Structural requirements of flavonoids for the selective inhibition of α-amylase versus α-glucosidase

In the present study, 14 structurally unique flavonoids were screened to systematically investigate structural requirements for selectively inhibiting human alpha-amylase versus alpha-glucosidase to obtain a slow but complete starch digestion for health benefit. The selective inhibition property of three flavonoids chosen against the two classes of starch digestive enzymes was confirmed through various analytical techniques - in vitro inhibition assay, fluorescence quenching, kinetic study, and molecular modeling. Considering the chemical structure of flavonoids, the double bond between C2 and C3 and OH groups at A5 and B3 are critical for the inhibition of alpha-amylase allowing flavonoids to lie parallel on the alpha-amylase catalytic active site, whereas the OH groups at B3 and C3 are important for alpha-glucosidase inhibition causing B-ring specific entry into the catalytic active site of alpha-glucosidase. Our findings provide insights into how to apply flavonoids to effectively control digestion rate for improving physiological responses.

Automated summary

This study identified the structural requirements for selectively inhibiting human alpha-amylase versus alpha-glucosidase using flavonoids, revealing the critical role of double bonds and hydroxyl groups in different positions. Through selective inhibition of the two classes of starch digestive enzymes, flavonoids can effectively control digestion rate to improve physiological responses.