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.
Clinical Pharmacology and Gerontology Research Unit, Department of Veterans Affairs Medical Center, Mountain State Medical Research Institute, Boise, Idaho 83702, USA.
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S
Zhai
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Dai
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Wei
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Friedman
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Vestal
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