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The effect of silibinin on non-alcoholic fatty liver disease (NAFLD) and the role of BECLIN-1 (Master thesis)

Κατσαρός, Ιωάννης/ Katsaros, Ioannis

Non-alcoholic fatty liver disease (NAFLD) the most common liver disease in Western countries. It is the result of adipose deposits in hepatocytes and is associated with metabolic syndrome. Silibinin, a natural flavonolignan, has hepatoprotective properties, due to its antioxidative, anti-inflammatory and antifibrotic action. Beclin1 is a protein of the Bcl-2 family and plays a crucial role in the autophagy. The aim of this study was to elucidate the role of silibinin on NAFLD and its effect on the expression of Beclin1 in an experimental model. MATERIALS AND METHODS Thirty-five male C57BL/6J (wild type) mice were fed high fat diet-HFD for 12 weeks. Then, they were randomized in three groups; baseline group (n=11), which were euthanized after the 12-week period, control group (n=12), which received HFD and 200μL water for injection daily for 4 weeks; silibinin group (n=12), which received HFD and silibinin 5mg/kg daily for 4 weeks. Histopathological evaluation of liver specimens was done utilizing NAS, whereas immunochemistry followed to assess Beclin1. RESULTS In total, mice had a NAS of 4.71±1.67 and 40% of them suffered from NASH. Control group had the highest NAS score (5.83±1.27) compared to both silibinin (4.5±1.57) and baseline (3.73±1.56). This finding was attributed mainly to the steatosis component, where control group had 59.17±25.39% steatosis compared to 27.6728.41 % for silibinin group and 9.09 ±11.9% for baseline group. Control group exhibited significantly higher rates of NASH compared to both silibinin group (OR:10,0; 95% CI:1.44–69.26; p-value:0.020) and baseline group (OR:96.6; 95% CI:4.14–2253.28; p-value: 0.004), but no significant difference was found between silibinin and baseline groups. Most mice (74.14%) had weak Beclin1 expression with a mean of 11.29±8.34 %. No difference was found between all three groups. CONCLUSIONS In conclusion, silibinin has a hepatoprotective effect on NAFLD by mainly lowering the steatosis of liver cells.