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。在最初的申请中，我们建议通过首先评估几种化学特征的当归提取物对阿片和3-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。在修订后的申请中，我们建议扩大研究范围，以包括其他相关的中枢神经系统受体和转运系统。因此，新的目的4将检查这些提取物对单胺受体和转运蛋白的亲和力。这些额外的研究将加快科学研究的步伐，并创造就业机会。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。竞争性修订将扩大研究范围，以解决当归通过单胺受体和转运蛋白的可能作用机制。除了获得新知识外，修订后的目标还将加快科学研究的速度，并通过直接雇用额外的工作人员和增加研究活动和支出产生的间接影响创造就业机会。

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 thi 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 the original application, we propose to test this hypothesis by first evaluating the affinity of several chemically characterized Angelica sinensis extracts to the opiate and 3-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. In the revised application, we propose to expand the scope of research to include other relevant CNS receptor and transporter systems. Accordingly, the new aim 4 will examine the affinity of these extracts to the monoamine receptors and transporters. The additional studies will accelerate the tempo of scientific research and allow for job creation. 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. The competitive revision will expand the scope of research to address the possible mechanisms of action through the monoamine receptors and transporters for Angelica sinensis. In addition to the new knowledge to be gained, the revised aims will accelerate the tempo of scientific research and allow for job creation through direct hiring of additional staff and indirect impact due to increased research activity and expenditure.