Discovery and characterization of flavonoids in vine tea as catechol-O-methyltransferase inhibitors

Vine tea has been used as a traditionally functional herbal tea in China for centuries, which exhibits paramount potential for chronic metabolic diseases. Herein, the inhibitory potential of vine tea toward human catechol-O-methyltransferase (hCOMT) was investigated. A practical bioactivity-guided fractionation combined with chemical profiling strategy was developed to identify the naturally occurring hCOMT inhibitors. Five flavonoids in vine tea displayed moderate to strong inhibition on hCOMT with IC50 values ranging from 0.96 μM to 42.47 μM, in which myricetin was the critically potent constituent against hCOMT. Inhibition kinetics assays and molecular docking simulations showed that myricetin could bind to the active site of COMT and inhibited COMT-catalyzed 3-BTD methylation in a mixed manner. Collectively, our findings not only suggested that the strong hCOMT inhibition of vine tea has guiding significance in the drug exposure of catechol drugs, but also identified a promising lead compound for developing more efficacious hCOMT inhibitors. [Display omitted] •The extract of vine tea strongly inhibited hCOMT in a dose-dependent manner.•A practical strategy via integrating bioactivity-guided fractionation and chemical profiling was used to identify hCOMT inhibitors from vine tea.•Myricetin in vine tea displayed the most potent hCOMT inhibition activity.•Inhibitory mechanism of myricetin was investigated by inhibition kinetic analyses and docking simulations.