Red wine acts through a familiar drug target

Excerpt

Resveratrol, a natural polyphenol first identified and named by a Japanese chemist in 1940 [1], is present in many plant products, including grape skin. It has been the focus of much attention recently because it provides a variety of potential health benefits, in particular protection from various age-related conditions (such as diabetes mellitus, vascular diseases, cognitive disorders, and cancer), and increases life span [2‐4]. Given that red wine is rich in resveratrol, and that moderate wine consumption has been shown to lower cardiovascular risk [5], the intake of resveratrol through the drinking of red wine may contribute to the “French paradox”—which refers to the fact that the mortality due to cardiovascular diseases is lower in France than in other European countries despite similar lifestyle-related risk factors [6]. Sirt1, an NAD⁺-dependent protein deacetylase, is thought to play an important role in the action of resveratrol [2]. Resveratrol stimulates the activity of Sirt1, and overexpression of Sirt1 protects mice from age-related diseases [2]. Moreover, orthologs of Sirt1 appear to contribute to life span extension by resveratrol in worms and flies [2]. Whereas an early study suggested that resveratrol directly stimulates the activity of Sirt1 [7], this notion has been challenged by more recent studies [8, 9]. Resveratrol was found to stimulate the activity of AMP-activated protein kinase (AMPK) [10], which can increase cellular NAD⁺ levels and thereby stimulate the activity of Sirt1 [11], but the effect of resveratrol on AMPK is also likely not direct. The direct target of resveratrol for its health-promoting effects has thus remained a mystery. Park et al. [12] have now revealed that a group of enzymes that serve as common drug targets are also targeted by resveratrol. …