title: Rengyolone inhibits inducible nitric oxide synthase expression and nitric oxide production by down-regulation of NF-kappaB and p38 MAP kinase activity in LPS-stimulated RAW 264.7 cells.
abstract: Nitric oxide (NO) is recognized as a mediator and regulator of inflammatory responses. Rengyolone, a cyclohexylethanoid isolated from the fruits of Forsythia koreana, exhibits anti-inflammatory 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-kappaB (NF-kappaB) activation. The LPS-induced DNA binding activity of NF-kappaB was significantly inhibited by rengyolone, and this effect was mediated through inhibition of the degradation of inhibitory factor-kappaBalpha and phosphorylation of p38 MAP kinase. Furthermore, rengyolone suppressed the expression of ICE protein in IL-1beta-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-kappaB and p38 MAPK activation in LPS-stimulated RAW 264.7 cells.
authors.affiliation: Immune Modulator Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon, Republic of Korea.
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Dong Hyun
authors.initials: DH
authors.lastname: Kim
authors.forename: Seung Hwa
authors.initials: SH
authors.lastname: Baek
authors.forename: Ho Jae
authors.initials: HJ
authors.lastname: Lee
authors.forename: Mee Ree
authors.initials: MR
authors.lastname: Kim
authors.forename: Ho Jeong
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Choong-Hwan
authors.initials: CH
authors.lastname: Lee
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000302:isolation & purification / Q000494:pharmacology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D015536:Down-Regulation; D031657:Forsythia / Q000737:chemistry; D005638:Fruit / Q000737:chemistry; D005663:Furans / Q000302:isolation & purification / Q000494:pharmacology*; D006574:Heterocyclic Compounds, 2-Ring / Q000302:isolation & purification / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D010766:Phosphorylation; D020133:Reverse Transcriptase Polymerase Chain Reaction; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; D008070:Lipopolysaccharides; D016328:NF-kappa B; C509673:Rengyolone; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D048051:p38 Mitogen-Activated Protein Kinases