Baicalein inhibits nuclear factor-κB and apoptosis via c-FLIP and MAPK in D-GalN/LPS induced acute liver failure in murine models.
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.
College of Pharmacy, Yanbian University, Yanji, 133002, Jilin Province, China., ,
CASP8 and FADD-Like Apoptosis Regulating Protein
Disease Models, Animal
Gene Expression Regulation, Enzymologic
Mice, Inbred C57BL
Mitogen-Activated Protein Kinases
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