Planta Medica · 2002 · 61 citations · 0 references
Veterinary MedicineMedicinal ChemistryPharmacologyApoptosisInflammationInnate ImmunityApoptosis In Liver ToxicityApoptosis ModulationApoptotic SignalingHepatic NecrosisHepatic ToxicityHepatocellular NecrosisAcute Hepatic NecrosisApoptosis In HepatotoxicityHepatic ApoptosisHepatocyte Cell Death MechanismsHepatoprotective AgentsHepatotoxic MechanismsHerbal Medicine HepatotoxicityLiver Cell Death Pathways
The hepatoprotective effect of majonoside R 2 (MR2), the major saponin constituent from Vietnamese ginseng ( Panax vietnamensis, Araliaceae), was evaluated in vivo on D-galactosamine ( D-GalN)/lipopolysaccharide (LPS)-induced hepatic apoptosis and subsequent liver failure in mice. Pretreatment of mice with MR2 (50 or 10 mg/kg, intraperitoneal) at 12 and 1 h before D-GalN/LPS injection significantly inhibited apoptosis and suppressed following hepatic necrosis. Importantly, the elevation of serum tumor necrosis factor-alpha (TNF-alpha) level, an important mediator for apoptosis in this model, was significantly inhibited by MR2 at a dose of 50 mg/kg. On the other hand, MR2 was found to protect primary cultured mouse hepatocytes from cell death by inhibiting apoptosis induced by D-GalN/TNF-alpha in vitro, as evidenced by DNA fragmentation analysis. These findings suggested that MR2 may have protected the hepatocytes from apoptosis via an inhibition of TNF-alpha production by activated macrophages and a direct inhibition of apoptosis induced by TNF-alpha.