Anti-apoptotic activity of gentiopicroside in D-galactosamine/lipopolysaccharide-induced murine fulminant hepatic failure

作者：Lian Li Hua; Wu Yan Ling; Wan Ying; Li Xin; Xie Wen Xue; Nan Ji Xing^*

来源：Chemico-Biological Interactions, 2010, 188(1): 127-133.

DOI：10.1016/j.cbi.2010.06.004

• Gentiopicroside
• D-Galactosamine
• (D-GalN)/lipopolysaccharide (LPS)
• Apoptosis
• Tumor necrosis factor (TNF)-alpha
• c-jun N-terminal kinase (JNK)
• Extracellular signal regulated kinase (ERK)

This study investigated the hepatoprotective effects of gentiopicroside on D-galactosamine (D-GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were administrated orally with gentiopicroside (40 or 80 mg/kg body weight) at 12h and 1 h before D-GalN (700 mg/kg)/LPS (10 mu g/kg) injection. Gentiopicrosicle markedly reduced the increases in serum aminotransferase activities and lipid peroxidation. The glutathione content decreased in D-GalN/LPS alone group, and this decrease was attenuated by gentiopicroside. Increases in serum tumor necrosis factor-alpha (TNF-alpha), which were observed in D-GalN/LPS alone group, were significantly reduced by gentiopicroside. Importantly, gentiopicroside attenuated D-GalN/LPS-induced apoptosis of hepatocytes, as estimated by the caspase-3 cleavage, poly(ADP-ribose) polymerase (PARP) cleavage, and DNA fragmentation. D-GalN/LPS-induced caspase-8 and -9 activation was significantly suppressed by gentiopicroside. Moreover, increased cytosolic cytochromec protein was reduced by gentiopicroside. Also, the increased ratio of Bax and Bcl-2 protein was significantly attenuated by gentiopicroside. After 6h of D-GalN/LPS injection, phosphorylated c-jun N-terminal kinase (INK) and extracellular signal regulated kinase (ERK) was significantly increased, whereas phosphorylation JNK and ERK were attenuated by gentiopicroside. Our results suggest that gentiopicroside offers remarkable hepatoprotection against damage induced by D-GalN/LPS related with its anti-apoptotic activities.

• 出版日期2010-10-6
• 单位延边大学