Abstract:
The antidiabetic effect of aqueous stem bark extract of A. polycarpa (AP) in male ICR mice and its sub-chronic toxicity in Sprague-Dawley rats were investigated. The effect of AP (20 mg/kg, 100 mg/kg, and 500 mg/kg) on fasting blood glucose, serum triglyceride and total cholesterol levels were determined over a period of 4 weeks. An oral glucose tolerance test was also conducted over 150 min post-glucose load. Organ specific toxicity of AP (20 mg/kg, 100 mg/kg, and 500 mg/kg) in Sprague- Dawley rats was also studied over a period of 3 months. Serum ALP, ALT, direct bilirubin and creatinine were measured at baseline and monthly intervals thereafter. Urinalysis was performed at baseline and at termination of treatments whilst hematological analysis was conducted at termination of treatments. Blood clotting time and pentobarbital-induced sleeping time were determined at termination of treatments. Phytochemical constituents and antioxidant activity of AP were also determined.
The AP, like glibenclamide and metformin, showed significant (p<0.05) hypoglycaemic, hypotriglyceridaemic and hypocholesterolaemic effects, which may possibly be due to increased secretion of insulin as a result of restoration of the morphology of beta cells of the pancreas that had become necrotic in the diabetic mice. AP showed significant antioxidant activity relative to the standard antioxidant, BHT evidenced by its ability to scavenge DPPH free radicals. This observed antioxidant activity may be due to the presence of phenolic compounds particularly flavonoids in AP.
The LD50 of AP in rats was greater than 5000 mg/kg with no observable signs of toxicity. AP showed selective organ specific toxicity of the lung in the alveolar areas which was characterized by interstitial fibrosis and alveolar septa thickening. AP had no adverse effect on the liver and kidney as shown by its lack of effect on serum ALP, ALT, direct bilirubin and creatinine and urinalysis, as well as the absence of adverse effects on the morphology of the cells of these organs. No adverse morphological effects were also observed with the heart muscle cells. AP did not also affect blood clotting time, hematological parameters and pentobarbital induced sleeping time. These results indicate that AP has significant antidiabetic activity and provides scientific evidence to validate the anecdotal evidence of its use in the management of diabetes mellitus. However, its selective toxicity to the alveolar cells of the lung is a cause for worry and, therefore, care must be taken in its use in humans.
