STANDARD OF BOTANICAL DIETARY SUPPLEMENT FOR WOMEN'S HEA

自1994年DSHEA授权以来，植物性膳食补充剂（BDSs）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，我们的植物中心通过对广泛用于恢复和/或维持女性健康的bds进行重要的（生物）化学和临床研究，参与了这一发展。延长赠款期的重点将继续是减轻围绝经期和经前综合症的症状。与此相关的中心假设是，植物药含有有效的次生植物代谢物，在雌激素和主要中枢神经系统（血清素、GAB A、多巴胺和阿片）系统中表现出活性。与中心的其他项目密切合作，Farnsworth项目将（目标1）评估和优先选择植物药物；（目标2）表明它们含有具有所需生物活性和特征的植物成分，在体外和体内；用现代光谱方法分离和结构表征这些活性成分，并使用它们（目标3）标准化植物药。本提案的长期目标是制备具有生物活性的次生植物代谢物的化学和生物学标准化的植物提取物，并且对人体研究是稳定的。将结合上一个资助期的有希望的植物与初步研究的结果，初步选择的12种植物和两种复杂的草药混合物将进行评估。广泛极性范围的主要提取物及其溶剂分割分数将由PROJECTS by Bolton在体外和体内进行分析，并使用评分系统进行优先排序，该评分系统衡量hit数、效力分组、强度和活性浓度。最高级别的植物药将按比例增加，并接受创新的生物测定指导分离程序（w/PROJECTS by Bolton和Analytical Core）。主要的活性原理将通过顺序应用适合提取物特定特征的现代色谱法（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，连字符MS）将导致主要活性原理的结构鉴定，最终为化学和生物标准化奠定基础。重点植物品种全面发展为标准化产品。啤酒花将在项目4的I期临床研究中进行评估。

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.