linarin and Liver-Failure--Acute

Linarin was isolated from Chrysanthemum indicum L. Fulminant hepatic failure is a serious clinical syndrome that results in massive inflammation and hepatocyte death. Apoptosis is an important cellular pathological process in d-galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury, and regulation of liver apoptosis might be an effective therapeutic method for fulminant hepatic failure. This study examined the cytoprotective mechanisms of linarin against GalN/LPS-induced hepatic failure. Mice were given an oral administration of linarin (12.5, 25 and 50mg/kg) 1h before receiving GalN (800 mg/kg)/LPS (40 μg/kg). Linarin treatment reversed the lethality induced by GalN/LPS. After 6h of GalN/LPS injection, the serum levels of alanine aminotransferase, aspartate aminotransferase, tumor necrosis factor (TNF)-α, interleukin-6 and interferon-γ were significantly elevated. GalN/LPS increased toll-like receptor 4 and interleukin-1 receptor-associated kinase protein expression. These increases were attenuated by linarin. Linarin attenuated the increased expression of Fas-associated death domain and caspase-8 induced by GalN/LPS, reduced the cytosolic release of cytochrome c and caspase-3 cleavage induced by GalN/LPS, and reduced the pro-apoptotic Bim phosphorylation induced by GalN/LPS. However, linarin increased the level of anti-apoptotic Bcl-xL and phosphorylation of STAT3. Our results suggest that linarin alleviates GalN/LPS-induced liver injury by suppressing TNF-α-mediated apoptotic pathways.

Topics: Alanine Transaminase; Animals; Apoptosis; Apoptosis Regulatory Proteins; Aspartate Aminotransferases; Bcl-2-Like Protein 11; bcl-X Protein; Caspase 3; Caspase 8; Cytochromes c; Cytoprotection; Cytosol; Fas-Associated Death Domain Protein; Galactosamine; Glycosides; Interferon-gamma; Interleukin-1 Receptor-Associated Kinases; Interleukin-6; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; Membrane Proteins; Mice; Phosphorylation; Proteolysis; Proto-Oncogene Proteins; RNA, Messenger; Signal Transduction; STAT3 Transcription Factor; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha