Flavonoids are divided into
flavones,
flavonols,
flavanones, and
isoflavones etc. according to their basal structure, and are known to include compounds with physiological and pharmacological effects such as
anti-oxidant, anti-
tumor, and anti-
inflammation activities. The ingestion of
flavonoids may induce pharmacokinetic interactions through the co-administration of drugs. In this study, we investigated the inhibitory potentials on
cytochrome P450 (CYP) 3A activity of 23
flavonoids using human liver microsomes, and tried to identify the molecular features that cause the inhibition of
CYP3A. The activity of
testosterone 6beta-hydroxylate was evaluated to quantify
CYP3A activity. We analyzed Quantification Theory I, in which extreme values of the inhibitory effects of
CYP3A activity were tested with
flavonoids supplied at a level of 10 microM. The inhibitory effects of
flavonoids ranged widely from 1.5 microM to more than 100 microM for the half maximal inhibitory concentration. Because the inhibitory effects were only weakly correlated with the pK(a) value, the inhibitory effects could not be accounted for by the molecular characteristics of the
flavonoids. On the other hand,
flavones with the basal structure and hydroxylation at positions 7 and 4' showed significantly increased inhibitory effects on
CYP3A activity. In addition, the hydroxylation of position 2' and 3', methoxylation of position 4', and the
isoflavone basal structure significantly decreased the inhibitory effects on
CYP3A activity. In conclusion, the basal structure and the substituents of
flavonoids are important in the inhibitory effects of
flavonoids on
CYP3A activity.