvedic drug actions*actions* A.D.B. Vaidya Bhavan’s Swami Prakashanand Ayurvedic Research Center (SPARC), Mumbai – 400 049. India Received: 28.7.2005 Revised: 22.5.2006 Accepted: 30.5.2006 Correspondence to: Ashok DB Vaidya Sir Ram Nath Chopra E-mail: [email protected] The human condition has been enhanced considerably by While Sir Ram Nath Chopra and other West-trained those biochemists and pharmacologists who have applied the scientists were evaluating the effects of ayurvedic drugs and scientific method to prove ancient myths and legends. For plant extracts on tissues and animals, eminent vaidyas such example, the mystical powers of the snakeroot plant of India, as Mahamahopadhyaya Gananath Sen were laying the either ignored or ridiculed by scientists for decades, were foundation of ‘Reverse Pharmacology’. The science of dispelled with the isolation and identification of its active integrating documented clinical/experiential hits into leads by transdisciplinary exploratory studies, reverse alkaloid. pharmacology further developed these leads into drug candidates by experimental and clinical research. The – Richard E Davis proposed approach is the new paradigm or a rediscovered paradigm. “Rediscovered” because, even in modern Sir Ram Nath Chopra (1882-1973) was a pioneer in the pharmacology, some of the major fundamental discoveries field of experimental pharmacology of indigenous drugs of evolved from plant effects in humans. Table 1 lists some India. Most of the medicinal plants he studied were in use, in such historical examples of reverse pharmacology. The animal ayurveda, for thousands of years. At the Calcutta School of models and/or mechanisms of such human effects often Tropical Medicine, he pioneered a paradigm, a pace and a provided the foundation of pharmacology. Novel phenomena pattern of research in studying the actions of medicinal plants, in healthy or ill humans still continue to occur and deserve a which influenced an entire generation of pharmacologists, critical study at different levels of biological organisation. This pharmacists and physiologists in India. Fortunately, now, at can be an engaging and challenging task. It is possible that the Regional Research Laboratory (RRL) Jammu-Tawi, the such a quest for biodynamic mechanisms can generate new Chopra Archives are safely lodged for posterity. The collected disciplines in life sciences. works, correspondence and materials may also serve as Ayurveda in India dates back to 3000 BC. It has a valuable sources for a biography which can be commissioned connotation of revealed knowledge, complete within itself and, by the Indian National Science Academy, which had the as some say, it has hardly any need for research. Lokmanya privilege of having Dr. R.N. Chopra as past president. Tilak coined the term ‘Ayurvidya’ to liberate the creative and G.V. Satyawati, former Director General, Indian Council of research energies of this great heritage of healing wisdom. Medical Research (ICMR) has rightly emphasised, “The credit India is a unique, democratic nation with a multi-population, for kindling the interest of Indian chemists and divergent lifestyles and pluralistic healthcare systems. Such pharmacologists in medicinal plants should rightfully go to diversity offers an immense scope to observe and document Sir Ram Nath Chopra, who has been acclaimed as the ‘Father the effects of ayurvedic drugs, medicinal plants, dietary habits of Indian Pharmacology’”.[1] and non-drug healing modalities. Reverse pharmacology *Based on the ‘Sir Ram Nath Chopra’ oration delivered by the author at the Annual Conference of the Indian Pharmacological Society on 10th January 2002 in Nagpur. Indian J Pharmacol | October 2006 | Vol 38 | Issue 5 | 311-315 311 Vaidya Table 1 the plant? It is worthwhile to apply combinatorial chemical methods for reserpine derivatives, which do not cross the Rediscovery of the paradigm of reverse pharmacology blood brain barrier, so that depression, a serious side effect, Medicinal Clinical Experimental is avoided. The uptake of norepinephrine by isolated plant effect correlate chromaffin granules, by inhibition of ATP-Mg2+ – dependent mechanism has to be studied afresh at the transcriptional Curare tomentosum Paralysis and death Neuromuscular level. Though reserpine is withdrawn globally, the extracts of [2] block the plant are still used in ayurveda with a rationale of Papaverum somniferum Analgesia Opioid receptors[3] ayurvedic pharmacodynamics. There is a need to conduct Physostigma venenosum Ordeal poison Anticholinesterase[4] pharmacovigilance on Sarpagandha ghanavati (water extract). Cinchona officinalis Antipyrexia Antimalarial[5] Psoralea corylifolia Linn (Bakuchi) Digitalis purpurea Dropsy relief Na+,K+-ATPase[6] The use of this plant in treating leucoderma is well Salix alba Fever and pain relief Prostaglandins[7] documented in Rajnighantu (Nighantu – a compendium of synonyms, properties and usages of medicinal plants) by Strychnos nuxvomica CNS stimulant Glycinergic Pandit Narahari.