Background: Glucose-lowering effects of Moringa oleifera extracts have been reported. However, the mechanism for its hypoglycemic effects is not yet understood. This study investigated the effect of oral administration of methanolic extracts of M. oleifera (MOLE) on glucose tolerance, glycogen synthesis, and lipid metabolism in rats with alloxan-induced diabetes. Methods: MOLE was screened for key phytochemicals and its total flavonoids and phenolic contents were quantified. Diabetes was induced by intraperitoneal injection of 120 mg/kg BW alloxan. Normal and diabetic control rats received saline, while rats in other groups received 300 or 600 mg/kg body weight of MOLE or metformin (100 mg/kg body weight of metformin) for 6 weeks. Food intake and body weight were monitored throughout the experiment. Intraperitoneal glucose tolerance was assessed and serum glucose, insulin, and lipids were measured at the end of the experiment. Liver and muscle glycogen synthase activities, glycogen content, and glucose uptake were determined. Results: Administration of MOLE did not affect food intake but inhibited weight loss, significantly (p<0.01) improved glucose tolerance, and increased serum insulin levels by 1.3–1.7-fold (p<0.01). MOLE treatment significantly (p<0.001) reduced serum concentrations of triglyceride, total cholesterol, and low-density lipoprotein (LDL)-cholesterol and enhanced serum level of high-density lipoprotein (HDL) by 2.4- to 3.2-fold (p<0.001). Glycogen synthase activities and glycogen contents were higher in MOLE-treated rats compared with rats receiving metformin or saline and the extract improved glucose uptake by 49%–59% (p<0.01). Conclusions: These results showed that hypoglycemic effects of MOLE might be mediated through the stimulation of insulin release leading to enhanced glucose uptake and glycogen synthesis.
1 February 2016 in International Journal of Pharmaceutics
The aim of this study was to design a controlled release vehicle for insulin to preserve its stability and biological activity during fabrication and release. A modified, double emulsion, solvent evaporation, technique using homogenisation force optimised entrapment efficiency of insulin into biodegradable nanoparticles (NP) prepared from poly (DL-lactic-co-glycolic acid) (PLGA) and its PEGylated diblock copolymers. Formulation parameters (type of polymer and its concentration, stabiliser concentration and volume of internal aqueous phase) and physicochemical characteristics (size, zeta potential, encapsulation efficiency, in vitro release profiles and in vitro stability) were investigated. In vivo insulin sensitivity was tested by diet-induced type II diabetic mice. Bioactivity of insulin was studied using Swiss TO mice with streptozotocin-induced type I diabetic profile. Insulin-loaded NP were spherical and negatively charged with an average diameter of 200-400 nm. Insulin encapsulation efficiency increased significantly with increasing ratio of co-polymeric PEG. The internal aqueous phase volume had a significant impact on encapsulation efficiency, initial burst release and NP size. Optimised insulin NP formulated from 10% PEG-PLGA retained insulin integrity in vitro, insulin sensitivity in vivo and induced a sustained hypoglycaemic effect from 3h to 6 days in type I diabetic mice.
Anthocleista vogelii Planch is a medicinal plant traditionally used in West Africa for the management and treatment of diabetes mellitus. To determine the antidiabetic activities of chloroform fraction (CF) of Anthocleista vogelii Planch root bark in rats with diet- and alloxan-induced obesity-diabetes. Inhibitory activities of CF against α-amylase and α-glucosidase activities were determined in vitro. Three weeks old rats were fed with high-fat diet for 9 weeks to induce obesity prior to further induction of diabetes using alloxan (150 mg/kg body weight, i.p.). Blood glucose levels and body weight were measured every 7 days throughout the experiment. Glucose tolerance was assessed in normal and CF-treated rats on day 21. Terminal blood samples were collected from sacrificed animals for the measurement of serum insulin levels. Pancreases were excised from treated and untreated animals for histopathological examination. LCMS/MS chromatographic profile of CF via positive and negative modes revealed 13 and 23 compounds respectively. Further analysis revealed quebrachitol (QCT), loganin, sweroside, oleoside 11-methyl ester and ferulic acid, which have been previously reported for their antidiabetic activities, as constituents of CF. CF inhibited activities of α-amylase (IC50 = 51.60 ± 0.92 µg/ml) and α-glucosidase (IC50 = 5.86 ± 0.97 µg/ml) in a dose-dependent manner. Treatment of animals with obesity-diabetes with 100 and 200 mg/kg CF significantly improved glucose tolerance (P < 0.001) and enhanced serum insulin levels (P < 0.05) compared to diabetic control rats. Antidiabetic activities of CF might be mediated via inhibition of α-amylase and α-glucosidase activities, elevation of serum insulin concentration, and enhancement of insulin and leptin sensitivity in obesity-diabetes rats. This study further substantiates the traditional use of A. vogelii in the management and treatment of diabetes in Africa and encourages further studies to investigate its mechanism of action.