Archives of Pharmacal Research

The Pharmaceutical Society of Korea (대한약학회)
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Effects of Hydroxyl Group Numbers on the B-Ring of 5,7-Dihydroxyflavones on the Differential Inhibition of Human CYP 1A and CYP1B1 Enzymes

  • Kim Hyun-Jung (School of Life Sciences and Biotechnology, Korea University) ;
  • Lee Sang Bum (School of Life Sciences and Biotechnology, Korea University) ;
  • Park Song-Kyu (Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim Hwan Mook (Korea Research Institute of Bioscience and Biotechnology) ;
  • Park Young In (School of Life Sciences and Biotechnology, Korea University) ;
  • Dong Mi-Sook (School of Life Sciences and Biotechnology, Korea University)
  • Published : 2005.10.01
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Abstract

Flavonoids are polyphenols composed of two aromatic rings (A, B) and a heterocyclic ring (C). In order to determine the effects of the number of hydroxyl groups in the B-ring of the flavonoids on human cytochrome P450 (CYP) 1 family enzymes, we evaluated the inhibition of CYP1A-dependent 7-ethoxyresorufin O-deethylation activity by chrysin, apigenin and luteolin, using bacterial membranes that co-express human CYP1A1, CYP1A2, or CYP1B1 with human NADPH-cytochrome P450 reductase. Chrysin, which possesses no hydroxyl groups in its B-ring, exhibited the most pronounced inhibitory effects on CYP1A2-dependent EROD activity, followed by apigenin and luteolin. On the contrary, CYP1A1-mediated EROD activity was most potently inhibited by luteolin, which is characterized by two hydroxyl groups in its B-ring, followed by apigenin and chrysin. However, all of the 5,7-dihydroxyflavones were determined to similarly inhibit CYP1B1 activity. Chrysin, apigenin, and luteolin exhibited a mixed-type mode of inhibition with regard to CYP1A2, CYP1B1, and CYP1A1, with apparent Ki values of 2.4, 0.5, and 2.0 ${\mu}M$, respectively. These findings suggested that the number of hydroxyl groups in the B-ring of 5,7-dihydroxyflavone might have some influence on the degree to which CYP1A enzymes were inhibited, but not on the degree to which CYP1B1 enzymes were inhibited.

Keywords

References

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