Oxidation of the flavonoids galangin and kaempferide by human liver microsomes and CYP1A1, CYP1A2, and CYP2C9.
There is very limited information on cytochrome P450 (P450)-mediated oxidative metabolism of dietary flavonoids in humans. In this study, we used human liver microsomes and recombinant P450 isoforms to examine the metabolism of two flavonols, galangin and kaempferide, and one flavone, chrysin. Both galangin and kaempferide, but not chrysin, were oxidized by human liver microsomes to kaempferol, with K(m) values of 9.5 and 17.8 microM, respectively. These oxidations were catalyzed mainly by CYP1A2 but also by CYP2C9. Consistent with these observations, the human liver microsomal metabolism of galangin and kaempferide were inhibited by the P450 inhibitors furafylline and sulfaphenazole. In addition, CYP1A1, although less efficient, was also able to oxidize the two flavonols. Thus, dietary flavonols are likely to undergo oxidative metabolism mainly in the liver but also extrahepatically.
Otake
Yoko
Y
Department of Cell and Molecular Pharmacology and Experimental Therapeutics, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Walle
Thomas
T
D001189:Aryl Hydrocarbon Hydroxylases; D019363:Cytochrome P-450 CYP1A1 / Q000378:metabolism*; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism*; D065729:Cytochrome P-450 CYP2C9; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D005419:Flavonoids / Q000378:metabolism*; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D044949:Kaempferols; D008862:Microsomes, Liver / Q000201:enzymology*; D009153:Mutagens / Q000378:metabolism; D010084:Oxidation-Reduction; D011794:Quercetin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism; D039181:Steroid 16-alpha-Hydroxylase; D013250:Steroid Hydroxylases / Q000378:metabolism*; D014312:Trisaccharides / Q000737:chemistry / Q000378:metabolism
D005419:Flavonoids; D007527:Isoenzymes; D044949:Kaempferols; D009153:Mutagens; D014312:Trisaccharides; C430221:kaempferide 3-O-glucopyranosyl-1-2-O-(rhamnopyranosyl-1-6)glucopyranoside; C037032:galangin; C043561:chrysin; C449720:kaempferide; C006552:kaempferol; D003577:Cytochrome P-450 Enzyme System; D011794:Quercetin; D013250:Steroid Hydroxylases; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases; C504573:CYP1A2 protein, human; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2; D039181:Steroid 16-alpha-Hydroxylase