Therapeutic potential of resveratrol: the in vivo evidence

Abstract

Resveratrol, a small polyphenol, has been discovered and re-discovered as a potential therapeutic in recent years. Although putative cardioprotective effects were first noted in 1982, it was only after a 1992 report of high levels of resveratrol in red wine that these effects were investigated extensively. In 1997, resveratrol was isolated in a screen for cyclooxygenase inhibitors, and was shown to be an effective chemotherapeutic and chemopreventive agent. Moreover, in 2003, it was identified as the top hit in a screen for activators of sirtuin deacetylases and was shown to extend the lifespans of lower organisms. The number of reported effects for resveratrol is constantly growing. Many direct targets have been identified in vitro, and protective effects have been demonstrated in various rodent models of disease. Pharmacokinetic studies have consistently shown that levels of resveratrol in serum do not reach the concentrations required for most of the reported in vitro effects, or do so only transiently. In vivo evidence has therefore become increasingly important in efforts to understand how resveratrol elicits its effects in mammals. One possibility that has been suggested based on data from lower organisms is that resveratrol acts as a caloric restriction mimetic. This hypothesis is intriguing because caloric restriction seems to slow the intrinsic rate of ageing, and improve general health, rather than block specific disease processes. The many reported in vivo effects of resveratrol are reviewed here and, whenever possible, have been related to putative mechanisms and targets. Determining the mechanism(s) by which resveratrol and similar molecules act, and developing methods to improve bioavailability and/or specificity, has enormous potential to benefit human health.