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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.
AuthorsJin Hee Kim, Dong Hyun Kim, Seung Hwa Baek, Ho Jae Lee, Mee Ree Kim, Ho Jeong Kwon, Choong-Hwan Lee
JournalBiochemical pharmacology (Biochem Pharmacol) Vol. 71 Issue 8 Pg. 1198-205 (Apr 14 2006) ISSN: 0006-2952 [Print] England
PMID16457781 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-Inflammatory Agents, Non-Steroidal
  • Furans
  • Heterocyclic Compounds, 2-Ring
  • Lipopolysaccharides
  • NF-kappa B
  • Rengyolone
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • p38 Mitogen-Activated Protein Kinases
Topics
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal (isolation & purification, pharmacology)
  • Cell Line
  • Cell Survival (drug effects)
  • Down-Regulation
  • Forsythia (chemistry)
  • Fruit (chemistry)
  • Furans (isolation & purification, pharmacology)
  • Heterocyclic Compounds, 2-Ring (isolation & purification, pharmacology)
  • Lipopolysaccharides (pharmacology)
  • Macrophages (drug effects, enzymology, metabolism)
  • Mice
  • NF-kappa B (metabolism)
  • Nitric Oxide (biosynthesis)
  • Nitric Oxide Synthase Type II (antagonists & inhibitors, biosynthesis)
  • Phosphorylation
  • Reverse Transcriptase Polymerase Chain Reaction
  • p38 Mitogen-Activated Protein Kinases (metabolism)

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