Resveratrol (3,5,4â€™-trihydroxystilbene) was first isolated from the roots of white hellebore (Veratrum grandiflorum O. Loes) and later from the roots of Polygonum cuspidatum.(1) This plant has long been used in Chinese and Japanese medicine where it is valued for diverse therapeutic effects. Resveratrol is a natural polyphenolic antioxidant of the stilbene family that is found in more than 70 plant species. Some of the more common botanical sources include berries, peanuts and grapes. Resveratrol is a major constituent of red wine as it is present in the skin of red grapes and concentrates as wine ferments. In nature, resveratrol is a phytoalexin, which functions to protect plants from stress, ultraviolet light and certain fungal infections.
Medical interest in this compound sparked when it was postulated that resveratrol may be responsible for the low incidence of heart disease seen in the French population whose diet is high in saturated fat.2 This phenomenon, coined by Dr. Serge Renaud and Dr. Michel de Lorgerial as the French Paradox, was attributed to a moderate intake of red wine. Since that time, resveratrol has been the subject of vigorous ongoing research to confirm its health and anti-aging benefits. Studies have shown that resveratrol binds to numerous cell-signaling molecules allowing it to modulate beneficial health effects through multiple pathways.4 Resveratrol has anti-diabetic, anti-inflammatory and anti-cancer activity.3-5 It also acts as a vasodilator, platelet inhibitor and has important cardioprotective effects.6 Recent studies have suggested that resveratrol may also be effective when applied topically to treat aged skin. In this review we will therefore describe some of the important targets of resveratrol, their clinical implications for treating aging skin and the challenges that have prevented resveratrol from being effectively incorporated into a topical formulation.
Resveratrol as an Antioxidant
Resveratrol is probably most recognized for its potent antioxidant activity. One of the more distinct features of this polyphenol is that it exhibits dual antioxidant capacity. In addition to directly scavenging free radicals resveratrol increases the intracellular expression of other naturally occurring enzymatic antioxidants. Specifically, resveratrol up-regulates expression of nuclear factor-E2-related factor-2 (Nrf2), a transcription factor, which regulates several genes responsible for detoxification of reactive oxygen species.7 For example, Nrf2 is known to increase the production of glutathione synthetase (GSH), the enzyme that is the rate limiting step in the synthesis of the antioxidant glutathione. Additionally, resveratrol has been shown to boost naturally occurring enzymatic antioxidants including superoxide dismutase, catalase and hemoxygenase-1 thus increasing intracellular antioxidant capacity.8 The direct free radical scavenging properties of pure resveratrol are well established and appear to be greatly dependent on the structural position of the hydroxyl group.9 Studies have determined resveratrol to be an effective scaven-