The study of inhibitory effect of natural flavonoids toward β-glucuronidase and interaction of flavonoids with β-glucuronidase.

β -Glucuronidase plays a vital role in the metabolism of drugs and endogenous substance. Herein, we assayed the inhibitory effects of thirty-six flavonoids (1–36) toward β -glucuronidase (Escherichia coli) using the probe reaction of DDAO-glu hydrolysis. The results showed that kushenol X (6), (2 S)-farrerol (10), 5,7,2′-trihydroxy-8,6′-dimethoxy flavone (20), demethylbellidifolin (31), and gentisin (32) exhibited potent inhibitory activities toward β -glucuronidase with the IC 50 values of 2.07 ± 0.26, 8.95 ± 0.74, 4.97 ± 0.61, 0.91 ± 0.11, and 0.68 ± 0.10 μM, respectively. Furthermore, the inhibition kinetics studies indicated that demethylbellidifolin (31) and gentisin (32) exhibited mixed-type inhibiton toward β -glucuronidase, the K i values were caculated to be 4.05 and 2.02 μM, respectively. Additionally, the circular change of dichroism (CD) spectrum verified the interaction between demethylbellidifolin (31) and gentisin (32) with β -glucuronidase; following by the molecular docking and molecular dynamics further revealed the potential interaction amino acid site in β -glucuronidase. All our findings not only developed some potent novel β -glucuronidase inhibitors but also indicated the potential herb drug interaction (HDI) effects of flavonoids with some clinical drugs which had enterohepatic circulation and further revealed the vital pharamcophoric requirement of natural flavonoids for β -glucuronidase inhibition activity. • The inhibitory effects of 36 kind nature flavonoids toward β -Glucuronidase were assayed; • The mixed-type inhibition behaviour and inhibition parameter was illustrated and obtained by inhibition kinetics; • The potential interaction between flavonoids and β -Glucuronidase were illustrated by molecular docking and dynamics; [ABSTRACT FROM AUTHOR]