Reverse pharmacology and Ayurveda

Reverse pharmacology correlates with Ayurvedic drug action. The approach has attracted considerable attention, nationally and internationally. Central Scientific Instrumental Research (CSIR) and Indian Council of Medical Research (ICMR) have done clinical trials with natural products. Moreover, Central Council for Research in Ayurveda and Siddha (CCRAS) has recently adopted the golden triangle approach for some new indications of old drugs, as well as for Ayurveda (Fig. 2.5). The golden triangle approach is a combination of Dravyagunavignyan, systems biology, and reverse pharmacology for the discovery of potent and cost-effective remedies. Dravyaguna deals with the Ayurvedic study of drugs derived from natural (plant, animal or marine) origin. Dravya refers to constituent of the universe and guna signifies property. In the recent past, the study of Dravyaguna has become more important because of global acceptance of the Ayurvedic system of medicine. Ayurveda has its own concept as far as drug formulation is concerned. Ayurveda has documented Dravya, Guna, Rasa, Virya, Vipaka, Prabhava and Karma for all medicinal agents and these represent the pharmacological aspects of drug usage in Ayurveda.

In Ayurveda, drugs have been classified in a number of ways but the classification based on action of the drug is widely accepted. For instance a drug used for alleviating worm infection is known as anthelmintic and in Ayurvedic language, as krimighana. In modern medicine, drugs have been classified according to pharmacological actions. Medicinal plants like Ashwagandha, Brahami, Tulsi, Guggul, Kutki, Kalmegha, Gokshura and Shatavari have been targeted for their application in modern science. Active constituents of the plants have been identified and highly purified extracts are being marketed.

Golden Triangle Approach
Fig. 2.5 Golden triangle approach.

Studying the Ayurvedic drugs at bimolecular levels may reveal the mechanism of action which has eluded scientists for long time. As far as the disease segment is concerned, hepatology and rheumatology are two areas where Ayurvedic remedies are even prescribed by allopathic physicians. Silybum marianum is a well-documented western herbal remedy used for liver diseases. In India, Picrorhiza kurroa (kutki), is considered a valued drug for liver diseases. When P. kurroa was compared with S. marianum, the hepatoprotective effect of P. kurroa was found to be similar, or in many cases, superior to the effect of S. marianum. However it can be seen that S. marianum is more popular than P. kurroa. Silymarin the active constituent of S. marianum has been isolated and purified and above all pharmacological and pharmacokinetic data is available for the drug.

The reverse approach in pharmacology has been quite successfully applied in the past. The drawback was the long time frame from the observational therapeutics to a new drug. For example, Rauwolfia serpentina (sarpagandha) was convincingly demonstrated to be anti-hypertensive by Sen and Bose in 1931. But a drug reserprine, emerged only after 20 yr of work by Vakil, Bein, Muller and Schlitter. This occurred because the path of reverse pharmacology was quite discontinuous.

The paradigm of reverse pharmacology is actually a rediscovery of the path, which founded modern pharmacology. Table 2.2 lists the names of plants, clinical effects, and experimental correlates. The list illustrates how novel clinical bio-dynamic effects can lead to the development of the basic disciplines in pharmacology and biology.

Table 2.2 Rediscovery of the paradigm of reverse pharmacology (see Fig. 2.6 also).

Medicinal Plant

Clinical Effect

Experimental Correlate

Chondrodendron tomentosum

Paralysis and death

Neuromuscular block

Cinchona officinalis

Fever

Antimalarial

Digitalis purpurea

Dropsy

Na+-K+ ATPase

Papaver somniferum

Analgesia

Opioid receptors

Physostigma venenosum

Ordeal poison

Anticholinesterase

Salix alba

Fever and pain

Prostaglandins

Strychnos nux-vomica

Stimulant and convulsant

Glycinergic receptors

^NHCH3

Physostigmine H3Cv

Physostigmine H3Cv

Morphine

Strychnine

Strychnine oh

Salicin oh oh

Salicin

H H2C

Indene Och3

OCH3

OCH3

CH3O.

D-tubocurarine Fig. 2.6 Active constituents of plants listed in Table 1.6.

There has been a renaissance in Ayurvedic research that western and Indian pharma companies have just started to notice. Reverse pharmacology was only sporadically applied to new drug development. It is the need of the hour to document unknown, unintended and desirable novel prophylactic and therapeutic effects in observational therapeutics. Several new classes of drugs have accidentally emerged by this path (Fig. 2.7).

Pharmacology Related Fig
Fig. 2.7 Scheme for drug discovery from plants used in Ayurveda.
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