摘要
目的:采用网络药理学、差异基因分析、分子对接方法初步阐明党参治疗免疫性血小板减少症(ITP)的分子机制。方法:在传统中药系统药理学数据库(TCMSP)、传统中药综合数据库(TCMID)和中医药百科全书数据库(ETCM)中检索党参的主要成分和相应的蛋白质靶标。在GeneCards、OMIM、DisGeNET数据库收集ITP的靶点,构建韦恩图获得复合靶标和疾病的交集靶点,并将靶标导入STRING数据库,使用Cytoscape3.9.1构建PPI网络。接着对交集靶点进行基因本体(GO)和京都基因与基因组百科全书(KEGG)富集分析,以探索ITP与党参的相关信号通路,最后对关键靶点和活性化合物进行分子对接研究。结果:共获得党参的84种潜在活性化合物、2354个疾病靶点与257个药物靶点,并得到86个交集靶点。通过蛋白互相作用网络图(PPI)分析确定了15个关键靶点,Degree值排名前5位的靶点包括血管内皮生长因子A(VEGFA)、Src原癌基因(SRC)、白细胞介素2(IL2)、过氧化物酶体增殖激活受体γ(PPARG)、表皮生长因子受体(EGFR)。GO和KEGG分析表明,党参治疗ITP主要涉及ERK1和ERK2级联的正向调控、信号转导、蛋白质磷酸化等生物学过程,信号通路主要包括PI3K/Akt、癌症通路、T细胞信号通路。分子对接结果表明,SRC、PPARG与11-hydroxyrankinidine具有较高的结合活性。肉豆蔻酸、乙基α-d果糖呋喃糖苷、黄豆黄素是重要的活性化合物并通过分子对接模拟进行验证。结论:本研究从多个角度阐明党参可能通过调节多个靶点和多条途径对ITP产生治疗作用,可为进一步深入研究党参对ITP的作用提供科学依据。
Objective:To preliminarily elucidate the molecular mechanism of Codonopsis pilosula in the treatment of immune thrombocytopenia(ITP)through network pharmacology,differential gene analysis,and molecular docking.Methods:The main components and corresponding protein targets of Codonopsis pilosula were searched in the TCMSP,TCMID and ETCM.The targets of ITP were collected from the GeneCards,OMIM,and DisGeNET databases.A Venn diagram was constructed to obtain the intersection targets between the compound targets and disease targets,and the qualified targets were imported into the STRING database.The PPI network was constructed using Cytoscape 3.9.1.Subsequently,GO and KEGG enrichment analyses were performed on the intersection targets to explore the relevant signaling pathways of ITP and Codonopsis pilosula.Finally,molecular docking studies were conducted on the key targets and active compounds.Results:A total of 84 potential active compounds,2354 ITP related targets,257 interaction targets,and 86 intersection targets of Codonopsis pilosula were collected.Through PPI network analysis,15 key targets were identified,with the top five targets ranked by Degree values including VEGFA,SRC,IL2,PPARG,and EGFR.GO and KEGG analyses indicated that Codonopsis′s treatment of ITP mainly involves biological processes such as positive regulation of the ERK1 and ERK2 cascade,signal transduction,and protein phosphorylation.The signaling pathways mainly include the PI3K-AKT,cancer,and T-cell signaling pathways.Molecular docking results showed that SRC and PPARG exhibited high binding activity with 1-hydroxyrankinidine.Myristic acid,ethylα-d-fructofuranoside,and glycitein are important active compounds and were verified through molecular docking simulations.Conclusion:This study clarifies from multiple perspectives that Codonopsis pilosula may exert therapeutic effects on ITP by regulating multiple targets and pathways,providing a scientific basis for further investigating the effects of Codonopsis pilosula on ITP.
作者
朱瑞芳
陈雨露
王倩
张珺
张淑文
吕亚茹
韩世范
王宏伟
ZHU Ruifang;CHEN Yulu;WANG Qian;ZHANG Jun;ZHANG Shuwen;LYU Yaru;HAN Shifan;WANG Hongwei(First Hospital of Shanxi Medical University,Shanxi 030001 China)
出处
《护理研究》
北大核心
2024年第9期1505-1515,共11页
Chinese Nursing Research
基金
山西省基础研究计划项目,编号:202203021221251
山西医科大学第一医院博士启动基金项目,编号:YB2203。
关键词
免疫性血小板减少症
党参
网络药理学
分子对接
分子机制
immune thrombocytopenia
Codonopsis pilosula
network pharmacology
molecular docking
molecular mechanisms
作者简介
朱瑞芳,教授,博士;通讯作者:王宏伟,E-mail:wanghw68@hotmail.com;通讯作者:韩世范,E-mail:shifan.han@sxmu.edu.cn。
