Consistent with the finding obtained in laboratory animals, a meta-analysis showed that resveratrol improves diabetes ( 20) and enhances vascular functions in individuals with mildly elevated blood pressure ( 21). Subjects who consumed resveratrol (up to 5 g/d) showed decreased circulating levels of insulin-like growth factor-1 (IGF-1) 4 and IGF-binding protein 3 ( 19). In healthy subjects, a single dose of resveratrol (100 mg) combined with polyphenols from a muscadine grape extract (75 mg) was shown to suppress oxidative and inflammatory meal-induced stress response ( 18). However, most of the proposed therapeutic cell- and organ-affecting activities were not confirmed in clinical trials as of yet, and to our knowledge, there are very few data regarding the bioavailability of resveratrol in humans. In addition, resveratrol has been shown to mediate therapeutic hepatic effects in acquired and genetic models of iron overload ( 17). Rodent models suggested that this substance might improve consequences of an unhealthy lifestyle resulting from high caloric intake ( 16). Moreover, it was postulated that resveratrol modulates signaling pathways that limit the spread of cancer cells ( 10), protects nerve cells from damage ( 11– 13), helps to prevent diabetes ( 14), and acts as an antiaging agent that improves age-related problems ( 15). It was later assumed that moderate drinking of red wine over a long period of time can protect against coronary heart disease and might be the cause of this paradoxical finding ( 7). This may account in part for the so-called French paradox originally formulated in 1981 by French epidemiologists who observed a lower mortality incidence of coronary heart disease in France despite high levels of dietary saturated fat and cigarette smoking ( 9). The hope and hype concerning resveratrol was initiated by the finding that phenolic compounds such as the stilbenes exhibit radical scavenger and antioxidant properties ( 7, 8). Experimental and preclinical studies have attributed several health-promoting effects to this compound, including cardioprotective effects, chemopreventive activity in diverse cancers, and a capacity to extend the lifespan of lower organisms ( 5, 6). Subsequently, resveratrol was isolated from several other plants, fruits, and derivatives, such as grapes, wines, apples, raspberries, blueberries, pistachios, plums, peanuts, and a multitude of medicinal and edible plant species undergoing response to stress conditions ( 3, 4). Structurally, this compound is a stilbenoid that was first isolated in 1939 from the roots of the white hellebore ( Veratrum grandiflorum) ( 2) and presumably received its name from the fact that it is a derivative of the benzene-1,3-diol resorcinol and isolated from the Veratrum species. It exerts multiple biological activities, including anti-inflammatory, antiproliferative, and antioxidant effects ( 1). Resveratrol is a naturally occurring phytoalexin that is produced by several plants in response to injury. We conclude with some thoughts about future research directions that might be meaningful for resolving controversies surrounding resveratrol. We also cover recent pharmacologic efforts to improve the poor bioavailability of resveratrol and influence the transition between body systems in humans. In the present review, we discuss the proposed therapeutic attributes and the mode of molecular actions of resveratrol. However, the notion of resveratrol as a “magic bullet" was recently challenged by clinical trials showing that this polyphenol does not have a substantial influence on health status and mortality risk. These health-promoting effects are particularly attractive given the prevalence of resveratrol-based nutraceuticals and the paradoxical epidemiologic observation that wine consumption is inversely correlated to the incidence of coronary heart disease. This compound and its glucoside, the trans-polydatin piceid, have received worldwide attention for their beneficial effects on cardiovascular, inflammatory, neurodegenerative, metabolic, and age-related diseases. Resveratrol can be isolated and purified from these biological sources or synthesized in a few steps with an overall high yield. It is produced by certain plants including several dietary sources such as grapes, apples, raspberries, blueberries, plums, peanuts, and products derived therefrom (e.g., wine). Resveratrol is a naturally occurring stilbene endowed with multiple health-promoting effects.
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