天然药物中乙酰胆碱酯酶抑制剂的快速发现  

Rapid discovery of acetylcholinesterase inhibitors from natural organism

作　　者：王蕊 赵川 唐生安[3] WANG Rui;ZHAO Chuan;TANG Sheng-an(Tianjin Heping Hospital of Traditional Chinese Medicine,Tianjin 300050,China;School of Basic Medical Sciences,Tianjin Medical University,Tianjin 300070,China;School of Pharmacy,Tianjin Medical University,Tianjin 300070,China)

机构地区：[1]天津市和平区中医医院,天津300050 [2]天津医科大学基础医学院,天津300070 [3]天津医科大学药学院,天津300070

出　　处：《中草药》2018年第24期5756-5760,共5页Chinese Traditional and Herbal Drugs

摘　　要：目的建立从天然药物中快速发现乙酰胆碱酯酶抑制剂的有效方法,为中药及其活性成分治疗阿尔茨海默病提供支持。方法通过Ellman比色法,对多种药用植物乙醇提取物的抗乙酰胆碱酯酶活性进行评价,筛选出活性较好的提取物样品,应用亲和超滤超高效液相色谱-四级杆-飞行时间串联质谱(UPLC-Q-TOF/MS)联用技术分离鉴定其中的活性成分。结果元胡、黄柏、钩藤、血三七具有较强的乙酰胆碱酯酶抑制活性。经过快速筛选,发现3-二氢异卡丹宾或者3-二氢卡丹宾、钩藤碱、异钩藤碱、柯诺辛或异柯诺辛可能为钩藤中的活性化合物。结论采用亲和超滤UPLC-Q-TOF/MS联用技术从天然药物中快速筛选出乙酰胆碱酯酶抑制剂,方法可行、快速,能够为治疗阿尔茨海默病的新药开发提供先导化合物。Objective To establish an effective method to rapidly detect acetylcholinesterase inhibitors from natural products, and provide support for the treatment of Alzheimer's disease with Chinese medicine and its active ingredients. Methods The activity of restraining acetylcholinesterase of crude extracts of a variety of medicinal plants were evaluated by applying Ellman's colorimetric, and the better activity of the extract sample solution was filtered out. The active ingredients of medicinal plants were identified and separated by the application of AS/UF-UPLC-MS. Results According to the experimental data, Corydais yanhusuo, Phellodendronchinense, Uncaria rhynchophylla, and Gynura segetum had significant restraining acetylcholinesterase activity. Rapid screening showed that 3α-dihydrocadambine, 3α-isodihydrocadambine, rhyncholphylline, isorhynchophylline, corynoxine, and isocorynoxine were active ingredients in U. rhynchophylla. Conclusion The results suggest that it is feasible to screen acetylcholinesterase inhibitors from natural organism plants. Using AS/UF-UPLC-MS methods, leading compounds for the development of new drugs for Alzheimer's disease would be developed and provided.

关 键 词：乙酰胆碱酯酶 Ellman比色法 超高效液相色谱-四级杆-飞行时间串联质谱 活性筛选 亲和超滤技术 天然产物 

分 类 号：R284.1[医药卫生—中药学]