In vitro inhibition of quercetin and its glycosides on P450 enzyme activities / 中国药学杂志

ABSTRACT

OBJECTIVE: To evaluate inhibitory effect of the flavonoids, quercetin and its glycosides, on the activities of human liver microsomes isoforms CYP2C19, CYP2D6, CYP3A4 CYP2E1 and CYP2C9 in vitro for predicting prudential drug-drug interactions in clinical application. METHODS: Human liver microsomes and five probes were incubated with tested flavonoids at 37°C, in presence of NADPH. The concentrations of produced metabolites in the reaction solution were determined by liquid chromatography/tandem mass spectrometry method, and compared for evaluating the activity of isoenzymes. RESULTS: Quercetin inhibited CYP3A4 and CYP2C9 activities with IC50 values of 13.14 and 23.09 μmol·L-1, respectively. While, the quercetin glycosides, quercetin-3-O-glu-curonide, isoquercitrin, hyperoside and rutin were found no significant inhibition effects on the five tested enzymes, with IC50 values higher than 100 μmol·L-1. CONCLUSION: Quercetin shows moderate inhibition on CYP3A4 and CYP2C9, there is very little inhibition on the other tested flavonoids because sufficiently high levels are not clinically achieved more than 100 μmol·L-1. The quercetin glycoside compounds are less likely to cause potential drug-drug interactions.