title: 6-shogaol, a major compound in ginger, induces aryl hydrocarbon receptor-mediated transcriptional activity and gene expression.
abstract: Xenobiotics are usually detoxified by drug-metabolizing enzymes and excreted from the body. The expression of many of drug-metabolizing enzymes is regulated by the aryl hydrocarbon receptor (AHR). Some substances in vegetables have the potential to be AHR ligands. To search for vegetable components that exhibit AHR-mediated transcriptional activity, we assessed the activity of vegetable extracts and identified the active compounds using the previously established stable AHR-responsive HepG2 cell line. Among the hot water extracts of vegetables, the highest activity was found in ginger. The ethyl acetate fraction of the ginger hot water extract remarkably induced AHR-mediated transcriptional activity, and the major active compound was found to be 6-shogaol. Subsequently, the mRNA levels of AHR-targeting drug-metabolizing enzymes (CYP1A1, UGT1A1, and ABCG 2) and the protein level of CYP1A1 in HepG2 cells were shown to be increased by 6-shogaol. This is the first report that 6-shogaol can regulate the expression of detoxification enzymes by AHR activation.
authors.affiliation: Research & Development Division, Kagome Co., Ltd. , 17 Nishitomiyama, Nasushiobara 329-2762, Japan.
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Yoshida
authors.forename: Hideo
authors.initials: H
authors.lastname: Satsu
authors.forename: Ayano
authors.initials: A
authors.lastname: Mikubo
authors.forename: Haru
authors.initials: H
authors.lastname: Ogiwara
authors.forename: Takafumi
authors.initials: T
authors.lastname: Yakabe
authors.forename: Takahiro
authors.initials: T
authors.lastname: Inakuma
authors.forename: Makoto
authors.initials: M
authors.lastname: Shimizu
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism; D000085:Acetates / Q000737:chemistry; D002396:Catechols / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D005233:Fatty Alcohols / Q000494:pharmacology; D005786:Gene Expression Regulation; D020939:Zingiber officinale / Q000737:chemistry*; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism; D056945:Hep G2 Cells; D006801:Humans; D008024:Ligands; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D028528:Petroselinum / Q000737:chemistry; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000378:metabolism*; D018724:Spinacia oleracea / Q000737:chemistry; D015533:Transcriptional Activation / Q000235:genetics*; D014867:Water / Q000737:chemistry; D000099148:UGT1A1 Enzyme
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000085:Acetates; D002396:Catechols; D019363:Cytochrome P-450 CYP1A1; D005233:Fatty Alcohols; D014453:Glucuronosyltransferase; D008024:Ligands; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D014867:Water; D000099148:UGT1A1 Enzyme; C116614:ABCG2 protein, human; C007650:ethyl acetate; C040115:shogaol; C007845:gingerol; C569463:CYP1A1 protein, human