Identification of α-glucosidase inhibitory phytochemicals from Erythrina crista-galli using combined experimental and computational methods.

α-Glucosidase inhibition is an important therapeutic strategy for managing type 2 diabetes. This study aims to identify compounds responsible for the α-glucosidase inhibitory activity of Erythrina crista-galli stem bark extract. The ethanol extract shows strong antioxidant activity and the highest α-glucosidase inhibitory activity among the samples tested. LC-MS/MS analysis tentatively identified 36 flavonoid constituents, which were subsequently evaluated through molecular docking against the crystal structure of isomaltase (PDB ID: 3A4A). When compared with isomaltose, the natural substrate of the enzyme, two compounds exhibited more favorable predicted binding affinities and engaged key catalytic residues within the active site, suggesting their potential to act as competitive inhibitors. Molecular dynamics simulations over 500 ns showed that isovitexin-2''-β-ᴅ-glucopyranoside (17) has the lowest MMGBSA binding energy and stable interactions with catalytic residues. ADMET analysis indicated good solubility, intestinal absorption, limited permeability, and low toxicity for isovitexin-2''-β-ᴅ-glucopyranoside (17). This work provides a scientific foundation for further exploration of E. crista-galli and its constituent flavonoids in the development of nutraceutical or pharmaceutical strategies for diabetes management.