title: Blockade of the dioxin pathway by herbal medicine Formula Bupleuri Minor: identification of active entities for suppression of AhR activation.
abstract: Environmental pollutants including dioxins activate the aryl hydrocarbon receptor (AhR) and cause a wide range of pathologies. Development of AhR antagonists will be useful for prevention and treatment of the diseases related to AhR activation. Towards this goal, we aimed at seeking for potential AhR antagonists in herbal medicines using the dioxin responsive element-based sensing via secreted alkaline phosphatase (DRESSA). Through initial rough screening, 4 formulae were selected from 20 herbal medicines and subjected to the second, detailed screening. We found that only Formula bupleuri minor (TJ-9) significantly inhibited activation of AhR by 2,3,7,8-tetrachlorodibenzo-p-dioxin. Among 7 raw herb extracts in TJ-9, Glycyrrhizae Radix and Scutellariae Radix were responsible for the antagonistic effect of TJ-9 against dioxin. Some constituents including Bupleuri Radix and Zingiberis Rhizoma rather activated AhR. Among 12 major constituents of Glycyrrhizae Radix and Scutellariae Radix, we identified that licopyranocoumarin, glycyrrhizic acid and genistein in Glycyrrhizae Radix and baicalein, wogonin and daidzein in Scutellariae Radix had substantial antagonistic effects on AhR. Among these, baicalein most effectively blocked activation of AhR triggered by cigarette smoke, a strong activator of AhR. The antagonistic substances identified here may be useful for prevention from diseases associated with aberrant activation of AhR.
authors.affiliation: Department of Molecular Signaling, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Shimokato 1110, Chuo, Yamanashi 409-3898, Japan.
authors.forename: Ayumi
authors.initials: A
authors.lastname: Kasai
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Hayakawa
authors.forename: Jian
authors.initials: J
authors.lastname: Yao
authors.forename: Masanori
authors.initials: M
authors.lastname: Kitamura
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001711:Biotransformation / Q000187:drug effects; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis; D004147:Dioxins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D004785:Environmental Pollutants / Q000037:antagonists & inhibitors / Q000494:pharmacology; D005562:Formazans; D006801:Humans; D007202:Indicators and Reagents; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000037:antagonists & inhibitors / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D012906:Smoke / Q000032:analysis; D014026:Nicotiana / Q000737:chemistry
chemical_list: D004147:Dioxins; D004365:Drugs, Chinese Herbal; D004785:Environmental Pollutants; D005562:Formazans; D007202:Indicators and Reagents; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D012906:Smoke; C461320:shosaiko-to; D019363:Cytochrome P-450 CYP1A1; D000469:Alkaline Phosphatase