Fraxinus rhynchophylla ethanol extract attenuates carbon tetrachloride-induced liver fibrosis in rats via down-regulating the expressions of uPA, MMP-2, MMP-9 and TIMP-1

Aim of the study: To investigate the effect of Fraxin us rhynchophylla ethanol extract (FREtOH) on liver fibrosis induced by carbon tetrachloride (CCl4) in rats. Materials and methods: Rat hepatic fibrosis was induced by oral administration of CCl4. Sixty SD rats were divided randomly into 6 groups: control, CCl4 group, silymarin group and three FREtOH-treated groups. Except for the rats in control group, all rats were administered orally with CCl4 (20%, 0.2 mL/100g body weight) twice a week for 8 weeks. Rats in FREtOH groups were treated daily with FREtOH (0.1, 0.5 and 1.0g/kg, p.o.) throughout the whole experimental period. Liver function parameters (such as activities of serum GOT and GPT levels), activities of liver anti-oxidant enzymes (such as catalase, SOD, GPx) and expressions of uPA, tPA, MMP-2, MMP-9 and TIMP-1, -2, -3, -4 in the liver fibrosis pathway were detected. Results: The results showed that FREtOH (0.1, 0.5 and 1.0g/kg BW) significantly reduced the elevated activities of sGOT and sGPT caused by CCl4. FREtOH (0.1 and 0.5 g/kg BW) and significantly increased the activities of GSH-Px. The histopathological study showed that FREtOH (0.1 and 0.5g/kg BW) reduced the incidence of liver lesions, including hepatic cells cloudy swelling, lymphocytes infiltration, cytoplasm vacuolization hepatic necrosis and fibrous connective tissue proliferated induced by CCl4 in rats. In our study it was showed that CCl4-treated group significantly increased the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. FREtOH (0.1 and 0.5 g/kg BW) could inhibit the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. Finally, the amount of esculetin in the FREtOH was 33.54 mg/g extract. Conclusions: Oral administration of FREtOH Significantly reduces CCl4-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular fibrosis by its free radical scavenging ability. FREtOH down-regulated the expressions of uPA, MMP-2 and MMP-9 in CCl4-induced liver fibrosis in rats. (C) 2009 Elsevier Ireland Ltd. All rights reserved.