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Silybin counteracts lipid excess and oxidative stress in cultured steatotic hepatic cells

World Journal of Gastroenterology 2016年第26期22卷 6016-6026页

作者： Giulia Vecchione Elena Grasselli Adriana Voci Francesca Baldini Ignazio Grattagliano David QH Wang Piero Portincasa Laura Vergani DISTAV Department of Earth Environment and Life Sciences University of Genova Department of Biomedical Sciences and Human Oncology University School of Medicine Department of Internal Medicine Division of Gastroenterology and Hepatology Saint Louis University School of Medicine

AIM: To investigate in vitro the therapeutic effect and mechanisms of silybin in a cellular model of hepatic ***: Rat hepatoma FaO cells were loaded with lipids by exposure to 0.75 mmol/L oleate/palmitate for 3 h to mimic liver steatosis. Then, the steatotic cells were incubated for 24 h with different concentrations (25 to 100 μmol/L) of silybin as phytosome complex with vitamin E. The effects of silybin on lipid accumulation and metabolism, and on indices of oxidative stress were evaluated by absorption and fluorescence microscopy, quantitative real-time PCR, Western blot, spectrophotometric and fluorimetric ***: Lipid-loading resulted in intracellular triglyceride (TG) accumulation inside lipid droplets, whose number and size increased. TG accumulation was mediated by increased levels of peroxisome proliferator-activated receptors (PPARs) and sterol regulatory element-binding protein-1c (SREBP-1c). The lipid imbalance was associated with higher production of reactive oxygen species (ROS) resulting in increased lipid peroxidation, stimulation of catalase activity and activation of nuclear factor kappa-B (NF-κB). Incubation of steatotic cells with silybin 50 μmol/L significantly reduced TG accumulation likely by promoting lipid catabolism and by inhibiting lipogenic pathways, as suggested by the changes in carnitine palmitoyltransferase 1 (CPT-1), PPAR and SREBP-1c levels. The reduction in fat accumulation exerted by silybin in the steatotic cells was associated with the improvement of the oxidative imbalance caused by lipid excess as demonstrated by the reduction in ROS content, lipid peroxidation, catalase activity and NF-κB ***: We demonstrated the direct anti-steatotic and anti-oxidant effects of silybin in steatotic cells, thus elucidating at a cellular level the encouraging results demonstrated in clinical and animal studies.

关键词： Non-alcoholic fatty liver disease Steatotic hepatocytes Silybin Lipid metabolism Oxidative stress Lipid droplets Mitochondrial β -oxidation

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