Acetylbritannilatone suppresses NO and PGE2 synthesis in RAW 264.7 macrophages through the inhibition of iNOS and COX-2 gene expression

Life Sci. 2004 Jun 25;75(6):675-84. doi: 10.1016/j.lfs.2003.12.022.

Abstract

In order to elucidate the mechanism of anti-inflammatory effect of 1-o-acetylbritannilatone (ABL) isolated from Inula Britannica-F, we investigated ABL for its ability to inhibit the inflammatory factor production in RAW 264.7 macrophages. The studies showed that ABL not only inhibited LPS/IFN-gamma-mediated nitric oxide (NO) production and inducible nitric synthase (iNOS) expression, but also decreased LPS/IFN-gamma-induced prostaglandin E2 (PGE2) production and cyclo-oxygenase-2 (COX-2) expression in a concentration-dependent manner. EMSA demonstrated that ABL inhibited effectively the association of NF-kappaB, which is necessary for the expression of iNOS and COX-2, with its binding motif in the promoter of target genes. These data suggest that ABL suppress NO and PGE2 synthesis in RAW 264.7 macrophages through the inhibition of iNOS and COX-2 gene expression, respectively. The anti-inflammatory effect of ABL involves blocking the binding of NF-kappaB to the promoter in the target genes and inhibiting the expression of iNOS and COX-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cyclooxygenase 2
  • Dinoprostone / biosynthesis*
  • Dose-Response Relationship, Drug
  • Drug Combinations
  • Gene Expression Regulation, Enzymologic / drug effects*
  • Interferon-gamma / pharmacology
  • Isoenzymes / biosynthesis
  • Isoenzymes / genetics*
  • Lactones / pharmacology*
  • Lipopolysaccharides / pharmacology
  • Macrophages / drug effects*
  • Macrophages / enzymology
  • Mice
  • NF-kappa B / metabolism
  • Nitric Oxide / biosynthesis*
  • Nitric Oxide Synthase / biosynthesis
  • Nitric Oxide Synthase / genetics*
  • Nitric Oxide Synthase Type II
  • Prostaglandin-Endoperoxide Synthases / biosynthesis
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • Anti-Inflammatory Agents
  • Drug Combinations
  • Isoenzymes
  • Lactones
  • Lipopolysaccharides
  • NF-kappa B
  • RNA, Messenger
  • acetylbritannilatone
  • Nitric Oxide
  • Interferon-gamma
  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Dinoprostone