Authors

N Mukherjee¹; S Banerjee¹; K Das Saha¹;  ¹ CSIR-Indian Institute of Chemical Biology, India

Discussion

Current drugs are inadequate for the treatment of visceral leishmaniasis an immunosuppressive ailment caused by Leishmania donovani. Regrettably, there is no plant-origin antileishmanial drug present. P2X₇R is constitutively present on macrophage surfaces and can be a putative therapeutic target in intra-macrophage pathogens with function attributes towards inflammation, host cell apoptosis, altered redox and phagolysosomal maturation by activating p₃₈MAPK. Here we demonstrated that the initial interaction of Spergulin-A, atriterpenoid saponinwith macrophages was mediated through P2X₇R involving the signaling cascade intermediates Ca⁺⁺, P₃₈MAPK, and NF-κβ. P₃₈MAPK involvement shown to have specific and stern importance in leishmanial killing with increased NF-κBp65. Phago-lysosomal maturation by Spergulin-A also campaigns for another contribution of P2X₇R. In vivo evaluation of the anti-leishmanial activity of Spergulin-A was monitored through P2X₇R, P₃₈MAPK, and NF-κβ in murine spleen and bone-marrow macrophages and advocated Spergulin-A of being a natural compound of leishmanicidal functions which acted through the P2X₇R-P₃₈MAPK axis.