<i>Platonia insignis</i> Mart., a Brazilian Amazonian Plant: The Stem Barks Extract and Its Main Constituent Lupeol Exert Antileishmanial Effects Involving Macrophages Activation

Abstract

<i>Platonia insignis</i> Mart., popularly known as "bacurizeiro," is used in traditional medical practices based on its diverse biological properties. This study was aimed at evaluating the antileishmanial effects of the ethanol extract (EtOH-Ext), hexane fraction (Hex-F), and its main isolated Lupeol obtained from stem barks of <i>P. insignis</i> against <i>Leishmania (Leishmania) amazonensis</i>, as well as their cytotoxicity and possible mechanisms of action. The EtOH-Ext, Hex-F, and Lupeol inhibited the growth of <i>L. amazonensis</i> promastigote forms at IC₅₀ of 174.24, 45.23, and 39.06 <i>µ</i>g/mL, respectively, as well as <i>L. amazonensis</i> axenic amastigote forms at IC₅₀ of 40.58, 35.87, and 44.10 <i>µ</i>g/mL, respectively. The mean cytotoxic concentrations for macrophages (CC₅₀) were higher than those for amastigotes (341.95, 71.65, and 144.0 <i>µ</i>g/mL, resp.), indicating a selective cytotoxicity towards the parasite rather than the macrophages. Interestingly, all treatments promoted antileishmanial effect against macrophage-internalized amastigotes at concentrations lower than CC₅₀. Furthermore, increases of lysosomal volume of macrophages treated with EtOH-Ext, Hex-F, and Lupeol were observed. On the other hand, only Lupeol stimulated increase of phagocytic capability of macrophages, suggesting this compound might be characterized as the biomarker for the antileishmanial effect of <i>P. insignis</i> stem bark, as well as the involvement of immunomodulatory mechanisms in this effect.