[15] Besides the traditional and classical use of [8] receptors P. corylifolia in treating leucoderma (shwitra kusta), there are many other indications described in classic ayurveda texts such as Bhavaprakash Nighantu.[16] These indications include would initiate the research process from the robust clinical promoting skin health, hair growth, relieving attacks of base of documented therapeutic or other effects of plants asthma and bronchitis and reducing inflammatory and and formulations. edematous conditions. Though the pharmacological As an academic discipline, it comprises 3 phases: correlates of its pigment enhancing and antipsoriasis actions 1. Experiential robust documentation of clinical have been studied, the other ayurvedic actions too deserve observations of the biodynamic effects of standardised attention.[17] The phytochemically induced covalent binding ayurvedic drugs by meticulous record keeping. of methoxalen to pyrimidine bases is responsible for its 2. Exploratory studies for tolerability, drug interactions, dose therapeutic effect. The photoconjunction involves thymine range finding in ambulant patients of defined subsets of dimer adducts on the opposite strands of DNA. With the the disease and para-clinical studies in relevant in vitro current advances in human genomics, it would be worthwhile and in vivo models to evaluate the target activity. to investigate whether such effects on DNA are localised to 3. Experimental studies, basic and clinical, at several levels the skin only and whether hair, retina and so on are also of biological organisation, to identify and validate the affected. The other ingredients of the plant need to be studied, reverse pharmacological correlate of ayurvedic drug in the reverse pharmacology mode, for the effects on edema, safety and efficacy. asthma cough and anaemia. An overt focus on a single active Such a creative research endeavour requires an excellent principle leads to the neglect of other active entities in the teamwork by multisystem and multidisciplinary experts. plant. The external uses described in ayurveda deserve due Reverse pharmacology, for drug development, has been attention.[18] highly productive and cost effective in the recent past. Berberis aristata D C (Daruharidra) Globally, this approach has now generated greater interest in ayurveda and Indian pharmacology. The multiple uses and actions of the plant, Berberis aristata (Daruharidra), have always intrigued pharmacologists Rauwolfia serpentina Benth (Sarpagandha) and clinicians. It is a topical antimicrobial par excellence in Sen and Bose[9] not only showed the antihypertensive ayurveda. Its use, as extract for eye drops in conjunctivitis, is effects of R. serpentina, but were also astute clinicians to widespread. The active principle of the plant, berberine, has note certain side effects such as Parkinsonism, depression, been extensively studied. The activity of berberine against a gynecomastia, acid peptic symptoms and so on. There was variety of organisms, including bacteria, viruses, fungi, almost a gap of two decades in discovering the protozoa, helminths and chlamydia, has been pharmacological basis of these actions. The storage vesicles demonstrated.[19] Berberine has been shown to bind to DNA are rendered dysfunctional as a result of their interaction and inhibit its cleavage.[20] There is an urgent need to develop with reserpine and the depletion of biogenic amines explained specially targeted drug delivery systems of berberine, for the actions by mechanistic correlates.[10] As a spin off of the topical and systemic antimicrobial use. Local anesthetic, side effects of R. serpentina, several new drugs were developed pigment inducing, enzyme inhibitory, antihypertensive, such as L-dopa, antidepressants, bromo-ergocriptine, and antipruritic and antipyretic activities have been reported with [11-13] [21, 22] H 2 receptor blockers and so on. The alkaloids of berberine. Recently, the antiamnesic activity of berberine R. serpentina, reserpine and ajmalcine, have served as has been reported.[23] Despite the diversity of activities, the research tools in many experiments.[14] proper clinical documentation of the reverse pharmacology However, there are still some unanswered questions. Does of the plant has been neglected. Its beneficial effects on reserpine have more incidence of depression and/or Plasmodium vivax relapses have been reported by Gogte.[18] extrapyramidal side
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