The special extract of Rheum rhaponticum (ERr 731®) does not stimulate uterine growth and proliferation in ovariectomized wistar rats

The special extract ERr 731® from the roots of Rheum rhaponticum L. is the major constituent of Phyto-Strol which has been used for the relief of menopausal symptoms for decades. We recently demonstrated the nearly pure estrogen receptor-β (ERβ) agonistic properties of ERr 731® in human endometrial and bone cell systems. Here we present investigations on the effects of ERr 731® on uterine growth and proliferation in ovariectomized (OvEx) rats following subcutaneous treatment for 72h with the therapeutic dose of ERr 731® (0.1mg/kg body weight (bw)/day), a pharmacological dosage range of 1–100mg/kg bw/d or with the positive control 17β-estradiol (E2; 4µg/kg bw/d). We assessed the uterine wet weight and analyzed the expression of the ERs and the proliferation marker Ki-67 by semiquantitative realtime-PCR. Treatment of the animals with E2 increased the uterine wet weight approximately five-fold in comparison to the control. ERr 731® did not affect the uterine wet weight at any dose. E2 induced a 19-fold expression of Ki-67, the response to ERr 731® was 1.3- to 1.6-fold. Interestingly, treatment with E2 remarkably down-regulated the expression of both ERs, whereas treatment with ERr 731® induced an increased expression of both ERs at the lowest dose and a disproportionate decline of the expression levels at higher doses in favour of ERβ.

We demonstrate for the first time that ERr 731® does not induce uterotrophy or uterine proliferation in OvEx rats. These experimental findings support clinical data on the uterine/endometrial safety of ERr 731®.