Resveratrol, a naturally occurring stilbene with antileishmanial activity

Research over the past several decades has revealed that resveratrol exerts pleiotropic health beneficial effects including potent antioxidant, anti-inflammatory, anti-aging, cardioprotective and neuroprotective activities. As a phytoalexin, resveratrol possesses considerable capacity to control fungal, bacterial and viral infections in plants, and possibly in infectious conditions in humans. Our interest in natural products with anti-infective potentials and a recent report on the antileishmanial activity of resveratrol prompted the present study. Using transgenic Leishmania major expressing green fluorescent protein (GFP) and FACS analysis, resveratrol revealed pronounced direct toxicity for extracellular promastigotes, with a maximal killing rate of ca. 97% at a sample concentration of 45µg/mL. When L. major GFP-infected BMM? were exposed to the test compound (5–75µg/mL), the resulting GFP signal was similarly reduced in a concentration-dependent manner (from 95% to 5%). However, cell cytotoxicity invariably increased with concentrations? 25µg/mL as evident from the number of propidium iodide positive events. The MTT-assay provided an IC50 of 83µM (20µg/mL) for non-infected BMM? This finding contrasts with the reported absence of toxic effects up to 45µg/mL in a microscopic study. The Diff-Quick stain verified changes in the morphology of infected cells. Although resveratrol is generally considered to be well tolerated [1], the method of assessment appears to be a critical issue as well as the kind of cells used in experiments [2, 3]. In conclusion, resveratrol showed potent antileishmanial activity in the range of 15–20µg/mL, while higher concentrations produced adverse effects on the host cells.

References: 1. Cottart, CH. et al. (2010) Mol. Nutr. Food Res. 54, 7–16.

2. Kedzierski, L. et al. (2007) Parasitol Res. 102: 91–97.

3. Kedzierski, L. et al. (2004) The Journal of Immunology 172: 4902–4906.