发现新结构类型的具有选择性GluN2B-NMDA受体拮抗作用及自由基清除能力的神经保护剂，已成为解决临床上缺血性脑卒中药物缺乏的研究热点。已有文献报道咖啡酰奎尼酸类化合物的神经保护作用，但相关研究仅限研究者分离得到的有限数量的化合物，且存在指标结果不统一、作用机制不深入、作用靶点和构效关系未明确等问题。前期工作中，申请者从牛蒡根中分离得到18个咖啡酰奎尼酸类化合物并进行了初步活性测试与机制探讨；首次揭示此类化合物可能通过作用于GluN2B-NMDA受体发挥神经保护作用；首次发现苹果酰基取代对其神经保护活性有重要影响。本项目拟在此基础上，进一步分离鉴定咖啡酰奎尼酸类化合物，得到更多及足量的样品；系统评价其神经保护活性，获得确切的构效关系；明确其作用机制和作用靶点；并在体内验证其抗缺血性脑损伤神经保护作用。为咖啡酰奎尼酸类化合物神经保护作用研究及结构修饰提供理论依据。

To find out a new structural neuroprotective agent which could selectively antagonize the GluN2B-NMDA receptors and scavenge the free radicals has been one of the hottest topics in searching medication to treat ischemic stroke. It has been reported the caffeoylquinic acids is effective on neuroprotection, but the studies only refer to limited number of compounds with inconsistent results, unclear mechanisms, undefined drug targets and unestablished structure-activity relationships. In our previous studies, 18 caffeoylquinic acids were isolated from Arctium lappa L. Roots, and the neuroprotective property and the action mechanisms have been investigated. As a result, it was the first time that we found the compounds potentially targeted on GluN2B-NMDA receptor and the influence of maloyl group to the neuroprotective effect of caffeoylquinic acids. On the basis of the above studies, sufficient amount of caffeoylquinic acids from Arctium lappa L. Roots will be isolated and identified. The neuroprotective effect will be evaluated systematically to reveal the structure-activity relationships, the mechanisms and drug targets. Furthermore, the neuroprotective effect on ischemic brain damage in vivo will be confirmed by tMCAO method. The study results will lay theoretical foundations for neuroprotection research and structural modification in caffeoylquinic acids.