Inhibition of inducible nitric oxide synthase and cyclooxygenase-2 expression by flavonoids in macrophage J774A.1

The present study focuses on the effect of various naturally occurring flav onoids (apigenin, galangin, morin, naringenin, quercetin, and silymarin) on nitric oxide (NO) and prostaglandin E-2 (PGE(2)) production induced by lip opolysaccharide (LPS) in the macrophage cell line J774A.1. Moreover, we eva luated flavonoid modulation of inducible nitric oxide synthase (iNOS) and c yclooxygenase-2 (COX-2) enzyme expression by western blot analysis. Apigeni n and quercetin (0.5-50 muM) were the most potent inhibitors of NO producti on and this effect was concentration-dependent and significant at 5 and 50 muM. These data were consistent with the modulation of iNOS enzyme expressi on. A similar pattern was observed considering the inhibitory effect of fla vonoids on LPS-induced PGE, release and COX-2 expression. Quercetin, galang in, apigenin, and naringenin markedly decreased PGE, release and COX-2 expr ession in a concentration-dependent manner. This study suggests that inhibi tion of iNOS and COX-2 expression by flavonoids may be one of the mechanism s responsible for their anti inflammatory effects. (C) 2001 Elsevier Scienc e Inc. All rights reserved.