基于代谢组学及液质联用技术的紫菀质量控制和抗哮喘作用机制研究

Ziwan (Radix Aster tataricus) has been used as a common traditional Chinese medicine for the relief of coughs and anti-asthma. Because of the complexity of the plant chemical compositions, the plant secondary metabolites of Aster tataricus and their pharmacological activity are not clear enough at present. In this research, a method of LC-MS/MS metabolic fingerprints will be established for the Aster tataricus based on LC-MS/MS plant metabolomics research, the metabolomics profiles of different parts, developmental stages, years, sources and processed products of Aster tataricus will be evaluated. Then, we will confirm significative metabolic biomarkers related to asthma by LC-MS/MS metabolomics, molecular biology and immunohistochemical techniques based on rats asthma model, which can be used to evaluate the anti-asthma treatment of Ziwan extract. With the cell-based β2AR agonists functional screening system combined with LC-MS/MS, the β2AR agonists in Ziwan extract will be purified and identified to be higenamine. In this research, the distribution of different organs and growth times will be investigated. It will provide the information for the study of the synthesis and transport of secondary metabolites of Aster tataricus. This research will explore therapeutic basis of Ziwan and elucidate mechanisms underlying drug action.

紫菀是一种具有止咳平喘功效的常用中药材，但现有研究未能揭示和明确紫菀次级代谢产物的时空变化规律及其药理作用机制。为此本研究拟采用LC-MS/MS技术结合代谢组学研究模式，对紫菀进行代谢表型研究，探讨不同生长部位、不同采收期等因素对紫菀代谢组变化及对药材品质的影响；拟基于LC-MS/MS技术的代谢组学方法，结合病理学观察、生化指标及免疫组化等手段，以大鼠哮喘模型为研究载体，从整体上评价紫菀抗哮喘作用；拟建立β2肾上腺素受体激动剂功能性细胞筛选体系结合LC-MS/MS技术，对紫菀中所含抗哮喘活性成分进行筛选。本研究旨在阐明紫菀代谢网络的时空变化规律，揭示紫菀抗哮喘药效物质基础和作用机制，为紫菀质量控制及新型抗哮喘药物研究提供有力技术支持。

紫菀是一种具有止咳平喘功效的常用中药材，但现有研究未能揭示和阐明紫菀次级代谢产物的时空变化规律及其药理作用机制。本研究采用UPLC-MS/MS法及HPLC-MS/MS法对紫菀中主要成分进行定量分析，为紫菀的质量控制提供了可靠地分析手段；采用UHPLC-Q-TOF/MS技术和代谢组学分析方法，对不同采收期的紫菀及其次级代谢产物进行快速分析和鉴定，同时采用GC-MS技术，对紫菀不同炮制品进行代谢组学分析，比较不同样品代谢物组的整体差异性，寻找到差异性代谢物，对其药效物质基础研究及质量控制提供了依据；采用卵蛋白（OVA）法制备C57BL/6小鼠哮喘模型，基于GC-TOF-MS技术进行血清代谢组学研究，分析了代谢谱型变化，并对潜在生物标志物进行分析和鉴定，从代谢组学角度评价了药物的有效性；基于已建立的液质联用数据采集方法和相应数据后处理策略，研究团队结合课题组其他研究方向和上述已完成研究内容，针对某些中药单体化合物，进行相应的体内外药物代谢动力学和药理活性拓展研究，取得了相应的研究成果。项目资助发表SCI论文15篇、核心论文1篇，待发表SCI论文1篇，会议论文1篇。共培养博士、硕士研究生11名。项目投入经费55万元，各项支出基本与预算相符。