OBJECTIVES: The hepatoprotective activity and molecular mechanism of betulinic acid (BA) was investigated on acute liver failure induced by d-galactosamine (D-GalN)/lipopolysaccharide (LPS) in vivo. METHODS: Mice were administered with different doses of BA (20 mg/kg or 50 mg/kg, i.p.) 1 h before injection of D-GalN (700 mg/kg)/LPS (10 µg/kg) and sacrificed 6 h after treatment with D-GalN/LPS. KEY FINDINGS: Pretreatment with BA significantly prevented the increases of serum aspartate aminotransferase and alanine aminotransferase, while it increased the content of glutathione and catalase, and reduced malondialdehyde. BA showed obvious anti-oxidant effects and prevented D-GalN/LPS-induced apoptosis, as indicated by DNA ladder. BA treatment resulted in regulation of the mitogen-activated protein kinase. We found that BA mediated production of c-jun NH(2) -terminal protein kinase and extracellular signal-regulated kinase induced by D-GalN/LPS, promoted the expression of B-cell CLL/lymphoma 2 (Bcl-2) and restored mitochondrial outer membrane permeabilization. CONCLUSIONS: The results suggested that BA prevented D-GalN/LPS-induced acute liver failure by upregulation of Bcl-2 and antioxidation and mediation of cytokines causing apoptotic cell death and lessened liver damage.
OBJECTIVES: The hepatoprotective activity and molecular mechanism of betulinic acid (BA) was investigated on acute liver failure induced by d-galactosamine (D-GalN)/lipopolysaccharide (LPS) in vivo. METHODS:Mice were administered with different doses of BA (20 mg/kg or 50 mg/kg, i.p.) 1 h before injection of D-GalN (700 mg/kg)/LPS (10 µg/kg) and sacrificed 6 h after treatment with D-GalN/LPS. KEY FINDINGS: Pretreatment with BA significantly prevented the increases of serum aspartate aminotransferase and alanine aminotransferase, while it increased the content of glutathione and catalase, and reduced malondialdehyde. BA showed obvious anti-oxidant effects and prevented D-GalN/LPS-induced apoptosis, as indicated by DNA ladder. BA treatment resulted in regulation of the mitogen-activated protein kinase. We found that BA mediated production of c-jun NH(2) -terminal protein kinase and extracellular signal-regulated kinase induced by D-GalN/LPS, promoted the expression of B-cell CLL/lymphoma 2 (Bcl-2) and restored mitochondrial outer membrane permeabilization. CONCLUSIONS: The results suggested that BA prevented D-GalN/LPS-induced acute liver failure by upregulation of Bcl-2 and antioxidation and mediation of cytokines causing apoptotic cell death and lessened liver damage.