Selective activation of the estrogen receptor-β by the polysaccharide from Cynanchum wilfordii alleviates menopausal syndrome in ovariectomized mice

The menopausal syndrome caused by rapid changes in hormone levels greatly influences the quality of life of women. Though hormone replacement therapy (HRT) is widely used to treat the menopausal syndrome, it exhibits many side effects, including the risk of thrombosis, cardiovascular diseases, and increased incidence of breast cancer; thus, diversifying the interest for phytotherapy-based materials as alternatives to HRT. Here, we isolated a crude polysaccharide fraction (CWPF) from Cynanchum wilfordii root that alleviated the ovariectomy-induced uterine atrophy and bone loss without changes in plasma estradiol concentration in mice. Increased plasma levels of follicle-stimulating hormone (FSH), alkaline phosphatase (ALP), osteocalcin (OC) in ovariectomized mice were also reduced to normal levels by CWPF administration. We found that the inhibitory effects of CWPF on menopausal symptoms were mediated by the estrogen receptor β (ER-β) specific activation, not ER-α. Moreover, CWPF treatment suppressed the phosphorylation of Akt, suggesting that CWPF alleviates post-menopausal symptoms by regulating ER-β related Akt signaling pathway. These results demonstrate that the polysaccharides corresponding to CWPF among the water-soluble extracts of CW could be used as a beneficial herbal alternative for the development of therapeutic agents to prevent menopausal syndrome in women.