INTRODUCTION
Resveratrol (3,5,4’-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-
