Phenolic compounds from the stems of Zanthoxylum piperitum and their inhibition of β-glucuronidase: Enzyme kinetics, molecular docking, and molecular dynamics analysis

초록

Zanthoxylum piperitum , commonly known as Japanese pepper, is a versatile plant from the Rutaceae family that has attracted significant scientific research interest due to its culinary and medical applications. Herein, we present a phytochemical investigation of Z. piperitum stems, leading to the isolation and characterization of a new compound, zanthopiperitol ( 1 ), along with four known phenolic compounds ( 2 - 5 ). Among them, ailanthoidiol ( 2 ) demonstrated potent fl -glucuronidase inhibition with an IC 50 of 68.39 +/- 2.29 mu M. The results of an enzyme kinetics analysis suggest that it acts as a competitive inhibitor of fl -glucuronidase while molecular docking simulation outcomes reveal that it can bind effectively to key amino acid residues in the main catalytic binding site of fl -glucuronidase. Moreover, the strong stability of compound 2 bound to the enzyme binding site is indicated via a 100-ns molecular dynamics simulation study. This study highlights the potential of exploiting naturally occurring fl -glucuronidase inhibitors such as ailanthoidiol for treating various gastrointestinal health issues.

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