Curcumol exhibits anti-inflammatory properties by interfering with the JNK-mediated AP-1 pathway in lipopolysaccharide-activated RAW264.7 cells

Eur J Pharmacol. 2014 Jan 15:723:339-45. doi: 10.1016/j.ejphar.2013.11.007. Epub 2013 Nov 20.

Abstract

Curcumol is one of the major components of the essential oil of Rhizoma Curcumae, a common traditional Chinese medicine with anti-inflammatory properties. However, the anti-inflammatory activity and the underlying molecular mechanisms of this compound remain unclear. In the present study, the anti-inflammation effect of curcumol on lipopolysaccharide (LPS)-induced RAW264.7 cells is demonstrated along with its underlying mechanisms. We show that curcumol inhibits LPS-induced NO production by suppressing iNOS mRNA expression and protein level but not iNOS activity. Moreover, curcumol inhibits LPS-induced production of TNF-α, IL-1β and IL-6 at both the transcriptional and translational levels. Further investigations reveal that these effects mainly act via suppressing JNK-mediated AP-1 rather than the NF-κB pathway; these effects include a decrease in the phosphorylation level of JNK and a direct inhibition of the activity of p-JNK. These data provide scientific molecular evidence that curcumol may be a potential lead compound for a novel anti-inflammatory drug because of its inhibitory activity on the production of various inflammatory mediators.

Keywords: AP-1 (activator protein-1); Anti-inflammation; Curcumol; JNK (c-Jun N-terminal kinase); Lipopolysaccharide (LPS).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology*
  • Cell Line
  • Cytokines / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism*
  • Lipopolysaccharides
  • Mice
  • Nitric Oxide / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • RNA, Messenger / metabolism
  • Sesquiterpenes / pharmacology*
  • Signal Transduction / drug effects
  • Transcription Factor AP-1 / metabolism*

Substances

  • Anti-Inflammatory Agents
  • Cytokines
  • Lipopolysaccharides
  • RNA, Messenger
  • Sesquiterpenes
  • Transcription Factor AP-1
  • Nitric Oxide
  • curcumol
  • Nitric Oxide Synthase Type II
  • Nos2 protein, mouse
  • JNK Mitogen-Activated Protein Kinases