A new insight into resveratrol as an atheroprotective compound: Inhibition of lipid peroxidation and enhancement of cholesterol efflux

Resveratrol, a polyphenolic constituent of red wine, is known for its anti-atherogenic properties and is thought to be beneficial in reducing the incidence of cardiovascular diseases (CVD). However, the mechanism of action by which it exerts its anti-atherogenic effect remains unclear. In this study, we investigated the relationship between the antioxidant effects of resveratrol and its ability to promote cholesterol efflux. We measured the formation of conjugated dienes and the rate of lipid peroxidation, and observed that resveratrol inhibited copper- and irradiation-induced LDL and HDL oxidation as observed by a reduction in oxidation rate and an increase in the lag phase (p < 0.05). We used DPPH screening to measure free radical scavenging activity and observed that resveratrol (0-50 mu M) significantly reduced the content of free radicals (p < 0.001). Respect to its effect on cholesterol homeostasis, resveratrol also enhanced apoA-1-mediated cholesterol efflux (r(2) = 0.907, p < 0.05, linear regression) by up-regulating ABCA-1 receptors, and reduced cholesterol influx or uptake in J774 macrophages (r(2) = 0.89, p < 0.05, linear regression). Incubation of macrophages (J774, THP-1 and MPM) with Fe/ascorbate ion, attenuated apoA-1 and HDL3-mediated cholesterol efflux whereas resveratrol (0-25 mu M) significantly redressed this attenuation in a dose-dependent manner (p < 0.001). Resveratrol thus appears to be a natural antioxidant that enhances cholesterol efflux. These properties make it a potential natural antioxidant that could be used to prevent and treat CVD. (C) 2009 Elsevier Ireland Ltd. All rights reserved.