Comparative Study on the Nuclear Hormone Receptor Activity of Various Phytochemicals and Their Metabolites by Reporter Gene Assays Using Chinese Hamster Ovary Cells(Molecular and Cell Biology)

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概要

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• Phytochemicals are naturally present in a wide variety of plants, and have been suggested to exert a number of effects beneficial to human health. Several phytochemicals possess estrogenic activity through estrogen receptor α (ERα) and ERβ, and are, therefore,termed phytoestrogens. In this study, we examined whether various phytochemicals have agonistic and/or antagonistic activity against six human nuclear receptors (ERα, ERβ, androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor α_1 (TRα_1) and TRβ_1) by in vitro reporter gene assays using Chinese hamster ovary cells. Of the 31 phytochemicals tested, including flavonoids, isoflavonoids, coumestan, lignans, catechins and their metabolites, 20 compounds showed estrogenic activity via ERα and/or ERβ, and we ranked these phytochemicals according to their estrogenic potency via ERα and ERβ. As a result, coumestrol and genistein strongly activated ERα and ERβ at very low concentrations of <1×10^<-10>M. Most phytochemicals showing estrogenic activity also exhibited agonistic activity against ERβ at lower concentrations than those for ERα, and two typical isoflavones, genistein and daidzein, in particular, showed a potent preference for ERβ. Further, we found that baicalein has ERβ antagonistic activity, and two compounds, enterolacton and O-desmethylangolensin, have AR antagonistic activity. Nevertheless, none of tested compounds showed AR agonistic activity together with GR, TRα_1 and TRβ_1 agonistic/antagonistic activity. These results suggest that various phytochemicals or their metabolites preferentially interact with ERα/β among the six nuclear hormone receptors tested, and that the ERβ agonistic activity, in particular, of these compounds may be associated with various beneficial effects on human health.

• 2009-02-01

著者

• Kojima Hiroyuki

  Hokkaido Institute of Public Health

• Takeuchi Shinji

  Hokkaido Institute of Public Health

• TAKAHASHI Tetsuo

  Hokkaido Institute of Public Health

• SAWADA Yukiharu

  Hokkaido Institute of Public Health

• IIDA Mitsuru

  Diagnostic Division, Otsuka Pharmaceutical Co., Ltd.

• MATSUDA Tadashi

  Department of Immunology, Graduate School of Pharmaceutical Sciences, Hokkaido University

• Matsuda Tadashi

  Department Of Cardiology Nagoya University Graduate School Of Medicine

• Iida Mitsuru

  Diagnostic Division Otsuka Pharmaceutical Co. Ltd.

• Matsuda Tadashi

  Department Of Immunology Graduate School Of Pharmaceutical Sciences Hokkaido University

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