血管性痴呆患病率占我国所有痴呆症的首位，随着老龄化社会的来临，血管性痴呆的防治已经成为急需解决的医学和社会问题。在前期研究中，我们对广西红树白骨壤果实的提取物进行了成分分离和活性筛选，发现5个富含苯乙醇苷类化合物的活性部位（P1-P5）能改善血管性痴呆大鼠认知能力并减少大鼠海马CA1区神经元细胞损伤，进一步从P1部位中分离到6个苯乙醇苷类单体化合物能显著改善血管性痴呆大鼠的认知能力。本项目拟运用HPLC-DAD(UV)-MS方法从P2-P5部位定向追踪分离苯乙醇苷类特征活性成分，运用现代波谱技术和化学手段鉴定单体化合物的结构，系统评价苯乙醇苷类化合物改善血管性痴呆大鼠的认知和对大鼠海马CA1区神经元细胞的保护能力，分析系列化合物的构效关系，并深入研究其对Keap1-Nrf2-ARE信号通路的影响，筛选出结构新颖、活性显著的苯乙醇苷类先导化合物，为研制治疗血管性痴呆的创新药物提供物质基础。

Vascular dementia (VD) refers to a kind of cognitive dysfunction syndrome induced by cerebrovascular diseases. Vascular dementia accounts for 68.5% of the prevalence according to current data from Chinese government reports. Along with the coming of aged society, the treatments of vascular dementia have increasingly become urgent, which are not only a serious social problem, but an important medical problem as well. The fruits of Avicennia marina are used as a folk food and herbal medicine in Beihai city, Guangxi province. In our previous study, we have discovered the fruits of A. marina are rich of characteristic phenylethyl glycosides. The fruits were collected, extracted and fractionated to yield five active parts (P1-P5) which contain phenylethyl glycosides and have protective effects potent on cognitive impairment induced by chronic cerebral hypoperfusion. The pyramidal neurons in the CA1 region of hippocampus in five parts group were tightly ranked in order, and the neurons were clear and moderate in size comparing with vehicle group. Initial searching for bioactive metabolites from Part 1 has led to the isolation of six phenylethyl glycosides (of which 3 compounds are new) showing protective effects potent on cognitive impairment induced by chronic cerebral hypoperfusion. In order to obtain highly efficient and specific anti-VD drugs with independent intellectual property, this project plans to systematically investigate the active anti-VD phenylethyl glycosides from the fruit of A. marina. The contents include: 1) targeted isolating phenylethyl glycosides from the Part 2 to Part 5 by HPLC-DAD(UV)-MS and various modern chromatography techniques; 2) determining the structures of phenylethyl glycosides by MS, 1D and 2D NMR, CD, ORD and chemical methods; 3) examining the activity of the isolated compounds based on the Morris water maze and Hematoxylin-Eosin (HE) staining and analyzing the Structure-Activity-Relationship (SAR) of phenylethyl glycosides; 4) studying the mode-of-action of lead compounds through activating Keap1-Nrf2-ARE signaling pathway in rats. The current research would provide fundamentally new phenylethyl glycosides as lead compound for treatment of vascular dementia.