筋骨草和金疮小草中抑制小胶质细胞活化作用活性成分的发现及构效关系的研究

项目名称： 筋骨草和金疮小草中抑制小胶质细胞活化作用活性成分的发现及构效关系的研究

项目编号： No.21302131

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 数理科学和化学

项目作者： 郭萍

作者单位： 沈阳药科大学

项目金额： 25万元

中文摘要： 从植物中寻找具有抑制小胶质细胞活化作用的活性成分是研究和开发治疗AD、PD等神经退行性疾病药物的途径之一。筋骨草属植物筋骨草和金疮小草，资源丰富、抗炎作用明显、小分子活性成分较多，开发潜力巨大。前期工作中，从金疮小草和筋骨草中分离得到了大量的新克罗烷型二萜类化合物，并利用建立的LPS诱导小胶质细胞BV-2异常活化的筛选平台对部分化合物进行筛选，共发现12个活性较强的成分。在此基础上，拟采用UPLC/Q-TOF-MS等仪器分析已鉴定化合物的MS、NMR 规律，并利用现代色谱手段，继续分离鉴定植物中的各类成分，包括微量成分，检测这些成分的活性并研究构效关系，寻找活性更高的化合物，并初步研究体外细胞毒性、血脑屏障透过率、药效学及作用机制，为充分合理利用我国尚待开发的植物资源，从中快速发现活性先导化合物提供新的方法和理论依据，更为从植物中开发防治AD、PD等神经退行性疾病的创新药物奠定物质基础。

中文关键词： 新克罗烷型二萜；筋骨草；金疮小草；小胶质细胞；构效关系

英文摘要： It is a good method that obtain the bioactive constitutents with the inhibitory effects on microglial activation from natural plants for treament of neurodegenerative diseases like AD and PD. In this way, Ajuga. ciliata and A. decumbens in genus Ajuga may have big value to study for their rich source in China, nice treatment of inflammation, and full of active micromolecule components. In our previous work, great amount of neo-clerodane diterpenes have been isolated from the whole plants of A. ciliata and A. decumbens, and some of these compounds were assessed by LPS-activated murine microglial BV-2 cells built by us to get 12 bioactive constitutents. Based on this, we project to utilize UPLC/Q-TOF-MS and the other instruments to analyze MS and NMR regularities of compounds, which have been identified by us, and use various kinds of modern chromatographic methods to continue isolating constituents, including micro constituents. Further more, we will give activity tests for all the compounds and study their Structure-Activity relationships to gain more significant ones. The cytotoxicity, barrier permeability, pharmacodynamics, and further mechanism of the compounds will also be studied. All of our research provide a new method and theory for utilizing undeveloped plant resources reasonably and sufficiently, and s

英文关键词： neo-clerodane diterpenes；Ajuga ciliata；Ajuga decumbens；microglial BV-2 cells；SAR