Effects Of Flavonoids From Astragalus Complanatus And Epigallocatechin-3-gallate On Carbon Tetrachloride-induced Hepatic Fibrosis In Mice And Their Mechanisms

Objective:To study the protective effects of flavonoids from astragalus complanatus (FAC) and epigallocatechin-3-gallate (EGCG) on hepatic fibrosis induced by carbon tetrachloride (CCl4) in mice and their mechanisms.Methods:KM mice were randomly divided into 9 groups: control, model, FAC-1, FAC-2, FAC-3, EGCG-1, EGCG-2, EGCG-3 and Colchicine . In the study, mice in control group received i.p. injection of normal sodium (NS) 1 ml/kg, the mice in model group were injected with CCl4 (mixed with equal volume of olive oil, 1 ml/ kg, i.p.) twice a week during the following six weeks. The mice in treated groups received the same dose of CCl4 associated with oral administration of FAC,EGCG and Colchicine (0.1 ml/10g) once daily for six weeks. At the end of the sixth week, liver weight and hepatic index were measured, blood samples were collected for ALT,AST,ALB assays. The tissues of liver were removed for histopathological examination and SOD,MDA,HYP assays. The expressions of PPARγandβ-catenin were detected by immunohistochemistry.Results: (1) The liver weight and hepatic index were significantly decreased in FAC and EGCG groups compared with the model group. (2) CCl4 injection caused the disruption of tissue architecture, centrilobular necrosis, focal, piecemeal necrosis, infiltration of inflammation cells, disarrangement of hepatic cords and distortion of hepatic sinusoid. FAC and EGCG treatments could dramatically reduce the abnormalities mentioned above, especially in the FAC-3 group,EGCG-2 group and EGCG-3 group (P<0.01). (3)As shown in transmission electron microscope (TEM), FAC and EGCG treatments could protect hepatocyte in hepatic fibrosis mice. (4) CCl4 injection resulted in an increase of the ALT and AST levels in serum, a decrease of ALB levels in serum. FAC and EGCG treatments reduced the ALT and AST levels (P<0.01), and restored the ALB contents compared with the model group. (5) CCl4 injection led to dramatic decrease in SOD activities and increase in MDA and HYP contents. FAC and EGCG treatments changed their levels (P<0.01, P<0.05). (6) The expression of PPARγdecreased during the development of fibrosis. In contrast, the PPARγpositive expression in FAC and EGCG treated mice remarkably increased compared with the model group. Meanwhile CCl4 injection led to the higher expression ofβ-catenin, FAC and EGCG treatments could decrease its levels (P<0.01).Conclusions: The FAC and EGCG could effectively reduce CCl4 induced hepatic fibrosis in mice. High degree of fibrosis in CCl4 treated mice was prevented by FAC and EGCG as evidenced by HE and TEM. The effects of FAC and EGCG in treating hepatic fibrosis might associated with reducing the serum ALT and AST levels and restoring the serum ALB contents to protect hepatocyte, increasing the tissues SOD activities and reducing the tissues MDA and HYP contents, reducing the expression ofβ-catenin and improving the expression of PPARγin liver tissues of mice. The anti-hepatic fibrosis effects in the study were different with various dosages of the FAC and EGCG treatments.