Inhibitory effect of silymarin on CCl4-induced liver fibrosis by reducing Ly6Chi monocytes infiltration

It has been well established that silymarin has hepatoprotective and anti-fibrotic effects. But the mechanisms are poorly understood. In recent years, the role of Ly6C(hi) monocytes in liver fibrosis has been well demonstrated. Thus, in present study we aimed to investigate whether silymarin can relieve liver fibrosis by reducing Ly6C(hi) monocytes infiltration. The mouse model of liver fibrosis was established by injected with carbon tetrachloride (CCl4) via intraperitoneal repeatedly. Mice in silymarin group received silymarin treatment by gavage. Silymarin significantly reduced liver inflammation and fibrosis of the mice induced by CCl4 injection, as revealed by liver histological and pathological analysis. Mice administrated by silymarin exhibited less infiltration of Ly6C(hi) monocytes. But there was no difference on other tested leukocyte subsets between CCl4 group and silymarin group. Meanwhile, further study found that silymarin significantly reduced CCl4-induced increased expression of tumor necrosis factor (TNF)-alpha, transforming growth factor (TGF)-beta 1 and monocyte chemoattractant protein 1 (MCP-1), which was in line with the decreased numbers of intrahepatic Ly6C(hi) monocytes. In conclusion, our study showed that the anti-inflammatory and anti-fibrotic effects of silymarin could be contributed to the prevention of Ly6C(hi) monocytes infiltration into the injured livers, which will give us a better understanding on the cellular mechanism of hepatoprotective and antifibrotic effect for silymarin.