Beneficial effects of silibinin against the progression of metabolic syndrome, increased oxidative stress, and liver steatosis in Psammomys obesus, a relevant animal model of human obesity and diabetes (在一种与人类肥胖以及糖尿病相关的动物模型肥沙鼠中，水飞蓟素具有拮抗代谢综合征进展、拮抗氧化应激增加以及拮抗肝脏脂肪变性的有益作用)

Abstract

Insulin resistance and oxidative stress are major pathogenic mechanisms leading to chronic liver diseases in diabetic subjects. The gerbil Psammomys obesus is a unique model of nutritional diabetes resembling the disease in humans. This study investigated whether the natural ingredient silibinin, known as hepatoprotective, could decrease oxidative stress and reduce liver damage in obese gerbils. Control animals were fed their vegetable-based low caloric diet while two other rat groups ingested a high calorie diet for 14 weeks. Silibinin, or its vehicle, was administrated by gastric intubation (100 mg/kg per day) from the 7th week of treatment, which corresponds to an established insulin resistance state. At the end of the experiments, the hepatic biochemical profile, markers of oxidative stress in either plasma or liver tissue, and histological alterations were examined. Diabetic P. obesus displayed many metabolic disturbances (hyperinsulinemia, hyperglycemia, dyslipidemia), which were aggravated for the last 8 weeks. These events were coupled with greater oxidative stress (decline in glutathione, rise in lipoperoxidation). In addition, glutathione peroxidase activity was reduced while the level of superoxide dismutase was elevated. Interestingly, treatment with silibinin alleviated most of the metabolic defects, especially high triglyceride levels, reduced insulin resistance and largely restored antioxidant status. Also, Masson's trichrome staining revealed distinct steatosis, yet silibinin partially reversed this manifestation. Silibinin affords substantial protection against the progression of insulin resistance in Type 2 diabetes mellitus for P. obesus by hampering the oxidative process and improving hepatic metabolism.