Metabolite footprinting of Plasmodium falciparum following exposure to Garcinia mangostana Linn. crude extract

Abstract

Multidrug resistant Plasmodium falciparum is the major health problem in the tropics. Discovery and development of new antimalarial drugs with novel modes of action is urgently required. The aim of the present study was to investigate antimalarial activities of Garcinia mangostana Linn. crude ethanolic extract including its bioactive compounds as well as the metabolic footprinting of P. falciparum following exposure to G. mangostana Linn. extract. The median (range) IC50 (concentration that inhibits parasite growth by 50%) values of ethanolic extract of G. mangostana Linn., α-mangostin, β-mangostin, gartanin, 9-hydroxycarbaxathone, artesunate, and mefloquine for 3D7 vs K1 P. falciparum clones were 12.6 (10.5–13.2) vs 4.5 (3.5–6.3)μg/ml, 7.3 (7.1–8.5) vs 5.0 (3.7–5.9)μg/ml, 47.3 (46.8–54.0) vs 35.0 (30.0–43.7)μg/ml, 9.2 (8.1–11.9) vs 6.8 (6.2–9.1)μg/ml, 0.6 (0.4–0.8) vs 0.5 (0.4–0.7)μg/ml, 0.4 (0.2–1.2) vs 0.7 (0.4–1.0)ng/ml, and 5.0 (4.2–5.0) vs 2.7 (2.5–4.6)ng/ml, respectively. The action of G. mangostana Linn. started at 12h of exposure, suggesting that the stage of its action is trophozoite. The 12-h exposure time was used as a suitable exposure time for further analysis of P. falciparum footprinting. G. mangostana Linn. extract was found to target several metabolic pathways particularly glucose and TCA metabolisms. The malate was not detected in culture medium of the exposed parasite, which may indirectly imply that the action of G. mangostana Linn. is through interruption of TCA metabolism.