Resveratrol inhibits human squalene monooxygenase

Epidemiological studies have suggested that moderate consumption of red wine may protect against the development of cardiovascular diseases. Resveratrol (trans-3,4 ' ,5-trihydroxystilbene) is a naturally occurring polyphenolic compound found in a variety of sources, including red wine, that has been shown to have a number of beneficial effects on cardiovascular health, including prevention of oxidative damage, promotion of vasodilation, and prevention of platelet aggregation. Herein we report that resveratrol specifically inhibits purified human squalene monooxygenase, a rate-limiting enzyme in cholesterol biosynthesis, in a noncompetitive manner with respect to both squalene (K-i = 35 muM) and FAD (K-i = 69 muM). These data raise the possibility that the protective effect of resveratrol on the development of cardiovascular disease may be explained in part by the inhibition of endogenous cholesterol biosynthesis. (C) 2001 Elsevier Science Inc. All rights reserved.