基于网络药理及分子对接研究远志治疗认知功能障碍的作用机制  

Mechanisms of Polygalae Radix in treatment of cognitive dysfunction based on network pharmacology and molecular docking

作　　者：沈俏嫔 何乐为 敖海清[1] 冯丽[1] 刘步平[1] 方春平[4] SHEN Qiaopin;HE Lewei;AO Haiqing;FENG Li;LIU Buping;FANG Chunping(School of Public Health and Management,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Second Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405,China;National Key Laboratory of Traditional Chinese Medicine Syndrome,Guangzhou University of Chinese Medicine,Guangzhou 510405,China;Chinese Materia Medica,Guangzhou University of Chinese Medicine,Guangzhou 510405,China)

机构地区：[1]广州中医药大学公共卫生与管理学院,广东广州510405 [2]广州中医药大学第二附属医院,广东广州510405 [3]广州中医药大学中医证候全国重点实验室,广东广州510405 [4]广州中医药大学中药学院,广东广州510405

出　　处：《现代药物与临床》2025年第1期55-62,共8页Drugs & Clinic

基　　金：国家中医药管理局创新团队和人才培养计划项目(国中医药人教函<2022>222号);广东省重点领域研发计划(第五批)项目(163-2018-XMZC-0001-165-0272)。

摘　　要：目的基于网络药理及分子对接探讨远志治疗认知功能障碍的成分与机制。方法采用数据库TCMSP、OMIM、Disgenet、GeneCards检索远志的活性成分、作用靶点与认知功能障碍靶点;获取远志活性成分靶点与认知功能障碍靶点的共同靶点,采用STRING数据库、Cytoscape 3.9.1软件构建远志活性成分–认知功能障碍共同靶点网络图、蛋白相互作用(PPI)网络图,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,预测关键成分与靶点作用;分别从数据库PubChem、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。结果共获远志活性成分24个、作用靶点544个、认知功能障碍相关基因1904个、远志活性成分与认知功能障碍疾病共同靶点189个、远志治疗认知功能障碍关键靶点26个,蛋白激酶B1(Akt1)、白蛋白(ALB)、信号转导和转录激活因子3(STAT3)、雌激素受体1(ESR1)、胱天蛋白酶3(CASP3)、V-Jun肉瘤病毒癌基因同源物(JUN)、表皮生长因子受体(EGFR)、过氧化物酶体增殖物激活受体γ(PPARG)、糖原合酶激酶3β(GSK3B)、哺乳动物雷帕霉素靶蛋白(MTOR)居前10位;GO分析显示,远志治疗认知功能障碍的作用机制涉及细胞对外源性刺激的增殖反应、磷酸化、炎性反应、蛋白质磷酸化等过程;KEGG通路主要富集在癌症、内分泌、病毒感染3类疾病相关通路;靶点Akt1、JUN、PPARG与成分胡椒内酰胺A、1-甲乙氧基-β-咔啉、降赛法拉二酮B的结合能≤-5.0 kcal/mol。结论远志治疗认知功能障碍可能与胡椒内酰胺A、1-甲乙氧基-β-咔啉、降赛法拉二酮B调控作用于Akt1/PPARG/JUN通路的多个靶点发生代谢/炎症/凋亡级联反应有关。Objective To analyze the potential components and mechanism of action underlying the therapeutic action of Polygalae Radix against cognitive dysfunction.Methods Using the database of TCMSP,OMIM,Disgenet,and GeneCards,we identified the main active components of Polygalae Radix,and the targets of Polygalae Radix and cognitive dysfunction were obtained.Then,Venn diagrams were used to obtain the common targets of both Polygalae Radix and cognitive dysfunction.The database of STRING and Cytoscape 3.9.1 was used to construct“component–target”network diagrams of the targets.The protein-protein interaction(PPI)network diagrams,gene ontology(GO),and Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathways of the targets were analyzed.Using Cytoscape 3.9.1 software to draw a“component–target–pathway”network diagram.The molecular docking of key components and targets was performed using AutoDock 4.2,and the docking results were visualized using Pymol.Results Twenty-four main active components of Polygalae Radix were predicted.A total of 544 action targets,1904 cognitive dysfunction-related genes,189 common targets of both Polygalae Radix and cognitive dysfunction,including 26 key targets related to cognitive dysfunction treatment.The grade values of Akt1,ALB,STAT3,ESR1,CASP3,JUN,EGFR,PPARG,GSK3B,and MTOR are in the top 10.GO analysis showed that the mechanism of action ofPolygalae Radix in treatment of cognitive dysfunction involved cell proliferation response,phosphorylation,inflammatory response and protein phosphorylation to exogenous stimuli.The KEGG pathway is mainly concentrated in the pathways related to cancer,endocrine and viral infection.Molecular docking revealed that the three core components of Polygalae Radix,including piperolactam A,1-carboethoxy-beta-carboline,and norcepharadione B,exhibited strong binding(≤−5.0 kcal/mol)with the core targets of Akt1,JUN,and PPARG.Conclusion Polygalae Radix is likely to exert its therapeutic effect on cognitive dysfunction by regulating the metabolic

关 键 词：远志 认知功能障碍 网络药理学 分子对接 胡椒内酰胺A、1-甲乙氧基-β-咔啉、降赛法拉二酮B 

分 类 号：R285.5[医药卫生—中药学]