Molecular mechanisms of Angelica sinensis (Oliv.) Diels in women's health

描述(申请人提供)：很大一部分女性人口受到经前综合症(PMS)和更年期症状的影响。可获得的医疗治疗有限，其中一些具有严重的不良反应。取而代之的是，许多女性转向植物性膳食补充剂。当归(Angelica sinensis(Oliv.)Diels是最常用的植物膳食补充剂之一，用于缓解经前综合症和更年期症状。虽然这种植物的干燥根，也被称为冬瓜，在中国身上已经使用了几个世纪的传统，目前正被许多美国妇女使用，但人们对它的作用机制知之甚少。我们推测当归可以通过中枢神经系统受体发挥作用，从而对经前综合症和更年期产生有益的影响。在这一应用中，我们建议通过首先评估几种具有化学特征的当归提取物对阿片剂和氨基丁酸(GABA)-A受体的亲和力来检验这一假设。这些提取物将通过测量G蛋白的激活和腺苷环化酶的抑制，以及通过测定突触体内的GABA门控的氯-内流来进一步测试它们对阿片受体的激活。目的3将在一个大鼠模型中确定两种提取物的体内疗效。虽然这些基于受体的结合和活性分析已经被用于药理研究，但应用这种分子方法来研究当归的作用机制是一种新的创新途径。这些研究结果将有助于明确当归的分子作用机制。这些信息不仅将为当归用于缓解经前综合症和更年期症状提供机械证据，还可能被用于未来临床研究的当归产品的生物学标准化。 公共卫生相关性：很大一部分女性人口受到经前综合征(PMS)和更年期症状的影响。虽然当归(Angelica sinensis(Oliv.)Diels是最常用的植物膳食补充剂之一，用于缓解经前综合症和更年期症状，但对其作用机制知之甚少。本申请旨在应用分子方法研究当归的作用机理。

DESCRIPTION (provided by applicant): A large segment of the female population is affected by premenstrual syndrome (PMS) and menopausal symptoms. Limited medical treatments are available, some with severe adverse effects. Instead, many women have turned to botanical dietary supplements. Angelica sinensis (Oliv.) Diels is one of the most commonly used botanical dietary supplements for the relief of PMS and menopausal symptoms. Although the dried root of this plant, also known as Dong quai, has been used traditionally in China for centuries and is currently being used by many American women, its mechanisms of action are poorly understood. We hypothesize that Angelica sinensis can act through CNS receptors to exhibit beneficial effects in PMS and menopause. In this application, we propose to test this hypothesis by first evaluating the affinity of several chemically characterized Angelica sinensis extracts to the opiate and -aminobutyric acid (GABA)-A receptors. The extracts will be further tested for their activation of opiate receptors by measuring G protein activation and adenylyl cyclase inhibition and the activation of the GABA(A) receptor by determining GABA-gated Cl- influx in synaptosomes. Aim 3 will determine the in vivo efficacy of two extracts in a rat model. Although these receptor-based binding and activity assays have been used in pharmacological studies, applying such molecular methods to study mechanisms of Angelica sinensis represents a new and innovative approach. Results from these studies will help to define the molecular mechanisms of action of Angelica sinensis. Such information will not only provide mechanistic evidence for the use of Angelica sinensis in relieving PMS and menopausal symptoms, but may also be used to biologically standardize an Angelica sinensis product for future clinical studies. PUBLIC HEALTH RELEVANCE: A large segment of the female population is affected by premenstrual syndrome (PMS) and menopausal symptoms. Although Angelica sinensis (Oliv.) Diels is one of the most commonly used botanical dietary supplements for the relief of PMS and menopausal symptoms, little is known for its mechanisms. This application aims to apply molecular methods to study mechanisms of action of Angelica sinensis.