Effect of Fugan Huaxian Decoction on MAPK signaling pathway in model rats with hepatic fibrosis / 中草药

ABSTRACT

Objective: To research the effect of Fugan Huaxian Decoction on MAPK signaling pathway in rats with hepatic fibrosis (HF) and explore the mechanism of anti-HF. Methods: A total of 120 SD rats were randomly divided into control group, model group, colchicine group and Fugan Huaxian Decoction group (high, medium and low dose groups), with 20 rats in each group. The rats in the normal group were SD rats, and the rats model in the remaining groups were established into HF rats with syndrome of qi deficiency, poison weakness and blood stasis on the basis of the HF model induced by carbon tetrachloride (CCl4). Moreover, the rats were also received tail clamping, forced swimming, abnormal of starvation and full as well as rhubarb gavage. Liver pathology was performed on all rats after six weeks of modeling. After the validation model was successful, each group was given different doses of gavage, colchicine group (2 mg/kg), high, medium and low dose groups of Fugan Huaxian Decoction were intra-gastrically administered (67.08, 33.54, and 16.77 g/kg), normal group and model group were given pure water 2 mL/d for three weeks continuously. On the second day of last gavage, the serum levels of ALT, AST, ALB, LN, HyP and PIIINP were detected in each group. HE staining and Masson staining were performed on liver tissues. The expression of ERK1/2, JNK1/2 and P38-related protein and their phosphorylated protein in liver MAPK signaling pathway were detected by Western blotting. The results of quantitative analysis were expressed as p-ERK/ERK, p-JNK/JNK, p-p38/p38 ratio. Results: In model group, hepatic tissue cells were severely infiltrated and fibrotic, while, the degree of liver injury and fibrosis were significantly reduced in other groups. Compared with normal group, the serum levels of ALT, AST, Hyp, LN and PIIINP in model group were increased significantly, ALB was decreased significantly (P < 0.01), and the protein expression of p-JNK, p-ERK and p-p38 was increased significantly (P < 0.01). Compared with model group, Fugan Huaxian Decoction decreased serum ALT, AST, Hyp, LN and PIIINP levels of rats, increased ALB content and down-regulated the expression of phosphorylated protein of p38, ERK1/2 and JNK1/2, and it showed in a dose-dependent manner, the high dose group worked the best. Conclusion: The model of qi deficiency, poison weakness and blood stasis combined with HF model rats was successfully established. Fugan Huaxian Decoction not only protects hepatocytes, alleviates liver injury and inhibits HF, but also regulates the protein expressions of p-JNK, p-ERK, p-p38, as well as inhibits MAPK signaling pathway activation, which may be one of the mechanisms of its anti-HF function.