Mechanistic study of α-glucosidase and α-amylase inhibition by taxifolin.

This study systematically investigated the inhibitory effects of the natural flavonoid taxifolin on the diabetes-related key hydrolytic enzymes α-glucosidase and α-amylase, as well as the underlying molecular mechanisms. The results demonstrated that taxifolin exhibited significant concentration-dependent inhibitory activity against both enzymes, acting as a competitive inhibitor of α-glucosidase and a mixed-type inhibitor of α-amylase. Fluorescence quenching analyses indicated that taxifolin primarily interacted with both enzymes through a static quenching mechanism, forming stable enzyme-ligand complexes. Further multispectroscopic analyses revealed that taxifolin markedly induced alterations in the secondary structure, conformation, and aggregation state of the enzymes, thereby impairing their catalytic activities. Molecular docking simulations showed that taxifolin could be accommodated within the active pockets of the enzymes and bind stably to key amino acid residues through multiple noncovalent interactions, including hydrogen bonding, π-π stacking, and hydrophobic interactions. In vitro simulated digestion experiments demonstrated that taxifolin significantly delayed starch hydrolysis and reduced glucose release. Moreover, in vivo zebrafish experiments confirmed that taxifolin markedly lowered postprandial glucose levels within 2 h. In summary, taxifolin binds the two enzymes and partially reduces postprandial glucose. Its mild hypoglycemic effect precludes its use as an antidiabetic drug, yet it shows promise as a functional food component with theoretical backing.