Protective Effects of Lupeol against d‑Galactosamine and Lipopolysaccharide-Induced Fulminant Hepatic Failure in Mice

Abstract

This study examined the hepatoprotective effects of lupeol (<b>1</b>, a major active triterpenoid isolated from <i>Adenophora triphylla</i> var. <i>japonica</i>) against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were orally administered <b>1</b> (25, 50, and 100 mg/kg; dissolved in olive oil) 1 h before GalN (800 mg/kg)/LPS (40 μg/kg) treatment. Treatment with GalN/LPS resulted in increased levels of serum alanine aminotransferase, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, as well as increased mortality, all of which were attenuated by treatment with <b>1</b>. In addition, levels of toll-like receptor (TLR)­4, myeloid differentiation primary response gene 88, TIR-domain-containing adapter-inducing interferon-β (TRIF), IL-1 receptor-associated kinase (IRAK)-1, and TNF receptor associated factor 6 protein expression were increased by GalN/LPS. These increases, except TRIF, were attenuated by <b>1</b>. Interestingly, <b>1</b> augmented GalN/LPS-mediated increases in the protein expression of IRAK-M, a negative regulator of TLR signaling. Following GalN/LPS treatment, nuclear translocation of nuclear factor-κB and the levels of <i>TNF-α</i> and <i>IL-6</i> mRNA expression increased, which were attenuated by <b>1</b>. Together, the present findings suggest that lupeol (<b>1</b>) ameliorates GalN/LPS-induced liver injury, which may be due to inhibition of IRAK-mediated TLR inflammatory signaling