Antihyperglycemic and α-Glucosidase Inhibitory Effects of Detarium microcarpum Fruit Extract in Diabetic Rats: Phytochemical and Kinetic Insights

Background: Diabetes mellitus (DM) is a global health challenge that is often managed with synthetic drugs that are associated with adverse effects and are less accessible in many low-resource settings. Detarium microcarpum is a medicinal plant traditionally used in African ethnomedicine to manage symptoms of DM. Objective: This study investigated the phytochemical composition, safety profile, antihyperglycemic potential in normal and alloxan-induced diabetic rats, and α-glucosidase inhibitory activity of the whole fruit ethanol extract of D. microcarpum. Methods: The fruit extract (70% ethanolic) was screened for phytochemicals. Acute toxicity was assessed in mice (500–1000 mg/kg). Oral glucose tolerance test (OGTT) was performed in normoglycemic rats, and antihyperglycemic activity was evaluated in alloxan-induced diabetic rats (50–800 mg/kg) for 28 days, with Glibenclamide as reference. In vitro α-glucosidase inhibition potential of the fruit extract and enzyme kinetics were analysed using Saccharomyces cerevisiae α-glucosidase and p-nitrophenyl-α-D-glucopyranoside substrate. Results: The extract exhibited dose-dependent glucose-lowering activity, with 800 mg/kg producing the highest reduction (67.5%) in diabetic rats, comparable to Glibenclamide. In the OGTT, higher doses improved glucose clearance with area under the curve values similar to Glibenclamide. The extract exhibited α-glucosidase inhibition (IC50 = 5.10 mg/mL) via mixed-type inhibition, altering both Michaelis constant, Km and maximum reaction velocity, Vmax. No mortality or behavioural changes were observed in toxicity testing. Conclusion: D. microcarpum fruit extract is safe and shows promising antihyperglycemic activity, partly mediated by mixed-type α-glucosidase inhibition. These findings support further development of the fruit as a potential adjunct in diabetes management.