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

The special extract ERr 73 (R) from the roots of Rheum rhaponticum is the major constituent of Phytoestrol (R) N which is used for the treatment of climacteric symptoms in menopausal women. However, the molecular mode of action of ERr 73 10 was unknown. For the first time, ERr 731 (R) and its aglycones trans-rhapontigenin and desoxyrhapontigenin were investigated with regard to the activation of the estrogen receptor-alpha or estrogen receptor-beta (ER alpha, ER beta). The related hydroxystilbenes cis-rhapontigenin, resveratrol and piceatannol were studied as comparators. As controls, 17 beta-estradiol or the selective ER alpha-(propylpyrazoltriol) or ER beta-agonists (diarylpropionitril) were used. Neither in ER alpha-expressing yeast cells, in the ER alpha-responsive Ishikawa cells, nor in human endometrial HEC-1B cells transiently transfected with the ER alpha an activation of ER alpha by ERr 731 (R) 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 ER beta, 100 ng/ml ERr 731 (R) and the single compounds significantly induced the ER beta-coupled luciferase activity in a range comparable to 10(-8) M 17 beta-estradiol. All effects were abolished with the pure ER antagonist ICI 182780, indicating an ER-specific effect. The ER beta agonistic activity by ERr 731 (R) could be of importance for its clinical use, as central functions relevant to climacteric complaints are proposed to be mediated via ER beta activation. (C) 2007 Elsevier Ltd. All rights reserved.