ABSTRACT
This chapter reviews prostaglandin biosynthesis, cyclooxygenase (COX) enzymology and pharmacology, and then describe the mechanism of action of resveratrol. The observation that resveratrol and other polyphenolic compounds inhibited platelet aggregation and eicosanoid biosynthesis in vitro implicated inhibition of COX as a potential mechanism of action. Resveratrol was rapidly oxidized by COX-1 during peroxidase cycle as evident by disappearance of the absorbance spectrum of drug in the presence of a peroxide cosubstrate. The Structure –Activity Relationships data with resveratrol analogs aided in identifying additional m-hydroquinones in red wine that were selective mechanism-based inactivators of COX-1. Resveratrol functions as both a mechanism-based inactivator and a coreductant of the COX-1 peroxidase. The cancer chemopreventive and antiinflammatory properties of resveratrol point to a mechanism whereby resveratrol regulates COX-2 expression. The pharmacokinetics of resveratrol and its inhibitory properties of COX-1 satisfy the criteria of antiplatelet agents that target this isoform.
