Screening North American Plants In Vitro Against Leishmania Donovani, The Causative Agent For Visceral Leishmaniasis

Visceral leishmaniasis, caused due to infection with Leishmania donovani, a protozoan parasite, is a major global health challenge. Severe toxicity of currently available drugs and emergence of resistance against the limited drugs, with severely depleted drug discovery pipeline, necessitate discovery of new antileishmanial drugs. Nature has been and shall remain to be rich source of molecules with novel structural prototypes. The plants from North American regions have shown significant medicinal use and have not been explored for new antiparasitic drug discovery. A library of 528 ethanolic extracts, prepared from the plants randomly collected from different regions of North America, was screened in vitro against Leishmania donovani promastigotes, axenic amastigotes and macrophage internalized amastigotes [1]. Several active plants extracts (36) with selective activity against internalized amastigotes were identified. The extracts from the plants namely, Cornus foemina, Balsamorhiza cf. serrata, Crinum asiaticum, Agastache foeniculum, Euonymus sp., Melia azedarach and Apocynum cannabinum showed selective activity against macrophage internalized amastigote with IC₅₀ < 5 µg/mL. Further activity-guided fractionation of these plants extracts and identification of active constituents is likely to yield antileishmanial drug leads with novel chemotypes. None of the lead extracts showed cytotoxicity against transformed THP1 cells.

Acknowledgements: US Army Medical Research & Material Command CDMRP grant # W81XWH-09-2-0093 and USDA-ARS cooperative scientific agreement with the NCNPR.

References: [1] Jain, S. et al. (2012) Journal of Visualized Experiments, 70: pii: 4054.