Effects of silibinin on antidiabetic and endothelial dysfunction in streptozotocin-induced diabetic rats

Diabetes mellitus (DM) is a chronic metabolic disease characterized by hyperglycemia and results from impaired insulin secretion, insulin action, or both. In spite of progress in the treatment of DM, it's not at all time possible to achieve therapeutic goals. This situation leads patients to turn to "complementary" medical alternatives in addition to DM treatment. Supplementary foods containing herbal medicinal products are widely used by healthy individuals and individuals with DM. In this study, the effects of silibinin, one of the active components of the Silybum marianum plant, on antidiabetic and endothelial dysfunction in healthy and streptozotocin (STZ)-induced experimental type I diabetes (T1DM) rats were investigated. In this study, 48 male Wistar albino rats weighing 350-440 g were used. Rats were randomly divided into 6 groups: healthy control (SK), diabetes control (DMK), SLB30 (silibinin 30 mg/kg), SLB60 (silibinin 60 mg/kg), DM+SLB30 (diabetes + silibinin 30 mg/kg), DM+SLB60 (diabetes + silibinin 60 mg/kg). To induce experimental T1DM, a single dose of 50 mg/kg STZ was administered to the DMK, DM+SLB30, DM+SLB60 groups, and the diabetes model was confirmed 72 hours after STZ administration. Silibinin was administered to SLB30, SLB60, DM+SLB30, DM+SLB60 groups for 8 weeks at two different doses: 30 mg/kg and 60 mg/kg. Blood glucose level and body weight measurements were made every two weeks. At the end of the 8th week, aorta, pancreatic tissues and blood samples were taken from the rats under anesthesia. Besides VCAM-1 and eNOS gene expression measurements by qRT-PCR in thoracic aortic tissues, acetylcholine-induced relaxation responses in isolated organ bath in vitro were investigated. Pancreatic tissues were examined immunohistochemically using rat insulin antibodies. HbA1c and insulin levels were measured from the blood samples taken. Silibinin treatment decreased hyperglycemia and HbA1c levels, and increased insulin levels in rats with STZ-induced T1DM. In addition, the intensity and prevalence of insulin antibody staining in pancreatic tissues of rats with T1DM treated with silibinin were increased compared to DMK. In addition, silibinin increased eNOS expression and decreased VCAM-1 expression. In parallel with the increase in eNOS expression, acetylcholine caused more relaxation than DMK in the aortic tissues of silibinin treatment groups with T1DM. In the study, healthy rats treated with high doses of silibinin had increased eNOS expressions. In conclusion, our findings from this study suggest that silibinin treatment can improve hyperglycemia, hypoinsulinemia and pancreatic damage in T1DM. It also shows that by increasing eNOS expressions, it may be protective on endothelial dysfunction in both healthy and T1DM.