Oleuropein activates autophagy to circumvent anti-plasmodial defense

Antimalarial drug-resistance and unavailability of effective vaccine warrants for newer drugs and drug-targets. Hence, anti-inflammatory activity of phyto-compound (oleuropein; OLP) was determined in antigen (LPS) stimulated human THP-1 macrophages (macrophage-model of inflammation; MMI). Reduction in the inflammation was controlled by the PI3K-Akt1 signalling to establish the “immune-homeostasis”. Also, OLP treatment influenced the cell death/autophagy axis leading to the modulated inflammation for extended cell-survival. The findings with MII prompted us detect the antimalarial-activity of OLP in the wild type (3D7), D10 expressing GFP-Atg18 parasite, and chloroquine resistant (Dd2) parasite. OLP did not show the parasite-inhibition in the routine in vitro culture of P. falciparum whereas OLP increased the antimalarial activity of artesunate. The molecular docking of autophagy related proteins (ARP), investigations with MMI and parasite inhibition-assays indicated the host activated the autophagy to survive OLP pressure. The challenge model of P. berghei infection showed to induce autophagy for circumventing anti-plasmodial defences.