Metabolomics for Determining Mechanism of Action of Botanical Medicines

用于确定植物药作用机制的代谢组学

• 批准号: 10229685
• 负责人: Heather Winter
• 金额: $ 3.46万
• 依托单位: UNIVERSITY OF NORTH CAROLINA GREENSBORO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-05-01 至 2024-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10229685
• 关键词: Acinetobacter baumannii; Address; Analytical Chemistry; Antibiotic Resistance; Antibiotics; Bacteria; Bacterial Infections; Biological; Biological Availability; Biological Models; Biomedical Research; Botanicals; Breathing; Cell membrane; Chemical Actions; Chemicals; Chemistry; Clinical; Communicable Diseases; Communities; Complementary Health; Complementary therapies; Complex; Cyclic Peptides; Data; Development; Digitalis (genus); Digitalis preparation; Digoxin; Drug Industry; Drug Prescriptions; Drug resistance; Effectiveness; Exhibits; Exposure to; Fellowship; Folklore; Future; Goals; Health; Heart failure; Human Development; Individual; Integrative Medicine; Investigation; Knowledge; Larva; Literature; Malignant Neoplasms; Mass Spectrum Analysis; Medical; Medical Research; Medicine; Mentors; Methodology; Methods; Modeling; Modern Medicine; Modernization; Morphine; Moths; Multi-Drug Resistance; Naloxone; Natural Products; North Carolina; Nosocomial Infections; Nutraceutical; Opium; Outcome; Paclitaxel; Pain management; Papaver; Pharmaceutical Preparations; Pharmacologic Substance; Plants; Quality Control; Records; Reporting; Reproducibility; Research; Research Methodology; Research Personnel; Resources; Science; Series; Source; Strategic Planning; System; Taxus; Taxus brevifolia; Techniques; Testing; Toxic effect; Training; Universities; Validation; Viola; Waxes; advanced analytics; antimicrobial; base; biological systems; biomarker identification; career; cytotoxicity; design; dietary supplements; doctoral student; experience; extracellular; in vivo Model; insight; instrumentation; large datasets; metabolomics; novel strategies; opioid overdose; pathogen; pathogenic bacteria; predictive modeling; professor; resistant strain; tool

PROJECT SUMMARY The effectiveness of botanical medical therapies has been observed for centuries and has served as a source of inspiration for modern medical practice, with 25% of prescribed pharmaceuticals derived from botanicals. Yet, understanding of the complex chemical interactions and mechanisms of action of botanical natural products has remained a challenge for the scientific community. With advanced analytical chemistry instrumentation and access to systems designed for processing large datasets, we are poised to develop a metabolomics tool to predict mechanism of action of complex botanical extracts to addresses this knowledge gap. To develop this model, we will evaluate activity of botanical natural products against highly-drug resistant Acinetobacter baumannii, a common bacterial pathogen. The botanicals tested will include Viola odorata, which is known to produce antimicrobial cyclic peptides, as well as a series of other botanicals with reported activity against A. baumannii. Activity of the botanicals will be compared with that of known antibiotics and pure compounds of botanical origin. Development of a metabolomics-based mechanism of action prediction approach with be the first goal of this project, while the second goal will be comparison of the mechanism of action demonstrated by a complex botanical extract to its known constituents. Botanicals displaying a mechanism of action different than its known constituents, as informed by the metabolomics approach, will be candidates for isolation and characterization of the combination effects. Finally, a previously established in vivo model using Galleria mellonella will be employed to predict the cytotoxicity of the botanical natural products. We expect that the findings of this study will be of benefit to other investigators studying mechanisms of action for complex botanical natural products and will not be limited to antimicrobial applications. The proposed research is relevant to the National Center for Complementary and Integrative Health (NCCIH) strategic plan because it involves the investigation of alterative and complementary health practices common in the US. These studies will be conducted by a highly qualified trainee (Heather Winter) who seeks to pursue a career in biomedical research. She has already established a track record for successful research in natural products, and will benefit from the proposed training plan by expanding her experience with mass spectrometry based metabolomics methodologies and by gaining experience characterizing complex botanicals. The mentor, Dr. Nadja Cech, is Patricia A. Sullivan Professor of Chemistry at the University of North Carolina Greensboro, and has effectively mentored multiple PhD students, including trainees supported by the F31 and T32 fellowships.

项目摘要 植物医学疗法的有效性已被观察了几个世纪，并已作为一个来源， 现代医学实践的灵感来源，25%的处方药来自植物。然而， 了解植物天然产物的复杂化学相互作用和作用机制， 这对科学界来说仍然是一个挑战。凭借先进的分析化学仪器和 访问为处理大型数据集而设计的系统，我们准备开发代谢组学工具， 预测复杂植物提取物的作用机制，以解决这一知识空白。发展这种 模型，我们将评估植物天然产物对高度耐药不动杆菌的活性 鲍曼不动杆菌，一种常见的细菌病原体。测试的植物将包括紫罗兰，这是众所周知的， 生产抗菌环肽，以及一系列其他植物药，据报道，对A。 鲍曼不动杆菌。将植物药的活性与已知的抗生素和抗生素的纯化合物进行比较。 植物起源开发基于代谢组学的作用机制预测方法， 本项目的第一个目标，而第二个目标将是比较的行动机制所证明的 是一种复杂的植物提取物。植物药的作用机制不同于 其已知的成分，如代谢组学方法所告知的，将是分离的候选者， 组合效应的表征。最后，使用Galleria先前建立的体内模型， 大蜡螟属可用于预测植物天然产物的细胞毒性。我们预计 本研究的结果将有利于其他研究人员研究复杂的植物作用机制， 天然产物，并且不限于抗微生物应用。拟议的研究与 国家补充和综合健康中心战略计划，因为它涉及 对美国常见的替代和补充健康实践的调查。这些研究报告将 由一个高素质的实习生（石楠冬季）谁寻求追求在生物医学研究的职业生涯进行。 她已经建立了成功研究天然产品的记录，并将受益于 通过扩展她在基于质谱的代谢组学方面的经验，提出了培训计划 方法和获得经验的特点复杂的植物。导师Nadja Cech博士 Patricia A.他是北卡罗来纳州格林斯伯勒大学的沙利文化学教授， 指导了多名博士生，包括由F31和T32奖学金支持的学员。