EVALUATION OF ANTIPLASMODIAL ACTIVITY AND SAFETY OF CHRYSANTHEMUM CINERARIAEFOLIUM EXTRACTS, SINGLY AND IN COMBINATION WITH CHLOROQUINE, LUMEFANTRINE AND PIPERAQUINE
Plasmodium falciparum is the major cause of global malaria morbidity and mortality. Chemotherapy remains the mainstay of malaria control strategy. Development of drug resistant falciparum malaria is the greatest challenge, thus need to search for new agents with novel mechanisms of action. Natural products have always been a rich source of drugs, including antimalarials. Very little data exists on Chrysanthemum cinerariaefolium (Pyrethrum) antiplasmodial activity. This study investigated the in vitro and in vivo antiplasmodial activity of Chrysanthemum cinerariaefolium flower extracts either singly or in combination with chloroquine(CQ), lumefantrine (LU) or piperaquine (PQ) against Plasmodium falciparum or P. berghei ANKA using serial micro-dilution assay (in vitro), classical 4-day suppressive test and established infection test in vivo. The safety of the C. cinerariaefolium flower extracts was also tested using Vero E6 cell lines and mice both in vitro and in vivo respectively. In vitro antiplasmodial assay showed that methanolic extract of C. cinerariaefolium flowers is active, petroleum ether extract was moderately active, water extract was inactive against both CQ- sensitive (3D7) and CQ-resistant (W2) P. falciparum. Methanolic extract combined with CQ against 3D7 and W2 showed marked synergy. Both methanol and water extracts (1000mg/kg) showed remarkable percentage chemosuppression of >45% in both 4-day suppression test and established infection test against P. berghei ANKA. Both PQ and LU combined with either methanol or water extracts showed percentage chemosuppression of >63% against resistant P. falciparum strains. Methanolic and water extracts of C. cinerariaefolium flowers showed less cytotoxic effect on Vero E6 cells and also showed no overt signs of toxicity in mice. Chrysanthemum cinerariaefolium flower extracts are safe in mammalian systems, have antiplasmodial activity and have potentiation effects toward conventional drugs, thus need to explore it further for bioactive molecules which can be used to develop new, novel, effective and affordable antimalarial agents.