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: 9135921
• 负责人: Laura Lillian Gauthier Tyler
• 金额: $ 4.25万
• 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/9135921
• 关键词: Accounting; Address; Affect; Aliquot; Anti-Inflammatory Agents; Anti-inflammatory; Antioxidants; Behavior; Benchmarking; Biochemistry; Biological; Biological Assay; Biological Availability; Botanical dietary supplements; 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; Natural Products; Permeability; Phytochemical; Plant Roots; Plants; Powder dose form; Procedures; Property; Protocols documentation; Public Health; Quality Control; Regulation; Safety; Sampling; Standardization; Techniques; Time; Training; absorption; base; countercurrent chromatography; design; estrogenic; 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(申请人提供)：植物提取物被广泛用作补充和替代医学的一种形式。与单独成分的活性相比，它是 越来越清楚的是，植物药的有效性是由于活性化合物和植物提取物本身的其他植物化学物质之间的药代动力学(PK)相互作用。1，2，3，4，5这一观察要求对植物提取物的化学表征和标准化采用整体技术。6协同学研究，如Birnbaum的异叶醇法7，接近整体视角，但最终达不到要求，因为它们仅限于一次不超过两种化合物的研究。这个项目试图用基于PK的方法来评估“类似协同作用”的相互作用：第一，确定植物混合物中的哪些成分增加了有效成分的生物利用度；第二，使提取物标准化。 根据这些成分形成了一种新型的植物学标记，称为渗透性调节(PM)标记。被研究的植物，甘草，或欧洲甘草，与这一概念验证研究相关。光滑素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的调和成分。8，9它的植物学标记光滑素与许多生物学特性有关，包括雌激素、抗氧化、抗炎活性和调节能量代谢。10虽然高纯度给予光滑素的吸收和代谢是众所周知的，但作为根粉或整个提取物给予光滑素的PK活性仍不清楚。11、12细胞和细胞外试验将用于比较光滑素作为粗提物一部分、人工部分和高纯度的生物利用度。那些存在于等分中的化合物导致光滑霉素渗透性增加，将被归类为PM标记。将使用最先进的计算机辅助技术，如定量核磁共振(QNMR)和1H迭代全旋分析(Hifsa)，开发一种多目标标准化方法。13这项研究的结果不仅将增加标准化方案的生物学相关性，而且还将为申请人提供分析技术方面的全面培训，包括分离化学、生物调查、核磁共振和质谱学。