STANDARD OF BOTANICAL DIETARY SUPPLEMENT FOR WOMEN'S HEA

自1994年DSHEA授权以来，植物膳食补充剂（BDS）不断发展成为更安全，更有效的制剂，有助于美国公众健康。自1999年成立以来，我们的植物中心参与了这一发展，对广泛用于恢复和/或维持妇女健康的BDS进行了重要的（生物）化学和临床研究。新的资助期的重点将继续是缓解围月经期和经前综合征（PMS）症状。与此相关的中心假设是，植物药含有在雌激素和主要CNS（5-羟色胺、GABA、多巴胺和阿片样物质）系统中表现出活性的有效次生植物代谢物。通过与中心的其他项目密切合作，Farnsworth的项目将（目标1）评估和优先选择植物药;（目标2）在体外和体内证明它们含有具有所需生物活性和特征的植物成分;通过现代光谱方法分离和结构表征这些活性成分，并将其用于（目标3）标准化植物药。该提案的长期目标是制备植物提取物，其在生物活性次生植物代谢物方面是化学和生物标准化的，并且对于人类研究是稳定的。结合有前途的植物药从以前的赠款期与初步研究的结果，初步选择12种植物加上两个复杂的草药混合物将进行评估。将通过博尔顿的PROJECTS在体外和体内对宽极性范围的一级浸提液及其溶剂分配级分进行测定，并使用评分系统进行优先排序，该评分系统对命中数、效价分组以及活性强度和浓度进行加权。具有最高等级的植物药将按比例放大，并进行创新的生物测定指导的分馏程序（由博尔顿和分析核心的w/PROJECTS）。主要活性成分将通过连续应用针对提取物特定特征定制的现代色谱法（HSCCC，凝胶/树脂-CC）获得。现代定性和定量光谱分析（1/2D和选择性NMR，qNMR，联用MS）将导致主要活性成分的结构鉴定，最终为化学和生物标准化奠定基础。重点植物药将全面发展成为标准化产品。将在项目4的I期临床研究中对啤酒花进行评价。

Since the 1994 DSHEA mandate, botanical dietary supplements (BDSs) are continuously developing into safer and more effective preparations that aid U.S. public health. Since its establishment in 1999, our BOTANICAL CENTER has participated in this development by performing significant (bio-)chemical and clinical research on BDSs that are widely used to restore and/or maintain women's health. The focus of a renewed grant period will continue to be the alleviation of perimenopausal and premenstrual syndrome (PMS) symptoms. Linked to this focus is the central hypothesis that botanicals contain potent secondary plant metabolites that exhibit activities in estrogenic and major CNS (serotonin, GAB A, dopamine, and opioid) systems. In close collaboration with the other projects of the CENTER, PROJECT by Farnsworth will (Aim 1) evaluate and prioritize select botanicals; (Aim 2) show that they contain phytoconstituents with the desired biological activities and profiles, in vitro and in vivo; isolate and structurally characterize these active principles by modern spectroscopical methods and use them to (Aim 3) standardize the botanicals. The long-term objective of this proposal is to prepare botanical extracts that are chemically and biologically standardized in terms of the bioactive secondary plant metabolite(s), and that are stable for human studies. Combining promising botanicals from the previous grant period with the results of preliminary studies, an initial selection of 12 plants plus two complex herbal mixtures will be evaluated. Primary extracts of a wide polarity range and their solvent partition fractions will be assayed in vitro and in vivo by PROJECTS by Bolton and prioritized using a scoring system that weighs hit numbers, grouping of potency, as well as strengths and concentration of activity. The botanicals with the highest rank will be scaled-up and subjected to an innovative bioassay-guided fractionation procedure (w/PROJECTS by Bolton and Analytical Core). The major active principles will be obtained through a sequential application of modern chromatography tailored to the specific characteristics of the extracts (HSCCC, Gel/Resin-CC). Modern qualitative and quantitative spectroscopic analysis (1/2D and selective NMR, qNMR, hyphenated MS) will lead to the identification of structures of the major active principles, which ultimately lays the foundation for chemical and biological standardization. Prioritized botanicals will be fully developed into standardized products. Hops will be evaluated in a Phase I clinical study in PROJECT 4.