Elaboration of host P2X7R-P38MAPK axis involvement against intracellular leishmania donovani by Spergulin-A: a comprehensive study

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, a triterpenoid saponin with 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.