老年斑（SP）是阿尔茨海默病（AD）的主要病理特征之一，淀粉样蛋白β（Aβ）是老年斑的主要成分，Aβ在神经细胞外的沉积是Aβ产生与清除之间不平衡的结果。靶向Aβ42的生成和清除是针对AD创新药物研究的策略之一。实验室前期研究发现三七花多糖RN1可以显著抑制CHO/APPBACE1细胞Aβ42的生成，但其构效关系及分子机制不明。本项目将通过酶降解法和衍生化方法，研究不同分子量、差异结构特征对该多糖抑制Aβ42生成的影响，并阐明三七花多糖抑制Aβ42生成的功能结构域和构效关系，在此基础上利用人神经母细胞瘤细胞SH-SY5Y、稳转淀粉样前体蛋白APP的SH-SY5Y/APP695及大鼠神经元细胞为模型对三七花多糖抑制Aβ42生成的作用机制进行深入研究，并利用APP/PS1转基因小鼠对三七花多糖进行药效学评价。该研究成果不但能阐明中药多糖新的活性机制，而且为针对AD的创新药物研究提供坚实理论基础。

The senile plaques (SP) is one of the principal pathological characteristics of Alzheimer’s Disease. Amyloid β (Aβ) is the major component of SP. The deposition of Aβ was the imbalance of Aβ production and its clearance. Currently, the drug discovery targeted to Aβ42 production or clearance was one of the advanced strategies employed in AD therapy. Our previous results had found that the polysaccharide named RN1 isolated from the flowers of Panax notoginseng could significantly inhibit the secretion of Aβ42 in vitro, but the structure-activity relationship and the mechanisms were unclear. Herein, we prepared diverse RN1 derivatives with different molecular weight or charge by enzyme degradation or chemical derivatization to further study the effects on the inhibition of Aβ42 production. Then, the mechanism study was comprehensively investigated by human neuroblastoma cells (SH-SY5Y) cells, double stably transfected cells of amyloid precursor protein (APP)–SH-SY5Y/APP695 cells and rat neurons as the major in vitro cell models. The in vivo pharmacological activity was evaluated by the APP/PS1 double transgenic mice model. These results will clarify a new bioactivity mechanism of the polysaccharides from Chinese Traditional Medicine and provide a solid theoretical basis for AD innovative drug development.