Hypoglycaemic activity of Oleanonic acid, a 3-oxotriterpenoid isolated from Aidia Genipiflora (DC.) Dandy, involves inhibition of carbohydrate metabolic enzymes and promotion of glucose uptake

Abstract

The present study evaluated the antidiabetic activities of the 70% ethanol stem bark extract of Aidia genipiflora (AGB) and one of its constituents, oleanonic acid in streptozotocin (40 mg/kg)-induced diabetic rats. In vitro assays of glucose uptake and inhibition of carbohydrate metabolizing enzymes were then used to investigate their mechanism(s) of hypoglycaemic action. In silico evaluation of the pharmacokinetic and toxicity properties of the compound was also carried out. Administration of AGB (100–400 mg/kg) and oleanonic acid (15 – 60 mg/kg) resulted in significant reductions (p < 0.001) in the blood glucose and considerable decrease (p < 0.05) in the elevated lipid parameters of the diabetic animals. AGB activity at 200 and 400 mg/kg; and oleanonic acid at 60 mg/kg were comparable to glibenclamide (5 mg/kg). The extract and its isolate strongly inhibited α-glucosidase and α-amylase activity with IC50 values of (10.48 ± 1.39 µg/mL and 14.51 ± 1.26 µg/mL) and (36.52 ± 1.95 µM and 105.84 ± 1.08 µM) respectively. The glucose uptake assays showed that AGB and oleanonic acid exerted both insulin-dependent and independent promotional effect of glucose transport into the periphery by upregulating the expression of PI3K and PPARγ transcripts with a concomitant increase in GLUT-4 transcripts. Although oleanonic acid was predicted to be teratogenic, it was found to be generally non-lethal with favourable pharmacokinetics properties making it suitable for further studies. The study has shown that the stem bark of A. genipiflora is a source of new hypoglycaemic agents and that oleanonic acid possesses hypoglycaemic and anti-hyperlipidaemic activities.