玛咖中乙内酰脲和乙内硫脲类化学成分及其生物活性的深度挖掘

Maca (Lepidium meyenii), belongs to the family of Brassicaceae, is traditionally used to increase fertility, improve sexual performance, and resist the fatigue and so on. Due to a long edible history and unique efficacy, Maca has been registered into the catalogue of new food resource of CHINA. However, recent years, Maca gradually fade out of sight. Moreover, someone began to question its efficacy. The main reason is that there is absence of enough evidence to indicate the importance of Maca. Thus, we need to further study Maca and confirm the effective substance of Maca from the relationship between chemical constituents and bioactivities. Our previous phytochemical investigation led to the isolation of a series of hydantoins and thiohydantoins analogues from Maca and the latter were first gained from nature. We know that hydantoins and thiohydantoins showed significant anti-prostate cancer and anti-depressive activities, which were well corresponding with the efficacy of Maca. Therefore, this project will directly isolate hydantoins and thiohydantoins from Lijiang’s Maca guided by HPLC and 1D NMR techniques. Meanwhile, we will test their anti-prostate cancer and anti-depressive activities, and propose their structure-activity relationship and bioactive mechanism. Our research will not only enrich the thiohydantoins in nature, but also lay the foundation for revealing the efficacy of Maca. In addition, the research on bioactivities will provide theoretical support for the development and utilization of Maca.

玛咖（Lepidium meyenii）传统上常被用于提高生育力，改善性功能，抗疲劳等。因其食用历史悠久，加之功效独特，已被列入我国食品新资源目录。然而，近年来有人开始质疑玛咖的功效。其根本的原因是对证明玛咖功能的证据不足。这需要我们对玛咖进行深入研究，从“成分-生物活性”的关系中证明玛咖的功效。本组前期从玛咖中分离得到乙内酰脲和硫代乙内酰脲的类似物，其中硫代乙内酰脲类成分是首次从自然界中分离得到的天然产物。其抗前列腺癌和抗抑郁方面活性，与玛咖的功能相吻合。由此，本项目在前期研究的基础上，利用HPLC和1D NMR的方法对丽江产玛咖中乙内酰脲和硫代乙内酰脲类成分进行定向分离，筛选其抗前列腺癌和抗抑郁活性，并阐明其构效关系和作用机制。这一方面可以丰富自然界中硫代乙内酰脲类成分，另一方面可以为揭示玛咖功效提供物质基础。此外，玛咖活性物质基础的研究可为丽江产玛咖的开发利用提供理论支持。

玛咖是南美著名的药食植物。因其食用历史悠久，加之功效独特，已被列入我国食品新资源目录。本组前期从玛咖中分离得到乙内酰脲和硫代乙内酰脲的类似物，其中硫代乙内酰脲类成分是首次从自然界中分离得到的活性天然产物，为玛咖功能物质基础的研究开辟了一个新的空间，得到了本项目的资助。本项目利用HPLC和1D NMR的方法定向分离玛咖中乙内酰脲和乙硫脲类成分，发现了一系列新颖天然产物及其新的生物活性。从5个丽江玛咖样品中分离纯化和鉴定了68个化合物，发现了23个新天然产物，其中8个具有二硫键的乙硫脲类二聚体，4个是具有二硫键的乙硫脲类化合物，这是首次从自然界发现的天然产物。生物活性实验表明这类含有二硫键的乙硫脲类6个化合物具有抑制前列腺癌PC-3细胞株和保护中枢神经PC12细胞的存活率的显著活性。同时建立了基于1H qNMR方法玛咖酰胺总含量测定的方法；还完成了乙硫脲类化学成分的化学合成制备方法的研究。发表项目资助标注SCI论文5篇，申请国家发明专利4件，其中1件已经授权。这些研究结果，为玛咖的活性物质基础的研究和玛咖的开发利用提供理论支撑。