In vitro and in vivo antileishmanial activity of the hanging sedge flavonoids based on bio- guided fractionation assay

As a major public health issue, cutaneous leishmaniasis (CL) has a number of complications, including drug resistance and poor response to conventional treatments. Over the last decade, research on natural sources for finding new antileishmanial agents has been a critical part of tropical disease research. Natural products also should be regarded as one of the most valuable applications for CL infection drug development. In this study, we assessed the in vitro and in vivo antileishmanial potential of Carex pendula Huds. (hanging sedge) methanolic extract and its fractions against Leishmania major produced cutaneous infection. Although the methanolic extract and its fractions exhibited suitable activity, the ethyl acetate fraction showed the best activity (with the half maximal inhibitory concentration IC50 = 1.627 +/- 0.211 mg/mL). The toxicity and selectivity indices (SI) of all samples were determined in murine peritoneal macrophage cells (J774A.1) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. The flavonoid components of the ethyl acetate fraction were identified using liquid chromatography electrospray ionization mass spectrometry (LC-ESI MS/MS). Nine chemical compounds were identified in this fraction, including three flavonols, four flavanonols, and two flavan derivatives. L. major-infected mice were used as an in vivo model because the methanolic extract was effective against L. major promastigotes in the mammalian cell line J774A.1 with SI = 2.514 (tail lesion size model). In silico analysis of identified compounds also revealed a favorable interaction between compounds 2-5 and L. major protein targets (3UIB, 4JZX, 4JZB, 5L4N, and 5L42). According to the findings of this study, the ethyl acetate fraction (as flavonoid fraction) exhibited considerable in vitro antileishmanial activity.