Comparative study of anti-diabetic effects of insulin, epigenin and Salvia mirzayanii extract in streptozotocin-induced diabetic male rats

The use of hypoglycemic medications for diabetes has several limitations, such as adverse reactions and high rates of secondary failure. These adverse effects have forced patients with diabetes to use herbal medicines that have a similar degree of potency without side effects. So, there has been a growing interest in hypoglycemic agents from natural products, in particular, those derived from plant materials. In other words, searching for better agents from herbs or natural products to treat diabetes is duly needed. The purpose of this study was to compare the anti-diabetic effects of Salvia mirzayanii extract with insulin and epigenin in diabetic male rats. The plant material was initially extracted and administered orally to the animals. After treatment of rats with insulin, epigenin or aqueous extract of S. mirzayanii, oral glucose tolerance test (OGTT), fasting blood glucose and animal weight changes were examined. To analyze the molecular function of insulin, epigeninand S. mirzayanii, expression of glucose transporter-4 (GLUT4), phosphoenol pyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase) genes in healthy and streptozotocin (STZ)-diabetic male rats were studied as well. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) was performed for all groups and the data were normalized using the formula 2-ΔΔCt.Statistical analysis was performed by one-way analysis of variance. In fasting blood glucose and OGTT, there was no significant difference between the normal control group and the diabetic groups treated with insulin, epigenin and S. mirzayanii. But there was a significant difference with the uncontrolled diabetic group (P < 0.05). Meanwhile, the uncontrolled diabetic group gained less weight compared to the other groups. RT-qPCR of beta-actin, GLUT4, G6Pase and PEPCK genes yielded products with lengths of 228, 140, 79 and 151 bp, respectively. In gene expression studies, there was a significant difference between the mRNA levels of GLUT4, G6Pase and PEPCK in control groups and the groups treated with insulin, epigenin and S. mirzayanii. The greatest effect on increasing the mRNA expression of GLUT4 was related to insulin, epigenin and S. mirzayanii, respectively. The greatest effect in reducing the mRNA expression of PEPCK was related to insulin, epigenin and S. mirzayanii, respectively. The greatest effect in reducing the mRNA expression of G6Pase was also related to insulin, but the effect of epigenin and S. mirzayaniiwas almost the same. Overall, obtained results show that S. mirzayanii can be utilized as a herbal medication with insulin and epigenin mimetic-activity.