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

Abstract

Aim of the study To investigate the effect of Fraxinus rhynchophylla ethanol extract (FR EtOH) on liver fibrosis induced by carbon tetrachloride (CCl 4) in rats. Materials and methods Rat hepatic fibrosis was induced by oral administration of CCl 4. Sixty SD rats were divided randomly into 6 groups: control, CCl 4 group, silymarin group and three FR EtOH-treated groups. Except for the rats in control group, all rats were administered orally with CCl 4 (20%, 0.2 mL/100 g body weight) twice a week for 8 weeks. Rats in FR EtOH groups were treated daily with FR EtOH (0.1, 0.5 and 1.0 g/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 FR EtOH (0.1, 0.5 and 1.0 g/kg BW) significantly reduced the elevated activities of sGOT and sGPT caused by CCl 4. FR EtOH (0.1 and 0.5 g/kg BW) and significantly increased the activities of GSH-Px. The histopathological study showed that FR EtOH (0.1 and 0.5 g/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 CCl 4 in rats. In our study it was showed that CCl 4-treated group significantly increased the protein levels of uPA, MMP-2, MMP-9 and TIMP-1. FR EtOH (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 FR EtOH was 33.54 mg/g extract. Conclusions Oral administration of FR EtOH significantly reduces CCl 4-induced hepatic fibrosis in rats, probably by exerting a protective effect against hepatocellular fibrosis by its free radical scavenging ability. FR EtOH down-regulated the expressions of uPA, MMP-2 and MMP-9 in CCl 4-induced liver fibrosis in rats.