Ĭontinued intake of ERr for 48 and 96 weeks demonstrated long-term safety of ERr as no endometrial hyperplasia was detected, and no adverse events related to ERr occurred. ĮRr reduces the occurrence and severity of climacteric symptoms during perimenopause in women and improves their health-related quality of life. Ĭlinical observations suggest that the mode of action of ERr is similar to that of hormones (i.e., estrogens). Estrogenic activities of ERr were assessed at biochemical, molecular and cellular as well as organism levels. Ligand binding assays and uterotrophic assays are two major methods to investigate the estrogenic activities of ERr. Bound estrogen receptors (ERs) usually modify transcriptional activity of target genes in a target cell. This process may be investigated by reporter gene assays in which a target cell is transfected by an expression plasmid for the ER of interest and a reporter gene construct, e.g. luciferase, whereby functional activity of ERs is quantified in target cells. Finally, an organism as a whole has a high metabolic capacity. A compound given to an organism may be subject to its metabolism thereby rendering its activity. Therefore, results obtained in vitro must be verified in vivo. Ovariectomized female rodent is the recommended animal model for estrogen-related studies. If a compound is administered to ovariectomized rodents and exhibits estrogenic activities, uterine growth will be stimulated. Relative binding affinities of trans-rhapontigenin and desoxyrhapontigenin were assessed by a fluorescence polarization assay. IC 50 values of compounds in comparison to estradiol and relative preference for the receptor subtypes are shown. ![]() This weak binding preference suggests that the stimulation of cell-based reporter genes is equally potent for both receptors. Rhapontigenin and desoxyrhapontigenin almost only act on ERβ. ERr extract activates reporter gene activity through ERβ in HEC-1B endometrial adenocarcinoma cells and an endometrial specific reporter gene construct (mC3-tk-Luc). In a study using bone-derived U2OS cells and a reporter gene construct ((ERE) 2-t-Luc), a weak activation of the reporter gene through ERα by the ERr extract and the two hydroxystilbenes was detected, whereas a strong activation of ERβ-dependent reporter gene by the ERr extract and the two hydroxystilbenes was observed.
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