Inhibition of methoxyresorufin demethylase activity by flavonoids in human liver microsomes.
Flavonoids are a class of dietary phytochemicals with anticarcinogenic properties. A series of ten structurally related flavonoids were evaluated for their effect on methoxyresorufin O-demethylase (MROD) activity in human liver microsomes. All compounds inhibited this cytochrome P450 1A2 (CYP1A2) mediated activity. 3,5,7-Trihydoxyflavone (galangin) was the most potent inhibitor, followed by 3-hydroxyflavone and flavone. The relative inhibitory potency of flavonoids is related to their structures. The results suggest that flavonoids may modulate pharmacological and toxicological effects mediated by CYP1A2.
Zhai
S
S
Clinical Pharmacology and Gerontology Research Unit, Department of Veterans Affairs Medical Center, Mountain State Medical Research Institute, Boise, Idaho 83702, USA.
Dai
R
R
Wei
X
X
Friedman
F K
FK
Vestal
R E
RE
D000328:Adult; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D047309:Flavones; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008862:Microsomes, Liver / Q000201:enzymology*; D010088:Oxidoreductases / Q000037:antagonists & inhibitors*
D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D047309:Flavones; D005419:Flavonoids; D007527:Isoenzymes; C037032:galangin; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; C076307:methoxyresorufin-O-demethylase; C043562:flavone; C041477:3-hydroxyflavone