Kaempferol Addition Increases the Antimalarial Activity of Artesunate in Experimental Mice

Sakaewan Ounjaijean; Nattida Benjasak; Suchanan Sae-Lao; Voravuth Somsak

doi:10.1155/2020/6165928

Kaempferol Addition Increases the Antimalarial Activity of Artesunate in Experimental Mice

J Trop Med. 2020 Jun 29:2020:6165928. doi: 10.1155/2020/6165928. eCollection 2020.

Authors

Sakaewan Ounjaijean¹, Nattida Benjasak², Suchanan Sae-Lao², Voravuth Somsak²

Affiliations

¹ Research Institute for Health Sciences, Chiang Mai University, Chiang Mai 50200, Thailand.
² School of Allied Health Sciences, Walailak University, Nakhon Si Thammarat 80161, Thailand.

Abstract

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 (ED₅₀) was also investigated using the standard 4-day suppressive test. The ED₅₀ 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 ED₅₀ and fixed-ratio combination (1 : 1) of their ED₅₀ 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 ED₅₀ and fixed-ratio combination (1 : 1) of their ED₅₀ 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.