Mechanistic study and synergistic effect on inhibition of a-amylase by structurally similar flavonoids

Natural plant-based flavonoids have the potential effect of reducing postprandial hyperglycaemia, thus they can be used to prevent and control type 2 diabetes mellitus. Here, to explore the antihyperglycemic mechanisms of flavonoids (apigenin, scutellarein, hispidulin and nepetin), their inhibition mechanisms against a-amylase were evaluated using multispectral methods and molecular docking in this study. As a result, nepetin, a competitive inhibitor, exhibited the best inhibitory effect than other three flavonoids, suggesting that adjacent dihydroxyl group on the B-ring played an important role in inhibiting the activity of a-amylase. At the same time, the combination of apigenin and scutellarein/hispidulin/nepe tin synergistically improved their inhibitory effects on a-amylase. In addition, fluorescence quenching analysis indicated that the addition of flavonoids could result in the static quenching of a-amylase and the formation of non-covalent complexes. The interaction further led to the alteration of microenvironment and secondary structure of alpha-amylase, thus reducing the catalytic activity of enzyme. In conclusion, this finding can provide vital insights into the use of flavonoids, especially nepetin, as the potential drug candidates for the treatment of diabetes. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

Natural plant-based flavonoids, especially nepetin, have the potential to reduce postprandial hyperglycemia by inhibiting the activity of α-amylase. The combination of apigenin and scutellarein/hispidulin/nepetin synergistically improves their inhibitory effects on α-amylase. The addition of flavonoids results in the static quenching of α-amylase and the formation of non-covalent complexes, leading to a decrease in the enzyme's catalytic activity.