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

Abstract

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. 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. 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. 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. Show more