The product of cytochrome P450 monooxygenase
(P450) ω-hydroxylation
of arachidonic acid (AA), 20- hydroxyeicosatetraenoic acid (HETE),
is a potent vasoconstrictor. Utilizing microsomes as well as individual
CYP4 isoforms we demonstrate here that flavonoids can block 20-HETE
formation. Apigenin inhibits CYP4F2 with an IC<sub>50</sub> value
of 4.6 μM and 20-HETE formation in human liver and kidney microsomes
at 2.4–9.8 μM. Interestingly, the structurally similar
naringenin shows no relevant effect on the formation of 20-HETE. Based
on these in vitro data, it is impossible to evaluate if a relevant
blockade of 20-HETE formation can result in humans from intake of
polyphenols with the diet. However, the potency of apigenin is comparable
to those of P450 inhibitors such as ketoconazole. Moreover, an IC<sub>50</sub> value in the micromolar range is also described for the
inhibition of CYP-mediated drug metabolism leading to food–drug
interactions. The modulation of the arachidonic acid cascade by food
polyphenols therefore warrants further investigation
