Carabrol suppresses LPS-induced nitric oxide synthase expression by inactivation of p38 and JNK via inhibition of I-kappaBalpha degradation in RAW 264.7 cells

Biochem Biophys Res Commun. 2010 Jan 15;391(3):1400-4. doi: 10.1016/j.bbrc.2009.12.073. Epub 2009 Dec 22.

Abstract

Carabrol, isolated from Carpesium macrocephalum, showed anti-inflammatory potential in LPS-induced RAW 264.7 murine macrophages. In present study, carabrol demonstrated the inhibitory activity on pro-inflammatory cytokines such as IL-1beta, IL-6 and TNF-alpha. In addition, mRNA and protein levels of iNOS and COX-2 were reduced by carabrol. Molecular analysis revealed that these suppressive effects were correlated with the inactivation of p38 and JNK via inhibition of NF-kappaB activation. Immunoblotting showed that carabrol suppressed LPS-induced degradation of I-kappaBalpha and decreased nuclear translocation of p65. Taken together, these results suggest that carabrol can be a modulator of pro-inflammatory signal transduction pathway in RAW 264.7 cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Active Transport, Cell Nucleus / drug effects
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Asteraceae / chemistry*
  • Cell Line
  • Cyclooxygenase 2 / biosynthesis
  • Cyclooxygenase 2 / drug effects*
  • I-kappa B Kinase / metabolism
  • Interleukin-1beta / antagonists & inhibitors
  • Interleukin-6 / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Lipopolysaccharides / pharmacology
  • Mice
  • NF-kappa B / antagonists & inhibitors
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / antagonists & inhibitors*
  • Nitric Oxide Synthase Type II / biosynthesis
  • Phosphorylation / drug effects
  • Sesquiterpenes / chemistry*
  • Sesquiterpenes / pharmacology
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Interleukin-1beta
  • Interleukin-6
  • Lipopolysaccharides
  • NF-kappa B
  • Sesquiterpenes
  • Tumor Necrosis Factor-alpha
  • carabrol
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • I-kappa B Kinase
  • JNK Mitogen-Activated Protein Kinases
  • p38 Mitogen-Activated Protein Kinases