title: Antidiabetic and gastric emptying inhibitory effect of herbalMelia azedarachleaf 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 ofMelia azedarachare used to control diabetes mellitus and various gastrointestinal disorders. The objective of this study was to clarify the antidiabetic effects ofM. azedarachleaf extracts in diabetic type 2 experimental animals. In this study, mice were injected withMeliaextract 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.Meliaextracts displayed acute, dose-dependent antidiabetic effects in ob/ob mice similar to glibenclamide (p<0.05-0.001). Long-term administration ofMeliaextract 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 withMeliaextract. In addition, theMeliaextract 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 theM. azedarachleaf 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.
authors.affiliation: Department of Biochemistry, College of Health Sciences, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia; Department of Medical Sciences, Uppsala University, Uppsala.
authors.forename: Daniel
authors.initials: D
authors.lastname: Seifu
authors.affiliation: Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Lars E
authors.initials: LE
authors.lastname: Gustafsson
authors.affiliation: Department of Biochemistry, College of Health Sciences, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Rajinder
authors.initials: R
authors.lastname: Chawla
authors.affiliation: Department of Biochemistry, College of Health Sciences, School of Medicine, Addis Ababa University, Addis Ababa, Ethiopia.
authors.forename: Solomon
authors.initials: S
authors.lastname: Genet
authors.affiliation: Department of Traditional Drug Development, Ethiopian Health and Nutrition Research Institute, Addis Ababa, Ethiopia.
authors.forename: Asfaw
authors.initials: A
authors.lastname: Debella
authors.affiliation: Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Holst
authors.affiliation: Department of Medical Sciences, Uppsala University, Uppsala.
authors.forename: Per M
authors.initials: PM
authors.lastname: Hellström
keywords: Goto-Kakizaki; Sprague-Dawley; glucose tolerance test; ob/ob mouse