Protective effects of resveratrol in age-related neurodegenerative diseases and gene regulatory action

Polyphenols found in red wine are believed to have beneficial health effects stemming from their ability to act as antioxidants. Polyphenols are divided into two main classes: flavonoids and nonflavonoids. Flavonoids, which have been measured in several natural extracts and edible plants and fruits, are the most abundant polyphenols, whereas stilbenes are only a minor class. The natural stilbene resveratrol (trans-3,4,5-trihydroxystilbene) is a nonflavonoid that appears to be one of the most biologically active polyphenols. The reported antioxidant properties of red wine that are thought to be associated with resveratrol are likely due to a unique cascade of events leading to activation of an antioxidant pathway. This observation becomes especially relevant when comparing the molar ratio of free radicals to the very modest amount of resveratrol. In other words, it appears that antioxidant effective concentrations are unlikely to be reached in plasma in vivo. Therefore, resveratrol is likely to stimulate an intracellular pathway leading to cytoprotection. As discussed here, several genes and proteins have been proposed as targeted pathways. Heme oxygenase (HO) is a good candidate, as we have discovered that resveratrol can significantly induce HO in cells, and also since HO activity and its metabolites have been demonstrated to be neuroprotective in vivo and in vitro, to be antiapoptotic and antiinflammatory, and to have vasodilatory effects. Several other enzymatic systems have been described to be either directly or indirectly modulated by members of the stilbene family. We propose that HO is neuroprotective and is a prototypical candidate for providing brain resistance against pharmacologic or physiologic stress. Resveratrol’s effect on cerebral blood flow, cell death, and inflammatory processes can contribute therapeutic actions in either acute or chronic neurodegenerative conditions. These actions are especially important when there is a reduction in cerebral blood flow, a lack of oxygen, and/or free radical damage, affecting especially vulnerable classes of neurons, leading to neuroinflammation and cell death. Polyphenol stilbenes can precondition the neurons and brain against such damage. More support and research are required to test resveratrol’s potential in preventing a number of neurodegenerative conditions such as stroke, amyotrophic lateral sclerosis, Parkinson’s and Alzheimer’s diseases, and a variety of age-related vascular disorders.