Screening inhibitors of flavin monooxygenase 3 (FMO3) is very important for treating trimethylamine N-oxide (TMAO) derived thrombotic diseases. Herein, focusing on Xuefu Zhuyu decoction (XFZYD) as a Chinese traditional medicine with antithrombotic efficacy, a facile and label-free fluorescence strategy was developed for evaluating the influence of the bioactive ingredients in XFZYD on FMO3 activity through indicator displacement assay. To this end, the optimized supramolecular host-guest (p-sulfonatocalix[4]arene-oxazine 1) reporter pair and FMO3 catalytic system were exploited to determine the influence of the bioactive compounds in XFZYD on the conversion from TMA to TMAO. From the nine compounds tested, naringin, paeoniflorin, β-ecdysterone, 18β-glycyrrhizic acid, amygdalin, albiflorin, and saikosaponin A downregulated FMO3 activity and reduced TMAO biosynthesis. Moreover, molecular docking was successfully applied to simulate the optimal conformation of a receptor-ligand complex between FMO3 and all tested compounds except for β-ecdysterone. Therefore, this approach provides a novel and promising strategy for screening FMO3 inhibitors from Chinese traditional medicine by supramolecular sensing.
Keywords: Flavin monooxygenase 3; Host-guest chemistry; Indicator displacement assay; Supramolecular sensing; Xuefu Zhuyu decoction.
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