Background: Hypoglycemic effect of Juglans regia leaves was reported in other previous researches.

Objective: To investigate the mechanism of hypoglycemic action of Julans regia Leaves Methanolic Extract (JRLME), we designed the following study.

Methods: Male wistar rats were classified in five groups, each of six, including alloxan-induced diabetic rats treated with JRLME at doses of 250 (D+JRLMEa), 500 mg/kg (D+JRLMEb), Acarbose at dose 20 mg/kg (D+Ac), vehicle alone (DC) and normal rats treated with vehicle alone (NC). The Postprandial blood glucose level was examined in a short time (after a single dose treatment) and a long time (after three weeks daily treatment) model. After three weeks of treatment, all groups’ animals were killed to dissect pancreatic and myocardium for RNA extraction and RT-PCR, to assess insulin and glut-4 genes expression, respectively. In addition, other normal rats were killed to extract intestinal brush border membrane for α-glucosidase solution preparation. The effect of JRLMEa on α-glucosidase activity was evaluated by an in vitro method, compared to Acarbose as a reference drug.

Results: The plant extract had a significant hypoglycemic action in both short and long term models. Decrease in PBG level was the most at 8 hour after treatment and more in D+Ac (53%), D+JRLMEa (40%) and D+JRLMEb (29%) versus DC, respectively. There was also permanent PBG reduction in treated groups in comparison with the DC one during long term period.