title: Dietary flavonoids activate the constitutive androstane receptor (CAR).
abstract: The constitutive androstane receptor (CAR) is known as a xeno-sensor that regulates genes involved in xenobiotic excretion and energy metabolism. This study tested a variety of polyphenols for their ability to modulate CAR activity. HepG2 cells were transfected with a CAR expression plasmid and a reporter plasmid containing the human CYP2B6 regulatory region and then treated with flavonoids, catechins, and other bioactive polyphenols. Luciferase assays revealed that baicalein (5,6,7-OH flavone) was a potent activator of both human and mouse CAR. Catechin gallates also activated human and mouse CAR. Wild-type and CAR knockout mice were treated with baicalein and chrysin (5,7-OH flavone), and their liver mRNA was analyzed by real-time polymerase chain reaction (PCR). A significant increase in cyp2b10 mRNA content was observed only in wild-type mice fed chrysin. These results suggest that dietary flavonoids regulate CAR activity and thereby accelerate both detoxification and energy metabolism.
authors.affiliation: Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657, Japan.
authors.forename: Ruiquing
authors.initials: R
authors.lastname: Yao
authors.forename: Akihito
authors.initials: A
authors.lastname: Yasuoka
authors.forename: Asuka
authors.initials: A
authors.lastname: Kamei
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Kitagawa
authors.forename: Norifumi
authors.initials: N
authors.lastname: Tateishi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Tsuruoka
authors.forename: Yoshionobu
authors.initials: Y
authors.lastname: Kiso
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Sueyoshi
authors.forename: Masahiko
authors.initials: M
authors.lastname: Negishi
authors.forename: Takumi
authors.initials: T
authors.lastname: Misaka
authors.forename: Keiko
authors.initials: K
authors.lastname: Abe
mesh_terms: D000731:Androstanes / Q000378:metabolism*; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics; D002392:Catechin / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D000090702:Constitutive Androstane Receptor; D000072467:Cytochrome P450 Family 2; D004032:Diet; D005419:Flavonoids / Q000494:pharmacology*; D017930:Genes, Reporter; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics; D008156:Luciferases / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D016133:Polymerase Chain Reaction / Q000379:methods; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000235:genetics
chemical_list: D000731:Androstanes; D000090702:Constitutive Androstane Receptor; D005419:Flavonoids; D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; C043561:chrysin; C417939:catechin gallate; D002392:Catechin; D008156:Luciferases; D013250:Steroid Hydroxylases; D001189:Aryl Hydrocarbon Hydroxylases; C101679:Cyp2b10 protein, mouse; D000072467:Cytochrome P450 Family 2