In vivo recovery effect of silibinin treatment on streptozotocin-induced diabetic mice is associated with the modulations of sirt-1 expression and autophagy in pancreatic [beta]-cell

• Published in: Journal of asian natural products research 2012-05, Vol.14 (5), p.413
• Main Authors: Wang, Qiong, Liu, Miao, Liu, Wei-Wei, Hao, Wen-Bo, Tashiro, Shin-ichi, Onodera, Satoshi, Ikejima, Takashi
• Format: Article
• Language: English
• ISSN: 1028-6020; 1477-2213
• DOI: 10.1080/10286020.2012.657180

Improper adjustments of autophagy and silent information regulator 1 (Sirt-1) expression were reported to be closely associated with metabolic disorders. In this study, we examined the roles of Sirt-1 and autophagy in streptozotocin-induced diabetes mellitus, assessed the relationship between autophagy and Sirt-1, and investigated the protective mechanism of silibinin. Diabetes was induced in 6-week-old mice by intravenous injection of streptozotocin (150 mg/kg/day, for 2 weeks). In the treatment groups, silibinin (50 mg/kg/day, intramuscular injection, for 8 weeks) or inhibitors (50 mg/kg/day, subcutaneous injection, for 8 weeks) were given. Diabetic control animals received vehicle for the same time. Compared with diabetic controls, silibinin or autophagy inhibitor, 3-methyladenine, treated mice showed decreased levels of glycosylated hemoglobin A1C (P < 0.01), serum triglyceride (P < 0.01), cholesterol (P < 0.01), blood glucose (P < 0.05), autophagy (P < 0.05), and apoptosis ratio (P < 0.05) of pancreatic [beta]-cells. Systemic administration of silibinin reversed streptozotocin-induced downregulation of Sirt-1 expression. Sirt-1 may play a role in regulating the physiological level of autophagy and is associated with loss of pancreatic [beta]-cells and metabolic biochemical disorders. Through promoting Sirt-1 expression and recovering autophagy physiologically, silibinin may reverse hyperglycemia and repair damaged pancreatic [beta]-cells. [PUBLICATION ABSTRACT]