The present study aimed to investigate the antidiabetic and anti-inflammatory effects of Trifolium alexandrinum (TA) and Trifolium Pretense (TP) against streptozotocin induced diabetic impairment in male rats. Forty adult Wistar albino male rats were divided into four groups: Group 1, Control; Group 2, streptozotocin (STZ); Group 3, STZ + TA -treated group and Group 4, STZ + TP-treated group. TA and TP showed a significant reduction in the blood glucose, glycosylated hemoglobin (Hb A1C) levels and elevation in insulin and C-peptide. They restored the glycogen content of liver and skeletal muscle, also showed improvements in the activities of α-amylase, carbohydrate metabolic enzymes, lipase and lipid profile. Treatment with TA and TP extracts resulted in an improvement of the oxidative parameters and enhancement in the antioxidant enzymes in the pancreas and liver. While, pancreatic TNF-α, IL-1β, IL-6, NO, iNos and caspase-3 levels were significantly reduced with the treatment of TA and TP extracts. Administration of TA and TP extracts to diabetic rats revealed elevation in the GLUT4 levels of the skeletal muscle and pancreas. They caused up regulation in pancreatic GLUT2 gene expression. TA and TP extracts showed signs of regeneration of β-cells and improvement in the pancreatic tissue. It could be concluded that TA and TP extracts possess antioxidant and hypoglycemic potential resulting in reduction of the elevated oxidative stress and pro-inflammatory cytokines.

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