Rapid Identification of Active Agents and Metabolomics of Botanical Supplements

植物补充剂活性成分和代谢组学的快速鉴定

基本信息

批准号：
9652301
负责人：
RICHARD B VAN BREEMEN
金额：
$ 9.08万
依托单位：
OREGON STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2013
资助国家：
美国
起止时间：
2013-08-01 至 2018-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9652301
关键词：
Rapid Identification Active Agents Metabolomics

项目摘要

RFA-AT-11-001; Mechanistic Research on CAM Natural Products (R01) Title: Rapid Identification of Active Agents and Metabolomics of Botanical Supplements Summary: This application addresses the unmet need for high-throughput methods to identify active components inbotanical dietary supplements and to determine their mechanisms of action through metabolomics studies. Ultrafiltration mass spectrometry (PUF-MS), which was invented in this laboratory, is more efficient than conventional bioassay-guided fractionation for the screening, characterization, isolation, and identification of pharmacologically significant ligands contained in botanical dietary supplements or other natural product mixtures. We propose to enhance the productivity of this technology 100-fold using a new ultrafast PUF-MS (UPUF-MS) approach and to develop new validated assays for the standardization of botanical dietary supplements based on UHPLC-MS-MS that are at least 10-fold faster than previously possible. We will incorporate UHPLC-MS into metabolomics studies of archived serum and urine samples from clinical trials of the effects of botanical dietary supplements black cohosh, red clover, hops, Prempro, and placebo on hot flashes in menopausal women. It is our hypothesis that this metabolomics approach will facilitate the discovery of biomarkers indicative of vasomotor symptoms such as hot flashes and night sweats. Then, these biomarkers may be used for the objective, quantitative determination of the effects of botanical dietary supplements on hot flashes instead of relying on subjective self reporting of hot flashes by subjects in clinical trials. Overall, these studies will address the central hypothesis that botanical dietary supplements contain pharmacologically active compounds that can be identified using UPUF-MS, used for chemical standardization with UHPLC-MS-MS and that the in vivo effects of these active constituents can be detected using UHPLC-MS-MS in combination with metabolomics.

RFA-AT-11-001； CAM天然产物机理研究（R01）标题：植物补充剂活性成分的快速鉴定和代谢组学概括：该应用解决了对高通量方法识别活性成分的未满足需求植物膳食补充剂并通过代谢组学研究确定其作用机制。该实验室发明的超滤质谱（PUF-MS）比传统生物测定引导的分级分离，用于筛选、表征、分离和鉴定植物膳食补充剂或其他天然产品中含有的具有药理学意义的配体混合物。我们建议使用新型超快 PUF-MS 将这项技术的生产力提高 100 倍 (UPUF-MS) 方法并开发新的经验证的植物膳食标准化测定方法基于 UHPLC-MS-MS 的补充剂，速度至少比以前快 10 倍。我们将将 UHPLC-MS 纳入临床试验中归档血清和尿液样本的代谢组学研究中植物膳食补充剂黑升麻、红三叶草、啤酒花、Prempro 和安慰剂对热的影响更年期女性出现闪光。我们假设这种代谢组学方法将促进这一发现指示血管舒缩症状（例如潮热和盗汗）的生物标志物。然后，这些生物标志物可用于客观、定量测定植物膳食补充剂对热的影响潮热而不是依赖于临床试验中受试者对潮热的主观自我报告。总体而言，这些研究将解决植物膳食补充剂含有药理活性的中心假设可以使用 UPUF-MS 进行鉴定的化合物，用于使用 UHPLC-MS-MS 进行化学标准化，以及可以使用 UHPLC-MS-MS 结合使用 UHPLC-MS-MS 检测这些活性成分的体内作用代谢组学。