Botanical Estrogens and Cognitive Function/Susan L. Schantz

具有雌激素活性的植物补充剂，包括大豆、野山药、甘草和当归， 寻求缓解更年期症状或减缓骨质流失的妇女食用，和/或 认知能力下降然而，对大多数这些药物的有效性或安全性知之甚少。 化合物.拟议中的植物研究中心将解决这一重要的未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 所有项目均以A区为原料，提取物和纯化合物分离物。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。 从项目1中的体外和基于细胞的研究中获得的关于作用机制的见解和信息 将使用核心B提供的药代动力学和生物利用度数据选择材料和剂量， 这些研究。我们将使用一组充分表征的认知任务，这些任务涉及多个认知领域 和多重存储系统，并且对以下两种情况的有利和不利影响敏感： 雌激素类。我们将包括具有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， 比较植物雌激素在这两个重要靶点fistrogens的相对疗效和安全性。 将进一步研究被鉴定为在脑和/或骨中有活性的化合物，以确定它们是否 证明了ER介导的acfion机制，如果是这样， 信号通路由于许多植物雌激素对ER β表现出选择性，我们假设它们 将通过ERp介导的途径来改变认知功能和骨骼健康。总之，我们 研究将通过提供解决疗效的高质量临床前数据， 大豆、山药、甘草和侗族植物雌激素的安全性和作用机制 quai对两个非常重要的雌激素反应终点：认知功能和骨。这些研究将 为将来临床试验的适当设计提供关键数据。

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.