民间药用微籽龙胆抗阿尔茨海默病的活性成分研究

阿尔茨海默病(AD)是一种中枢神经系统退行性疾病，严重威胁老年人的健康并对整个社会发展带来沉重的负担。寻找高效、低毒的乙酰胆碱酯酶抑制剂一直是抗AD药物研发的主要发展方向。微籽龙胆为龙胆科龙胆属一年生草本植物，是滇西北地区白族民间常用药材，用于治疗痴呆有一定疗效，前期研究证实该药材的粗提物，特别是氯仿部位显示有明显的抑制乙酰胆碱酯酶活性。本项目以其抑制乙酰胆碱酯酶活性及抗氧化活性为靶标，对微籽龙胆抗AD活性部位的活性成分进行分离、鉴定。采用MTT法评价活性组分和单体的细胞毒性，采用东莨菪碱复制小鼠记忆获得障碍模型，评价其活性组分及单体对东莨菪碱致小鼠记忆获得障碍的改善作用，初步探讨其抗AD的作用机制。该研究成果将为微籽龙胆中抗AD活性化合物的发现提供实验依据。

Alzheimer's disease (AD) is a progressive neurodegenerative disorder which seriously causes the dementia in elderly people and afflicts millions of people worldwide. It is extremely urgent to find novel acetylcholinesterase inhibitors with higher potency and less adverse effects. Gentiana delavayi Franch, an annual herb belonging to Gentianaceac of Gentiana, is a frequently used Bai traditional medicine in Northwestern, Yunnan. It was found to possess the inhibitory effect against Alzheimer's disease, and its chloroform extract demonstrated potent anti-acetylcholinesterase activities in our previous investigation. The project is study on the effective fraction and bioactive constituents of Gentiana delavayi to Alzheimer's disease. The bioactive constituents are isolated and identified from G. delavayi by screening the inhibition of acetylcholinesterase and antioxidant activity of the effective fraction. By evaluating the cytotoxicities of the bioactive constituents with MTT bioassays, and evaluating effects of the effective fraction and bioactive constituents from G. delavayi on mice with learning and memory acquisition impairment induced by scopolamine, and discussing the preliminary probe into their mechanisms. These results will provide experimental bases for the discovery of new bioactive constituents with anti-Alzheimer's disease from G. delavayi.