Identifying molecular targets and biological signatures of CAM natural products

识别 CAM 天然产物的分子靶标和生物特征

• 批准号: 8196695
• 负责人: CHUO CHEN
• 金额: $ 45.29万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8196695
• 关键词: Adverse effects; Affinity; Affinity Chromatography; African; Anti Inflammatory Analgesics; Antioxidants; Arthritis; Benefits and Risks; Binding; Biochemical; Biological; Biological Assay; Biological Factors; Cardiovascular system; Cells; Chemicals; Claw; Clinical; Clinical Trials; Complementary DNA; Complementary and alternative medicine; Complex; Development; Drug usage; Ensure; Family; Folk Medicine; Future; Goals; Grapes; Health; Health Benefit; Human; Investigation; Knowledge; Label; Measures; Methodology; Methods; Modification; Molecular; Molecular Target; National Center for Complementary and Alternative Medicine; Pathway interactions; Peptide Initiation Factors; Pharmaceutical Preparations; Play; Property; Proteins; Proteomics; Reporting; Research; Resveratrol; Rheumatism; Risk; Role; Skin; Work; anti aging; base; cell type; chronic pain; design; dietary supplements; human FRAP1 protein; improved; in vivo; interest; novel; polyphenol; programs; protein profiling; response; small molecule; tool

DESCRIPTION (provided by applicant): Many natural product extracts have been widely used as complementary and alternative medicines (CAM). However, their health benefits and risks have not been subjected to rigorous study, nor have their mechanisms of action been fully understood. The long-term goal of our research program is to validate the medicinal effects of these CAM natural products. The focus of this proposed research is to develop assays that will allow us to identify the molecular targets of CAM natural products of high priority to the NCCAM, and to broadly capture the signatures of biological activities indicative of their complex medicinal effects. Both chemical and biological tools will be used. For the target identification component, we will develop proteomic and cDNA strategies based on both labeled and label-free target identification methods to identify the direct binding targets of resveratrol and Devil's claw, two classes of widely used CAMs. For the signature component, we will use protein profiling to assess the broad biological effects and pharmaco-response pathways of CAM natural products, and develop specific assays and probes to report on the signature response proteins of CAM natural products, thus measuring their in vivo efficacy and facilitating the design of future clinical trials. PUBLIC HEALTH RELEVANCE: Considering the extensive use of natural products as complementary and alternative medicines (CAM) in the US, it is important to study how these natural products work to ensure their proper use. Presently, however, there is little known about the mechanisms of their functions. We propose to identify the molecular targets and drug-response signatures of resveratrol and Devil's claw, two classes of widely used CAMs, to help improve the knowledge of their functions and reduce the risk of their use.

描述（由申请人提供）：许多天然产品提取物已被广泛用作互补和替代药物（CAM）。但是，他们的健康益处和风险尚未受到严格的研究，也没有完全理解其行动机制。我们的研究计划的长期目标是验证这些CAM天然产品的药物影响。这项拟议的研究的重点是开发测定方法，使我们能够确定NCCAM高优先级的CAM天然产物的分子靶标，并广泛捕获生物活性的特征，以表明其复杂的药物影响。将使用化学和生物工具。对于目标识别组件，我们将基于标记和无标记的目标识别方法开发蛋白质组学和cDNA策略，以识别白藜芦醇和魔鬼的爪的直接结合目标，这是两类广泛使用的凸轮。对于签名组件，我们将使用蛋白质分析来评估CAM天然产物的广泛生物学效应和药物反应途径，并开发特定的测定和探针来报告CAM天然产物的签名反应蛋白，从而衡量其体内功效并促进未来临床试验的设计。 公共卫生相关性：考虑到美国将天然产品广泛使用为互补药物（CAM），重要的是研究这些天然产品如何工作以确保其正确使用。但是，目前，对其功能的机制鲜为人知。我们建议确定白藜芦醇和魔鬼的爪子的分子靶标和药物反应特征，这两类使用了广泛使用的凸轮，以帮助提高其功能知识并降低其使用风险。