TY - JOUR
T1 - Ginsenosides Are Novel Naturally-Occurring Aryl Hydrocarbon Receptor Ligands
AU - Hu, Qin
AU - He, Guochun
AU - Zhao, Jing
AU - Soshilov, Anatoly
AU - Denison, Michael S.
AU - Zhang, Aiqian
AU - Yin, Huijun
AU - Fraccalvieri, Domenico
AU - Bonati, Laura
AU - Xie, Qunhui
AU - Zhao, Bin
PY - 2013/6/11
Y1 - 2013/6/11
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84878829776&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84878829776&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0066258
DO - 10.1371/journal.pone.0066258
M3 - Article
C2 - 23776647
AN - SCOPUS:84878829776
VL - 8
JO - PLoS One
JF - PLoS One
SN - 1932-6203
IS - 6
M1 - e66258
ER -