In silico discovery of α-glucosidase inhibitors from Mitragyna speciosa for antidiabetic therapy

INTRODUCTION: Mitragyna speciosa (kratom) is a medicinal plant known for its richness in phytochemicals with potential antidiabetic activity. α-glucosidase is an enzyme that plays a key role in carbohydrate hydrolysis. The inhibition of α-glucosidase activity represents a validated therapeutic approach to manage postprandial hyperglycaemia in type 2 diabetes. This study investigates the potential of M. speciosa leaf extract as an α-glucosidase inhibitor. OBJECTIVE(S): To identify bioactive compounds in M. speciosa ethanolic leaf extract that inhibit α-glucosidase and to evaluate their interaction with the enzyme through in silico molecular docking. MATERIALS & METHODS: Phytochemical profiling of the 95% ethanolic extract of M. speciosa leaf was performed using LC-MS QTOF. In vitro α-glucosidase inhibition assay was conducted to determine the IC₅₀ value of the extract. Selected compounds were subjected to molecular docking analysis using AutoDock software against α-glucosidase enzyme (PDB ID: 3A4A), and key binding interactions were analysed. RESULTS: A total of 16 putative bioactive compounds were identified from the extract. The extract exhibited α-glucosidase inhibitory activity with an IC₅₀ of 21.64 µg/mL. In the molecular docking analysis, Rhyncophylline showed strong binding to α-glucosidase (ΔG = -8.8 kcal/mol), comparable to standard inhibitors. Its interaction with ASP352, a known catalytic residue, suggests that Rhyncophylline may act as a potential α-glucosidase inhibitor. CONCLUSION: The ethanolic leaf extract of M. speciosa exhibits α-glucosidase inhibitory activity. Rhyncophylline, identified via in silico docking, is a promising lead compound for future antidiabetic drug development.