阿尔兹海默病(Alzheimer's Disease, AD)的发病机制复杂，涉及多条分子信号通路，但目前抗AD药物的研发多针对单一靶点，往往实验效果好而临床疗效有限。天然药物具有多靶点、多环节的作用特点，是AD药物研发的重要来源。五味子属植物具有益气滋补、强壮安神等功效，民间多用于治疗失眠、抗衰老等，其对神经系统的作用引人关注。前期研究结果显示，瘤枝五味子、绿叶五味子和兴山五味子等三种五味子属植物的提取物均具有良好的抗氧化、神经保护和BACE1抑制活性。对其活性部位的追踪分离发现其中的抗AD有效成分多为木脂素类化合物，主要类型涵盖二芳基丁烷类、四氢呋喃类和联苯环辛烯类等。本课题拟围绕AD发病机制的多个作用靶点，包括AchE、BACE1、α和γ分泌酶、GSK-3激酶、神经保护等，以多靶点机制综合挖掘三种五味子属植物及其内生真菌的抗AD活性成分和作用机制，以期发现高效低毒抗AD先导化合物。

The pathogenesis of Alzheimer's disease is complex, involving multiple signaling pathways. Current research and development of anti-AD drugs are mostly aimed at a single target, which always has good experimental results but limited clinical efficacy. Natural medicine has the characteristics of multi-targets, which is an important source of anti-AD drug R&D. Schisandra plants have the functions of tonifying Qi, nourishing, and soothing the nerves in traditional Chinese medicine, which are used for the treament of insomnia and consenescence. Preliminary studies on the extracts of Schisandra bicolor var. tuberculate, S. viridis, and S. incarnate showed that they all have good antioxidant, neuroprotective and BACE1 inhibitory activities. The isolated lignans, which covered dibenzylbutane, tetrahydrofuran, and Dibenzocyclooctadiene types, were found to be the active components. Targeting multiple targets of AD, including AchE、BACE1、α, γ-scretases, GSK-3 and neuroprotective, etc., the aim of this project is to identify the active anti-AD components as well as their mechanisms from the three Schisandra species and their endophytic fungi. The final purpose is to find high effective and low toxic anti-AD lead compounds.