摘要
目的利用网络药理学方法,探讨银杏叶治疗阿尔茨海默病(Alzheimer’s disease,AD)的潜在机制。方法通过中药系统药理学数据库和分析平台(TCMSP),筛选银杏叶高度活性化学成分,预测潜在靶点;通过GeneCards、OMIM、CTD、TTD和Drugbank数据库检索AD相关靶点。通过Uniprot数据库转换活性成分潜在靶点并与AD相关靶点取交集,得到银杏叶抗AD的相关靶点。利用STRING11.0数据库构建靶蛋白相互作用网络图,筛选关键基因,并通过软件Cytoscape 3.8.2中的“Clue GO”插件,对银杏叶治疗AD的作用靶点进行GO功能富集分析及KEGG信号通路分析。结果共检测到银杏叶有效化学成分32种,有效成分靶标144个;AD相关靶点470个;取交集后获得银杏叶治疗AD的潜在靶点51个。活性成分β-谷甾醇、豆甾醇、邻苯二甲酸二丁酯等主要作用于ALB、PTGS2、ESR1、BCL-2等关键靶点,通过GABA能突触信号通路、钙信号通路、PI3K-Akt信号通路等发挥抗炎、抗氧化、抗凋亡、活血通络等功能治疗AD。结论利用中药“多成分-多靶点-多通路”的特点,探究银杏叶治疗AD的潜在作用机制,为银杏叶治疗AD以至扩大适应证的后续科学研究和临床应用提供一定基础。
Objective To explore the potential mechanism of Ginkgo biloba against Alzheimer’s disease(AD)using the network pharmacology method.Methods Via the Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),highly active chemical components of Ginkgo biloba were screened to predict potential targets.GeneCards,OMIM,CTD,TTD and Drugbank databases were searched for AD-related targets.Based on the Uniprot database,the potential targets of the active ingredients were converted while AD-related targets were crossed to obtain the AD-related targets of Ginkgo biloba.The STRING11.0 database was used to construct the target protein interaction network diagram.The key genes were screened,and the“Clue GO”plug-in in the software Cytoscape 3.8.2was used for GO function enrichment analysis and KEGG signal pathway analysis of AD-related targets.Results A total of 32 effective chemical constituents of Ginkgo biloba leaves,144 effective constituent targets,470 AD-related targets,and 51 potential targets of Ginkgo biloba against AD were detected.Such active ingredients asβ-sitosterol,stigmasterol and dibutyl phthalate mainly acted on such key targets as ALB,PTGS2,ESR1 and BCL-2 by exerting antiinflammatory,anti-oxidation and anti-apoptosis effects or by activating blood through the GABA synaptic signaling pathway,calcium signaling pathway or PI3K-Akt signaling pathway.Conclusion Based on the multi-component,multi-target and multi-pathway properties of traditional Chinese medicine,the potential mechanism of Ginkgo biloba against Alzheimer’s disease has been explored,which is expected to facilitate research on clinical application of Ginkgo biloba in the treatment of Alzheimer’s disease.
作者
李媛媛
刘胜伟
任忠洋
丁玲
刘洁
廖原
LI Yuanyuan;LIU Shengwei;REN Zhongyang;DING Ling;LIU Jie;LIAO Yuan(Shalingzi Hospital of Zhangjiakou City,Zhangjiakou Hebei 075100;Yongchuan Hospital of Chongqing Medical University,Chongqing 402160,China;Jiangjin Hospital of Traditional Chinese Medicine,Chongqing 402284,China;Jiangjin Central Hospital of Chongqing,Chongqing 402260,China;College of Life and Environmental Sciences,Hangzhou Normal University,Hangzhou,Zhejiang,310036)
出处
《中国药物警戒》
2022年第9期967-972,共6页
Chinese Journal of Pharmacovigilance
基金
国家自然科学基金资助项目(31701189)
重庆市科卫联合中医药技术创新与应用发展项目(2021ZY3591)
重庆医科大学附属永川医院资助项目(YJJC202009)。
