Metabolomic botanical standardization for pharmacokinetic interactions

药代动力学相互作用的代谢组植物学标准化

• 批准号: 8986909
• 负责人: Laura Lillian Gauthier Tyler
• 金额: $ 4.21万
• 依托单位: UNIVERSITY OF ILLINOIS AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2018-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8986909
• 关键词: Accounting; Address; Affect; Aliquot; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Behavior; Benchmarking; Biochemistry; Biological; Biological Assay; Biological Availability; Biological Factors; Botanicals; Cell Fraction; Cells; Chemicals; Chinese People; Chromatography; Complementary and alternative medicine; Complex; Computer Assisted; Crude Extracts; Doctor of Philosophy; Dose; Drug Kinetics; Effectiveness; European; Exhibits; Fingerprint; Fractionation; Glycyrrhiza; Goals; Individual; Investigation; Licorice; Marketing; Mass Spectrum Analysis; Membrane; Metabolism; Methods; Microscopy; Modification; NMR Spectroscopy; National Center for Complementary and Alternative Medicine; Permeability; Phytochemical; Plant Roots; Plants; Powder dose form; Procedures; Property; Protocols documentation; Public Health; Quality Control; Regulation; Safety; Sampling; Solutions; Standardization; Techniques; Time; Training; absorption; base; countercurrent chromatography; design; dietary supplements; falls; glabridin; improved; metabolomics; novel; novel marker; prevent; public health relevance

 DESCRIPTION (provided by applicant): Botanical extracts are widely used as a form of complementary and alternative medicine. In contrast to the activity of isolated constituents, it is becoming increasingly clear that the effectiveness of botanicals is due to pharmacokinetic (PK) interactions between active compounds and other phytochemicals native to the botanical extract.1,2,3,4,5 This observation calls for holistic techniques for the chemical characterization and standardization of botanical extracts.6 Synergy studies, like Birnbaum's isobole method7 approach a holistic perspective but ultimately fall short as they are limited to the investigation f no more than two compounds at a time. This project seeks to evaluate "synergy-like" interactions using PK based methods: first, to determine which constituents in a botanical mixture increase the bioavailability of the active principles and second, to standardize an extract according to those constituents as a new type of botanical marker called the permeability modulating (PM) markers. The plant to be studied, Glycyrrhiza glabra L. or European licorice, is relevant for this proof of concept study. G. glabra is one of the most pervasive botanical products on the US market and has long been used as a harmonizing ingredient in Traditional Chinese Medicine.8,9 Its botanical marker, glabridin, is associated with many biological properties including estrogenic, antioxidant, anti-inflammatory activity, and the regulation of energy metabolism.10 Though the absorption and metabolism of glabridin administered at high purity is well known, the PK activity of glabridin administered as root powder or whole extract remains unclear.11,12 Cell and cell free assays will be used to compare the bioavailability of glabridin as part of the crude extract, in artificial fractions, and at high purity. Those compound present in aliquots resulting in the increased permeability of glabridin will be classified as PM markers. A multi target standardization method will be developed using state of the art computer assisted techniques like quantitative NMR (qNMR) and 1H iterative Full Spin Analysis (HiFSA).13 The results of this study will not only increase the biological relevance of standardization protocols, but also provide the applicant with thorough training in analytical techniques including separation chemistry, biological investigation, NMR, and mass spectroscopy.

 描述（由适用提供）：植物提取物被广泛用作一种完整和替代药物的形式。与孤立构成的活动相反，它是 Becoming increasingly clear that the effectiveness of botanicals is due to pharmacokinetic (PK) interactions between active compounds and other physical extracts native to the botanical extracts.1,2,3,4,5 This observation calls for holistic techniques for the chemical characterization and standardization of botanical extracts.6 Synergy studies, like Birnbaum's isobole method7 approach a holistic perspective but ultimately fall short as they are limited to the investment f一次不超过两种化合物。该项目旨在使用基于PK的方法评估“类似协同的”相互作用：首先，确定植物混合物中的哪些构成的构成，增加了主动原理的生物利用度，其次是标准化提取物。 根据这些宪法，作为一种新型的植物标记，称为渗透率调制（PM）标记。要研究的植物Glycyrrhiza Glabra L.或欧洲甘草与此概念验证有关。 G. glabra是美国市场上最普遍的植物产品之一，长期以来一直被用作传统中药中的和谐成分。8,9，其植物标志物glabridin与许多生物学特性有关，与雌激素，抗氧化剂，抗抑制剂和抗抗病性的调节和元素的调节有关。10纯度是众所周知的，glabridin的PK活性作为根粉或整个提取物尚不清楚。11,12细胞和无细胞的分析将用于比较glabridin作为粗提取物的一部分，在人造馏分中的生物利用度，并具有很高的纯度。在等分试样中存在的那些化合物导致glabridin的渗透性增加将被归类为PM标记。将使用最先进的计算机辅助技术（例如定量NMR（QNMR）和1H迭代完整自旋分析（HIFSA））开发多个目标标准化方法。13本研究的结果不仅会增加标准化协议的生物学相关性，而且还可以在包括分离化学，NMR的分析技术中进行全面的培训，并提供适用的培训。