Insights into inhibitory mechanisms: Unraveling the structure-activity relationship of dietary flavonoids on gut bacterial β-glucuronidase

Dietary flavonoids are regarded as potent inhibitors of gut bacterial β-glucuronidase (β-GUS), although the precise structure-activity relationship between dietary flavonoids and β-GUS remains elusive. In this study, 24 dietary flavonoids of 6 common different structural types were selected as model molecules to investigate this relationship through enzymatic inhibition kinetics and molecular docking simulations. The findings revealed that delphinidin (1) and baohuoside I (16) exhibited robust inhibitory activities, while the formation of ionic bond and hydrogen bonds was found to play crucial roles in these interactions. Moreover, the core structure, position, and quantity of hydroxyl groups; type and number of glycosyls, and the presence of isopentenyl group all played pivotal roles in influencing inhibitory activities against β-GUS derived from Escherichia coli. These results offer valuable insights into the relationship between flavonoid structure and enzyme inhibition, which could prove invaluable for the development of novel drugs and flavonoid dietary supplements.