基于网络药理学研究栀子入血成分抗阿尔茨海默病的作用机制  

Study on mechanisms of anti-Alzheimer′s disease action of absorbed components of Gardeniae Fructus based on network pharmacology

作　　者：张锐 张季林[2] 李冰涛[3] 花昌林 刘芮祺 ZHANG Rui;ZHANG Ji-lin;LI Bing-tao;HUA Chang-lin;LIU Rui-qi(Modern Preparation of Traditional Chinese Medicine,Ministry of Education,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China;Jiangxi People's Hospital,Nanchang 330006,China;Research Center for Differentiation and Development of Traditional Chinese Medicine Basic Theory,Jiangxi University of Traditional Chinese Medicine,Nanchang 330004,China)

机构地区：[1]江西中医药大学现代中药制剂教育部重点实验室,江西南昌330004 [2]江西省人民医院,江西南昌330006 [3]江西中医药大学中医基础理论分化发展研究中心,江西南昌330004

出　　处：《中国中药杂志》2020年第11期2601-2610,共10页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81560579,81160523);江西省教育厅科技项目(GJJ14609)。

摘　　要：栀子具有传统的益智开窍功效,但是其作用机制不明确。该研究以栀子传统益智开窍功效与抗阿尔茨海默症之间的关系为切入点,采用网络药理学方法研究预测栀子中主要入血成分的抗阿尔茨海默症药理作用机制,建立其"入血成分-靶标-通路-疾病"的网络药理学研究模式。研究采用活性成分筛选、靶点预测技术,确定栀子抗阿尔茨海默症的有效成分及作用靶点,利用生物信息注释数据库(DAVID)富集通路及生物过程,分子对接验证网络分析结果,阐述栀子抗阿尔茨海默症的作用机制。结果显示,栀子35个入血成分可能调控胆碱酯酶(cholinesterase,BCHE)和碳酸酐酶2(carbonic anhydrase 2,CA2)等48个靶点,显著影响转录因子活性、核受体活性、类固醇激素受体活性、酰胺结合和肽结合等11条生物过程及丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)信号通路、阿尔茨海默病、促性腺激素释放激素信号通路和雌激素信号途径等7条代谢通路。且分子对接验证显示,60%以上的有效成分与关键靶点具有结合活性,相关文献也显示结果所得活性成分能够抑制关键靶点MAPK1表达,说明结果可靠性较高。研究结果表明栀子可能通过"多成分、多靶点、多通路"发挥抗阿尔茨海默症的作用,为栀子的进一步研究及其产品开发提供了科学依据。Gardeniae Fructus has the traditional effects of promoting intelligence and inducing resuscitation,but its mechanism is unclear.In this study,the relationship between Gardeniae Fructus′s traditional effect of promoting intelligence and inducing resuscitation and anti-Alzheimer′s disease effect was taken as the starting point to investigate the anti-Alzheimer′s disease mechanism of the major absorbed components in Gardeniae Fructus by the network pharmacology method.The network pharmacology research model of"absorbed composition-target-pathway-disease"was adopted.In this study,the active components screening and target prediction technology were used to determine the active components and targets of Gardeniae Fructus in treatment of Alzheimer′s disease.The enrichment pathway and biological process of Gardeniae Fructus were studied by using the bioinformatics annotation database(DAVID),and the results of molecular docking validation network analysis were used to elaborate the mechanism of Gardeniae Fructus in treatment of Alzheimer′s disease.It was found that 35 absorbed components of Gardeniae Fructus not only regulated 48 targets such as cholines-terase(BCHE)and carbonic anhydrase 2(CA2),but also affected 11 biological processes(e.g.transcription factor activity,nuclear receptor activity,steroid hormone receptor activity,amide binding and peptide binding)and 7 metabolic pathways(MAPK signaling pathway,Alzheimer disease and estrogen signaling pathway,etc.).Molecular docking results showed that more than 60%of the active components could be well docked with key targets,and the relevant literature also showed that the active components could inhibit the MAPK1 expression of key targets,indicating a high reliability of results.These results indicated that Gardeniae Fructus may play its anti-Alzheimer′s disease action via a"multi-ingredients-multi-targets and multi-pathways"mode,providing a scientific basis for further drug research and development.

关 键 词：栀子 入血成分 阿尔茨海默病 网络药理学 分子对接 生物过程 通路分析 

分 类 号：R285[医药卫生—中药学]