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

描述（由申请人提供）：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。可用的医疗方法有限，其中一些有严重的副作用。相反，许多女性转向植物性膳食补充剂。当归（白芷）Diels是最常用的植物膳食补充剂之一，用于缓解经前症候群和更年期症状。虽然这种植物的干根，也被称为“侗族菜”，在中国已有几个世纪的传统，目前许多美国妇女也在使用，但人们对其作用机制知之甚少。我们假设当归可以通过中枢神经系统受体发挥作用，在经前综合症和更年期表现出有益的作用。在本应用中，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-氨基丁酸(GABA)-A受体的亲和力来验证这一假设。通过测量G蛋白激活和腺苷酸环化酶抑制，以及通过测定GABA门控的突触体Cl-内流来测定GABA(A)受体的激活，将进一步测试提取物对阿片受体的激活。目的3将在大鼠模型中确定两种提取物的体内功效。虽然这些基于受体的结合和活性测定已经用于药理学研究，但将这种分子方法应用于当归的机制研究是一种新的创新方法。这些研究结果将有助于明确当归的分子作用机制。这些信息不仅将为使用当归缓解经前综合症和更年期症状提供机理证据，而且可能用于生物学标准化当归产品，为未来的临床研究提供依据。

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.