Reverse pharmacology for antimalarial plants goes global

Sir, A recent issue of the Malaria Journal has been dedicated to the research and development of natural products for treatment of malaria. All the articles in the issue are interesting. The article on Reverse Pharmacology (RP) by Willcox et al [1] is of particular interest, which suggested that this transdiscipline of RP has global appeal. The RP path, as Willcox et al have rightly mentioned in their article, has originated in India for new drug discovery and is based on Ayurveda, India's ancient traditional system of medicine. However, the statement of Willcox et al supported by the reference of Patwardhan and Mashelkar [2] that " RP still involves classical pathway of isolating compounds for further development " is true only to a certain extent. RP in India focuses mainly on the development of Ayurveda-inspired standardized formulations, the safety, and activity of which is implied through its long history of usage. Several other paths may be considered for the development of drugs from Ayurvedic therapeutics and natural products, one of them is isolation and identification of active compounds. It was notable to see that Merlin Willcox and group have used RP approach to develop antimalarial complementary formulation from the ethnobotanical/folklore leads. In deference to African folklore uses of medicinal plants for fever, the Ayurvedic approach to Malaria (visham-jwara) makes use of diagnostic components (nidan) and Ayurvedic Pharmacology of Medicinal plants (dravya-guna-vigyan). Classical Ayurvedic descriptions of ailments and their management besides a long tradition of usage of medicines by Ayurvedic physicians form a basis for the selection of the medicine for evaluation through RP. Willcox et al evolved a standard score system to prioritize a plant from folklore practices. This includes meticulous analysis and scoring of ethnobotanical data for (i) frequency of citation of a plant, (ii) efficacy in vitro and in vivo, and (iii) safety and activity based on retrospective treatment outcome (RTO) study. Ayurveda-inspired RP on the other hand provides foundation of long-term experience of clinical usage, Ayurvedic-pharmacodynamic rationale and evidence generated through current biomedical integration for the development of drugs. Here we illustrate RP approach with respect to the Nyctanthes arbor-tristis Linn. (Parijat) for the antimalarial activity. The plant, indicated in Ayurveda for the treatment of visham-jwara is used by Ayurvedic physicians for recurrent fevers and hepatosplenomegaly. Parijat has been extensively studied by our group through the three stages of RP (experiential, exploratory, and experimental) as defined by …