STANDARDIZATION OF BOTANICAL DIETARY SUPPLEMENT FOR WOMEN'S HEALTH

自1994年DSHEA授权以来，植物膳食补充剂(BDSS)不断发展成为有助于美国公共健康的更安全、更有效的制剂。自1999年成立以来，我们的植物学中心通过对BDSS进行重要的(生物)化学和临床研究，参与了这一发展，这些BDSS被广泛用于恢复和/或维持妇女的健康。新的赠款期间的重点将继续是缓解围绝经期和经前综合症(PMS)症状。与这一焦点相关的中心假设是，植物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(5-羟色胺、GABA、多巴胺和阿片类药物)系统中表现出活性。在与该中心的其他项目的密切合作下，Farnsworth的项目将(目标1)对选定的植物性药物进行评估和优先排序；(目标2)显示它们含有在体外和体内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这些活性成分并对其结构进行表征，并将它们用于(目标3)植物成分的标准化。这项建议的长期目标是制备在化学和生物标准化方面具有生物活性的次生植物代谢物(S)的植物提取物，并且对人体研究来说是稳定的。结合上一次赠款期间的有希望的植物药物和初步研究的结果，将对12种植物和两种复杂的草药混合物进行初步选择。博尔顿的项目将在体外和体内对广泛极性范围的初级提取物及其溶剂分配部分进行测试，并使用衡量命中次数、效力分组以及活性强度和浓度的评分系统对其进行优先排序。排名最高的植物药将被放大，并接受创新的生物测定指导的分级程序(由Bolton和Analytical Core项目)。主要活性成分将通过针对提取物(HSCCC、Gel/Resin-CC)的特定特性而定制的现代层析的顺序应用来获得。现代定性和定量光谱分析(1/2D和选择性核磁共振、定量核磁共振、联用MS)将有助于确定主要活性成分的结构，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.