Inhibition effect of vitamin B6 on α-glucosidase and mechanism of its synergistic inhibition with liquiritigenin

This study investigated the inhibitory effect of vitamin B6 (VB6) on α-glucosidase (Glu) and its synergistic inhibition mechanism with liquiritigenin (LTG). VB6 was identified as a weak mixed-type inhibitor of α-Glu (IC 50  = 2.76 ± 0.95 mM). VB6 quenched the endogenous fluorescence mainly through hydrogen bonding, reducing surface hydrophobicity and loosening the structure of α-Glu. Furthermore, the combination of 6 μM LTG and 0.5 mM VB6 produced the strongest synergistic inhibition on α-Glu without changing the mixed-inhibition pattern. Computer simulation results showed that VB6 reversibly occupied the allosteric cavity of α-Glu, causing structural rearrangements and conformational changes, which allowed LTG to penetrate deeper into the active center, forming hydrogen bonds with the residues Asp69, Asp352 and Arg442, thereby enhancing LTG's binding affinity and inhibitory effect. These findings provided the potential of VB6 in enhancing LTG's anti-α-Glu activity and a basis for the formulation design of hypoglycemic functional food.