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. ERr extract activates reporter gene activity through ERβ in HEC-1B endometrial adenocarcinoma cells and an endometrial specific reporter gene construct (mC3-tk-Luc). Rhapontigenin and desoxyrhapontigenin almost only act on ERβ.
This weak binding preference suggests that the stimulation of cell-based reporter genes is equally potent for both receptors. IC 50 values of compounds in comparison to estradiol and relative preference for the receptor subtypes are shown. Relative binding affinities of trans-rhapontigenin and desoxyrhapontigenin were assessed by a fluorescence polarization assay. If a compound is administered to ovariectomized rodents and exhibits estrogenic activities, uterine growth will be stimulated. Ovariectomized female rodent is the recommended animal model for estrogen-related studies. Therefore, results obtained in vitro must be verified in vivo. A compound given to an organism may be subject to its metabolism thereby rendering its activity. Finally, an organism as a whole has a high metabolic capacity. luciferase, whereby functional activity of ERs is quantified in target cells. 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. Bound estrogen receptors (ERs) usually modify transcriptional activity of target genes in a target cell. Ligand binding assays and uterotrophic assays are two major methods to investigate the estrogenic activities of ERr. Estrogenic activities of ERr were assessed at biochemical, molecular and cellular as well as organism levels. Ĭlinical observations suggest that the mode of action of ERr is similar to that of hormones (i.e., estrogens). ĮRr reduces the occurrence and severity of climacteric symptoms during perimenopause in women and improves their health-related quality of life. 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. ERr is effective in reducing anxiety in perimenopausal women according to the Hamilton Anxiety Scale. No adverse events were detected in relation to ERr intake. Importantly, no difference was observed in gynecological findings including endometrial biopsies, bleeding weight, blood pressure and tested laboratory safety parameters. After 12 weeks the overall menopause-related quality of life was significantly better in ERr-treated women than in those who received placebo. After four weeks of treatment, the number and severity of hot flushes were decreased. The treatment with ERr after 12 weeks significantly reduced the Menopause Rating Scale II symptoms as compared to control.
SIBERIAN MOUSE BJ TRIAL
The effectiveness of ERr to treat menopausal symptoms was validated by a 3-month prospective randomized controlled trial on 54 perimenopausal women with climacteric complaints receiving a daily dose of 4 mg of ERr. While hormone therapy (HT) effectively relieves menopausal symptoms, many women seek alternative treatments due to increased risks for breast and endometrial cancer associated with HT, as well as venous thromboembolism. About 80% of menopausal women suffer from hot flushes, sweating, heart complaints, sleep disturbances, depression, anxiety, physical/mental exhaustion, sexual problems, urinary tract complaints and vaginal dryness. Perimenopause is the period of time (up to five years) prior to the last menstruation. Postmenopause is established after 12 months of amenorrhea. Ovarian failure during menopausal transition evokes a variety of symptoms.
Since 1993 when ERr was first used in human to treat menopausal symptoms, and before when it used to treat women with child bearing potential suffering from oligomenorrhea or amenorrhea, no severe adverse events have been reported. Effectiveness of ERr in treating menopause