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首页> 外文期刊>Journal of Pharmaceutical and Biomedical Analysis: An International Journal on All Drug-Related Topics in Pharmaceutical, Biomedical and Clinical Analysis >An UHPLC-MS/MS method for simultaneous determination of ten sex steroid hormones in ovariectomy-induced osteoporosis rat and its application in discovery of sex steroid hormones regulatory components of Xian-Ling-Gu-Bao capsule
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An UHPLC-MS/MS method for simultaneous determination of ten sex steroid hormones in ovariectomy-induced osteoporosis rat and its application in discovery of sex steroid hormones regulatory components of Xian-Ling-Gu-Bao capsule

机译：一种UHPLC-MS / MS方法，用于同时测定卵巢切除术诱导的骨质疏松大鼠的十个性类固醇激素及其在西岭宫胶囊的性类固醇激素监管组分发现中的应用

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摘要

Sex steroid hormones could directly affect the bone metabolism by regulating cell physiological functions. In female, it inevitably causes the abnormal levels of sex steroid hormones at post-menopause in vivo. Ovariectomized rats and mice are classic animal models of osteoporosis to better understand the action mechanism of anti-osteoporosis drugs. However, it is not clear whether Xian-Ling-Gu-Bao capsule (XLGB), a kidney-tonifying traditional Chinese medicine prescription, treat osteoporosis via regulating multiple sex steroid hormones. In the present study, a reliable method involving ultra high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLCITQ-XS-MS) was developed for simultaneous quantitative analysis of ten sex steroid hormones (three estrogens, five androgens and two progestogens) in rat and mouse serum. The results of methodology were acceptable. The validated method was then successfully applied in the determination of the levels of sex steroid hormones in ovariectomy-induced osteoporosis rats, as well as drug (17 beta-estradiol and XLGB) intervened rats. As a result, XLGB could not only significantly increase the level of 17 beta-estradiol, but also improve the levels of progesterone, 17 alpha-hydroxyprogesterone and androstenedione. Combined with molecular docking results and pharmacokinetic parameters, psoralen, isopsoralen and sweroside were considered as the key effective components of XLGB to activate adenylyl cyclase on promoting the biosynthesis of multiple sex steroid hormones. It is the first time to evaluate the regulatory effect of kidney-tonifying traditional Chinese medicine prescription on the levels of steroids in ovariectomy-induced osteoporosis rat, as well as the potential substance basis and mechanism of steroid hormone regulation. (C) 2020 Elsevier B.V. All rights reserved.
机译：性类固醇激素通过调节细胞生理功能直接影响骨代谢。在女性体内，它不可避免地导致绝经后体内性类固醇激素水平异常。去卵巢大鼠和小鼠是骨质疏松症的经典动物模型，以更好地了解抗骨质疏松药物的作用机制。然而，目前尚不清楚补肾中药仙灵骨宝胶囊（XLGB）是否通过调节多种性类固醇激素来治疗骨质疏松症。本研究建立了超高效液相色谱-三重四极杆质谱联用（UHPLCITQ-XS-MS）同时定量分析大鼠和小鼠血清中10种性类固醇激素（3种雌激素、5种雄激素和2种孕激素）的可靠方法。方法学的结果是可以接受的。该验证方法随后成功应用于测定卵巢切除诱导的骨质疏松大鼠以及药物（17β-雌二醇和XLGB）干预大鼠的性类固醇激素水平。因此，XLGB不仅能显著提高17β-雌二醇的水平，还能提高孕酮、17α-羟孕酮和雄烯二酮的水平。结合分子对接结果和药代动力学参数，补骨脂素、异补骨脂素和獐牙菜苷被认为是XLGB激活腺苷酸环化酶促进多种性类固醇激素生物合成的关键有效成分。首次评价补肾中药方剂对去卵巢骨质疏松大鼠类固醇激素水平的调节作用，以及类固醇激素调节的潜在物质基础和机制。（C） 2020爱思唯尔B.V.版权所有。

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