Resveratrol: One molecule, many targets

Abstract

SummaryResveratrol is one of the numerous polyphenolic compounds found in several vegetal sources. In recent years, the interest in this molecule has increased exponentially following the major findings that resveratrol (i) is shown to be chemopreventive in some cancer models, (ii) is cardioprotective, and (iii) has positive effects on several aspects of metabolism, leading to increased lifespan in all the metazoan models tested thus far, including small mammals. Such remarkable properties have elicited a vast interest towards the identification of target proteins of resveratrol and have led to the identification of enzymes inhibited by resveratrol and others whose activation is enhanced. In the vast majority of cases, resveratrol displays inhibitory/activatory effects in the micromolar range, which is potentially attainable pharmacologically, although targets with affinities in the nanomolar range have also been reported. Here, we provide an overview of the various classes of enzymes known to be inhibited (or activated) by resveratrol. It appears that resveratrol, as a pharmacological agent, has a wide spectrum of targets. The biological activities of resveratrol may thus be dependent on its simultaneous activity on multiple molecular targets.2008 IUBMB IUBMB Life, 60(5): [323][324][325][326][327][328][329][330][331][332] 2008

The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster

“…Resveratrol has been shown to increase lifespan and promote health span in model organisms ranging from yeast, worms, flies, and mice (Allard et al 2009;Pirola and Frojdo 2008). However, the prolongevity effect of resveratrol and its underlying mechanisms have been challenged by studies from several labs and remain controversial (Bass et al 2007b;Kaeberlein et al 2005).…”

“…Sirtuins are generally thought to mediate lifespan by DR, although this view along with the prolongevity effect of resveratrol has been challenged (Baur 2010). A number of follow-up studies have revealed that resveratrol modulates activities of many targets besides sirtuins, including AMP-activated protein kinase (AMPK) and PGC-1α, known to be regulated by DR in mammals (Pirola and Frojdo 2008). Through these targets, resveratrol exerts numerous beneficial effects in mammals ranging from increased insulin sensitivity, reduced plasma glucose and triglyceride levels, and attenuated oxidative damage.…”

“…For example, resveratrol, a phytoallexin that is a member of the stilbene family, has been shown to extend lifespan in yeast, worms, flies, and a shortlived fish (Howitz et al 2003;Wood et al 2004;Valenzano et al 2006). Resveratrol affects activities of a number of proteins involved in aging, such as sirtuins and PGC-1α, to exert beneficial effects on health and lifespan (Pirola and Frojdo 2008). Numerous studies have revealed health benefits of resveratrol supplementation, including delayed decline of age-related cognitive function, improved pancreatic β-cell function, and reduced cardiac hypertrophy in rodent models (Pearson et al 2008;Lee et al 2011;Chan et al 2008;Baur 2010).…”

Effect of different presentations of resveratrol on cell proliferation and epitelial thickness of the oral mucosa of wistar rats

“…Thus, the objective of this study was to analyze the effect of different presentations of resveratrol on cell proliferation and epithelial thickness of the oral mucosa of Wistar rats 11,12 .…”

Resolution of the direct interaction with and inhibition of the human GLUT1 hexose transporter by resveratrol from its effect on glucose accumulation

“…For instance, resveratrol prevents the proliferation of cancer cells, reduces the risk of cardiovascular diseases, and displays antidiabetic properties (2,3,5,7,8,16,33,45,49,53,59,70). The exact mechanism of action of resveratrol remains unclear, but in vivo and in vitro studies have suggested that this compound somehow affects glucose metabolism (7,10,33,41,58,66) perhaps by inhibiting GLUT1 activity.…”