Water Extract of Rhizoma Drynaria Selectively Exerts Estrogenic Activities in Ovariectomized Rats and Estrogen Receptor-Positive Cells.

Liping Zhou,Wenxuan Yu,Huihui Xiao,Man-Sau Wong,Chi-On Chan,Christina Chui-Wa Poon,Ka-Ying Wong,Daniel Kam-Wah Mok

doi:10.3389/fendo.2022.817146

Abstract

Our previous study demonstrated that the bone protective actions of herbal medicine Rhizoma Drynariae (Gusuibu, RD) were mainly mediated by flavonoid phytoestrogens via estrogen receptors, raising concerns about the safety of using RD as it may induce estrogen-like risk-benefit profile and interact with other ER ligands, such as selective estrogen receptor modulators (SERMs), when coadministered. The present study evaluated the estrogenic activities of RD and its potential interaction with tamoxifen, a SERM, in estrogen-sensitive tissues by using mature ovariectomized (OVX) rats and ER-positive cells. Similar to but weaker than tamoxifen, RD at its clinical dose dramatically ameliorated OVX-induced changes in bone and dopamine metabolism-related markers in OVX rats. However, tamoxifen, but not RD, induced uterotrophic effects. No significant alteration in mammary gland was observed in OVX rats treated with RD, which was different from the inhibitory actions of tamoxifen. The two-way ANOVA results indicated the interactions between RD and tamoxifen in the bone, brain, and uterus of OVX rats while RD did not alter their responses to tamoxifen. Our results demonstrate that RD selectively exerts estrogenic actions in a different manner from tamoxifen. Moreover, RD interacts with tamoxifen without altering its effects in OVX rats.

Highlights

Hormone replacement therapy (HRT) carries considerable benefits for treatment of menopausal syndrome, like vasomotor symptoms and postmenopausal osteoporosis
High-performance liquid chromatography (HPLC) assay confirmed that the quality of rhizoma drynariae raw herb has fulfilled the requirements on the presence of naringin (Supplementary Data 3A)
In response to OVX, a significant increase in body weight was observed in OVX rats in comparison with Sham rat (p < 0.01 vs. Sham), which was reversed by the treatments with E2, tamoxifen, or cotreatment of tamoxifen and RD (p < 0.001, vs. OVX) but not RD alone (Figure 1A)

Summary

Introduction

Hormone replacement therapy (HRT) carries considerable benefits for treatment of menopausal syndrome, like vasomotor symptoms and postmenopausal osteoporosis. HRT significantly increases the risk of breast cancer, endometrial cancer, and cardiovascular disease, making HRT a subject of argument [1]. Selective estrogen receptor modulators (SERMs) act as either estrogen receptor (ER) antagonist or agonist depending on the tissue type and are clinically prescribed to postmenopausal women as an alternative to HRT. Tamoxifen is clinically used for treatment of breast cancer as it is an ER antagonist in breast. It exerts antiosteoporotic effects in menopausal women as an ER agonist in bone [2]. Due to undesirable uterine abnormalities, depression, and increased risk of endometrial cancer after tamoxifen administration, menopausal women try to seek help from alternative approaches [3]

Methods

Results

Conclusion