Protective effect of linarin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure.

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.

Kim SJ ，Cho HI ，Kim SJ ，Park JH ，Kim JS ，Kim YH ，Lee SK ，Kwak JH ，Lee SM ... -  《-》

Genipin protects lipopolysaccharide-induced apoptotic liver damage in D-galactosamine-sensitized mice.

Kim SJ ，Kim JK ，Lee DU ，Kwak JH ，Lee SM ... -  《-》

Scoparone attenuates D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure through inhibition of toll-like receptor 4 signaling in mice.

The purpose of this study was to investigate the protective effects and molecular mechanisms of scoparone on d-galactosamine (D-GalN)/lipopolysaccharide (LPS)-induced fulminant hepatic failure (FHF) in mice. FHF was induced in mice by intraperitoneal injection of D-GalN (800 mg/kg)/LPS (40 μg/kg). Mice were treated intraperitoneally with scoparone 1h before D-GalN/LPS treatment. Treatment with d-GalN/LPS markedly increased mortality, serum aminotransferase activity, and tolllike receptor 4 (TLR4) protein expression, and these increases were attenuated by scoparone. Treatment with d-GalN/LPS markedly increased myeloid differentiation primary response gene 88 protein expression, phosphorylation of p38, extracellular signal-regulated kinase and c-Jun N-terminal kinase, nuclear protein expression of nuclear factor κB and phosphorylated c-Jun, and levels of serum tumor necrosis factor-α and interleukin-6 and these increases were attenuated by scoparone. In addition, increased levels of toll-receptor-associated activator of interferon protein expression, phosphorylation of interferon (IFN) regulatory factor 3, and serum IFN-β level in D-GalN/LPS-treated mice were attenuated by scoparone. Our results suggest that scoparone attenuates d-GalN/LPSinduced liver damage by inhibition of the TLR-mediated inflammatory pathway.

Kang JW ，Kim DW ，Choi JS ，Kim YS ，Lee SM ... -  《-》

Protective mechanisms of acacetin against D-galactosamine and lipopolysaccharide-induced fulminant hepatic failure in mice.

Cho HI ，Park JH ，Choi HS ，Kwak JH ，Lee DU ，Lee SK ，Lee SM ... -  《-》

Etoposide prevents apoptosis in mouse liver with D-galactosamine/lipopolysaccharide-induced fulminant hepatic failure resulting in reduction of lethality.

Nakama T ，Hirono S ，Moriuchi A ，Hasuike S ，Nagata K ，Hori T ，Ido A ，Hayashi K ，Tsubouchi H ... -  《HEPATOLOGY》