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.
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.
Kim
Jin Hee
JH
Immune Modulator Research Laboratory, Korea Research Institute of Bioscience and Biotechnology, Yuseong, Daejeon, Republic of Korea.
Kim
Dong Hyun
DH
Baek
Seung Hwa
SH
Lee
Ho Jae
HJ
Kim
Mee Ree
MR
Kwon
Ho Jeong
HJ
Lee
Choong-Hwan
CH
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*
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