Resveratrol Article by Robert Ritch, MD

Resveratrol Article by Robert Ritch, MD

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Resveratrol (3,5,40-trihydroxystilbene), a powerful polyphenolic antioxidant, is found largely in the skins of red grapes and berries and came to scientific attention as a possible explanation for the low incidence of heart disease among the French, who eat a relatively high-fat diet (the French paradox). Many studies suggest that consuming alcohol (especially red wine) may reduce the incidence of coronary heart disease (CHD). Grape juice, which is not a fermented beverage, is not a significant source of resveratrol. A large number of studies in the past few years suggests its benefit in vitro and in vivo in a variety of human disease models, including cardioprotection, neuroprotection, immune regulation, and cancer chemoprevention. For an extensive review, see (Pervaiz & Holme 2009). Substantial data show that actions of resveratrol include inhibition of lipid peroxidation and platelet aggregation, metal chelating (primarily copper), free radical–scavenging activity, antiinflammatory activity, modulation of lipid metabolism, antifungal properties, and anticancer and estrogen-like activity.(Pervaiz & Holme 2009)

Resveratrol increases the lifespan of the yeast, Saccharomyces cerevisiae, the nematode, Caenorhabditis elegans, and the fruitfly, Drosophila melanogaster. It was later shown to extend the lifespan of the short-lived fish, Nothobranchius furzeri,(Valenzano & Cellerino 2006) and has now been shown to significantly increase the health and survival of mice on a high-calorie diet, pointing to a new approach to treating diseases of aging.(Baur et al. 2006) Among its multiple functions, resveratrol activates sirtuins (silent information regulator proteins), a family of proteins that play an important role in DNA repair, gene silencing, chromosomal stability and longevity.(Michan & Sinclair 2007)

The physiologic effects of resveratrol appear to be related to its ability to regulate nutrition and longevity genes.(Pervaiz & Holme 2009) Resveratrol is an effective antioxidant.(Frankel et al. 1993; Chanvitayapongs et al. 1997; Shigematsu et al. 2003) It inhibits lipid peroxidation of low-density lipoprotein (LDL), prevents the cytotoxicity of oxidized LDL, and protects cells against lipid peroxidation.(Chanvitayapongs et al. 1997) Resveratrol protects against the degeneration of neurons after axotomy.(Araki et al. 2004) A single infusion of resveratrol can elicit neuroprotective effects on cerebral ischemia-induced neuron damage through free radical scavenging and cerebral blood elevation due to nitric oxide release.(Lu et al. 2006) Its antiapoptotic activity has led to the suggestion that resveratrol may make a useful dietary supplement for minimizing oxidative injury in immune-perturbed states and human chronic degenerative diseases.(Losa 2003)

Levels of intracellular heme (iron-protoporphyrin IX), a pro-oxidant, increase after stroke. In neuronal cell cultures, resveratrol induces heme oxygenase 1, suggesting that increased heme oxygenase activity is a unique pathway by which resveratrol can exert its neuroprotective actions.(Zhuang et al. 2003)

Resveratrol directly inhibits CYP1B1. The versatility of RSV lies in its diverse targeting of membrane and intracellular receptors, signaling molecules, biogenesis enzymes, oxidative systems, DNA-repair mechanisms, and transcription factors, and it can activate or repress a number of signal-transducing pathways found throughout the cell (Pervaiz & Holme 2009)

There appears to be an association between aging and neurodegenerative diseases, such as Alzheimer’s, and that modulation by both caloric restriction and drugs which mimic caloric restriction, such as resveratrol, can ameliorate these diseases.(Liu et al. 2007) Resveratrol reduces the levels of secreted and intracellular amyloid-ß peptides by proteosomal degradation.(Marambaud et al. 2005)

In the eye, resveratrol suppresses selenite-induced oxidative stress and cataract formation in rats.(Doganay et al. 2006) The authors suggested that the presence of oxidative stress in selenite cataract development and its prevention by resveratrol support the possibility that high natural consumption of resveratrol in food can help prevent human senile cataract. Resveratrol also induces dilation of retinal arterioles, suggesting a potential benefit for this compound in the treatment of retinal vascular disease.(Nagaoka et al. 2007) Sirtuin-1 activators (such as resveratrol) demonstrate neuroprotective properties in mouse models of optic neuritis and multiple sclerosis.(Shindler et al. 2007)

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