acanthoic-acid and Liver-Diseases--Alcoholic

In alcoholic liver disease, alcohol and lipopolysaccharide (LPS) are major stimulation factors of hepatic lipogenesis. Our objective was to determine the protective mechanism of acanthoic acid (AA) in EtOH- and LPS-induced hepatic lipogenesis.. HSC-T6 cells were treated with ethanol (200 mm) plus LPS (1 μg/ml) for 1 h, followed by AA (10 or 20 μm) for another 6 h. C57BL/6 mice were pretreated with of AA (20 and 40 mg/kg) or equal volume of saline and then exposed to three doses of ethanol (5 g/kg body weight) within 24 h. The mice were sacrificed at 6 h after the last ethanol dosing.. Acanthoic acid significantly decreased the expressions of α-SMA, collagen-I, SREBP-1, and lipin1/2 induced, also decreased fat droplets caused by EtOH/LPS. AA treatment decreased the protein expressions of TLR4, CD14, IRAK4, TRAF3, p-TAK1 and NF-κB increased by EtOH/LPS on HSC cells. Results in vivo were consistent with results in vitro.. Our data demonstrated that AA might modulate hepatic fibrosis and lipid deposition in HSC-T6 cell stimulated with ethanol combined with LPS by decreasing lipin1/2 via TLR4 and IRAK4 signalling pathways, and AA might be considered as a potential therapeutic candidate for alcoholic liver disease.

Topics: Actins; Animals; Cells, Cultured; Collagen; Diterpenes; Ethanol; Lipogenesis; Lipopolysaccharide Receptors; Lipopolysaccharides; Liver; Liver Diseases, Alcoholic; MAP Kinase Kinase Kinases; Mice; NF-kappa B; Phosphatidate Phosphatase; Protein Serine-Threonine Kinases; Rats; Signal Transduction; Sterol Regulatory Element Binding Proteins; TNF Receptor-Associated Factor 3; Toll-Like Receptor 4