民族药材小槐花抗阿尔茨海默病物质基础与构效关系研究

阿尔茨海默病（AD）是21世纪五大重点疾病之一，随着我国人口老龄化速度日益加快，该疾病已起社会广泛关注。民族药材豆科山蚂蝗属植物小槐花的化学研究较少，活性研究尚属空白领域。在我国侗族等少数民族聚居地，该药材一直用于散瘀消肿和宁神开窍等。课题组前期研究发现小槐花中的主要成分为黄酮，特别是二氢黄酮和异黄酮含量较高，且多具有异戊烯基取代。初步药效学研究表明，总黄酮和上述黄酮类成分在体内、外均表现出良好的抗AD活性，其作用机制不同于目前研究较多的乙酰胆碱酯酶抑制，为一新型抗AD成分。课题将以前期研究所建立的HPLC-MS和NMR选择性分离为基础，以抗AD活性为出发点，以异黄酮、二氢黄酮、异戊烯基取代黄酮为重点，分别采用细胞和动物模型，首次快速、系统、深入的对侗药小槐花抗AD活性成分进行研究，总结构效关系，确定几种不同类型的活性先导化合物，为发现活性高、特异性强的新型抗AD药物提供新的方法和理论依据

Alzheimer's Disease (AD) is one of the five major diseases of the 21st century. With the rapid pace of China's aging population, AD has become a seriouse problem in the whole society. Desmodium caudatum （Thunb.） DC. (Family: Leguminous, Genus: Desmodium) has been used for a long time in Dong nation in the south of China for the treatments of stasis swelling and Nervous system diseases. So far, there are few chemical constituents studies on it and no bioactivity studies, either. Our preliminary studies found that the main ingredient in this plant are flavonoids, flavanone and isoflavone, and there are plenty fo isopentenyl substituents in the skeleton of flavonoids. Preliminary pharmacological studies have shown that total extraction and part of flavonoids compounds, especially those with isopentenyl substituents exhibited good anti-AD activities in vitro and in vivo, and its mechanism is far different from inhibition of acetylcholinesterase, which is a new anti-AD ingredients. Base on the established HPLC-MS and NMR selective separation technology, the project will focus on anti-AD ingredients in D caudatum, especially the isoflavone, flavanone and isopentenyl substituted flavonoids. By cell model in vitro and animal model in vivo, the activies of the plant and compounds will be evaluated and the mechanisms will be studied. As a result, the structure-activity relationship will be summarized and 2-4 leading compounds with different skeleton and substituent will be confirmed. This is the first systematically study on D caudatum，which will provide new methods and theoretical basis for the new anti-AD drugs.