Lupeol Protects D-Galactosamine and Lipopolysaccharide-Induced Liver Injury

Fulminant hepatic failure (FHF) is a life-threatening clinical syndrome that results from severe impairment of liver function. Recently, reduced hepatic damage against FHF model was found in toll-like receptor (TLR) 4-null mice, implicating TLR4 as a potential therapeutic target in FHF. Lupeol is one of the major triterpenoid constitutions of Adenophora triphylla var. japonica which has been shown to exhibit antihepatotoxic and antioxidant properties. This study examined the protective effect of lupeol against D-galactosamine (GalN)/lipopolysaccharide (LPS)-induced hepatic failure. Mice were treated with lupeol at 100 mg/kg orally (dissolved in olive oil) 1 h before the GalN (800 mg/kg)/LPS (40 µg/kg) injection. Mice were sacrificed, and liver and blood samples were collected 6 h after GalN/LPS injection. The survival rate of the lupeol-treated group was significantly higher than the control. GalN/LPS significantly increased serum aminotransferase activities and interleukin (IL)-6 level. These increases were attenuated by lupeol. Lupeol reduced the levels of IL-6, interferon-β and tumor necrosis factor-α mRNA expression, which were increased by GalN/LPS. Moreover, lupeol attenuated the increased levels of TLR4, MyD88 and TRIF protein expressions. Our findings suggest that lupeol protects against FHF-induced damage by suppressing TLR4-mediated signaling pathways.