Myrianthus libericus: Possible mechanisms of hypoglycaemic action and in silico prediction of pharmacokinetics and toxicity profile of its bioactive metabolite, friedelan-3-one

Abstract

The hypoglycaemic and anti-hyperlipidaemic effects of the 70% ethanol stem bark extract of Myrianthus libericus (MLB), used traditionally in the management of diabetes in Ghana, was evaluated in this study using streptozotocin (45 mg/kg)-induced diabetic rats. In vitro hypoglycaemic activities of the extract and one of its principal compounds, friedelan-3-one were then investigated using α-amylase inhibitory and glucose uptake assay in C2C12 myotubes. In silico analysis of the pharmacokinetic and toxicity properties of the compound was also performed. MLB significantly (p < 0.001) reduced the elevated blood glucose levels and corrected considerably (p < 0.01) the altered serum lipid profiles of the diabetic rats which was comparable to glibenclamide (5 mg/kg). Together with friedelan-3-one, the extract markedly inhibited the activity of α-amylase and promoted glucose uptake in C2C12 cells. Whereas MLB significantly (p < 0.001) up-regulated PI3K and PPARγ transcripts with a corresponding increase in GLUT-4 transcripts within the muscle cells, friedelan-3-one only up-regulated PI3K and GLUT-4 transcripts to promote glucose transport. Friedelan-3-one was shown to be non-carcinogenic, non-hepatotoxic, has decent oral bioavailability and a good compound for optimisation into a drug candidate. The study has demonstrated that MLB possess hypoglycaemic and anti-hyperlipidaemic activities and could be used as a therapeutic agent in the management of diabetes mellitus.