Isozyme- and species-specific susceptibility of cDNA-expressed CYP1A P-450s to different flavonoids

Biochim Biophys Acta. 1994 Apr 13;1205(2):325-35. doi: 10.1016/0167-4838(94)90252-6.


The inhibitory and stimulatory effects of six flavonoids with distinct hydroxylation patterns on the recombinant and hepatic mouse and human CYP1A P-450s were studied. cDNA-expressed mouse CYP1A1 and CYP1A2 differed in their sensitivity to both hydroxylated and nonhydroxylated flavonoids, respectively. A comparison between the mouse and human CYP1A2 revealed that alpha-naphthoflavone and flavone did not change the benzo[a]pyrene 3-hydroxylation activity of human CYP1A2 but inhibited its 7-ethoxyresorufin and 7-methoxyresorufin O-dealkylation activities. In contrast, hydroxylated flavonoids increased the 7-methoxyresorufin O-demethylation and acetanilide 4-hydroxylation activities of cDNA-expressed human CYP1A2 and in human liver microsomes. These compounds inhibited the benzo[a]pyrene 3-hydroxylase activity of cDNA-expressed CYP1A1 and CYP1A2s as well as in mouse and human liver microsomes. Hydroxylated flavonoids did not inhibit NADPH-cytochrome P-450 oxidoreductase activity but inhibited NADPH-2,6-dichlorophenolindophenol oxidoreductase activity in liver microsomes and in microsomes from recombinant Hep G2 cells. Structure-activity relationships indicated the importance of hydroxyl groups in the 5- and 7-positions on the A ring of the flavane nucleus. These hydroxyl groups accounted for the inhibitory potency of chrysin on each of the activities of the expressed P-450s, while presence of a hydroxyl group at the 4'-position on the B ring decreased the inhibitory potency of naringenin compared to that of chrysin. The ortho-orientation of a hydroxyl group on the B ring was of importance, inasmuch as quercetin was more potent than morin as an inhibitor of cDNA-expressed and hepatic microsomal monooxygenases.

Publication types

  • Comparative Study

MeSH terms

  • Animals
  • Cytochrome P-450 CYP1A2
  • Cytochrome P-450 Enzyme Inhibitors*
  • Cytochrome P-450 Enzyme System / drug effects*
  • Flavonoids / pharmacology*
  • Humans
  • Isoenzymes / drug effects*
  • Mice
  • Microsomes, Liver / enzymology
  • NADH, NADPH Oxidoreductases / drug effects
  • Oxidoreductases, N-Demethylating / drug effects*
  • Recombinant Proteins / drug effects
  • Species Specificity
  • Structure-Activity Relationship


  • Cytochrome P-450 Enzyme Inhibitors
  • Flavonoids
  • Isoenzymes
  • Recombinant Proteins
  • Cytochrome P-450 Enzyme System
  • Cytochrome P-450 CYP1A2
  • Oxidoreductases, N-Demethylating
  • NADH, NADPH Oxidoreductases