title: Protective effects of lupeol against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice.
abstract: This study examined the hepatoprotective effects of lupeol (1, a major active triterpenoid isolated from Adenophora triphylla var. japonica) against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were orally administered 1 (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 1. 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 1. Interestingly, 1 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 TNF-α and IL-6 mRNA expression increased, which were attenuated by 1. Together, the present findings suggest that lupeol (1) ameliorates GalN/LPS-induced liver injury, which may be due to inhibition of IRAK-mediated TLR inflammatory signaling.
authors.affiliation: School of Pharmacy, Sungkyunkwan University , Suwon, 440-746, Republic of Korea.
authors.forename: So-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Hong-Ik
authors.initials: HI
authors.lastname: Cho
authors.forename: Seok-Joo
authors.initials: SJ
authors.lastname: Kim
authors.forename: Joon-Sung
authors.initials: JS
authors.lastname: Kim
authors.forename: Jong-Hwan
authors.initials: JH
authors.lastname: Kwak
authors.forename: Dong-Ung
authors.initials: DU
authors.lastname: Lee
authors.forename: Sang Kook
authors.initials: SK
authors.lastname: Lee
authors.forename: Sun-Mee
authors.initials: SM
authors.lastname: Lee
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D029422:Campanulaceae / Q000737:chemistry*; D005688:Galactosamine / Q000494:pharmacology*; D015850:Interleukin-6 / Q000032:analysis / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects; D017114:Liver Failure, Acute / Q000139:chemically induced*; D008297:Male; D051379:Mice; D008954:Models, Biological; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism; D053978:Pentacyclic Triterpenes / Q000737:chemistry / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D056910:Republic of Korea; D015398:Signal Transduction / Q000187:drug effects; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000494:pharmacology; D000094042:Lupanes
chemical_list: D000410:Alanine Transaminase; D005688:Galactosamine; D015850:Interleukin-6; D008070:Lipopolysaccharides; D016328:NF-kappa B; D053978:Pentacyclic Triterpenes; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; C495345:TLR4 protein, human; C010480:lupeol; D000094042:Lupanes