【摘要】 目的 探讨巴戟天治疗认知功能障碍(CD)的可能机制。方法 采用数据库TCMSP及OMIM、Disgenet、GeneCards检索巴戟天的活性成分、作用靶点与CD靶点；取巴戟天活性成分靶点与CD靶点的共同靶点，予STRING数据库、Cytoscape 3.9.1软件构建巴戟天活性成分-治疗CD共同靶点网络图、蛋白互作网络图(PPI),筛选关键化合物与关键靶点；通过生物信息注释数据库(DAVID)进行基因本体(GO)、基因组百科全书(KEGG)信号通路的富集分析，运用Cytoscape 3.9.1软件绘制成分-靶点-通路网络图，预测关键靶点作用机制；分别从数据库Pubchem、蛋白质结构数据库(PDB)获取活性成分、靶点蛋白结构，导入Autodock 4.2软件进行对接验证。结果 共获巴戟天活性成分20个、作用靶点283个、CD相关基因1 904个、巴戟天活性成分与CD疾病共同靶点103个、巴戟天治疗CD关键靶点21个，AKT1、BCL2、EGFR、CASP3、GSK3B、ESR1、HIF1A居前7位；GO分析显示，巴戟天治疗CD的作用机制涉及β淀粉样蛋白的细胞反应、肽基酪氨酸磷酸化、学习记忆、蛋白质磷酸化等过程；KEGG通路主要富集在癌症、内分泌、神经退行性三类疾病相关通路；靶点AKT1、BCL2、CASP3、GSK3B、HIF1A与成分大黄素-A和/或1-羟基-3-甲氧基-9,10-蒽醌的结合能≤-5.0 Kcal/mol。结论 巴戟天治疗CD可能通过大黄素-A、1-羟基-3-甲氧基-9,10-蒽醌通过调控AKT1/GSK3B/BCL2/CASP3通路的多个靶点发生氧化/磷酸化/凋亡级联反应而发挥作用。更多还原

【Abstract】 Objective To analyze the potential targets and mechanism of action underlying the therapeutic action of Morindae Officinalis Radix(MOR) against cognitive dysfunction(CD).Methods The active ingredients, action targets and Crohn’s disease(CD) targets of MOR were retrieved using the databases TCMSP,OMIM,Disgenet and GeneCards.The common targets of the active ingredient targets and CD targets of MOR were taken, and the STRING database and Cytoscape 3.9.1 software were used to construct the network diagram of active ingredients of MOR-common targets for treating CD and the protein-protein interaction network diagram(PPI),and to screen the key compounds and key targets.The enrichment analysis of Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) signaling pathways was carried out through the Database for Annotation, Visualization and Integrated Discovery(DAVID),and the Cytoscape 3.9.1 software was used to draw the network diagram of ingredients-targets-pathways to predict the action mechanism of the key targets.The structures of the active ingredients and target proteins were respectively obtained from the databases Pubchem and PDB,and imported into the Autodock 4.2 software for docking verification.Results A total of 20 MOR active ingredients, 283 action targets, 1 904 CD-related genes, 103 common targets of both MOR and CD,and 21 key targets related to CD treatment were obtained.AKT1,BCL2,EGFR,CASP3,GSK3B,ESR1,HIF1A ranked the top 7.GO analysis showed that the mechanism of action of MOR for the treatment of CD involves the cellular response of β-amyloid protein, peptidyl tyrosine phosphorylation, learning and memory, protein phosphorylation, etc.KEGG pathway is mainly enriched in three disease-related pathways: cancer, endocrine, and neurodegenerative.The binding energies of the targets AKT1,BCL2,CASP3,GSK3B,and HIF1A to the components rhodopsin-A and/or 1-hydroxy-3-methoxy-9,10-anthraquinone were ≤-5.0 Kcal/mol.Conclusion The treatment of CD with MOR may exert its effect by regulating multiple targets of the AKT1/GSK3B/BCL2/CASP3 pathway through the oxidation/phosphorylation/apoptosis cascade reaction of rhodopsin-A,1-hydroxy-3-methoxy-9,and10-anthraquinone.更多还原