Activation of estrogen receptor-β by a special extract of Rheum rhaponticum (ERr 731®), its aglycones and structurally related compounds

The special extract ERr 731® from the roots of Rheum rhaponticum is the major constituent of Phytoestrol® N which is used for the treatment of climacteric symptoms in menopausal women. However, the molecular mode of action of ERr 731® was unknown. For the first time, ERr 731® and its aglycones trans-rhapontigenin and desoxyrhapontigenin were investigated with regard to the activation of the estrogen receptor-α or estrogen receptor-β (ERα, ERβ). The related hydroxystilbenes cis-rhapontigenin, resveratrol and piceatannol were studied as comparators. As controls, 17β-estradiol or the selective ERα-(propylpyrazoltriol) or ERβ-agonists (diarylpropionitril) were used. Neither in ERα-expressing yeast cells, in the ERα-responsive Ishikawa cells, nor in human endometrial HEC-1B cells transiently transfected with the ERα an activation of ERα by ERr 731® or the other single compounds was detected. Furthermore, an antiestrogenic effect was not observed. In contrast in human endometrial HEC-1B cells transiently transfected with the ERβ, 100 ng/ml ERr 731® and the single compounds significantly induced the ERβ-coupled luciferase activity in a range comparable to 10−8 M 17β-estradiol. All effects were abolished with the pure ER antagonist ICI 182780, indicating an ER-specific effect. The ERβ agonistic activity by ERr 731® could be of importance for its clinical use, as central functions relevant to climacteric complaints are proposed to be mediated via ERβ activation.