Euclea natalensis Suppresses Postprandial Hyperglycemia in Rats via the Inhibition of α-Glucosidase: In vitro, in vivo, and Molecular Docking Studies

Background:: Postprandial hyperglycemia is a key factor in type 2 diabetes, and its management is critical in alleviating the deleterious consequences of diabetes and its associated micro and macrovascular complications. Objective:: The current study aims to determine the effect of Euclea natalensis leaf extracts on α- glucosidase inhibition in vitro and postprandial hyperglycemia in vivo in rats. Methods:: Sequentially extracted leaf extracts of Euclea natalensis were evaluated for their inhibitory effects on α-glucosidase in vitro and the suppression of postprandial hyperglycemia in normoglycemic rats. The extracts were fingerprinted using a Fourier-transform infrared spectrophotometer (FTIR), and the bioactive compounds were evaluated by molecular docking for their interaction with α-glucosidase. Results:: FTIR fingerprinting of the extracts showed that they contain functional groups of important bioactive phytochemicals. The extracts inhibited α-glucosidase in vitro, with the methanol extract (1 mg/mL) showing the highest inhibitory effect of 93.52 ± 1.50% compared to 69.62% ± 1.45 of the standard drug acarbose (0.05 mg/mL). The extracts also reduced postprandial hyperglycemia in rats in a sucrose tolerance test, where the hexane and methanol extracts performed similarly to Acarbose. Molecular docking studies showed that 20(29)-lupene-3β- isoferulate 3 is the most potent α-glucosidase inhibitor with the lowest binding energy of -10.79 kcal/mol, 2 hydrogen bonds with residues ASP1526 and ASP1157, and numerous Van der Waal interactions with amino acids in the binding pocket of α-glucosidase. Conclusion:: Euclea natalensis leaf extracts were found to suppress postprandial hyperglycemia by inhibiting α-glucosidase activity; thus, it has a promising potential for use as an antidiabetic agent.