Interaction of isoflavonoids with human liver microsomal cytochromes P450: inhibition of CYP enzyme activities.
1. The possibility of interaction of isoflavonoids with concomitantly taken drugs to determined isoflavonoids safety was studied. Inhibition of nine forms of cytochrome P450 (CYP3A4, CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C19, CYP2C9, CYP2D6 and CYP2E1) by 12 isoflavonoids (daidzein, genistein, biochanin A, formononetin, glycitein, equol and six glucosides, daidzin, puerarin, genistin, sissotrin, ononin and glycitin) was studied systematically. 2. The most potent inhibitors were genistein and daidzein inhibiting noncompetitively the CYP2C9 with Kiof 35.95 ± 6.96 and 60.56 ± 3.53 μmol/l and CYP3A4 (inhibited by genistein with Kiof 23.25 ± 5.85 μmol/l also by a noncompetitive mechanism). Potent inhibition of CYP3A4 was observed also with biochanin A (Kiof 57.69 ± 2.36 μmol/l) and equol (Kiof 38.47 ± 2.32 μmol/l). 3. Genistein and daidzein inhibit noncompetitively CYP3A4 and CYP2C9. With plasma levels in micromolar range, a clinically important interaction with concomitantly taken drugs does not seem to be probable.
a Department of Pharmacology , Faculty of Medicine, Palacky University at Olomouc , Olomouc , Czech Republic.|b Institute of Molecular and Translational Medicine, Faculty of Medicine, Palacky University at Olomouc , Olomouc , Czech Republic.
Michaela
M
Kopečná-Zapletalová
a Department of Pharmacology , Faculty of Medicine, Palacky University at Olomouc , Olomouc , Czech Republic.|b Institute of Molecular and Translational Medicine, Faculty of Medicine, Palacky University at Olomouc , Olomouc , Czech Republic.
Kristýna
K
Krasulová
a Department of Pharmacology , Faculty of Medicine, Palacky University at Olomouc , Olomouc , Czech Republic.|b Institute of Molecular and Translational Medicine, Faculty of Medicine, Palacky University at Olomouc , Olomouc , Czech Republic.
Pavel
P
Anzenbacher
c Department of Biochemistry , Faculty of Sciences, Charles University , Prague , Czech Republic , and.
Petr
P
Hodek
d Department of Medical Chemistry and Biochemistry , Faculty of Medicine, Palacky University at Olomouc , Olomouc , Czech Republic.
Eva
E
Anzenbacherová
D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D004347:Drug Interactions; D005960:Glucosides; D006801:Humans; D007529:Isoflavones / Q000378:metabolism*; D008099:Liver / Q000201:enzymology; D008862:Microsomes, Liver / Q000201:enzymology*
D005960:Glucosides; D007529:Isoflavones; C526426:calycosin-7-O-beta-D-glucoside; C040641:genistin; C007768:formononetin; D003577:Cytochrome P-450 Enzyme System; C086566:glycitein; C504573:CYP1A2 protein, human; D019388:Cytochrome P-450 CYP1A2; D065731:Cytochrome P-450 CYP2C19; C433283:glycitin; C033607:puerarin
Daidzein; drug interactions; genistein; inhibition studies