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

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• 作者：So-Jin Kim ; Hong-Ik Cho ; Seok-Joo Kim ; Joon-Sung Kim ; Jong-Hwan Kwak ; Dong-Ung Lee ; Sang Kook Lee ; Sun-Mee Lee
• 刊名：Journal of Natural Products
• 出版年：2014
• 出版时间：November 26, 2014
• 年：2014
• 卷：77
• 期：11
• 页码：2383-2388
• 全文大小：339K
• ISSN：1520-6025

文摘

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 渭g/kg) treatment. Treatment with GalN/LPS resulted in increased levels of serum alanine aminotransferase, tumor necrosis factor (TNF)-伪, 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-尾 (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-魏B and the levels of TNF-伪 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.