Resveratrol inhibits human squalene monooxygenase

Epidemiological studies have suggested that moderate consumption of red win e may protect against the development of cardiovascular diseases. Resveratr ol (trans-3,4 ' ,5-trihydroxystilbene) is a naturally occurring polyphenoli c compound found in a variety of sources, including red wine, that has been shown to have a number of beneficial effects on cardiovascular health, inc luding prevention of oxidative damage, promotion of vasodilation, and preve ntion of platelet aggregation. Herein we report that resveratrol specifical ly inhibits purified human squalene monooxygenase, a rate-limiting enzyme i n 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 possi bility that the protective effect of resveratrol on the development of card iovascular disease may be explained in part by the inhibition of endogenous cholesterol biosynthesis. (C) 2001 Elsevier Science Inc. All rights reserv ed.