Plants for Human Health Institute, North Carolina Research Campus, North Carolina State University, 600 Laureate Way, Kannapolis, NC 28081, USA.
Department of Food, Bioprocessing & Nutrition Sciences, North Carolina State University, 400 Dan Allen Drive, Raleigh, NC 27695, USA.
Int J Mol Sci. 2021 Jan 21;22(3):1032. doi: 10.3390/ijms22031032.
Ovarian insufficiency and ovariectomy are characterized by deregulated heat loss mechanisms. Unlike hormone therapy, ERr 731 (a standardized botanical extract of Siberian rhubarb L. high in rhaponticin) acts like a selective estrogen receptor modulator for ERβ receptors and may offer a higher degree of safety while maintaining the desired efficacy profile. In this study, we examined the relationship between oral administration of ERr 731 and the underlying components of skin vasomotion responses in an ovariectomized (OVX) rat model. ERr 731 dose-dependently reduced tail skin temperature (T) values by an average of 1 °C. The rapid onset of this effect was observed in 1 and 3 mg/kg/day ERr 731 groups as early as day 2 of administration, and remained in place for the duration of the treatment (2 weeks). Substituting ERr 731 after E withdrawal helped maintain body temperature similarly to E alone, suggesting the usefulness of ERr 731 for replacing existing hormonal therapy in humans. ERr 731 also acted as a highly selective agonist for ERβ in the hypothalamus of OVX rats, as well as in ERα/β cell-based reporter assays. These data validate the OVX/T rat model as a suitable screening platform to evaluate botanical and pharmaceutical treatments of menopause, while providing further evidence for the efficacy of ERr 731 towards alleviating vasomotor menopausal symptoms and improving wellbeing during the menopausal transition.
卵巢功能不全和卵巢切除术后的特征是热损失机制失调。与激素治疗不同，ERr 731（西伯利亚大黄 L. 的一种标准化植物提取物，富含虎杖苷）作为 ERβ 受体的选择性雌激素受体调节剂，在保持所需疗效的同时，可能具有更高的安全性。在这项研究中，我们检查了口服 ERr 731 与去卵巢（OVX）大鼠模型皮肤血管运动反应的潜在成分之间的关系。ERr 731 剂量依赖性地降低了尾巴皮肤温度（T）值，平均降低了 1°C。在 1 和 3 mg/kg/天的 ERr 731 组中，这种作用的快速起效早在给药第 2 天就观察到了，并且在整个治疗期间（2 周）都保持不变。在用 E 替代 ERr 731 后，体温的维持与单独使用 E 相似，这表明 ERr 731 对于替代现有的激素治疗在人类中是有用的。ERr 731 还作为 ERβ 的高度选择性激动剂，在 OVX 大鼠的下丘脑以及 ERα/β 细胞基于报告基因的测定中发挥作用。这些数据验证了 OVX/T 大鼠模型作为评估植物和药物治疗更年期的合适筛选平台，同时进一步证明了 ERr 731 缓解血管舒缩更年期症状和改善更年期过渡期间幸福感的功效。
