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

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.

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  • 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.

    , , , ,

    Source

    Chemico-biological interactions 188:1 2010 Oct 06 pg 127-33

    MeSH

    Alanine Transaminase
    Animals
    Apoptosis
    Aspartate Aminotransferases
    Blotting, Western
    Caspases
    Enzyme Activation
    Galactosamine
    Glucosides
    Glutathione
    Iridoid Glucosides
    Iridoids
    Lipid Peroxidation
    Lipopolysaccharides
    Liver Failure
    Male
    Mice
    Mice, Inbred C57BL
    Tumor Necrosis Factor-alpha

    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 -