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

Abstract

Resveratrol 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) against Leishmania amazonensis. Our results demonstrate that resveratrol possesses both antipromastigote and antiamastigote effects, with 50% inhibitory concentrations (IC 50 s) of 27 and 42 M, respectively. The association of resveratrol with AMB showed synergy for L. amazonensis amastigotes, as demonstrated by the mean sums of fractional inhibitory index concentration (mean ⌺FIC) of 0.483, although for promastigotes, this association was indifferent. Treatment with resveratrol increased the percentage of promastigotes in the sub-G 0 /G 1 phase of the cell cycle, reduced the mitochondrial potential, and showed an elevated choline peak and CH 2 -to-CH 3 ratio 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-Leishmania effect of resveratrol and its potential synergistic association with AMB indicate that these compounds should be subjected to further studies of drug association therapy in vivo.

Recent updates and perspectives on leishmaniasis

“…Resveratrol, a polyphenol found in black grapes and red wine that has many biological activities, in association with amphotericin B, showed synergy against L. amazonensis in vitro [35].…”

Chemical constituents from the rhizome of Polygonum paleaceum and their antifungal activity

“…Quercetin (3), vincetoxicoside B (6), kaempferol (8), and (-)-epicatechin (9) showed synergistic antifungal activities with the FICI (fractional inhibitory concentration index) [16,17] values <0.5. A preliminary structure-activity relationship could be observed that free 3-OH was important for synergistic antifungal activity in flavonoids, because in the structure of compounds 4, 5, and 7, which showed no synergistic antifungal activity, 3-OH group was not free and linked by methyl or glycosyl.…”

Antileishmanial Thioureas: Synthesis, Biological Activity and <i>in Silico</i> Evaluations of New Promising Derivatives

“…39) It has been shown that different compounds affect the leishmanial cell cycle, some with characteristics suggesting the induction of incidental death, an apoptosis-like mechanism. 22,30,40) Therefore, we analyzed the effect of derivatives on parasite cell cycle.…”

“…Derivatives 3k and 3p decreased 1.13-and 1.24-fold, respectively, cells in G2/M phase (Table 3). In a previous work published by our group 30) amphotericin B (0.1 µM) did not affect the cell cycle of the parasite.…”