基于三元-气血论和BACE-1/GSK-3β双重抑制作用的三种土家药抗阿尔茨海默病药效物质基础研究

随着人口老龄化发展，AD成为继心血管病、脑血管病和癌症之后，老年人健康“第四大杀手”。尽管目前合成药众多，但其新颖性、安全性、体内相关性等仍无法与天然药物相比。我国民族药是天然药物的重要组成，其中位于“华中药仓”武陵地区的土家药以其丰富的资源，悠久的历史和独到的理论，引起广泛关注。本课题在前期研究基础上，以土家医“三元”理论中关于AD的“上元”论为指导，以土家药“补气”、“清血”治则为标准，选择性的对三种土家药中具有BACE-1/GSK-3β双重抑制作用的成分进行系统研究，揭示其作用于“上元”的物质基础和活性机制，总结其“补气”、“清血”的构效关系，发现其中先导化合物，为设计更理想的新药提供独特的结构和理论基础，也为土家药材的保护性开发提供支持。本课题还将从科学角度阐述土家医药“阳主阴从”理论中“三元”论和“气血”论的科学意义，为其与现代科学的有机融合，以及民族药学的传承与发扬做出贡献。

With an aging population development, AD has become "the fourth largest killer" for elderly health after cardiovascular disease, cerebrovascular disease and cancer. In the aspects of novelty, safety, and correlations in vivo, the synthetic drugs could not be compared with those of the natural medicines, yet. Our national medicine is an important component of the natural drugs. The Tujia medicine which located in Wuling area are famous for the "drug storehouse of central China", with its abundant resources, long history and unique theoretical. Based on the previous studies and guided by “Ternary Theory” and “Qi and Blood treatment” of Tujia medicine, the Anti-Alzheimer’s Disease components from three Tujia Medicines with BACE-1 and GSK-3β inhibitory effects will be studied systemically. The project will reveal their material basis and the active mechanisms for anti-AD effects in “Ternary Theory”, and summarize the structure-activity relationship in "Reinforcing Qi, Regulating Xue" treatment. At the same time, the leading compounds will also be found in order to establish the foundation for designing new drugs in the future. The project could elaborate scientific significances of “Ternary Theory” and “Qi and Blood” theory from a scientific point of view, which will make the contribution for the inheritance of national medicine and its combination with modern science.