Curcumin inhibits NF-kappaB activation and reduces the severity of experimental steatohepatitis in mice

J Hepatol. 2004 Dec;41(6):926-34. doi: 10.1016/j.jhep.2004.08.010.


Background/aims: While oxidative stress is a feature of non-alcoholic steatohepatitis, the causal link between oxidative stress and inflammatory recruitment has yet to be demonstrated. We analysed the role of NF-kappaB redox-sensitive signalling pathway of inflammatory recruitment in experimental steatohepatitis.

Methods: Mice were fed the methionine and choline deficient (MCD) or the control diet, with or without curcumin, an NF-kappaB inhibitor, for up to 4 weeks. Histopathology, lipoperoxides, NF-kappaB/DNA binding and expression of NF-kappaB-regulated genes were assessed.

Results: MCD-fed mice developed steatohepatitis accompanied by dramatic accumulation of hepatic lipoperoxides, activation of NF-kappaB and induction of pro-inflammatory ICAM-1, COX-2, MCP-1 and CINC mRNA. Curcumin significantly reduced MCD-induced inflammation but had no effect on steatosis or on the level of hepatic lipid peroxides. Curcumin prevented the MCD-induced activation of NF-kappaB and decreased downstream induction of ICAM-1, COX-2 and MCP-1. However, it failed to reduce activation of AP-1, MAPK pathways or CINC expression.

Conclusions: Curcumin alleviates the severity of hepatic inflammation in experimental steatohepatitis induced by the MCD diet, an effect likely to be mediated via inhibition of NF-kB activation and dependent pro-inflammatory genes. The NF-kappaB pathway is one among several possible signalling pathways by which inflammation is recruited in experimental steatohepatitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemokine CCL2 / genetics
  • Choline Deficiency / complications
  • Collagen Type I / genetics
  • Curcumin / pharmacology*
  • Cyclooxygenase 2
  • Deficiency Diseases / complications
  • Diet
  • Enzyme Inhibitors / pharmacology*
  • Fatty Liver / etiology
  • Fatty Liver / metabolism
  • Fatty Liver / pathology
  • Fatty Liver / physiopathology*
  • Female
  • Hepatitis / etiology
  • Hepatitis / metabolism
  • Hepatitis / pathology
  • Hepatitis / physiopathology*
  • Inflammation Mediators / metabolism
  • Intercellular Adhesion Molecule-1 / genetics
  • Methionine / deficiency
  • Mice
  • Mice, Inbred C57BL
  • Mitogen-Activated Protein Kinases / metabolism
  • NF-kappa B / antagonists & inhibitors*
  • Prostaglandin-Endoperoxide Synthases / genetics
  • RNA, Messenger / antagonists & inhibitors
  • Severity of Illness Index
  • Transcription Factor AP-1 / metabolism


  • Ccl2 protein, mouse
  • Chemokine CCL2
  • Collagen Type I
  • Enzyme Inhibitors
  • Inflammation Mediators
  • NF-kappa B
  • RNA, Messenger
  • Transcription Factor AP-1
  • Intercellular Adhesion Molecule-1
  • Methionine
  • Cyclooxygenase 2
  • Prostaglandin-Endoperoxide Synthases
  • Mitogen-Activated Protein Kinases
  • Curcumin