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.

项目总结 植物医学疗法的有效性已经被观察了几个世纪，并作为一个来源 现代医疗实践的灵感来源，25%的处方药来自植物药。然而， 对植物天然产物的复杂化学相互作用和作用机理的了解 对科学界来说，这仍然是一项挑战。配备先进的分析化学仪器和 访问专为处理大数据集而设计的系统，我们准备开发一种代谢组学工具来 预测复杂植物提取物的作用机制以解决这一知识缺口。发展这一点 模型中，我们将评估植物天然产物对高度耐药不动杆菌的活性 鲍曼氏杆菌是一种常见的细菌病原体。检测的植物成分将包括紫花地丁，众所周知 生产抗微生物环肽，以及一系列据报道具有抗A. 鲍曼尼。这些植物药的活性将与已知的抗生素和纯化合物进行比较。 起源于植物学。基于代谢组学的BE作用机制预测方法的发展 该项目的第一个目标，而第二个目标将是比较 一种复杂的植物提取物，用于其已知成分。表现出不同于 它的已知成分，如代谢组学方法所知，将是分离和 组合效应的表征。最后，使用Galeria建立了先前建立的体内模型 梅隆菌可用于预测植物天然产物的细胞毒性。我们预计， 这一研究结果将对其他研究复杂植物学作用机制的研究者有所裨益 这是一种天然产品，不会局限于抗菌应用。建议的研究与 国家补充和综合健康中心(NCCIH)战略计划，因为它涉及 对美国常见的替代性和互补性健康实践进行调查。这些研究将是 由一位寻求从事生物医学研究事业的高素质实习生(希瑟·温特饰)主持。 她已经在天然产品研究方面建立了成功的记录，并将受益于 通过扩大她在基于质谱学的代谢组学方面的经验提出了培训计划 方法，并通过获得复杂植物学特征的经验。导师纳贾·切赫博士是 帕特里夏·A·沙利文(Patricia A.Sullivan)是北卡罗来纳大学格林斯伯勒分校的化学教授，他有效地 指导了多名博士生，包括F31和T32奖学金支持的实习生。