Evaluation of Antiplasmodial Activity and Safety of Flower Extracts of Chrysanthemum cinerariaefolium, Singly and in Combination with Chloroquine, Lumefantrine and Piperaquine
Godfrey K. Wachira
Department of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, P.O.Box 62000-00200, Nairobi, Kenya and Department of Health and Applied Science, Thika Technical Training Institute, P.O.Box 91-0I000, Thika, Kenya
Francis W. Muregi *
Department of Biological Sciences, Mount Kenya University, P.O.Box 342-01000, Thika, Kenya
Francis T. Kimani
Centre for Biotechnology Research and Development, Kenya Medical Research Institute, P.O.Box 5840-00200, Nairobi, Kenya
Jeremiah W. Gathirwa
Centre for Traditional Medicine and Drug Research, Kenya Medical Research Institute, P.O.Box 5840-00200, Nairobi, Kenya
Joseph K. Ng’ang’a
Department of Biochemistry, Jomo Kenyatta University of Agriculture and Technology, P.O.Box 62000-00200, Nairobi, Kenya
Peter G. Mwitari
Centre for Traditional Medicine and Drug Research, Kenya Medical Research Institute, P.O.Box 5840-00200, Nairobi, Kenya
Festus M. Tolo
Centre for Traditional Medicine and Drug Research, Kenya Medical Research Institute, P.O.Box 5840-00200, Nairobi, Kenya
Lucia Keter
Centre for Biotechnology Research and Development, Kenya Medical Research Institute, P.O.Box 5840-00200, Nairobi, Kenya
Beatrice Irungu
Centre for Biotechnology Research and Development, Kenya Medical Research Institute, P.O.Box 5840-00200, Nairobi, Kenya
*Author to whom correspondence should be addressed.
Abstract
Objective: To evaluate the antiplasmodial activity and safety of organic and aqueous flower extracts of Chrysanthemum cinerariaefolium from Kenya, singly and in combination with chloroquine, lumefantrine and piperaquine.
Methodology: Antiplasmodial activity of organic and aqueous flower extracts of C. cinerariaefolium was assessed in vitro by serial micro-dilution assay technique against Plasmodium falciparum, and in vivo using the 4-day suppressive test as well as the established infection test against P. berghei ANKA in mice. To determine the safety of the extracts, cytotoxicity evaluation of extracts against Vero E6 cells and acute toxicity studies in mice were also done.
Results: In vitro antiplasmodial assays showed that methanolic extract of C. cinerariaefolium flowers was active, petroleum ether extract was moderately active, while the aqueous extract was inactive. Methanolic extract combined with chloroquine (CQ) against CQ-sensitive (3D7) and CQ-resistant (W2) P. falciparum showed marked synergy. Both methanol and aqueous extracts (1000mg/kg) showed chemosuppression of >45% (P<0.05) in both 4-day suppression test and established infection test against P. berghei ANKA in mice. Lumefantrine (LU) or piperaquine (PQ) combined with either methanol or aqueous extracts showed chemosuppression of >63% (P<0.05) against LU-resistant and PQ-resistant P. berghei ANKA strains, indicating synergistic interactions. Methanolic and aqueous flower extracts of C. cinerariaefolium had no cytotoxic effect on Vero E6 cells and no overt signs of toxicity in mice.
Conclusion: The findings showed that C. cinerariaefolium flower extracts are safe in mammalian systems, have antiplasmodial activity and have potentiation effect of conventional antimalarials. There is need therefore to further explore the plant’s bioactive molecules which may serve as template for development of novel, effective and affordable antimalarial agents for management of malaria.
Keywords: Antiplasmodial, Chrysanthemum cinerariaefolium, combination therapy, drug efficacy, drug-drug interactions, drug toxicity