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 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.

First report on the presence of Alloxan in bleached flour by LC-MS/MS method

“…Since 1943, it was found to have toxicological effects on pancreatic b-cells leading to diabetogenic action, therefore (Jacobs, 1937;Pincus, 2013) is commonly employee for the development of Type-I Diabetes Mellitus in animal models. (Carvalho et al, 2003;Dunn et al, 1943;Goldner and Gomori, 1943;Lenzen and Panten, 1988;Saadia et al, 2005;Saleem Mir et al, 2013;Seifu et al, 2017;Shaw Dunn and Mcletchie, 1943;Szkudelski, 2001;Webb, 1966).…”

Ethnomedicinal Investigation of Medicinal Plants of Chakrata Region (Uttarakhand) Used in the Traditional Medicine for Diabetes by Jaunsari Tribe

“…It increased glucose-6-phosphate dehydrogenase activity and hepatic, skeletal muscle glycogen content, after 21 days of treatment. The study revealed the regeneration of insulin-producing cells and a corresponding increase in the plasma insulin and c-peptide levels with the treatment [ 60 ] Melia azedarach L. Mahaneem (S), Bakain (H), Persian lilac (E) Tree (W/C)/all parts Azedarachic acid ( 15 ), nicotinic acid, gallic acid, para-coumaric acid, vanillic acid, chlorogenic acid, syringic acid, caffeic acid, ferulic acid, fatty acids (caproic, palmitic, stearic, oleic, linoleic, and linolenic acid) [ 61 ] The decoction of aerial parts is taken in the morning (1) Bioassay-guided fractions and isolates of fruits and leaves showed inhibitory effects on protein tyrosine phosphatase-1B enzyme as well as glucose uptake stimulation on C 2 Cl 2 myoblasts cells in vitro [ 62 ] (2) Aqueous leaf extracts (300, and 400 mg/kg, intraperitoneal) displayed anti-diabetic on type 2 mice [ 63 ] Menispermaceae Cissampelos pareira L. Patha (S), midwife’s herb (E), Padi/Parh (L) Climber (W/C)/whole plant Pelosine, l -curine, hayatinine, hayatidine, cissampareine, cissamine, dicentrine, cycleanine, insularine, cycleanine, nuciferine, bulbocarpine, corytuberine, magniflorine, norimeluteine, pareitropone, berberine (8), reserpine [ 64 ] The dried root powder (half teaspoon) is taken with water once a day for 40 days The hydro-alcoholic leaves extract (200 and 400 mg/kg, p.o.) showed anti-diabetic activity by decreasing fasting blood glucose and increasing the body weight of on STZ-induced diabetic rats when compared to glibenclamide (5 mg/kg) [ 65 ] Stephania glabra (Roxb.)…”

“…(2) Aqueous leaf extracts (300, and 400 mg/kg, intraperitoneal) displayed anti-diabetic on type 2 mice [ 63 ]…”

Implications for Drug Characterization in Glucose Tolerance Tests Without Insulin: Simulation Study of Power and Predictions Using Model‐Based Analysis

“…These samples are analyzed with regard to glucose and insulin to generate dynamic profiles in the absence and presence of the study compound. Preclinically, the glucose protocols differ slightly from other glucose administrations (e.g., intraperitoneal), different duration of, or no, fasting prior to glucose challenge, but, most importantly, sometimes only measuring glucose …”

“…Preclinically, the glucose protocols differ slightly from other glucose administrations (e.g., intraperitoneal), different duration of, or no, fasting prior to glucose challenge, but, most importantly, sometimes only measuring glucose. [6][7][8] Pharmacometric analysis based on time-course data is increasingly used in drug development, due to its integrative nature and the ease with which it can handle dynamic relationships. [9][10][11] There are several examples in which pharmacometric analysis has been shown to be highly powerful in phase II trials.…”