Kaempferol Addition Increases the Antimalarial Activity of Artesunate in Experimental Mice

Kaempferol (KMF) is a member of flavonol widely found in tea, broccoli, apples, strawberries, and beans. It has been demonstrated to present several pharmacological properties with potent antimalarial activity against Plasmodium berghei-infected mice. Hence, the search for a safe and new antimalarial compound with combinations to delay the development of resistance was the aim of this study. Thus, the therapeutic effect of the combination of KMF and artesunate (ART) in P. berghei-infected mice was evaluated. Combination of KMF and ART in P. berghei ANKA- (PbANKA-) infected ICR mice in a fixed-ratio combination (1 : 1) and fractions of their median effective dose (ED(50)) was also investigated using the standard 4-day suppressive test. The ED(50) levels of KMF and ART in mice infected with PbANKA were 20.06 ± 2.65 and 6.06 ± 1.33 mg/kg, respectively. Moreover, KMF showed promising synergistic combination with ART at the doses of their ED(50) and fixed-ratio combination (1 : 1) of their ED(50) of 1/2 with combination index (CI) values of 0.86 and 0.47, respectively. Additionally, KMF, ART, and its combination at the doses of their ED(50) and fixed-ratio combination (1 : 1) of their ED(50) of 1/2 also presented significantly (P < 0.001) prolonged mean survival time (MST). The findings of this study showed that a combination of KMF and ART enhanced the antimalarial activity of ART and prolonged MST. This study supports the basis for the selection of KMF as a prospective compound for further consideration as a partner drug for ART.