Antileishmanial Effect of 5,3′-Hydroxy-7,4′-dimethoxyflavanone ofPicramnia gracilisTul. (Picramniaceae) Fruit:In VitroandIn VivoStudies

Abstract

Species ofPicramniagenus are used in folk medicine to treat or prevent skin disorders, but only few species have been studied for biological activity and chemical composition.P. gracilisTul. is a native species from Central and South America and although its fruits are edible, phytochemical analysis or medicinal uses of this species are not known. In the search of candidates to antileishmanial drugs, this work aimed to evaluate the antileishmanial activity ofP. gracilisTul. inin vitroandin vivostudies. Only ethanolic extract of fruits showed leishmanicidal activity. The majoritarian metabolite was5,3′-hydroxy-7,4′-dimethoxyflavanoneether that exhibited high activity againstL. (V.) panamensis(EC5017.0 + 2.8 mg/mL, 53.7 μM) and low toxicity on mammalian U-937 cells, with an index of selectivity >11.8.In vivostudies showed that the flavanone administered in solution (2 mg/kg/day) or cream (2%) induces clinical improvement and no toxicity in hamsters with CL. In conclusion, this is the first report about isolation of5,3′-hydroxy-7,4′-dimethoxyflavanoneofP. gracilisTul. The leishmanicidal activity attributed to this flavanone is also reported for the first time. Finally, thein vitroandin vivoleishmanicidal activity reported here for5,3′-hydroxy-7,4′-dimethoxyflavanoneoffers a greater prospect towards antileishmanial drug discovery and development.