老年痴呆（AD）系多病因的中枢神经系统退行性疾病，针对单一靶点的治疗未能取得满意的疗效。中药复方抑肝散用于AD临床治疗效果显著。本项目从抑肝散不同化学物质类群体内外跨血脑屏障的成分入手，基于现代分析技术建立复杂体系多组分的快速识别与同时定量表征的方法体系，采用细胞和整体动物模型，基于AD不同致病环节的关键靶点（AChE、PRAP-1、BACE-1和Caspase-3）追踪抑肝散具胆碱功能调节与神经元保护作用的活性成分，揭示抑肝散多靶点阻抑AD的效应物质；并且采用稳定过度表达转运蛋白的细胞系，阐明活性成分的脑转运机制和相互作用，从活性成分透过血脑屏障的视角揭示抑肝散的配伍机理。本研究围绕表征方剂复杂物质、多靶点生物活性评价、分析入脑机制三个相互衔接的关健环节，从分子水平阐明抑肝散阻抑脑神经损伤级联反应的效应物质和转运机制，为复方配伍的基础研究和脑源性疾病的多靶点治疗提供理论依据。

Alzheimer's disease (AD) is a central nervous system degenerative disease caused by multiple etiologies, the treatments focused on a single target failed to obtain satisfactory curative effects. It has been recently reported that the traditional Chinese medicine Yi-gan San was safe and bene?cial in treating AD clinically. This project fixes the attention on the composition of the different chemical groups of Yi-gan San crossing the blood-brain barrier in vivo and in vitro to establish a method for the rapid identification of the active components. The different pathogenic key targets(AChE, PRAP-1,BACE-1 and Caspase-3) are screening by the cells and the whole animal models for these components to clarify the active compounds and multi-target effects for cholinergic regulation and neuron protective effects of Yi-gan San. Furthermore, the brain transport mechanisms and interaction of main active ingredients of Ramulus Uncariae cum Uncis, Radix Glycyrrhizae and Rhizoma Chuanxiong will be studied by MDCKII-MDR1 cells to reveal the compatibility mechanism of Yi-gan San.