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

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-κB 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-κB inhibitor, for up to 4 weeks. Histopathology, lipoperoxides, NF-κB/DNA binding and expression of NF-κB-regulated genes were assessed. Results MCD-fed mice developed steatohepatitis accompanied by dramatic accumulation of hepatic lipoperoxides, activation of NF-κB 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-κB 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-κB pathway is one among several possible signalling pathways by which inflammation is recruited in experimental steatohepatitis.