β-淀粉样蛋白(Aβ)在脑部的异常沉积是阿尔茨海默症(AD)的始动因素与中心环节，然而以Aβ为靶标的药物临床试验反复的令人失望。研究显示，Aβ可特异性与纤维蛋白原结合并诱导结构异常和难以降解的蛋白凝块的形成，抑制“Aβ-纤维蛋白原”之间的相互作用是新型AD治疗策略。钩藤为中医临床治疗痴呆善忘证的常用药源，含多种生物碱。本项目以钩藤总碱为对象，采用荧光法研究钩藤总碱对“Aβ-纤维蛋白原”的抑制作用，以现代分析技术构建钩藤总碱全息色谱/质谱指纹图谱；引入化学计量学建立它们的组成(组)与靶标抑制率(IC50)之间的定量“组-效”关系模型，揭示靶标活性组分群；基于体外和整体动物模型阐明药物-靶蛋白相互作用机理和逆转AD、改善认知的分子机制。本研究针对AD治疗新靶标，以成分和结构基本清晰的有效部位为对象，从药物-蛋白相互作用的分子水平阐明群体作用的分子机制，对中药治疗AD的研究具有重要的科学意义。

The abnormal deposition of β-amyloid (Aβ) peptide in the brain is an initiating and central factor of Alzheimer’s disease (AD) pathophysiology. However, candidates targeting Aβ have suffered disappoinment in major clinical trials. It has been reported that Aβ specifically binds to fibrinogen, thereby altering fibrin clot structure and delaying clot degradation. Therefore, inhibiting the Aβ-fibrinogen interaction is a novel strategy for AD treatment. Gouteng, mainly containing a variety of alkaloids, is a commonly used Traditional Chinese Medicine(TCM) for treatment of dementia. This work will focuse on the Gouteng total alkaloids, an effective part of Gouteng. A fluorescence method will be developed to investigate the inhibitory efficacy of Gouteng total alkaloids on Aβ-fibrinogen interaction. At the same time, modern analytical technology will be used to construct their holographic chromatography/mass spectrometry fingerprint. A quantitative composition-effectiveness relationship model will be constructed based on the fingerprint and half-maximal inhibitions (IC50) using chemometrics to reveal the active constituents. Using in vitro and integral animal model to illustrate the interaction mechanism of drug-target, and molecular mechanism of Gouteng total alkaloids reversing cerebrovascular abnormalities and improving cognitive impairment of AD. Because Gouteng total alkaloids have an approximately clear composition, this research aims at the new target of AD treatment and will elucidate the molecular mechanism of group effection of TCM on molecular level of drug-protein interaction, which will give an valuable supportment for developing AD therapies.