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

Diabetes Mellitus is one of the most common metabolic disorders. Although oral hypoglycemic drugs are used in the treatment of diabetes, these drugs do not provide a radical cure and can cause adverse effects. Therefore, new agents are still being researched. Herbal sources are an important research topic for discovering new antidiabetic agents. Saffron plant is frequently used in traditional medicine for therapeutic and aromatic purposes. There are many in vivo and clinical studies showing the antidiabetic effects of saffron extract. However, there is not enough information in the literature regarding the antidiabetic effect potential of safranal, one of the active components of saffron. In this thesis, the antidiabetic and potential protective efficacy of saffron against endothelial damage caused by diabetes was investigated. In the study, 40 male 4-month-old Wistar albino rats; healthy control (SK), diabetes control (DM), diabetes + safranal (0.5 mg/kg/day), diabetes + safranal (0.75 mg/kg/day), diabetes + safranal (1 mg/kg/day) were divided into five groups. STZ (50 mg/kg) i.p. was administered to 4 groups except the healthy control group and diabetes model was created by applying this method. Safranal was administered 0.5, 0.75 and 1 mg/kg (i.p.) to the treatment groups for eight weeks. Blood glucose levels and weights of the rats were measured every two weeks. At the end of eight weeks, HbA1c and insulin levels were measured in the blood samples of sacrified rats, and the aorta and pancreas tissues were dissected. Immunohistochemical examination was performed on pancreatic tissues, and VCAM-1 and eNOS gene expression levels were examined by qRT-PCR in one part of the samples taken from thoracic aorta tissues, and relaxation responses in the isolated organ bath in the other part. Three different doses of safranal treatment did not have an effect on weight but lowered blood glucose levels depending on the dose and duration of safranal administration. Safranal reduced HbA1c levels at all treatment doses while significantly increasing insulin levels. The staining prevalence and severity of insulin antibody in pancreatic tissues increased significantly in rats treated with safranal. In isolated thoracic aortic tissues, safranal treatment reduced VCAM-1 gene expression levels compared to the DM group, while eNOS gene expression levels increased significantly. According to isolated organ bath examinations, safranal treatment significantly increased acetylcholine relaxation responses depending on the dose. In conclusion, safranal exhibited antidiabetic activity in rats induced with diabetes by STZ. The potential protective effect of safranal treatment against endothelial dysfunction caused by diabetes was also shown.