acacetin and Liver-Failure--Acute

This study examined the hepatoprotective effects of acacetin (1), a flavonoid isolated from Agastache rugosa, against d-galactosamine (GalN) and lipopolysaccharide (LPS)-induced fulminant hepatic failure. Mice were given an intraperitoneal injection of 1 (25, 50, and 100 mg/kg), or the vehicle alone (5% dimethyl sulfoxide-saline), 1 h before GalN (800 mg/kg)/LPS (40 μg/kg) treatment and sacrificed at 6 h after GalN/LPS injection. GalN/LPS markedly increased mortality and serum aminotransferase activity, and these increases were attenuated by 1. GalN/LPS increased serum tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels, while 1 attenuated TNF-α levels and further increased IL-6 levels. GalN/LPS increased protein expression of toll-like receptor 4, phosphorylation of extracellular signal-related kinase, and p38 and c-Jun N-terminal kinase and increased nuclear protein expression of nuclear factor κB; these increases were attenuated by 1. GalN/LPS increased Atg5 and Atg7 protein expressions, and these increases were augmented by 1. GalN/LPS activated autophagic flux as indicated by decreased microtubule-associated protein 1 light chain 3-II and sequestosome1/p62 protein expression. This activation was enhanced by 1. These findings suggest that 1 protects against GalN/LPS-induced liver injury by suppressing TLR4 signaling and enhancing autophagic flux.

Topics: Animals; Flavones; Galactosamine; Interleukin-6; JNK Mitogen-Activated Protein Kinases; Lipopolysaccharides; Liver; Liver Failure, Acute; Male; Mice; Molecular Structure; NF-kappa B; Phosphorylation; Plant Components, Aerial; Republic of Korea; Signal Transduction; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha