Botanical Estrogens and Cognitive Function/Susan L. Schantz

植物雌激素与认知功能/Susan L. Schantz

• 批准号: 8007127
• 负责人: William G Helferich
• 金额: $ 25.09万
• 依托单位: UNIVERSITY OF ILLINOIS AT URBANA-CHAMPAIGN
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-07-01 至 2011-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8007127
• 关键词: Address; Affect; Aging; Agonist; Angelica sinensis preparation; Animal Model; Animals; Architecture; Attenuated; Behavioral; Binding; Biological Availability; Botanicals; Brain; Brain region; Cells; Clinical Research; Clinical Trials Design; Cognition; Cognitive; Collaborations; Complex; Corpus striatum structure; Coupled; Cyclic AMP Response Element; Data; Dose; Drug Kinetics; Estradiol; Estrogen Receptors; Estrogens; Extracellular Signal Regulated Kinases; Female; Future; GTP-Binding Proteins; Genistein; Goals; Hippocampus (Brain); ICI 182780; Impaired cognition; In Vitro; Individual; Infusion procedures; Investigation; Knowledge; Learning; Licorice; Measures; Mediating; Membrane; Memory; Menopausal Symptom; Menopause; Mitogens; Molecular; Nuclear Receptors; Pathway interactions; Pattern; Performance; Phytoestrogens; Plant Extracts; Plant Roots; Plants; Play; Prefrontal Cortex; Protein Kinase; Public Health; Pyrazoles; Rattus; Receptor Signaling; Relative (related person); Research; Research Project Grants; Rodent Model; Role; Safety; Sampling; Short-Term Memory; Signal Pathway; Signal Transduction; Source; System; Systems Biology; Testing; Time; Tissues; Woman; Yam - dietary; antagonist G; base; bone; bone health; bone loss; bone mass; cognitive function; diarylpropionitrile; dietary supplements; equol; estrogenic activity; healthy aging; human subject; improved; in vivo; insight; meetings; metabolic abnormality assessment; middle age; older women; pre-clinical; pre-clinical research; preclinical study; receptor; research study; response; soy; soy protein isolate; transcription factor

Botanical supplements with estrogenic activity including soy, wild yam, licorice root and dong quai are widely consumed by women seeking to gain relief from menopausal symptoms or to slow bone loss and/or cognitive decline during aging. However, very little is known about the efficacy or safety of most of these compounds. The proposed Botanical Research Center will address this important unmet public health need through a highly integrated set of Research Projects and Cores. Verified botanical materials will be provided to all ofthe Projects by Core A as raw materials, extracts and pure compound isolates. Project 3 will use a rodent model to examine the impact of these botanical estrogens on cognifive funcfion and bone health. Insights about mechanism of action gained from in vitro and cell-based studies in Project 1 and informafion on pharmacokinetics and bioavailability available from Core B will be used to select materials and doses for these studies. We will use a well-characterized battery of cognifive tasks that tap multiple cognifive domains and mulfiple memory systems, and that are sensitive to both the beneficial and detrimental effects of estrogens. We will include as positive controls estrogens with known activities, and, in collaboration with Project 2, we will evaluate brain and bone health in the same experimental animals allowing direct comparisons of the relative efficacy and safety of botanical estrogens in these two important target fissues. Compounds that are identified as active in brain and/or bone will be studied further to identify whether they demonstrate an ER-mediated mechanism of acfion, and, if so, the involvementof well-established ER signaling pathways. Because many botanical estrogens show selecfivity for ERp, we hypothesize that they will act through ERp-mediated pathways to alter both cognifive function and bone health. In summary our research will fill a critical gap in knowledge by providing high quality preclinical data addressing the efficacy, safety and mechanism of action of botanical estrogens derived from soy, wild yam, licorice root and dong quai on two very important estrogen responsive endpoints: cognitive funcfion and bone. These studies will provide crifical data needed for the appropriate design of clinical trials in the future.

具有雌激素活性的植物补充剂，包括大豆，野生山药，甘草根和Dong Quai 寻求缓解更年期症状或减慢骨质流失和/或的妇女消费 衰老期间的认知能力下降。但是，对大多数的功效或安全知之甚少 化合物。拟议的植物学研究中心将解决这一重要的未满足的公共卫生需求 通过高度集成的研究项目和核心。将提供经过验证的植物材料 核心A作为原材料，提取物和纯化合物分离株。项目3将使用 啮齿动物模型，以检查这些植物雌激素对认知功能和骨骼健康的影响。 关于项目1和Informafion中基于细胞的研究获得的有关作用机制的见解 关于核心B的药代动力学和生物利用度，将用于选择材料和剂量 这些研究。我们将使用良好的认知任务来点击多个认知领域 和Mulfiple记忆系统，并且对 雌激素。我们将作为具有已知活动的阳性对照雌激素，并与 项目2，我们将评估同一实验动物的大脑和骨骼健康，以直接 比较这两个重要靶标的植物雌激素的相对疗效和安全性。 将进一步研究被鉴定为大脑和/或骨骼活性的化合物，以确定它们是否是否 展示ACFION的ER介导的机制，如果是的，则涉及良好的ER 信号通路。因为许多植物雌激素都显示出ERP的选秀，所以我们假设它们 将通过ERP介导的途径作用，以改变认知功能和骨骼健康。总而言之 研究将通过提供有关疗效的高质量临床前数据来填补知识的关键空白， 源自大豆，野生山药，甘草根和董事的植物雌激素的安全性和机制 在两个非常重要的雌激素响应终点上的quai：认知功能和骨头。这些研究会 提供适当设计临床试验所需的额外数据。