Effects of Hydroxysafflor Yellow A on the PI3K/AKT Pathway and Apoptosis of Pancreatic beta-Cells in Type 2 Diabetes Mellitus Rats

Background and Aim: Type 2 diabetes mellitus (T2DM), a complex metabolic disease, has become a major public health issue around the world. Hydroxysafflor yellow A (HSYA) is the major active chemical ingredient of Carthamus tinctorius L. (safflower), which is widely used in patients with cardiovascular and cerebrovascular diseases in China. The aim of this study was to investigate the anti-diabetic effect and potential mechanism of HSYA on the high-fat diet (HFD) and streptozotocin (STZ-)-induced T2DM rats. Materials and Methods: T2DM rats were induced by feeding HFD (60% fat) for four weeks followed by intraperitoneal injection of a low dose of streptozocin (35mg/kg). The T2DM rats were treated with HSYA (120mg/kg) or metformin (90mg/kg) for eight weeks. Biochemical analysis, histological analysis and Western blot analysis were conducted after 8 weeks of intervention. Results: The treatment with HSYA evidently reduced fasting-blood glucose and insulin resistance in T2DM rats, indicated by results from fasting-blood glucose, oral glucose tolerance test, fasting insulin levels and histology of pancreas islets. The Western blot results revealed that HSYA reversed the down-regulation of PI3K and AKT in liver. The TUNEL assay analysis of pancreatic tissue showed that HSYA could inhibit the apoptosis of pancreatic beta-cells to a certain extent. Moreover, HSYA-treatment increased the levels of glycogen synthase and hepatic glycogen and improved lipid metabolism by reducing the triglyceride, total and low-density lipoprotein cholesterol levels, even though it did not change the rats' body weights. Conclusion: The results of this study suggested that HSYA could promote PI3K/Akt activation and inhibit the apoptosis of pancreatic beta-cells directly or indirectly, which might be the underlying mechanisms in HSYA to improve insulin resistance and regulate glycolipid metabolism in T2DM rats.