滇产黄皮属植物抗单胺氧化酶活性分子的发现及机制研究

项目名称： 滇产黄皮属植物抗单胺氧化酶活性分子的发现及机制研究

项目编号： No.21462048

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 环境科学、安全科学

项目作者： 汪云松

作者单位： 云南大学

项目金额： 53万元

中文摘要： 抑郁症（MDD）、帕金森氏综合症（PD）、阿尔茨海默病（AD）等疾病带来严重的社会和家庭问题。这些疾病病因不明，发病机理复杂，患者体内单胺氧化酶(MAO)的活性异常。MAO是催化包括体内单胺神经传递物质以及神经毒素等生物活性单胺的一种线粒体膜复合酶，对于中枢神经系统和外周组织中作用于神经和心血管的胺类代谢起重要作用，是治疗上述疾病的重要靶点。单胺氧化酶抑制剂(MAOIs)是控制MAO异常、治疗上述疾病的临床用药。7-氧代香豆素是一类源自天然的重要MAOIs，黄皮属植物含有结构多样的该类香豆素，我们前期研究表明细叶黄皮提取物显示了较强的MAO 抑制活性。申请者拟对3种具有代表性黄皮属植物的化学成分进行研究，研究其抑制MAO活性的化学物质基础，找出高活性成分，结合构效关系研究、探讨作用机理，为发现具有抑制MAO活性的新型分子及化学结构规律，开发特异性可逆MAOIs药作基础性研究工作。

中文关键词： 黄皮属；单胺氧化酶；活性分子；作用机制；构效关系

英文摘要： Major Depressive Disorder (MDD), Parkinson's disease (PD) and Alzheimer's disease(AD) are the most common neurological diseases. There are no treatments that can prevent, delay, slow or stop their progression. Patients with these diseases are unknown etiology and pathogenesis is complex, the activity of monoamine oxidase (MAO) is abnormalities in the body. MAO is a FAD-containing enzyme with two known isoforms (MAO-A and MAO-B) and is present in the mitochondrial outer membrane of glial, neuronal and other cells. MAO enzymes have essential roles in vital physiological processes and are involved in the pathogenesis of various human diseases. This enzymatic function increases the synaptic concentration of these neurotransmitters and conditions to a great extent the neurone's excitement of those possessing receptors for these mediators. Therefore, MAOs have received an extensive attraction on developing new drugs as targets. The MAO inhibitors(iMAOs) are a class of compounds that act by blocking the MAO enzymatic action, being used by several years in the treatment of the depression and anxiety diseases (iMAO-A) or in PD (iMAO-B). Nowadays is being studied also in AD. Some coumarins, in particular 7-Hydroxycoumarins had been previously described as monoamine oxidase inhibitors from natural products. The plants of the genus Clausena (Rutaceae) are rich in different 7-Hydroxycoumarins. Our previous researchers on the genus Clausena anisum-olens revealed that the EtOAc fraction displayed strong inhibit activity against MAO. In this project, systemic phytochemical research will be carried out on three plants of Clausena collected from Yunnan Province, base on our previous study. By studying their inhibition on the monoamine oxidase, efforts aimed at discovering the new inhibitors of MAOs, giving the relationship between structure and function of active lead compounds, and finding the binding site with the MAOs.

英文关键词： Clausena;monoamine oxidase;Phytochemistry;bioassays;structure-activity relationship