ABSTRACT
Objectives: Inhibition of carbohydrate digestion enzymes (α-amylase and α-glucosidase) has been reported in studies as a therapeutic approach for the management or treatment of type 2 diabetes mellitus, owing to its potential to decrease postprandial hyperglycemia. The anti-diabetic potential of Allium sativum (also known as garlic) against diabetes mellitus has been established. Therefore, in this study, we assessed the antidiabetic potential of A. sativum using in vitro enzyme assays after which we explored computational modelling approach using the quantified GC-MS identities to unravel the key bioactive compounds responsible for the anti-diabetic potential. Methods: We used in vitro enzyme inhibition assays (α-amylase and α-glucosidase) to evaluate antidiabetic potential and subsequently performed gas chromatography-mass spectroscopy (GC-MS) to identify and quantify the bioactive compounds of the plant extract. The identified bioactive compounds were subjected to in silico docking and pharmacokinetic assessment. Results: A. sativum phenolic extract showed high dose-dependent inhibition of α-amylase and α-glucosidase (p < 0.05). Interestingly, the extract inhibited α-glucosidase with a half maximal inhibitory concentration of 53.75 µg/mL, a value higher than that obtained for the standard acarbose. Docking simulation revealed that morellinol and phentolamine were the best binders of α-glucosidase, with mean affinity values of -7.3 and -7.1 kcal/mol, respectively. These compounds had good affinity toward active site residues of the enzyme, and excellent drug-like and pharmacokinetic properties supporting clinical applications. Conclusions: Our research reveals the potential of A. sativum as a functional food for the management of type 2 diabetes, and suggests that morellinol and phentolamine may be the most active compounds responsible for this anti-diabetic prowess. Therefore these compounds require further clinical asessment to demonstrate their potential for drug development.
