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Anti-apoptotic activity of gentiopicroside in D-galactosamine/lipopolysaccharide-induced murine fulminant hepatic failure.
Chem Biol Interact 2010; 188(1):127-33CB

Abstract

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.

Authors+Show Affiliations

Key Laboratory for Natural Resource of ChangBai Mountain & Functional Molecules, Ministry of Education, College of Pharmacy, Yanbian University, Yanji, Jilin Province 133002, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20558151

Citation

Lian, Li-Hua, et al. "Anti-apoptotic Activity of Gentiopicroside in D-galactosamine/lipopolysaccharide-induced Murine Fulminant Hepatic Failure." Chemico-biological Interactions, vol. 188, no. 1, 2010, pp. 127-33.
Lian LH, Wu YL, Wan Y, et al. Anti-apoptotic activity of gentiopicroside in D-galactosamine/lipopolysaccharide-induced murine fulminant hepatic failure. Chem Biol Interact. 2010;188(1):127-33.
Lian, L. H., Wu, Y. L., Wan, Y., Li, X., Xie, W. X., & Nan, J. X. (2010). Anti-apoptotic activity of gentiopicroside in D-galactosamine/lipopolysaccharide-induced murine fulminant hepatic failure. Chemico-biological Interactions, 188(1), pp. 127-33. doi:10.1016/j.cbi.2010.06.004.
Lian LH, et al. Anti-apoptotic Activity of Gentiopicroside in D-galactosamine/lipopolysaccharide-induced Murine Fulminant Hepatic Failure. Chem Biol Interact. 2010 Oct 6;188(1):127-33. PubMed PMID: 20558151.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Anti-apoptotic activity of gentiopicroside in D-galactosamine/lipopolysaccharide-induced murine fulminant hepatic failure. AU - Lian,Li-Hua, AU - Wu,Yan-Ling, AU - Wan,Ying, AU - Li,Xin, AU - Xie,Wen-Xue, AU - Nan,Ji-Xing, Y1 - 2010/06/15/ PY - 2010/04/30/received PY - 2010/06/06/revised PY - 2010/06/08/accepted PY - 2010/6/19/entrez PY - 2010/6/19/pubmed PY - 2010/10/5/medline SP - 127 EP - 33 JF - Chemico-biological interactions JO - Chem. Biol. Interact. VL - 188 IS - 1 N2 - 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. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/20558151/Anti_apoptotic_activity_of_gentiopicroside_in_D_galactosamine/lipopolysaccharide_induced_murine_fulminant_hepatic_failure_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(10)00386-8 DB - PRIME DP - Unbound Medicine ER -