Identifying molecular targets and biological signatures of CAM natural products

描述(申请人提供)：许多天然产品提取物已被广泛用作补充和替代药物(CAM)。然而，它们的健康益处和风险尚未得到严格的研究，其作用机制也没有得到充分了解。我们研究计划的长期目标是验证这些CAM天然产品的药用效果。这项拟议研究的重点是开发分析方法，使我们能够识别对NCCAM具有高度优先级的CAM天然产物的分子靶标，并广泛捕获指示其复杂药效的生物活性的特征。化学和生物工具都将被使用。对于靶标识别部分，我们将开发基于标记和非标记靶标识别方法的蛋白质组学和cDNA策略来识别白藜芦醇和魔爪这两类广泛使用的CAM的直接结合靶标。对于标志性成分，我们将使用蛋白质图谱来评估CAM天然产物的广泛生物效应和药物反应途径，并开发专门的分析和探针来报告CAM天然产物的标志性反应蛋白，从而衡量它们的体内疗效，并为未来临床试验的设计提供便利。

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.