抗AD中药火麻仁和束骨姜黄的调节SIRT1有效物质研究

项目名称： 抗AD中药火麻仁和束骨姜黄的调节SIRT1有效物质研究

项目编号： No.81473323

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 范培红

作者单位： 山东大学

项目金额： 71万元

中文摘要： 单靶点药物防治阿尔茨海默症（AD）疗效不理想，多靶点药物成为研究热点，新研究表明对组蛋白去乙酰化酶SIRT1调节能发挥多靶点（淀粉样肽、tau蛋白、氧化应激、炎症）AD防治功能。申请者对具有抗AD潜力的中药进行SIRT1调节活性筛选发现火麻仁、束骨姜黄含有促细胞SIRT1表达或激活SIRT1活性的物质，是潜在的SIRT1调节剂；而文献对两药材抗AD研究仅关注了提取物或主成分抗淀粉样肽毒性或抗氧化作用。本项目拟结合快速活性筛选，发现并获得药材中典型的SIRT1调节剂；细胞水平研究SIRT1调节剂对多个AD病理通路的影响；研究促细胞SIRT1表达与SIRT1激活物质间的协同作用；动物水平评价典型SIRT1调节剂或具有协同作用的调节剂组合的多靶点抗AD作用。本项目将采用多靶点设计的新思路研究中药防治AD的新物质基础与作用机理，对抗AD药物的发现和设计具有重要的理论意义和潜在的应用价值。

中文关键词： 阿尔茨海默症；多靶点；组蛋白去乙酰化酶SIRT1；火麻仁；协同作用

英文摘要： Single-target drugs against Alzheimer's disease (AD) are not effective enough, multi-target drugs raise as a potentially more effective strategy for AD treatment. Recent study revealed that multi-targets of AD (amyloid, tau, oxidative stress, inflammation) could be touched simultaneously by regulating histone deacetylase SIRT1, and that SIRT1 modulators have multi-target effects against AD. During screening SIRT1 modulators from anti-AD herbs, we found that Fructus cannabis and Curcuma xanthorrhiza were potent SIRT1 modulators resources by up-regulating cellular SIRT1 level or activating SIRT1. Presently, the study of anti-AD effect of these two herbs only focused on traditional target amyloid or anti-oxidant effect. This project aimed to search for SIRT1 modulators from the two traditional medicines with the help of fast screening, to study their multi-target anti-AD effects using cell models, and meanwhile to study the possible synergistic effect between compounds regulating SIRT1 expression and SIRT1 activators. At last the multi-target anti-AD effects of SIRT1 modulators or their groups were evaluated using AD animal models. The project will illustrate novel material basis of traditional medicines according to new idea about multi-target drug design. The study has important theory significance and potent application value for anti-AD drug discovery and design.

英文关键词： Alzheimer's disease;multi-target;histone deacetylase SIRT1;Fructus cannabis;synergistic effect