Rengyolone inhibits inducible nitric oxide synthase expression and nitric oxide production by down-regulation of NF-κB and p38 MAP kinase activity in LPS-stimulated RAW 264.7 cells

Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. Rengyolone, a cyclohexylethanoid isolated from the fruits of Forsythia koreana, exhibits antiinflammatory activity with unknown mechanism. in this study, we found that rengyolone has a strong inhibitory effect on the production of nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha). Rengyolone also inhibited inducible nitric oxide synthase (iNOS) gene expression and cyclooxygenase 2 (COX-2) by lipopolysaccharide (LPS). In order to explore the mechanism responsible for the inhibition of iNOS gene expression by rengyolone, we investigated its effect on LPS-induced nuclear factor-kappa B (NF-kappa B) activation. The LPS-induced DNA binding activity of NF-kappa B was significantly inhibited by rengyolone, and this effect was mediated through inhibition of the degradation of inhibitory factor-kappa B alpha and phosphorylation of p38 MAP kinase. Furthermore, rengyolone suppressed the expression of ICE protein in IL-1 beta-treated D10S cells. Taken together, these results suggest that rengyolone attenuates the inflammation through inhibition of NO production and iNOS expression by blockade of NF-kappa B and p38 MAPK activation in LPS-stimulated RAW 264.7 cells. (c) 2006 Elsevier Inc. All rights reserved.