title: Interaction between the aryl hydrocarbon receptor and its antagonists, flavonoids.
abstract: Flavonoids have been reported to be dietary antagonists of an aryl hydrocarbon receptor (AhR). However, little is known about the molecular mechanism on their antagonistic effects. In this study, the inhibitory effect of flavonoids on ligand binding to the AhR and interaction between flavonoids and the AhR complex (AhRc) were investigated in each flavonoid subclass. Flavone, flavonol, and flavanone but not catechin inhibited the specific binding between the AhR and 3-methylcholanthrene dose-dependently, indicating that the former three subclasses possibly act as competitive antagonists of the AhR. However, catechin in addition to the former three subclasses directly interacted with the AhRc by surface plasmon resonance analysis. The dissociation constant values showed an inverse correlation with the suppressive effect on the DNA binding activity. These results suggest that flavone, flavonol, and flavanone act as competitive antagonists of the AhR, while catechin associates with the AhRc and indirectly exhibits its antagonistic effects.
authors.affiliation: Research Center for Food Safety and Security, Graduate School of Agricultural Science, Kobe University, Kobe, Hyogo 657-8501, Japan. itsuko@silver.kobe-u.ac.jp
authors.forename: Itsuko
authors.initials: I
authors.lastname: Fukuda
authors.forename: Rie
authors.initials: R
authors.lastname: Mukai
authors.forename: Masaya
authors.initials: M
authors.lastname: Kawase
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ashida
mesh_terms: D000818:Animals; D002458:Cell Fractionation; D003600:Cytosol / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008748:Methylcholanthrene / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D020349:Surface Plasmon Resonance
chemical_list: D005419:Flavonoids; D018336:Receptors, Aryl Hydrocarbon; D008748:Methylcholanthrene