Flavonoids inhibit six cytochrome P450 enzymes from human liver microsomes as analyzed by LC-MS/MS method
HE Fan
ZHONG Guo-ping
ZHAO Li-zi
BI Hui-chang
HUANG Min
Abstract：Objective: To determine the inhibitory effect of flavonoids on six cytochrome P450 enzymes from human liver microsomes as analyzed by LC -MS/MS method. Methods: Six cytochrome P450 probe substrate metabo-lites (including paracetamol for CYP1 A2, 4-hydroxytolbutamide for CYP2C9, 5-hydroxyomeprazole for CYP2C19,dextrorphan for CYP2D6, 6-hydroxychlorzoxazone for CYP2E1 and dehydronifedipine for CYP3A4) were measured by LC-MS/MS with positive and negative ion SRM detection. Flavonoids were incubated with human liver micro-somes in the presence of six probe substrates of CYP450 isozymes, and the inhibitory effect were evaluated with IC_(50) values. Results: Flavonoids were classified as the potent, marginal, or weak inhibitors to the CYP450 isozymes. The IC_(50) values of flavonoids for glycosides substitutions ( silybin, hyperoside, catechin, epicatechin, puerarin, rutin,liquiritin and naringin) were above 50μmol·L~(-1),but did not show any inhibitory effect on the six CYP450 isoforms.All flavonoid aglycones such as quercetin showed inhibitory effects on CYP1A2 ( IC_(50) values ranged from 0.054μmol·L~(-1) to 31.91μmol·L~(-1));some of them were able to inhibit other CYP450 isoforms such as CYP2C9,CYP2C19,CYP2E1,and CYP3A4.All flavonoids did not inhibit CYP2D6.Otherwise,flavone also stimu.lated the CYP3 A4 activity.Conclusion:The presented method has acceptable accuracy,precision and sensitivity.and it is suitable for in vitro inhibition study.Flavonoids show different inhibitory effects on the activity of CYP450 isozymes;the information is useful for the prediction of flavonoids.drug interactions.
Keywords：LC-MS/MSflavonoidscytochrome P450probe substrate
Publication Date：2009-01-01
Online Publishing Date：2026-08-14(First online date of this platform, not the publication date of the document)
Pages：6( 2340-2344,2348 )