Inhibitory Activity of Bioactive Phloroglucinols from the Rhizomes of Dryopteris crassirhizoma on Escherichia coli   β -Glucuronidase: Kinetic Analysis and Molecular Docking Studies.

Phloroglucinols-one of the major secondary metabolites in Dryopteris crassirhizoma -exhibit various pharmacological effects, such as antiviral, antioxidant, and antidiabetic activities. This study evaluated 30 phloroglucinols isolated from the rhizomes of D. crassirhizoma for their inhibitory activity on β -glucuronidase via in vitro assays. Among them, dimeric phloroglucinols 13 - 15 moderately inhibited β -glucuronidase, and trimeric phloroglucinols 26 - 28 showed strong inhibitory effects, with IC 50 values ranging from 5.6 to 8.0 μM. Enzyme kinetic analysis confirmed all six active compounds to be in a competitive mode of inhibition. Molecular docking simulations revealed the key binding interactions with the active site of β -glucuronidase protein and the binding mechanisms of these active metabolites. Our results suggest that the rhizomes of D. crassirhizoma and trimeric compounds 26 - 28 may serve as potential candidates for discovering and developing new β -glucuronidase inhibitors.