title: Ginsenosides are novel naturally-occurring aryl hydrocarbon receptor ligands.
abstract: The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor that mediates many of the biological and toxicological actions of structurally diverse chemicals. In this study, we examined the ability of a series of ginsenosides extracted from ginseng, a traditional Chinese medicine, to bind to and activate/inhibit the AHR and AHR signal transduction. Utilizing a combination of ligand and DNA binding assays, molecular docking and reporter gene analysis, we demonstrated the ability of selected ginsenosides to directly bind to and activate the guinea pig cytosolic AHR, and to stimulate/inhibit AHR-dependent luciferase gene expression in a recombinant guinea pig cell line. Comparative studies revealed significant species differences in the ability of ginsenosides to stimulate AHR-dependent gene expression in guinea pig, rat, mouse and human cell lines. Not only did selected ginsenosides preferentially activate the AHR from one species and not others, mouse cell line was also significantly less responsive to these chemicals than rat and guinea pig cell lines, but the endogenous gene CYP1A1 could still be inducted in mouse cell line. Overall, the ability of these compounds to stimulate AHR signal transduction demonstrated that these ginsenosides are a new class of naturally occurring AHR agonists.
authors.affiliation: Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Hu
authors.forename: Guochun
authors.initials: G
authors.lastname: He
authors.forename: Jing
authors.initials: J
authors.lastname: Zhao
authors.forename: Anatoly
authors.initials: A
authors.lastname: Soshilov
authors.forename: Michael S
authors.initials: MS
authors.lastname: Denison
authors.forename: Aiqian
authors.initials: A
authors.lastname: Zhang
authors.forename: Huijun
authors.initials: H
authors.lastname: Yin
authors.forename: Domenico
authors.initials: D
authors.lastname: Fraccalvieri
authors.forename: Laura
authors.initials: L
authors.lastname: Bonati
authors.forename: Qunhui
authors.initials: Q
authors.lastname: Xie
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D036145:Ginsenosides / Q000494:pharmacology*; D006168:Guinea Pigs; D006801:Humans; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D051381:Rats; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000378:metabolism*
chemical_list: D036145:Ginsenosides; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon