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、野山药、甘草和冬瓜被广泛使用。 由寻求缓解更年期症状或减缓骨丢失和/或 在衰老过程中认知能力下降。然而，人们对大多数这些药物的有效性或安全性知之甚少。 化合物。拟议的植物研究中心将解决这一重要的未得到满足的公共卫生需求 通过一套高度集成的研究项目和核心。将提供经过验证的植物材料 以A芯所有项目为原料，提取液和纯化合物分离物。项目3将使用 建立啮齿动物模型，研究这些植物雌激素对认知功能和骨骼健康的影响。 对项目1中体外和基于细胞的研究获得的作用机制的见解和信息 关于药代动力学和生物利用度的研究将被用于选择药物的材料和剂量 这些研究。我们将使用一组具有良好特性的认知五项任务，这些任务涉及多个认知领域 和多存储系统，并且对以下两者的有益和有害影响敏感 雌激素。我们将包括已知活性的雌激素作为阳性对照，并与 项目2，我们将在相同的实验动物中评估大脑和骨骼健康，允许直接 比较植物雌激素在这两个重要靶点的相对有效性和安全性。 将进一步研究在大脑和/或骨骼中被鉴定为活性的化合物，以确定它们是否 展示内质网介导的Acfion的机制，如果是这样的话，则涉及成熟的内质网 信号通路。因为许多植物雌激素对erp显示出选择性，我们假设它们 将通过事件相关电位介导的途径改变认知功能和骨骼健康。总而言之，我们的 研究将通过提供解决疗效的高质量临床前数据来填补知识的关键空白， 大豆、野山药、甘草、冬枣中植物雌激素的安全性及作用机制 关于两个非常重要的雌激素反应终点：认知功能和骨骼。这些研究将 为将来临床试验的适当设计提供必要的关键数据。