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: So-Jin Kim, Hong-Ik Cho, Seok-Joo Kim, Joon-Sung Kim, Jong-Hwan Kwak, Dong-Ung Lee, Sang Kook Lee, Sun-Mee Lee
• Journal: Journal of natural products (J Nat Prod) Vol. 77 Issue 11 Pg. 2383-8 (Nov 26 2014) ISSN: 1520-6025 [Electronic] United States
• PMID: 25325613 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Interleukin-6
• Lipopolysaccharides
• NF-kappa B
• Pentacyclic Triterpenes
• TLR4 protein, human
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha
• Galactosamine
• Alanine Transaminase
• lupeol

Topics

• Alanine Transaminase (blood)
• Animals
• Campanulaceae (chemistry)
• Galactosamine (pharmacology)
• Interleukin-6 (analysis, metabolism)
• Lipopolysaccharides (pharmacology)
• Liver (drug effects)
• Liver Failure, Acute (chemically induced)
• Male
• Mice
• Models, Biological
• Molecular Structure
• NF-kappa B (metabolism)
• Pentacyclic Triterpenes (chemistry, pharmacology)
• Plant Roots (chemistry)
• Republic of Korea
• Signal Transduction (drug effects)
• Toll-Like Receptor 4
• Tumor Necrosis Factor-alpha (analysis, pharmacology)