In silico and in vivo evaluation of flavonoid extracts on CYP2D6-mediated herb-drug interaction.

Flavonoid extracts are widely used for preventing and treating ischemic heart disease. However, because many flavonoid extracts have been verified to inhibit CYP2D6 the main metabolic enzyme for the majority of antiarrhythmics and beta-blockers, co-administration of flavonoid extracts with these drugs may cause adverse herb-drug interaction in clinic. Here, we evaluated 43 common flavonoids on CYP2D6 inhibition in sillico and four commercial flavonoid extracts in vivo on the pharmacokinetics and pharmacodynamics of metoprolol in rats. Surprisingly, we found that the core skeletons of flavonoids instead of their substituents determine the extent of inhibiting CYP2D6 by a flavonoid extract. Isoflavones are less likely to inhibit CYP2D6, compared with other categories of flavonoids. Consistently, co-administration of soy extract that mainly contains isoflavones did not significantly increase plasma concentration of metoprolol and alter the systolic blood pressure of rats. Our results have implication in rationally selecting flavonoid extracts for therapeutic application.