Van Breemen: Project 1; Metabolomic Analysis, Design and Standardization of Botanical Extracts (Pauli)

我们植物学中心的中心主题是提高植物性饮食的安全和健康益处 被美国女性广泛使用的补充剂。在前几个资助期，项目1开创了 开发植物学植物分析方法，并提供三种严格标准化的提取物 I期或II期临床试验。继续与所有中心项目和 项目1将表明，植物代谢物的复杂化学成分可以：(1)选择性地 控制以产生独特的调制提取物，(2)广泛监测以实现多目标标准化， (3)系统探索，以更好地理解植物学标记的拓扑学。专注于 复杂的草药代谢组，项目1假设代谢组分析能够实现多靶点 植物学的标准化和整体性评估。考虑到我们最近在三个“充分研究”方面的进展 植物，我们假设创新的植物化学可以分解和准备控制代谢组 混合，使代谢组标准化可行，并揭开以前未知/低水平的代谢物。在……里面 三个具体目标，我们将充分发展逆流为基础的“化学减法”，以 生成文库和数量的敲除、敲入和其他植物化学控制的提取物 (设计者摘录)，用于中心的生物学研究(目标1)。使新陈代谢，多靶点 标准化更实际，我们将开发主要的分析方法，利用核磁共振消除 LC方法广泛依赖于相同的参考标准(目标2)。系统地挖掘 代谢组化学多样性(代谢组挖掘)将发现新的初级和次级代谢物 发展作为中心背景下的潜在标志。目标3中的这一努力将包括天然化合物 深度共熔溶剂(“NADS”)，是植物提取物中丰富但未被开发的成分。这个 项目1的长期目标是促进对植物质量控制措施和 拓宽植物药品化学和生物标准化基础。

The central theme of our Botanical Center is to enhance safety and health benefits of botanical dietary supplements that are widely used by U.S. women. In the previous funding periods, Project 1 has pioneered the development of phytoanalytical methods for botanicals and supplied rigorously standardized extracts for three Phase I or II clinical trials. Continuing the close interdisciplinary collaboration with all Center Projects and Cores, Project 1 will show that the complex chemical composition of plant metabolomes can be (1) selectively controlled to generate unique modulated extracts, (2) broadly monitored to achieve multi-target standardization, and (3) systematically explored to better comprehend the topology of botanical markers. Focusing on the complex herbal metabolome, Project 1 hypothesizes that metabolomic analysis enables multi-target standardization and holistic assessment of botanicals. Considering our recent progress with three "well-studied" plants, we hypothesize that innovative phytochemistry can resolve and preparatively control metabolomic mixtures, make metabolomic standardization feasible, and unravel previously unknown/low-level metabolites. In three Specific Aims, we will fully develop the countercurrent-based method of "chemical subtraction" to generate libraries and quantities of knock-out, knock-in, and other phytochemically controlled extracts (DESIGNER extracts) for biological studies in the Center (Aim 1). To make metabolomic, multi-target standardization more practical, we will develop primary analytical methods that utilize NMR to eliminate the widespread dependence of LC methods on identical reference standards (Aim 2). Systematic mining of metabolomic chemodiversity (metabolomic mining) will uncover new primary and secondary metabolites for development as potential markers in the Center context. This effort in Aim 3 will include compounds of natural deep eutectic solvents ("NADES") which are abundant but underexplored constituents of botanical extracts. The long-term objective of Project 1 is to advance the understanding of botanical quality control measures and broaden the base for chemical and biological standardization of botanicals.