Resveratrol Is Active against Leishmania amazonensis:In VitroEffect of Its Association with Amphotericin B

Abstract

ABSTRACTResveratrol is a polyphenol found in black grapes and red wine and has many biological activities. In this study, we evaluated the effect of resveratrol alone and in association with amphotericin B (AMB) againstLeishmania amazonensis. Our results demonstrate that resveratrol possesses both antipromastigote and antiamastigote effects, with 50% inhibitory concentrations (IC50s) of 27 and 42 μM, respectively. The association of resveratrol with AMB showed synergy forL. amazonensisamastigotes, as demonstrated by the mean sums of fractional inhibitory index concentration (mean ΣFIC) of 0.483, although for promastigotes, this association was indifferent. Treatment with resveratrol increased the percentage of promastigotes in the sub-G0/G1phase of the cell cycle, reduced the mitochondrial potential, and showed an elevated choline peak and CH2-to-CH3ratio in the nuclear magnetic resonance (NMR) spectroscopy analysis; all these features indicate parasite death. Resveratrol also decreased the activity of the enzyme arginase in uninfected and infected macrophages with and without stimulation with interleukin-4 (IL-4), also implicating arginase inhibition in parasite death. The anti-Leishmaniaeffect of resveratrol and its potential synergistic association with AMB indicate that these compounds should be subjected to further studies of drug association therapyin vivo.