Hormetic response of resveratrol against cardioprotection

Resveratrol, a grape- and red wine-derived polyphenolic phytoalexin, shows diverse health benefits including cardioprotection. Recent studies implicate that resveratrol displays hormetic action, protecting the cells at a lower dose while killing them at relatively higher doses. Because such hormetic behaviour may have a significant impact on epidemiological and clinical studies, the present study sought to determine dose-response curves for resveratrol action. In parallel, another resveratrol formulation was tested, namely, Longevinex (Resveratrol Partners LLC, USA). A group of rats were force-fed three different doses of resveratrol or Longevinex (2.5 mg/kg, 25 mg/kg and 100 mg/kg) for up to 30 days, while the control group was only given placebo. The results showed hormesis for pure resveratrol, which was cardioprotective at lower doses and detrimental for higher doses, but surprisingly Longevinex did not display any hormetic action. In the concentration range studied, Longevinex remained cardioprotective even at 100 mg/100 g body weight - a dose that killed 100% of the hearts when tested with pure resveratrol. To further test whether Longevinex doses are beneficial for other animal species, Longevinex was gavaged to a group of rabbits for six months, and showed exactly the same degree of cardioprotection. Cardioprotection was examined in isolated working hearts subjected to 30 min of ischemia followed by 2 h of reperfusion; left ventricular performance and infarct size was also examined. It appears that Longevinex does not show any hormetic action, while resveratrol clearly does.