Antidiabetic and gastric emptying inhibitory effect of herbal <em>Melia azedarach</em> leaf extract in rodent models of diabetes type 2 mellitus

Abstract

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 <i>Melia azedarach</i> are used to control diabetes mellitus and various gastrointestinal disorders. The objective of this study was to clarify the antidiabetic effects of <i>M. azedarach</i> leaf extracts in diabetic type 2 experimental animals. In this study, mice were injected with <i>Melia</i> 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. <i>Melia</i> extracts displayed acute, dose-dependent antidiabetic effects in ob/ob mice similar to glibenclamide (<i>p</i><0.05-0.001). Long-term administration of <i>Melia</i> extract reduced plasma glucose (<i>p</i><0.001) and insulin (<i>p</i><0.01-0.001) levels over 21 days, concurrent with body weight loss. Glucose tolerance test showed reduced basal glucose levels (<i>p</i><0.05-0.01), but no difference was found in glucose disposal after long-term treatment with <i>Melia</i> extract. In addition, the <i>Melia</i> extract at 400 mg/kg slowed gastric emptying rate of normal Sprague-Dawley (<i>p</i><0.001) and diabetic Goto-Kakizaki rats (<i>p</i><0.001) compared with controls. It is concluded that the <i>M. azedarach</i> 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.