Anti-fibrotic effects of Silimarit® dry extract in the STAM™ model of non-alcoholic steatohepatitis

Non-alcoholic fatty liver disease (NAFLD)/non-alcoholic steatohepatitis (NASH) is a major health concern in western countries with increasing prevalence. Until now, effective therapies are missing and the most effective way treating NASH/NAFLD is a change in nutrition and life style. The search for novel therapeutic agents is a challenging problem, because most of the in vivo models fail to represent the situation in disease progression in humans. Milk thistle, Silybum marianum, is a traditionally used medical plant for the treatment of liver injuries. Its potential in NAFLD/NASH is only poorly characterized. In this study the STAM™ model, a preclinically validated animal model, was applied to induce NAFLD/NASH-like symptoms in mice. 6 weeks after NAFLD/NASH induction mice received a standardized milk thistle extract (Silimarit®, 20 and 100 mg/kg each day). After 9 weeks body weight, serum parameters, liver damage, fibrosis, and steatosis were analyzed. Histological analysis of vehicle-treated control animals revealed severe symptoms of NAFLD/NASH which was indicated by fat accumulation in hepatocytes and fibrosis of liver tissue. Additionally, body weight decreased and serum parameters like blood glucose and triglceride levels increased. Treatment with Silybum marianum extract had no effect on body weight, blood glucose and triglycerid levels. However, histological analysis of sirius red staining showed a marked effect of Silybum marianum extract on the development of fibrosis. The extract significantly reduced fibrotic areas of the liver which were stained positive for Sirius red.