Polyphenol from Rosa roxburghii Tratt Fruit Ameliorates the Symptoms of Diabetes by Activating the P13K/AKT Insulin Pathway in db/db Mice

About 4% of the world's population has type 2 diabetes mellitus (T2DM), and the available hypoglycemic drugs for treating diabetes have some side effects. Therefore, research on the extraction of hypoglycemic components from plants has gradually become popular. This study aimed to investigate the hypoglycemic effects of polyphenol-rich Rosa roxburghii Tratt extract (RP) isolated from Rosa roxburghii Tratt fruit and of four constituents (IRP 1-4 ) isolated from RP on db/db mice. The results indicated that the oral administration of RP and IRP 1-4 could markedly decrease the food intake, water intake, fasting blood glucose (FBG), and serum insulin levels in the db/db mice. Glucose intolerance, insulin resistance, and oxidative stress were ameliorated in the RP and IRP 1-4 groups. Histopathological observation revealed that RP and IRP 1-4 could effectively protect the liver fat against damage and dysfunction. RP and IRP 1-4 also increased the hepatic and muscle glycogen contents by increasing the phosphorylation and reducing the expression of glycogen synthase kinase 3 beta (GSK3 beta). The activities of glucokinase (GCK), phosphoenolpyruvate carboxylase (PEPCK), and glucose-6-phosphatase (G6PC) and their respective mRNA expression levels in the liver of db/db mice were simultaneously increased and decreased in the intervention groups. RP and IRP 1-4 significantly increased the expression of phosphatidylinositol 3-kinase (P13K) and the phosphorylation of protein kinase B (AKT). These results indicate that RP and IRP 1-4 exhibit good hypoglycemic effects by activating the P13K/AKT signaling pathway and regulating the expression of FOXO1 and p-GSK3 beta proteins, controlling hepatic gluconeogenesis and improving hepatic glycogen storage insulin resistance. Therefore, RP and IRP 1-4 could be utilized as the hypoglycemic functional component to alleviate the symptoms of T2DM.