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

当归对女性健康的分子机制

• 批准号: 7812964
• 负责人: Zaijie Jim Wang
• 金额: $ 14.56万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-09-30 至 2011-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7812964
• 关键词: 3-aminobutyric acid; Address; Adenylate Cyclase; Adverse effects; Affect; Affinity; Agonist; American; American Psychiatric Association; Angelica sinensis; Angelica sinensis preparation; Anxiety; Attenuated; Binding; Biological Assay; Body Temperature; Botanicals; Cell Line; Cells; China; Clinical Research; Cyclic AMP; Data; Disease; Dopamine Receptor; Dose; Drug usage; Effectiveness; Ensure; Exhibits; Expenditure; Female; Future; GABA-A Receptor; GTP-Binding Proteins; Health; Herb; Hormonal; Hot flushes; Hyperalgesia; Inhibitory Concentration 50; Knowledge; Ligands; Measures; Medical; Menopausal Symptom; Menopause; Methods; Modeling; Molecular; Molecular Mechanisms of Action; Mood Disorders; Neurotransmitters; Norepinephrine; Occupations; Opiates; Opioid Receptor; Pharmaceutical Preparations; Pharmacologic Substance; Physiological; Plant Roots; Plants; Population; Premenstrual syndrome; Rattus; Receptor Activation; Research; Research Activity; Rodent; Serotonin; Site; Sleeplessness; Symptoms; Synaptosomes; System; Testing; Time; United States; Woman; Women' s Health; Work; base; depression; dietary supplements; gamma-Aminobutyric Acid; high throughput screening; in vivo; monoamine; mood regulation; premenstrual dysphoric disorder; protein activation; public health relevance; receptor; receptor binding; research study

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.

描述（由申请人提供）：大部分女性受到经前综合征（PMS）和绝经症状的影响。有限的医疗治疗可用，有些患有严重的不良反应。取而代之的是，许多妇女转向植物饮食补充剂。当归天然气（Oliv。）Diels是最常用的植物饮食补充剂之一，可缓解PMS和更年期症状。尽管该植物的干燥植物（也称为Dong Quai）传统上已经在中国使用了几个世纪，并且目前正在许多美国妇女使用，但其作用机制知之甚少。我们假设当今的Sinensis可以通过中枢神经系统受体作用，以在PMS和更年期表现出有益的作用。在最初的应用中，我们提议通过首先评估几种化学表征的当归天然化素提取物与阿片类药物和3-氨基丁酸（GABA）A受体的亲和力来检验这一假设。提取物将通过测量G蛋白激活和腺苷酸环化酶抑制和GABA受体（A）受体的激活来进一步测试其鸦片受体的激活，并通过确定突触体中GABA门控的Cl-涌入。 AIM 3将确定大鼠模型中两个提取物的体内功效。在修订后的应用中，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蛋白系统。因此，新目标4将检查这些提取物对单胺受体和转运蛋白的亲和力。其他研究将加快科学研究的速度，并允许创造就业机会。这些研究的结果将有助于定义当归天然气的作用的分子机制。这样的信息不仅将提供用于缓解PMS和更年期症状的当归中的机械证据，而且还可以用来生物学地标准化当归的Senensis产品以进行未来的临床研究。 公共卫生相关性：大部分女性受到经前综合征（PMS）和绝经症状的影响。尽管当归天然气（Oliv。）Diels是缓解PMS和更年期症状的最常用的植物饮食补充剂之一，但其机制几乎不知所措。该应用旨在将分子方法应用于研究当归sinensis的作用机理。竞争性的修订将扩大研究范围，以解决通过单胺受体和当归天然气的转运蛋白的可能作用机理。除了要获得的新知识外，修订的目标还将加速科学研究的节奏，并通过直接雇用额外的员工和由于增加的研究活动和支出而导致间接影响来创造就业机会。