Anti-apoptotic activity of gentiopicroside in D-galactosamine/lipopolysaccharide-induced murine fulminant hepatic failure.
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 1h before d-GalN (700 mg/kg)/LPS (10 microg/kg) injection. Gentiopicroside 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 cytochrome c 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 (JNK) 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.
Lian
Li-Hua
LH
Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.
Wu
Yan-Ling
YL
Wan
Ying
Y
Li
Xin
X
Xie
Wen-Xue
WX
Nan
Ji-Xing
JX
D000410:Alanine Transaminase / Q000097:blood; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001219:Aspartate Aminotransferases / Q000097:blood; D015153:Blotting, Western; D020169:Caspases / Q000378:metabolism; D004789:Enzyme Activation; D005688:Galactosamine / Q000633:toxicity*; D005960:Glucosides / Q000494:pharmacology*; D005978:Glutathione / Q000378:metabolism; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology*; D015227:Lipid Peroxidation; D008070:Lipopolysaccharides / Q000633:toxicity*; D017093:Liver Failure / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D005960:Glucosides; D057888:Iridoid Glucosides; D039823:Iridoids; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; C012997:gentiopicroside; D005688:Galactosamine; D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D020169:Caspases; D005978:Glutathione