STANDARD OF BOTANICAL DIETARY SUPPLEMENT FOR WOMEN'S HEA

女性 HEA 植物膳食补充剂标准

• 批准号: 6954969
• 负责人: NORMAN R FARNSWORTH
• 金额: $ 25.98万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6954969
• 关键词: alternative medicine; bioassay; chemical standardization; dietary supplements; drug discovery /isolation; electron microscopy; high performance liquid chromatography; light microscopy; liquid chromatography; mass spectrometry; medicinal plants; menopause; metabolomics; nutrition related tag; plant extracts; polymerase chain reaction; premenstrual syndrome; women' s health

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.

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，有助于美国公共卫生。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。更新资助期的重点将继续是缓解围绝经期和经前综合症（PMS）症状。与这一焦点相关的是一个中心假设，即植物药含有有效的次生植物代谢物，这些代谢物在雌激素和主要中枢神经系统（血清素、GABA、多巴胺和阿片类药物）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）评估并优先考虑选定的植物成分； （目标 2）表明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和结构表征这些活性成分，并使用它们来（目标 3）标准化植物药。该提案的长期目标是制备在生物活性次生植物代谢物方面进行化学和生物学标准化的植物提取物，并且对人类研究来说是稳定的。结合上一资助期的有前途的植物药和初步研究的结果，将对 12 种植物和两种复杂草药混合物的初步选择进行评估。广泛极性范围的初级提取物及其溶剂分配分数将通过 Bolton 的 PROJECTS 进行体外和体内分析，并使用衡量命中数、效力分组以及活性强度和浓度的评分系统进行优先级排序。排名最高的植物将被扩大规模，并接受创新的生物测定引导的分馏程序（w/Bolton 和 Analytical Core 的项目）。主要活性成分将通过连续应用根据提取物的具体特征定制的现代色谱法（HSCCC、凝胶/树脂-CC）来获得。现代定性和定量光谱分析（1/2D 和选择性 NMR、qNMR、联用 MS）将有助于鉴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。重点植物药将全面开发成标准化产品。啤酒花将在项目 4 的 I 期临床研究中进行评估。