Daniel Seifu, Lars E Gustafsson, Rajinder Chawla, Solomon Genet, Asfaw Debella, Mikael Holst, Per M Hellström

Diabetes type 2 is associated with impaired insulin production and increased insulin resistance. Treatment with antidiabetic drugs and insulin strives for normalizing glucose homeostasis. In Ethiopian traditional medicine, plant extracts of Melia azedarach are used to control diabetes mellitus and various gastrointestinal disorders. The objective of this study was to clarify the antidiabetic effects of M. azedarach leaf extracts in diabetic type 2 experimental animals. In this study, mice were injected with Melia extract intraperitoneally. Plasma glucose was studied by using tail vein sampling in acute experiments over 4 h and chronic experiments over 21 days with concurrent insulin and body weight assessments. Glucose tolerance was studied by using intraperitoneal glucose (2 mg/g) tolerance test over 120 min. Gastric emptying of a metabolically inert meal was studied by the gastric retention of a radioactive marker over 20 min. Melia extracts displayed acute, dose-dependent antidiabetic effects in ob/ob mice similar to glibenclamide (p<0.05-0.001). Long-term administration of Melia extract reduced plasma glucose (p<0.001) and insulin (p<0.01-0.001) levels over 21 days, concurrent with body weight loss. Glucose tolerance test showed reduced basal glucose levels (p<0.05-0.01), but no difference was found in glucose disposal after long-term treatment with Melia extract. In addition, the Melia extract at 400 mg/kg slowed gastric emptying rate of normal Sprague-Dawley (p<0.001) and diabetic Goto-Kakizaki rats (p<0.001) compared with controls. It is concluded that the M. azedarach leaf extract elicits diabetic activity through a multitargeted action. Primarily an increased insulin-sensitizing effect is at hand, resulting in blood glucose reduction and improved peripheral glucose disposal, but also through reduced gastric emptying and decreased insulin demand.