本项目在前期大量研究基础上，将聚焦从中药中获得、经过体内/外生物活性测试初步确认有较好功效的抗老年痴呆活性部位/活性单体进行深入研究。对活性部位，将采用多种AD整体动物模型确认药效，并在进一步阐明成分、体内过程与功效的相关性基础上，探讨其成药性；对活性很好、但同时表现有某种毒副作用的活性部位，将深入研究其中所含成分，分析它们与活性/毒副作用的相关性，探讨其成药性；对前期工作中积累的大量单体活性化合物，将采用计算机反向筛选技术，从分子水平开展预测抗AD作用靶点，并对预测的靶点进行功能验证，快速寻找具有成药前景的活性分子，再进行药效学和成药性研究。本项目探索老年痴呆疾病的防治药物，方向符合国家和社会的重大需求；以传统中药天然药物为切入点，实行化学-生物学紧密结合攻关，从不同层次开展研究，体现中国特色；研究结果对探索基于中药天然药物活性物质的创新药物研究方法及对中药现代化均具有重要意义。

On the basis of plenty previous studies, the aim of the present project is to investigate the potential bioactive fractions/components from Chinese natural medicines, which were proved to show good anti-dementia effects in previous in vivo or in vitro studies. For bioactive fractions, a variety of dementia animal models would be applied for further pharmacodynamics evaluation. The druggability of those bioactive fractions would be estimated based on the clarification of the components, revelation of their pharmacokinetics and efficiency. For some bioactive fraction with toxicity, the research of toxicity-guided components isolation and function-toxicity confirmation would be carried out to evaluate their druggability. For a large number of active compounds achieved from previous studies, structure-based virtual screening would be applied to predict their molecular targets related to anti-dementia function. The structures and functions of those predicted targets would be further validated and those potential compounds would be put through further pharmacodynamics and druggabilty studies. The aim of the present study complies with national requirements since anti-dementia drugs are in great need of Chinese people. Taking Chinese natural medicines as breakthrough point, the research will be performed by close cooperation between chemists and biologists from different levels, and thus this research will be labeled with strong Chinese characteristics. Results obtained from this project are expected to provide innovative research methods for new drug discovery based on Chinese natural bioactive components, and are of great significance for Chinese medicine modernization.