Protective Effects And Mechanism Of Betulinic Acid On Liver Injury Induced By Alcohol In Mice

Alcoholic liver disease is an alcohol abusing disease in liver which causes health problems on people. A growing body of evidence indicates that oxidative stress is a key mechanism underlying alcohol-mediated hepatotoxicity. Betulinic acid (BA) is an abundant naturally occurring pentacyclic triterpene which possesses a wide spectrum of biological and pharmacological activities such as anti-oxidative, scavenging free radical, immunomo-dulatoy, and anti-inflammatory effects. It was reported that BA prevents d-galactosamine/ lipopolysaccharide/ carbon tetrachloride induced liver damage by improving the antioxidant system. However, BA prevents liver injury induced by alcohol has not been previously reported in vivo. The objective of this study was to investigate the possible hepatoprotective effects of BA against alcohol induced acute liver damage in mice and elucidate the underlying mechanism.Objective:to investigate the possible hepatoprotective effects of BA against alcohol induced acute liver damage in mice and elucidate the underlying mechanism.Method:Fifty six KM male mice were randomly divided into eight groups:normal control group (NC), model control group (MC), low-dosage, medium-dosage and high-dosage BA group (L-BA, M-BA and H-BA,0.25,0.5,1.0 mg/kg bw), low-dosage, medium-dosage and high-dosage BA with alcohol group (L-BAA, M-BAA and H-BAA). The NC and MC groups were administered orally with 1% starch and the other groups were administered orally with different doses of BA (0.25,0.5, and 1.0 mg/kg bw) daily for 14 d. The model of liver injury was set up in mice induced by 50% alcohol at the dosage of 10 ml/kg bw after last administration of BA. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), alkaline phosphatase (ALP), total cholesterols (TC), triacylglycerides (TG), albumin (ALB) and total protein (TP), and the liver levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), glutathione (GSH), cytochromeP4502E1 (CYP2E1), and malondialdehyde (MDA) were detected, and histopathological changes were observed in liver, and protein expression of Bcl-2, Bax, Caspase-9, Caspase-3 were detected by western boltting.Results:BA pretreatment reduced significantly the serum levels of ALT, AST, ALP, TC and TG in mice induced by alcohol in a dose dependent manner. Hepatic levels of GSH, SOD, GSH-Px and CAT were increased remarkably, while the levels of MDA and CYP2E1, the ratio of Bax/Bcl-2, the expression of caspase-9 and caspase-3, and pathological changes were decreased remarkably by BA pretreatment after alcohol-induced liver injury in a dose dependent manner.Conclusion: It was suggested that the hepatoprotective mechanism of BA might be due to its antioxidant capacity, mainly by improving the tissue redox system, maintaining the antioxidant system, and decreasing lipid peroxidation in the liver. These findings reveal a potential protective capability of BA against alcohol-induced oxidative stress via mitochondrial mediated signal pathway.