Effects of Salvia mirzayanii extract administration on hyperglycemia improvement in diabetic rats: The role of GLUT4, PEPCK and G6Pase genes

Diabetes is a dangerous metabolic disorder by increasing incidence in human societies worldwide. Recently, much attention has been focused on the development of hypoglycemic agents, particularly the derivatives of herbal drugs, in the treatment of diabetes. This research aimed to study the anti -diabetic effect of Salvia mirzayanii in the diabetic rat models. First, the plant material was extracted from the leaves, and orally administered to the rats. After treating the animals with the aqueous extract of S. mirzayanii at a dose of 600 mg/kg, animal body weight for 12 weeks, fasting blood glucose, oral glucose tolerance test (OGTT), and body weight changes were examined. To analyze the anti -diabetic function of S. mirzayanii, we measured the expression of glucose transporter -4 (GLUT4), phosphoenolpyruvate carboxykinase (PEPCK), and glucose 6-phosphatase (G6Pase) genes in healthy and streptozotocin (STZ)-diabetic rats. The expression levels of the genes of interest in muscle and liver tissues were determined using reverse transcriptionquantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry (IHC). There were no significant differences in fasting blood glucose and OGTT between normal control (NC) group and the diabetic control (DC) group treated with S. mirzayanii. In contrast, there was a significant difference with the untreated DC (P < 0.05). The treatment of diabetic rats with S. mirzayanii significantly increased the expression of GLUT4 in the muscle and decreased the expression levels of PEPCK and G6Pase in the liver compared to the DC group (P < 0.05). These findings clearly show that S. mirzayanii can improve hyperglycemia by increasing the GLUT4 expression, and inhibiting the gluconeogenesis pathway in the liver. In general, the obtained results provided a new insight into the efficacy of S. mirzayanii aqueous extract as an anti -diabetic herbal medicine.