TY - JOUR AB - Non-alcoholic steatohepatitis (NASH) is characterized by hepatocellular injury and initial fibrosis severity has been suggested as an important prognostic factor of NASH. Silymarin was reported to improve carbon tetrachloride-induced liver fibrosis and reduce the activation of hepatic stellate cells (HSC). We investigated whether silymarin could suppress the activation of HSCs in NASH induced by methionine- and choline-deficient (MCD) diet fed to insulin-resistant rats. NASH was induced by feeding MCD diet to obese diabetic Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Non-diabetic Long-Evans Tokushima Otsuka (LETO) rats were fed with standard chow and served as the control. OLETF rats were fed on either standard laboratory chow, or MCD diet or MCD diet mixed with silymarin. Histological analysis of the liver showed improved non-alcoholic fatty liver disease (NAFLD) activity score in silymarin-fed MCD-induced NASH. Silymarin reduced the activation of HSCs, evaluated by counting α-smooth muscle actin (SMA)-positive cells and measuring α-SMA mRNA expression in the liver lysates as well as in HSCs isolated from the experimental animals. Although silymarin decreased α1-procollagen mRNA expression in isolated HSCs, the anti-fibrogenic effect of silymarin was not prominent so as to show significant difference under histological analysis. Silymarin increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2) and decreased tumor necrosis factor (TNF)-α mRNA expression in the liver. Our study suggested that the possible protective effect of silymarin in diet induced NASH by suppressing the activation of HSCs and disturbing the role of the inflammatory cytokine TNF-α. AD - Department of Internal Medicine, Division of Gastroenterology, Inha University School of Medicine, Jung-Gu, Incheon, Republic of Korea Utah-Inha DDS and Advanced Therapeutics Research Center, Yeonsu-Gu, Incheon, Republic of Korea Department of Pathology, Inha University School of Medicine, Jung-Gu, Incheon, Republic of Korea AU - Kim,Mina AU - Yang,Su-Geun AU - Kim,Joon ,Mi AU - Lee,Jin-Woo AU - Kim,Young ,Soo AU - Lee,Jung ,Il DA - 2012/09/01 DO - 10.3892/ijmm.2012.1029 EP - 479 IS - 3 JO - Int J Mol Med KW - non-alcoholic steatohepatitis methionine- and choline-deficient diet insulin resistance hepatic stellate cell silymarin PY - 2012 SN - 1107-3756 1791-244X SP - 473 ST - Silymarin suppresses hepatic stellate cell activation in a dietary rat model of non-alcoholic steatohepatitis: Αnalysis of isolated hepatic stellate cells T2 - International Journal of Molecular Medicine TI - Silymarin suppresses hepatic stellate cell activation in a dietary rat model of non-alcoholic steatohepatitis: Αnalysis of isolated hepatic stellate cells UR - https://doi.org/10.3892/ijmm.2012.1029 VL - 30 ER -