School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, 232 WaiHuan East Road, Guangzhou University Town, Guangzhou, PR China.
J Ethnopharmacol. 2012 Dec 18;144(3):567-75. doi: 10.1016/j.jep.2012.09.041. Epub 2012 Oct 2.
Radix Astragali (root of Astragalus membranaceus (Fisch.) Bge. var. mongholicus (Bge.) Hsiao, RA), Radix Angelicae sinensis (root of Angelica sinensis (Oliv.) Diels, RAS) and Folium Epimedii (leaves of Epimedium brevicomum Maxim., FE) are three of the extensively applied herbal remedies among traditional Chinese medicines for gynecological disorders and osteoporosis. A derivative herbal recipe-RRF, composed of the three medicines with a weight ratio of 5:1:5, is derived from a famous Chinese herbal formula-Danggui Buxue Tang (DBT). RRF has shown noteworthy protective effect in ovariectomized rats, which might represent a promising candidate for the treatment of perimenopausal disorders. The aim of this study was to investigate the herbal recipe RRF for its efficacy on perimenopausal disorders and the underlying mechanisms via ovariectomy (OVX) models.
An experimental model of OVX female rats was applied. Vehicle (Sham and OVX group), RRF (564, 282 and 141 mg/kg/d) and conjugated equine estrogens (CEE, 0.1mg/kg/d, reference drug) were all administrated orally once daily for 16 weeks post operation. After the treatment, radioimmunoassay for estradiol (E(2)), lutenizing hormone (LH), follicle stimulating hormone (FSH) and β-endorphin (β--EP), neurotransmitter determination by high-performance liquid chromatography with electrochemical detector (HPLC-ECD) for norepinephrine (NE), dopamine (DA), 5-hydroxytryptamine (5-HT) and 5-HIAA (5-hydroxyindoleacetic acid), bone mineral density (BMD) assay as well as lipid peroxidation assessment, were carried out to probe into the effectiveness of RRF.
(1) RRF treatment enhanced E(2) synthese while diminished the elevated serum FSH and LH levels; in terms of neurotransmitter, β-EP syntheses rallied whereas the hypothalamic NE, DA and 5-HT release experienced varying mitigation in OVX female rats. (2) Repeated administration of RRF was able to attenuate osteoporosis by elevating the BMD levels of total body, and arrest the bone trabeculae degradation. (3) RRF exposure decreased serum levels of constituent MDA and increased endogenous SOD activity.
Results of the current studies revealed that RRF was capable of acting at multiple targets which presumably underlay its potential protective effect in OVX rats mimicking symptoms as observed in perimenopausal women. Hence, RRF might represent a promising candidate in the treatment of perimenopausal disorders in midlife women.
ETHNOPHARMACOLOGICAL 相关性：黄芪（膜荚黄芪（Fisch.）Bge. var. 蒙古黄芪（Bge.）Hsiao，RA）、当归（当归（Oliv.）Diels，RAS）和淫羊藿叶（淫羊藿短柄草 Maxim.，FE）是中药治疗妇科疾病和骨质疏松症的三种广泛应用的草药。一种衍生草药配方-RRF，由三种药物按 5:1:5 的重量比组成，源自著名的中草药配方-当归补血汤（DBT）。RRF 对去卵巢大鼠表现出显著的保护作用，这可能是治疗围绝经期疾病的有前途的候选药物。本研究旨在通过去卵巢（OVX）模型研究草药配方 RRF 对围绝经期疾病的疗效及其潜在机制。
应用去卵巢雌性大鼠实验模型。给予载体（假手术和 OVX 组）、RRF（564、282 和 141 mg/kg/d）和结合马雌激素（CEE，0.1mg/kg/d，参考药物），每天口服一次，术后 16 周。治疗后，用放射免疫法测定雌二醇（E（2））、促黄体生成激素（LH）、促卵泡生成激素（FSH）和β-内啡肽（β--EP），用高效液相色谱电化学检测器（HPLC-ECD）测定神经递质去甲肾上腺素（NE）、多巴胺（DA）、5-羟色胺（5-HT）和 5-羟吲哚乙酸（5-HIAA），测定骨矿物质密度（BMD）和脂质过氧化评估，以探讨 RRF 的疗效。
（1）RRF 治疗增强了 E（2）的合成，同时降低了升高的血清 FSH 和 LH 水平；就神经递质而言，β-EP 合成增加，而下丘脑 NE、DA 和 5-HT 释放则有所减轻。（2）重复给予 RRF 可通过提高全身 BMD 水平来减轻骨质疏松症，并阻止骨小梁降解。（3）RRF 暴露降低了血清中 MDA 的水平，增加了内源性 SOD 活性。
本研究结果表明，RRF 能够作用于多个靶点，这可能是其在模拟围绝经期妇女症状的去卵巢大鼠中具有潜在保护作用的基础。因此，RRF 可能是治疗中年妇女围绝经期疾病的有前途的候选药物。
