title: Food Polyphenol Apigenin Inhibits the Cytochrome P450 Monoxygenase Branch of the Arachidonic Acid Cascade.
abstract: 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 IC50value 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 IC50value 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.
authors.affiliation: Department of Food Chemistry, University of Wuppertal , Wuppertal, Germany.
authors.forename: Maryvonne
authors.initials: M
authors.lastname: Steuck
authors.affiliation: Department of Food Chemistry, University of Wuppertal , Wuppertal, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hellhake
authors.affiliation: Department of Food Chemistry, University of Wuppertal , Wuppertal, Germany.|Institute for Food Toxicology and Analytical Chemistry, University of Veterinary Medicine Hannover , Hannover, Germany.
authors.forename: Nils Helge
authors.initials: NH
authors.lastname: Schebb
mesh_terms: D047310:Apigenin / Q000494:pharmacology*; D016718:Arachidonic Acid / Q000378:metabolism*; D000072470:Cytochrome P450 Family 4 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D018565:Food-Drug Interactions; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000378:metabolism; D006900:Hydroxylation; D020128:Inhibitory Concentration 50; D007668:Kidney / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D059808:Polyphenols / Q000494:pharmacology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D006893:Hydroxyeicosatetraenoic Acids; D059808:Polyphenols; D014662:Vasoconstrictor Agents; D016718:Arachidonic Acid; C055987:20-hydroxy-5,8,11,14-eicosatetraenoic acid; D047310:Apigenin; D000072470:Cytochrome P450 Family 4; C117480:CYP4F2 protein, human
keywords: eicosanoids; enzyme inhibition; flavonoides; food drug interaction; oxylipins; polyphenols