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Baicalein inhibits nuclear factor-κB and apoptosis via c-FLIP and MAPK in D-GalN/LPS induced acute liver failure in murine models.

Abstract

The hepatoprotective effects and molecular mechanisms of baicalein on acute liver failure induced by d-galactosamine (d-GalN)/lipopolysaccharides (LPS) were investigated in vivo. Mice were administered with different doses of baicalein (50, 100 or 150mg/kg, p.o.) 1h before injection of d-GalN (700mg/kg)/LPS (10μg/kg) and then sacrificed 6h after treatment with d-GalN/LPS. Pretreatment with baicalein prevented d-GalN/LPS-induced liver damage by preventing associated increases of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and by reducing serum tumor necrosis factor α (TNF-α), nitric oxide (NO) or inducible nitric oxide synthase (iNOS) expressions. The molecular mechanisms involved in baicalein-induced inhibition of d-GalN/LPS-caused apoptosis were associated with the protection of mitochondria, increasing the Bcl-2/Bax ratio, blocking the release of cytochrome c, and suppressing the phosphorylation of IκBα, ERK and JNK. Moreover, baicalein activated c-FLIP(L), XIAP and cIAP2 proteins, potentially blocking the recruitment of NF-κB signaling molecules. The results support the investigation of baicalein as a therapeutic candidate for acute liver apoptosis or injury and indicate that baicalein might inhibit liver apoptosis by mediating one or more of these pathways.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China.

    , ,

    Source

    Chemico-biological interactions 188:3 2010 Dec 05 pg 526-34

    MeSH

    Alanine Transaminase
    Animals
    Apoptosis
    Aspartate Aminotransferases
    CASP8 and FADD-Like Apoptosis Regulating Protein
    Caspase 3
    Cytochromes c
    Cytoprotection
    Disease Models, Animal
    Flavanones
    Galactosamine
    Gene Expression Regulation, Enzymologic
    Lipopolysaccharides
    Liver
    Liver Failure
    Male
    Mice
    Mice, Inbred C57BL
    Mitogen-Activated Protein Kinases
    NF-kappa B
    Nitric Oxide
    Nitric Oxide Synthase Type II
    Proto-Oncogene Proteins c-bcl-2
    Tumor Necrosis Factor-alpha
    X-Linked Inhibitor of Apoptosis Protein

    Pub Type(s)

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

    Language

    eng

    PubMed ID

    20850421

    Citation

    Wu, Yan-Ling, et al. "Baicalein Inhibits Nuclear factor-κB and Apoptosis Via c-FLIP and MAPK in D-GalN/LPS Induced Acute Liver Failure in Murine Models." Chemico-biological Interactions, vol. 188, no. 3, 2010, pp. 526-34.
    Wu YL, Lian LH, Wan Y, et al. Baicalein inhibits nuclear factor-κB and apoptosis via c-FLIP and MAPK in D-GalN/LPS induced acute liver failure in murine models. Chem Biol Interact. 2010;188(3):526-34.
    Wu, Y. L., Lian, L. H., Wan, Y., & Nan, J. X. (2010). Baicalein inhibits nuclear factor-κB and apoptosis via c-FLIP and MAPK in D-GalN/LPS induced acute liver failure in murine models. Chemico-biological Interactions, 188(3), pp. 526-34. doi:10.1016/j.cbi.2010.09.008.
    Wu YL, et al. Baicalein Inhibits Nuclear factor-κB and Apoptosis Via c-FLIP and MAPK in D-GalN/LPS Induced Acute Liver Failure in Murine Models. Chem Biol Interact. 2010 Dec 5;188(3):526-34. PubMed PMID: 20850421.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Baicalein inhibits nuclear factor-κB and apoptosis via c-FLIP and MAPK in D-GalN/LPS induced acute liver failure in murine models. AU - Wu,Yan-Ling, AU - Lian,Li-Hua, AU - Wan,Ying, AU - Nan,Ji-Xing, Y1 - 2010/09/17/ PY - 2010/07/02/received PY - 2010/09/07/revised PY - 2010/09/07/accepted PY - 2010/9/21/entrez PY - 2010/9/21/pubmed PY - 2010/12/22/medline SP - 526 EP - 34 JF - Chemico-biological interactions JO - Chem. Biol. Interact. VL - 188 IS - 3 N2 - The hepatoprotective effects and molecular mechanisms of baicalein on acute liver failure induced by d-galactosamine (d-GalN)/lipopolysaccharides (LPS) were investigated in vivo. Mice were administered with different doses of baicalein (50, 100 or 150mg/kg, p.o.) 1h before injection of d-GalN (700mg/kg)/LPS (10μg/kg) and then sacrificed 6h after treatment with d-GalN/LPS. Pretreatment with baicalein prevented d-GalN/LPS-induced liver damage by preventing associated increases of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) and by reducing serum tumor necrosis factor α (TNF-α), nitric oxide (NO) or inducible nitric oxide synthase (iNOS) expressions. The molecular mechanisms involved in baicalein-induced inhibition of d-GalN/LPS-caused apoptosis were associated with the protection of mitochondria, increasing the Bcl-2/Bax ratio, blocking the release of cytochrome c, and suppressing the phosphorylation of IκBα, ERK and JNK. Moreover, baicalein activated c-FLIP(L), XIAP and cIAP2 proteins, potentially blocking the recruitment of NF-κB signaling molecules. The results support the investigation of baicalein as a therapeutic candidate for acute liver apoptosis or injury and indicate that baicalein might inhibit liver apoptosis by mediating one or more of these pathways. SN - 1872-7786 UR - https://www.unboundmedicine.com/medline/citation/20850421/Baicalein_inhibits_nuclear_factor_κB_and_apoptosis_via_c_FLIP_and_MAPK_in_D_GalN/LPS_induced_acute_liver_failure_in_murine_models_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0009-2797(10)00552-1 DB - PRIME DP - Unbound Medicine ER -