Cell Therapy Center, Xuanwu Hospital Capital Medical University, Beijing, China.
Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University, Hong Kong, Hong Kong SAR, China.
Front Endocrinol (Lausanne). 2022 Feb 24;13:817146. doi: 10.3389/fendo.2022.817146. eCollection 2022.
Our previous study demonstrated that the bone protective actions of herbal medicine (Gusuibu, RD) were mainly mediated by flavonoid phytoestrogens 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.
我们之前的研究表明，草药（骨碎补，RD）的护骨作用主要是通过类黄酮植物雌激素与雌激素受体介导的，这引起了人们对使用 RD 的安全性的担忧，因为它可能会在与其他 ER 配体（如选择性雌激素受体调节剂（SERMs））共同给药时，诱导出类似雌激素的风险-效益特征并相互作用。本研究通过使用成熟去卵巢（OVX）大鼠和雌激素受体阳性细胞，评估了 RD 的雌激素活性及其与 SERM 他莫昔芬在雌激素敏感组织中的潜在相互作用。与他莫昔芬相似但作用较弱，RD 在其临床剂量下可显著改善 OVX 大鼠骨和多巴胺代谢相关标志物的变化。然而，只有他莫昔芬而非 RD 引起了子宫肥大效应。在 RD 处理的 OVX 大鼠中，乳腺没有明显变化，这与他莫昔芬的抑制作用不同。双向方差分析结果表明，RD 和他莫昔芬在 OVX 大鼠的骨骼、大脑和子宫之间存在相互作用，而 RD 并未改变它们对他莫昔芬的反应。我们的研究结果表明，RD 以不同于他莫昔芬的方式选择性地发挥雌激素作用。此外，RD 与他莫昔芬相互作用而不改变其在 OVX 大鼠中的作用。
