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J Hepatol. 2004 Dec;41(6):926-34.

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

Author information

1
Gastroenterology Unit, Université Catholique de Louvain (UCL), GAEN/UCL 53/79, Avenue E. Mounier, 53, B-1200 Brussels, Belgium. isabelle_leclercq@wmi.usyd.edu.au

Abstract

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.

PMID:
15582125
DOI:
10.1016/j.jhep.2004.08.010
[Indexed for MEDLINE]

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