Protective Effect And Molecular Mechanism Of Betulin And Betulinic Acid In D-GalN/LPS Induced Acute Liver Failure Models Of Murine

OBJECTIVE In the present study, the hepatoprotective activitis and molecular mechanism of Betulin and Betulinic acid (BT&BA) were investigated on acute liver failure induced by D-galactosamine (D-GalN)/Lipopolysaccharides (LPS) in vitro. METHODS Mice were administered with different doses of BT or BA (20,50 mg/kg, suspended in 0.5%tween-80, i.p.) at 1h before injection D-GalN (700 mg/kg)/LPS (10μg/kg) and sacrificed after 6h treated with D-GalN/LPS. Blood were obtained to measure ALT and AST levels, and liver was divided into two parts. One was keep in 10% neutral formalin, the other was deposited in-80℃deep freeze refrigerator to detect GSH, MDA and CAT activities and other cytokines in liver tissure. Histological examination observed histopathology change of the livers, and cytokines in liver were detected using Western blot. RESULTS Serum ALT/AST activities were markedly increased at 6 h after GalN/LPS treatment, massive apoptosis were observed in liver histological sections of GalN/LPS-treated mice. Betulin and Betulinic acid treatment could decrease serum AST, ALT activities and hepatic MDA level significantly, and critically increased hepatic GSH and CAT levels. The mechanism of protection by BT or BA was perhaps through inhibition of activation on c-jun NH2-terminal protein kinase (JNK) activated by D-GalN/LPS, thus preventing downstream Bcl-2 and XIAP inactivation and protecting from mitochondiral permeabilization and cyrochrome c release. CONCLUSION Betulin and Betulinic acid prevent D-GalN/LPS induced hepatic injury through antioxidation, removing free radicals, mediating cytokines, and lessen liver damage.