Curcumin protects against liver fibrosis by attenuating infiltration of Gr1hi monocytes through inhibition of monocyte chemoattractant protein-1.

Background And Aims: Liver fibrosis is concomitant with monocyte infiltration, which has been highlighted as novel therapeutic targets for chronic liver diseases. We aimed to investigate whether curcumin might protect the liver from carbon tetrachloride (CCl4)-induced fibrosis by attenuating the recruitment of Gr1hi monocytes through inhibition of monocyte chemoattractant protein-1 (MCP-1).

Methods: Mice were intraperitoneally injected with CCl4 to induce liver fibrosis. Curcumin was orally administrated to mice. Hepatic inflammation and fibrosis were evaluated by analysis of liver function and hepatic histopathology. Infiltration of the Gr1hi monocytes was assessed by flow cytometry and immunohistochemistry. Moreover, mRNA expression levels of tumor necrosis factor (TNF)-α, interleukin (IL)-6, IL-1β, and transforming growth factor (TGF)-β1 were determined by real time PCR. Hepatic expression of MCP-1 was determined by real time PCR and immunohistochemistry.

Results: Curcumin significantly attenuated inflammation and fibrosis, as revealed by histological and biochemical analysis. The intrahepatic infiltration of Gr1hi monocytes was attenuated by curcumin administration. T cells, NK cells, NKT cells, and dendritic cells were not affected by curcumin. Curcumin significantly reduced the expression of TNF-α and TGF-β1, which is in line with the decreased numbers of intrahepatic Gr1hi monocytes. Intrahepatic MCP-1 expression of CCl4-challenged mice was inhibited by curcumin.

Conclusions: The anti-inflammatory and antifibrotic effects of curcumin could be contributed to its prevention of Gr1hi monocyte infiltration into the injured livers through inhibition of MCP-1. These new findings extend our understanding on the mechanisms of the anti-inflammatory and antifibrotic effects of curcumin.