玛咖活性成分及其不同加工方式下化学成分变化的研究

	玛咖活性成分及其不同加工方式下化学成分变化的研究
	张然然
导师	邱明华
关键词	十字花科，玛咖，硫代乙内酰脲，生物活性， UPLC-MS/MS-MRM，成分分析 Cruciferous, Lepidium meyenii, Thiohydantoin, Bioactivity, UPLCMS/MS-MRM, Analysis of chemical constituents
摘要	本论文由三章组成，第一章论述了十字花科独行菜属玛咖（ Lepidium meyenii Walp）块根的化学成分及其生物活性研究；第二章论述基于 UPLCMS/MS-MRM 模式探究不同加工方式下玛咖中化学成分的变化；第三章综述了含硫天然产物研究进展及目前测定玛咖化学成分所建立的分析方法。基于 HPLC-UV 的指导，针对玛咖中（硫代）乙内酰脲类化合物进行定向分离，结合不同色谱分离技术与波谱分析鉴定手段，最终从玛咖丙酮提取浸膏中分离得到 47 个化合物，其中新化合物 13 个，包括两个以二硫键连接的硫代乙内酰脲二聚体类化合物 (1 和 2)，化合物 3 中含有咪唑并哌啶结构片段，化合物 4 和 5 为含有新颖的二硫键片段硫代乙内酰脲化合物，化合物 6 和 7 均为硫代乙内酰脲衍生物；除了硫代乙内酰脲衍生物，新化合物结构类型还包括吡咯类生物碱 (18, 19 和 20)，三唑类生物碱(23)，木脂素 (28) 和玛咖酰胺 (31)。经手性柱分析，发现新化合物 1-5 均为对映异构体。活性测试结果显示化合物 (–)- 4 和 (–)-5 对结肠癌细胞 SW480 以及人前列腺癌细胞 PC-3 具有一定的抑制作用，在 40 μM 浓度下，抑制率为 56-63%；在皮质酮诱导的 PC12 神经细胞损伤模型中，化合物 (–)-5 在 20 μM 的浓度下抑制率为 68.63%。质谱多反应检测 (MRM) 技术相比于其他分析方法具有灵敏度高、特异性强、准确度高、重现性好等优点。本文基于 UPLC-MS/MS-MRM 模式，探究不同加工处理下的玛咖样品化学成分变化，研究发现烘箱烘干相比自然晒干对于玛咖化学成分种类及含量分布并无显著影响，但随着烘箱温度的升高，硫苷化合物含量不断积累；另外，随着玛咖样品碎裂程度增高，玛咖酰胺含量呈增长趋势。文章最后综述了自然界中含硫天然产物的研究进展，并对近年来采用不同分析方法测定玛咖中的化学成分含量等相关研究进行概述，为后续玛咖活性成分的挖掘以及成分分析提供基础。; This dissertation primarily consisted of three chapters. In the first chapter, we stated the study on the chemical constituents and biological activities of Lepidium meyenii. The changes of chemical constituents under different processing methods based on UPLC-MS/MS-MRM were mainly described in the second chapter. Finally, we summarized the sulfur-containing natural products and the analytical methods currently established for the chemical constituents of L. meyenii. Recently, we conducted a systematic study on chemical constituents and biological activities of L. meyenii, and thiohydantoin derivatives were firstly reported by us. Considering that compounds with nitrogen heterocycles play important role in development of drug, an in-depth research on thiohydantoins was conducted. In the present study, 47 compounds, including 13 new ones, which contained two disulfidelinked thiohydantoin dimer compounds (1 and 2), compound 3 contains thioxohexahydroimidazo [1,5-a] piperidine moiety, compounds 4 and 5 contain novel disulfide bond fragments, and two thiohydantoin derivatives (6 and 7) were isolated. In addition, pyrrole alkaloids (18, 19 and 20), triazole alkaloid (23), lignan (28), and macamide (31) were also obatained. After chiral column analysis, the new compounds 1-5 are all enantiomers. At the concentration of 40 μM, compounds (–)-4 and (–)-5 showed potential antiproliferative activity against colon cancer cell SW480 and human prostate cancer cell PC-3 with inhibition ration from 56 to 63%. In the LPSinduced damage of PC12 cell model, the cell viability of compound (–)-5 was 68.63% at the concentration of 20 μM. Compared with other analytical methods, multiple reaction monitoring (MRM) method has the advantages of high sensitivity, strong specificity, high accuracy and good reproducibility. Thus, we used UPLC-MS/MS-MRM to analyze the changes of chemical constituents of L. meyenii under different process modes. The results showed that no obvious difference was observed in the types and content of chemicalcomponents in L. meyenii between oven drying and natural drying. However, when the oven temperature increased, the content of glucosinolates significantly increased. The content of macamide increased if the degree of crushing of samples increased, which provided a certain reference for the process of L. meyenii in the future. Finally, the natural sulfur-containing natural products were reviewed. Meanwhile, the different analytical methods of L. meyenii in recent years were summarized.
语种	中文
	2022-05
学位授予单位	中国科学院大学
文献类型	学位论文
条目标识符	http://ir.kib.ac.cn/handle/151853/75129
专题	昆明植物所硕博研究生毕业学位论文
推荐引用方式 GB/T 7714	张然然. 玛咖活性成分及其不同加工方式下化学成分变化的研究[D]. 中国科学院大学,2022.

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