Resveratrol and its dimers ε-viniferin and δ-viniferin in red wine protect vascular endothelial cells by a similar mechanism with different potency and efficacy

Red wine compounds have been reported to reduce the rate of atherosclerosis by inducing nitric oxide (NO) production and antioxidant enzyme expression in vascular endothelial cells (VECs). The present study compared the effects of the three red wine compounds resveratrol and its dimers, epsilon-viniferin and delta-viniferin, on VECs function for the first time. Both 5 mu M epsilon-viniferin and delta-viniferin, but not 5 mu M resveratrol, significantly stimulated wound repair of VECs. Increased levels of wound repair induced by 10 and 20 mu M epsilon-viniferin were significantly higher than those stimulated by 10 and 20 mu M resveratrol, respectively. These stimulatory effects of the three compounds were suppressed by the NO synthase inhibitor L-NAME. When VECs were exposed to each compound, endothelial NO synthase was activated and the expression of sirtuin 1 (SIRT1) and HO-1 was induced. Addition of the SIRT1 and HO-1 inhibitors EX527 and ZnPPiX, respectively, suppressed wound repair stimulated by the three compounds, demonstrating that SIRT1 and HO-1 are involved in these wound repair processes. Furthermore, each compound induced the suppression of H2O2-dependent reduction of cell viability as well as the expression of the antioxidant enzyme catalase. These data suggest that not only resveratrol, but also its dimers, epsilon-viniferin and delta-viniferin, may be effective in preventing atherosclerosis by a similar molecular mechanism with different potency and efficacy.