Study of the Antidiabetic Activity of Punica granatum L. Fruits Aqueous Extract on the Alloxan-Diabetic Wistar Rats

Iran J Pharm Res. 2019 Winter;18(1):358-368.

Abstract

Pancreatic β-cells dysfunction and impairment of insulin action usually leads to hyperglycemia. Punica granatum L. is a well-known traditional herbal remedy in Iran due to its positive effects on ameliorating blood glucose homeostasis. In this study, Alloxan-diabetic male Wistar rats were administrated with pomegranate fruits aqueous extract (PE) in different doses of 100, 200, and 350 mg/kg bw (PE+Da, PE+Db and PE+Dc, respectively), and the effects of PE polyphenols content on glucose metabolism in treated groups were examined using oral glucose tolerance test (OGTT), short-term and long-term PE consumption periods models followed by evaluation of plasma insulin, free fatty acids, and triglycerides levels and tissues contents of glycogen and triglycerides; compared with diabetic control (DC) and healthy control (NC) groups. By using Real-time PCR, the possibility of modulations of the Insulin receptor substrate 1 (IRS-1), Protein kinase B (Akt), Glucose transporter 2 and 4 (Glut-2, 4) mRNAs expression levels in PE treated rats were investigated. The obtained data showed noticeable reduction in fasting blood glucose (FBG) by 28.1% and 67.9% in short-term and long-term treatment models, respectively, in PE + Dc group. Also, there existed marked increase in the mRNAs expression levels of IRS-1, Akt, Glut-2, and Glut-4, which results in improvement of glucose uptake and promotes its storage. Taking together, it is suggested that PE administration contributes to the modulation of both hyperglycemia and hyperlipidemia in Alloxan-diabetic Wistar rats.

Keywords: Alloxan monohydrate; Diabetes mellitus; Glucose uptake and storage; Insulin expression and secretion; Insulin signaling mediators; Pomegranate fruits aqueous extract.