Host P2X7R-p38MAPK axis mediated intra-macrophage leishmanicidal activity of Spergulin-A

Abstract

Current drugs are inefficient 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 (Sp A), a triterpenoid saponin with RAW 264.7 macrophages was mediated through P2X7R involving the signaling cascade intermediates Ca++, p38MAPK, and NF-κβ. Phospho (P)-p38MAPK involvement is shown to have specific and firm importance in leishmanial killing with increased NF-κβp65. Phago-lysosomal maturation by Sp A also campaigns for another contribution of P2X7R. In vivo evaluation of the anti-leishmanial activity of Sp A was monitored through expression analyses of P2X7R, P-p38MAPK, and NF-κβp65 in murine spleen and bone-marrow macrophages and supported Sp A being a natural compound of leishmanicidal functions which acted through the P2X7R-p38MAPK axis.