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利用代谢组学技术研究橘属中药物质基础及其体内作用

批准号:
81573569
项目类别:
面上项目
资助金额:
54.0 万元
负责人:
刘元艳
依托单位:
学科分类:
中药药效物质
结题年份:
2019
批准年份:
2015
项目状态:
已结题
项目参与者:
刘振丽、吕诚、宋志前、宁张弛、曾鸿莲、赵思宇、赵婷、邹慧琴、杜智勇

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中文摘要
橘属植物极高的食用及药用价值,使其成为国内外研究的热点。中国药典收录的橘属中药达九种,同为理气药,但其功效各有偏重。本课题拟从品种、药用部位及生长阶段不同的橘属中药物质基础及其体内作用切入,借助代谢组学技术在定性定量描述中药成分代谢物,客观反映机体内源性生物代谢物的优势,初步探讨橘属中药功效差异机理。.假说:基于代谢组学技术研究橘属中药物质基础及其体内作用,对于揭示其功效差异机理具有实际意义。.以九种橘属中药为研究对象,采用LC-MSn辅以NMR分析及检测手段,结合多变量统计学方法,开展基于化学表征差异鉴别橘属中药的植物代谢组学研究;利用NMR方法,开展不同橘属中药引起大鼠生物代谢物差异性应答的体内代谢组学研究,借助生物信息学方法进行代谢通路分析;利用多元回归方法关联分析两组代谢组学数据,构建橘属中药物质基础及其体内作用的新型研究模式,探索橘属中药功效差异机理,为临床合理用药提供依据。
英文摘要
Because of the high edible and medicinal value, Citrus plants become a hot research object all over the world. Nine Chinese medicines from Citrus species are listed in the Chinese Pharmacopoeia, which belong to qi-regulation drug in TCM. However, the efficacy during them is different. The efficacy based on the chemical substances is important to ensure their safety and effectiveness in clinical use. Metabonomics is a well-established field in systems biology. Plants metabonomics could be applied in research of chemical substances in plants..Hypothesis: The chemical substances in different Citrus Chinese medicines are varied, which can lead to diversify responses of endogenous metabolites. Even, the metabolic pathway will be disturbed due to the irritation. The relationship between metabolism pathway and chemical substances could be used to indicate different effective mechanism...In the present study, nine Chinese medicines of Citrus species were investigated using LC-MSn complemented by NMR technique. Furthermore, a multivariate statistical method was applied to distinguish different Citrus Chinese medicines according to their chemical substances. Meanwhile, the endogenous metabolites disturbances after administrated with nine Citrus Chinese medicines are revealed by NMR-based metabonomics. The data between the two metabonomics will be fitted based on decision tree analysis and support vector machine analysis. The established two-dimension metabonomics strategy will be assist in quality assessment of Citrus Chinese medicines.
本项目收集了九种橘属中药,分别建立其活性提取部位的质量控制方法及提取工艺(发表文章并申请专利)。采用LC-MSn辅以NMR分析及检测手段,结合多变量统计学方法,开展基于化学表征差异鉴别橘属中药的植物代谢组学研究,分别建立初生及次生代谢产物化学分类学方法,可有效区分亲缘相近,但品种、药用部位及生长阶段不同的橘属中药(发表文章并申请专利)。通过分析不同橘属中药引起大鼠内源性代谢物的差异性应答,发现药效物质基础的差异分别引起体内不同代谢通路的激活,借助网络药理学方法阐释代谢通路与其调节蛋白及功效差异的相关性(发表文章)。基于以上结果,筛选出橘属中生物活性较强的四味中药,建立了体内ADMET分析,进一步阐释体内活性成分及其代谢轮廓(发表文章)。筛选出橘属中药活性提取部位分别表现出多样性生物活性,其中,枳实、枳壳分别通过抑制MAPK信号通路和激活PPAR-AKT信号通路对LPS诱导的炎症反应发挥不同的抗炎作用,枳实中活性提取部位对药源性肝损伤具有保护作用等(发表文章)。通过以上研究,我们建立了橘属中药体内体外量-效关联性研究模式,对于系统阐释中药药效物质基础具有借鉴意义,并为临床合理用药提供依据。
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Integrated and global pseudotargeted metabolomics strategy applied to screening for quality control markers of Citrus TCMs
综合性全局假靶向代谢组学策略应用于柑橘类中药质量控制标志物筛选
DOI: 10.1007/s00216-017-0428-1
发表时间: 2017-08-01
期刊: ANALYTICAL AND BIOANALYTICAL CHEMISTRY
影响因子: 4.3
作者: [Shu, Yisong, Liu, Zhenli, Liu, Yuanyan]
通讯作者: Liu, Yuanyan
Anti-inflammatory effects of Zhishi and Zhiqiao revealed by network pharmacology integrated with molecular mechanism and metabolomics studies
网络药理学结合分子机制和代谢组学研究揭示枳实和枳壳的抗炎作用。
DOI: 10.1016/j.phymed.2018.09.184
发表时间: 2018-11-15
期刊: PHYTOMEDICINE
影响因子: 7.9
作者: [Zhao Siyu, Liu Zhenli, Lu Aiping]
通讯作者: Lu Aiping
Vascular Protection of TPE-CA on Hyperhomocysteinemia-induced Vascular Endothelial Dysfunction through AA Metabolism Modulated CYPs Pathway
TPE-CA 通过 AA 代谢调节 CYP 途径对高同型半胱氨酸血症诱导的血管内皮功能障碍进行血管保护
DOI: 10.7150/ijbs.35245
发表时间: 2019-01-01
期刊: INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES
影响因子: 9.2
作者: [Li, Hui, Liu, Zhenli, Liu, Yuanyan]
通讯作者: Liu, Yuanyan
Chemotaxonomic Classification Applied to the Identification of Two Closely-Related Citrus TCMs Using UPLC-Q-TOF-MS-Based Metabolomics.
使用基于 UPLC-Q-TOF-MS 的代谢组学将化学分类学分类应用于两种密切相关的柑橘类中药的鉴定
DOI: 10.3390/molecules22101721
发表时间: 2017-10-13
期刊: Molecules (Basel, Switzerland)
影响因子: --
作者: [Zhao SY, Liu ZL, Shu YS, Wang ML, He D, Song ZQ, Zeng HL, Ning ZC, Lu C, Lu AP, Liu YY]
通讯作者: Liu YY
12
    基于HPLC/DAD-MSn技术枳实总黄酮药效物质基础与药材品质相关性研究
    • 批准号:
      81001623
    • 项目类别:
      青年科学基金项目
    • 资助金额:
      22.0万元
    • 批准年份:
      2010
    • 负责人:
      刘元艳
    • 依托单位:
    国内基金
    海外基金