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

描述（由申请人提供）：大部分女性受经前综合征（PMS）和更年期症状的影响。可用的医疗手段有限，有些有严重的副作用。相反，许多女性已经转向植物性膳食补充剂。当归（当归）Diels是最常用的植物膳食补充剂之一，用于缓解PMS和更年期症状。虽然这种植物的干根，也被称为当归，在中国传统上使用了几个世纪，目前被许多美国妇女使用，但人们对其作用机制知之甚少。我们推测当归可以通过中枢神经系统受体发挥作用，在PMS和更年期表现出有益的效果。在此应用中，我们建议首先评估几种化学特征的当归提取物的阿片和-氨基丁酸（GABA）-A受体的亲和力来测试这一假设。将通过测量G蛋白活化和腺苷酸环化酶抑制进一步测试提取物对阿片受体的活化，并通过测定突触体中GABA门控Cl-内流来测试GABA（A）受体的活化。目的3将确定两种浸提液在大鼠模型中的体内有效性。虽然这些基于受体的结合和活性测定已被用于药理学研究，应用这种分子方法来研究当归的机制代表了一种新的和创新的方法。这些研究结果将有助于确定当归作用的分子机制。这些信息不仅为当归在缓解PMS和更年期症状中的应用提供了机制证据，而且还可用于生物标准化当归产品以用于未来的临床研究。 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。当归Angelica sinensis（Oliv.）Diels是最常用的植物膳食补充剂之一，用于缓解PMS和更年期症状，其机制知之甚少。本申请旨在应用分子生物学方法研究当归的作用机制。

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.