All results confirm that emodin protected the liver from injury and fibrogenesis caused by CCl4 in the rat model. Chronic liver injury may lead to development of fibrosis, a process in which HSC play a major role. As a result of liver injury, HSC, which in the healthy organ store vitamin A, undergo a process of activation that is mediated by the concerted action of resident hepatic cell types such as Kupffer cells, liver endothelial cells, and hepatocytes. The phenotype of activated HSC is characterized by smooth muscle actin expression . SMA expression in the liver tissues is an indicator of hepatic stellate cell activation, which is recognized as being critical in liver fibrogenesis. Thus inhibition of the accumulation of activated HSCs is an important therapeutic strategy . Our results showed the levels of SMA in rat liver tissues increased significantly after CCl4 administration for 12 wk. Emodin reduced SMA expression at mRNA and protein levels. Inflammation is commonly associated with hepatic fibrogenesis during chronic liver diseases . CCl4 is metabolized in the liver by cytochrome P450 into the free radical CCl3 .
The free radical attacks hepatocytes and causes necrosis of parenchymal cells, which promotes inflammatory responses in the liver . Results in this study indicated that emodin suppressed inflammation caused by CCl4, which might lead to the protection of the liver from injury. It is now widely accepted that the pro inflammatory cytokine TGF 1 is a major cytokine in the regulation of the production, degradation, and accumulation of ECM , and it screening compounds has been suggested that overexpression of TGF 1 for a prolonged period of time after tissue damage may induce a fibroproliferative response and deposition of ECM, resulting in fibrosis in vital organs . Many studies have detected the presence of TGF 1, in the form of either protein or message, in the fibrotic tissues of animal models or human samples . Partial inhibition of the accumulation of ECM using either anti TGF 1 serum or a TGF 1 binding protein has been reported in fibrosis models . Our results showed that TGF 1 mRNA levels and serum TGF 1 protein levels in normal rat were low.
After TH-302 dissolve solubility injection of CCl4 for 12 wk, mRNA and protein levels of TGF 1 increased significantly. Emodin down regulated mRNA levels of TGF 1 expression in liver tissue. Furthermore, serum TGF 1 levels in the model rats were also significantly down regulated by emodin treatment in a manner similar to hepatic fibrosis attenuation. These findings imply that emodin might attenuate hepatic fibrosis through down regulation of TGF 1 expression in vivo. Smad4 is well known to function as one of the downstream effectors of TGF 1, and it mediates TGF 1 induced collagen synthesis .