Curcumin, a Curcuma Longa Constituent, Acts on MAPK p38 Pathway Modulating COX-2 and iNOS Expression in Chronic Experimental Colitis

Int Immunopharmacol. 2007 Mar;7(3):333-42. doi: 10.1016/j.intimp.2006.11.006. Epub 2006 Dec 18.

Abstract

Ulcerative colitis (UC) is a nonspecific inflammatory disorder characterized by oxidative and nitrosative stress, leucocyte infiltration and up-regulation of pro-inflammatory cytokines. Mitogen-activated protein kinases (MAPKs), such as the p38 and the c-Jun N-terminal kinase (JNK) modulate the transcription of many genes involved in the inflammatory process. Curcumin is a polyphenol derived from Curcuma longa, which is known to have anti-inflammatory activity. The aim of this study was to study the effects and mechanisms of action of curcumin, on chronic colitis in rats. Inflammation response was assessed by histology and myeloperoxidase activity (MPO). We determined the production of Th1 and Th2 cytokines and nitrites in colon mucosa, as well as the expression of inducible nitric oxide synthase (iNOS), cyclo-oxygenase(COX)-1 and-2 by western blotting and inmmunohistochemistry. Finally, we studied the involvement of MAPKs signaling in the protective effect of curcumin in chronic colonic inflammation. Curcumin (50-100 mg/kg/day) were administered by oral gavage 24 h after trinitrobenzensulfonic acid (TNBS) instillation, and daily during 2 weeks before sacrifice. Curcumin significantly attenuated the damage and caused substantial reductions of the rise in MPO activity and tumour necrosis factor alpha (TNF)-alpha. Also curcumine was able to reduce nitrites colonic levels and induced down-regulation of COX-2 and iNOS expression, and a reduction in the activation of p38 MAPK; however, no changes in the activation of JNK could be observed. In conclusion, we suggest that inhibition of p38 MAPK signaling by curcumin could explain the reduced COX-2 and iNOS immunosignals and the nitrite production in colonic mucosa reducing the development of chronic experimental colitis.

MeSH terms

  • Animals
  • Chronic Disease
  • Colitis / drug therapy*
  • Colitis / metabolism
  • Colitis / pathology
  • Curcumin / pharmacology*
  • Cyclooxygenase 2 / genetics*
  • Female
  • Gene Expression Regulation, Enzymologic / drug effects*
  • MAP Kinase Signaling System / drug effects*
  • Male
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type II / genetics*
  • Rats
  • Rats, Wistar
  • Trinitrobenzenesulfonic Acid / toxicity
  • Tumor Necrosis Factor-alpha / physiology
  • p38 Mitogen-Activated Protein Kinases / antagonists & inhibitors*
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Tumor Necrosis Factor-alpha
  • Nitric Oxide
  • Trinitrobenzenesulfonic Acid
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • p38 Mitogen-Activated Protein Kinases
  • Curcumin