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: 10401795
• 负责人: Heather Winter
• 金额: $ 2.49万
• 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 2022-12-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10401795
• 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; National Center for Complementary and Integrative Health; 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 已经观察到植物医学疗法的有效性已有数百年历史，并一直是来源 现代医学实践的灵感，有25％的处方药源自植物学。然而， 了解复杂的化学相互作用和植物天然产品作用机制 对于科学界仍然是一个挑战。具有高级分析化学仪器和 访问用于处理大型数据集的系统，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理，以解决这一知识差距。开发这个 模型，我们将评估植物天然产物对高药耐药性杆菌的活性 Baumannii，一种常见的细菌病原体。测试的植物药将包括Viola Odorata，已知 产生抗菌循环肽，以及一系列其他植物学作用，报告了对A的活性。 鲍曼尼。将植物学的活性与已知抗生素和纯化合物的活性进行比较 植物性。开发基于代谢组学的动作预测方法的发展 该项目的第一个目标，而第二个目标将是对所证明的行动机理的比较 其已知成分的复杂植物提取物。植物学表现出一种不同的作用机制 由代谢组学方法告知的其已知成分将成为孤立和 组合效应的表征。最后，使用Galleria的先前建立的体内模型 将使用梅洛内拉（Mellonella）来预测植物天然产物的细胞毒性。我们期望 这项研究的结果将对其他研究人员有益于研究复杂植物的作用机制 天然产品，并且不仅限于抗菌应用。拟议的研究与 国家互补健康和综合健康中心（NCCIH）战略计划，因为它涉及 对美国常见的改变和互补健康实践的调查。这些研究将是 由一位高素质的实习生（Heather Winter）主持，他试图从事生物医学研究的职业。 她已经建立了在天然产品中成功研究的往绩，并将受益于 提出的培训计划通过扩大基于质谱的代谢组学的经验来扩大她的经验 方法论并获得表征复杂植物的经验。导师Nadja Cech博士是 北卡罗来纳大学格林斯伯勒大学化学教授Patricia A. Sullivan，并有效地 指导了多个博士生，包括受训者和T32奖学金支持的学员。