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

Abstract

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 alpha (ERalpha) and ERbeta, and are, therefore, termed phytoestrogens. In this study, we examined whether various phytochemicals have agonistic and/or antagonistic activity against six human nuclear receptors (ERalpha, ERbeta, androgen receptor (AR), glucocorticoid receptor (GR), thyroid hormone receptor alpha(1) (TRalpha(1)) and TRbeta(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 ERalpha and/or ERbeta, and we ranked these phytochemicals according to their estrogenic potency via ERalpha and ERbeta. As a result, coumestrol and genistein strongly activated ERalpha and ERbeta at very low concentrations of <1x10(-10) M. Most phytochemicals showing estrogenic activity also exhibited agonistic activity against ERbeta at lower concentrations than those for ERalpha, and two typical isoflavones, genistein and daidzein, in particular, showed a potent preference for ERbeta. Further, we found that baicalein has ERbeta 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, TRalpha(1) and TRbeta(1) agonistic/antagonistic activity. These results suggest that various phytochemicals or their metabolites preferentially interact with ERalpha/beta among the six nuclear hormone receptors tested, and that the ERbeta agonistic activity, in particular, of these compounds may be associated with various beneficial effects on human health.