Genesis of Reverse Pharmacology in India: Akin to Dr.Youyou Tu’s Nobel for an anti-malarial

youyou tu strathclyde

Pathak N. A slide in Roots of modern medicine in Reverse Pharmacology, Presentation made to visiting Faculty, Strathclyde University, Kasturba Health Society, Mumbai, India.2012 (Click to enlarge)

An organized effort to discover an anti-malarial bioactive from Traditional Chinese Medicine experience, led to a Nobel Prize for Dr.Youyou Tu in Oct 2015. Motivated by the Vietnamese war, it was an orchestrated effort to streamline those organic, spontaneous processes which have often led to discovering modern drugs from traditional medicine/plants.

I share below one such tale is of Reserpine discovered from Sarpagandha. In India too, an organized effort to discover drugs from medicinal plants had ensued in the last three decades led by Dr.Ashok Vaidya, Dr.RA Mashelkar, Dr. Bhushan Patwardhan and many other interdisciplinary experts. Unlike Dr.Youyou Tu’s mission it was not on a ‘war’-footing. I do hope that the newly formed AYUSH ministry is willing to examine this case to invest its energies in meaningful directions!

Reserpine story in brief

In 1930, an ace Ayurvedic physician, Vd.Gananath Sen found that a medicinal plant, Sarpagandha (Rauwolfia serpentina Linn.) reduces raised blood pressure. As anti-hypertensives were not available as yet, patients flocked to get that herb from him. Intrigued, a renowned cardiologist Dr.Rustom Jal Vakil decided to test in his patients while chemists like Ajmal Khan began isolating potential actives from the plant. Eventually at CIBA-Geigy, Reserpine, the catecholamine depletor (which reduces the tone of the sympathetic nervous system) was identified as an active and one of the first anti-hypertensives was developed. Studying Sarpagandha and reserpine had also helped understand mechanisms of depression, schizophrenia and Parkinson’s disease. For more details, click here.

Genesis of Reverse Pharmacology

Why couldn’t we replicate this with some many other clinical observations in a vaidya’s clinic today, questioned Dr.Ashok Vaidya. For over three decades, he and his team relentlessly pursued a path of scientific documentation and investigation of Ayurvedic products. There had to be a new path of medicinal product development which documented the existing clinical experience, asked relevant questions to create standardized products of value. The path came to be christened ‘Reverse Pharmacology’, eventually nurtured by many other academic and industry leaders. In the last decade, the Government of India orchestrated a nationwide team effort, called CSIR-NMTILI to develop global products (for malaria, arthritis and diabetes) using this path. It is now being increasingly used by industry to spur innovation in light of the increasingly dry drug pipelines.

Reverse pharmacology is now defined as the trans-discipline that initiates drug discovery and development from traditional knowledge/practices at the bedside through robust and objective clinical documentation.

Key conceptual publications are found here:

i) Vaidya ADB. Reverse Pharmacological correlates of Ayurvedic drug actions. Indian J Pharmac. 2006; 38(5), 311-15

ii) Patwardhan B, Mashelkar RA. Traditional medicine inspired approaches to drug discovery. Can Ayurveda show the way forward? Drug discovery today 2009; 14, 804 – 5

I will share more stories of Science in Ayurveda (both contemporary and fundamental) which I am fortunate to belong to. I also invite people to share more of these lesser known stories of India’s efforts in the last couple of centuries.

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Herb drug interactions

Herb drug interactions can and do occur, and must be actively taken care of by you and your physician. Although extensive literature is not available on this topic, here are possible interactions with Ayurveda and herbal supplements.  These are based on some observations and plausible confounding mechanisms. The list is not exhaustive and will be expanded.

In general, it is a good practice to leave a gap of atleast an hour between plant based supplements and conventional medicines.

Common in Ayurvedic medicine

1. Warfarin is combined with ginkgo (Ginkgo biloba), garlic (Allium sativum), dong quai (Angelica sinensis), or danshen (Salvia miltiorrhiza) may cause bleeding.

2.Liquorice (Glycyrrhiza glabra, yashtimadhu, jethimadh) may cause a potentiation of oral and topical corticosteroids.

3. Anthranoid-containing plants (including senna [Cassia senna] and cascara [Rhamnus purshiana]) and soluble fibres (including guar gum and psyllium) can decrease the absorption of drugs. Senna is the main ingredient of a common laxative – Kayam churna and avipattikar churna.

4.Indian gooseberry and turmeric (Amla- haldi), very commonly used by diabetics,  may reduce the bioavailability of metformin when used together in diabetes.(Ref 2)

5.Ayurvedic syrup shankhapushpi may decrease concentrations of anti-epileptic phenytoin.(Ref 3)

Common in Traditional Chinese medicine and Herbal medicine

1.Panax ginseng and antidepressants causes an induction of mania in depressed patients.

2.St John’s wort (Hypericum perforatum) with serotonin-reuptake inhibitors may cause mild serotonin syndrome. It may also decrease bioavailability of digoxin, theophylline, cyclosporin, and phenprocoumon.

3.Yohimbine (Pausinystalia yohimbe) and tricyclic antidepressants may lead to increased risk of hypertension.

4. Xaio chai hu tang (sho-salko-to) by decreased blood concentrations of prednisolone when taken with the Chinese herbal product.

References
1.Windrum P, Hull DR, Morris TC. Herb-drug interactions. Lancet. 2000 Mar 18;355(9208):1019-20.

2.Puranik A, Nabar N, Joshi J et al. Single dose metformin kinetics after co-adminstration of nisha-amalaki powder or mamejawa gahnwati, ayurvedic anti-diabetic formulations: A randomized crossover study in healthy volunteers. J Obes Metab Res 2014;1:99-104

3.Dandekar UP et al.Analysis of a clinically important interaction between phenytoin and Shankhapushpi, an Ayurvedic preparation.J Ethnopharmacol. 1992 Jan;35(3):285-8.

 

Other good resources on herb drug interaction

1.http://www.itmonline.org/arts/herbdrug.htm

2.https://nccih.nih.gov/training/videolectures/clinically-relevant-herb-drug-interactions

3.University of Maryland interactio checker: http://umm.edu/health/medical/altmed