摘要
目的探讨基于网络药理学探讨大承气汤治疗退行性腰椎管狭窄症(Degenerative Lumbar Spinal Stenosis,DLSS)的分子机制。方法检索建库至2024年7月10日,中药系统药理学数据库与分析平台(Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,TCMSP)获取大承气汤相关的化学成分及基因信息。对于TCMSP中未涵盖的中药或缺乏靶点基因信息的化合物,使用PubChem数据库获取相关化合物的分子式,并通过SwissADME数据库进行筛选。符合条件的化学物质通过SwissTarget Prediction数据库进行靶标预测,并使用UniProt数据库规范基因名称。检索建库至2024年7月10日GenCards、OMIM及DrugBank数据库获取DLSS相关疾病基因信息,并将其与药物靶点进行映射。将共有基因导入STRING数据库(Search Tool for the Retrieval of Interacting Genes/Proteins,STRING)构建蛋白质-蛋白质相互作用(Protein-Protein Interaction,PPI)网络,并导入Metascape数据库进行通路富集分析。使用Cytoscape 3.10.2软件绘制“药物-化学成分-靶标”网络图,并使用Net workAnalyzer工具对主要活性成分及靶点进行网络拓扑学分析。结果筛选获得了芦丁(Rutin)、5,7,4'-三甲基芹菜素(5,7,4'-Trimethylapigenin)、桉叶油素(Eucalyptol)等10个主要活性成分,以及环氧合酶2(Prostaglandin-Endoperoxide Synthase 2,PTGS2)、热休克蛋白β(Heat Shock Proteinβ,HSPCB)等10个主要靶点。通路富集分析发现,大承气汤可能通过PI3K-Akt信号通路、AGE-RAGE信号通路、神经退行性病变途径、细胞活动等多个生物过程改善DLSS患者的主观症状。结论大承气汤不仅能够改善DLSS患者的便秘及便秘相关性症状加重,还可通过其相关化学成分、靶点及信号通路,对DLSS的炎症反应、氧化应激反应及神经细胞组织修复起到重要的调控作用。
Objective To explore the molecular mechanisms of Dachengqi decoction in the treatment of degenerative lumbar spinal stenosis(DLSS)using a network pharmacology approach.Methods The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was searched to retrieve information on the chemical components and genes related to Dachengqi decoction as of July 10,2024.For compounds not covered by TCMSP or without target gene information,the molecular formulas were obtained from the PubChem database,and SwissADME was used for screening.Target prediction for eligible compounds was performed using the SwissTargetPrediction database,and gene names were standardized using the UniProt database.On the same day,the GenCards,OMIM,and DrugBank databases were searched to collect information on DLSS-related disease genes,which was then mapped to the drug targets.Common genes were imported into the STRING(Search Tool for the Retrieval of Interacting Genes/Proteins)database to construct a protein-protein interaction(PPI)network,followed by pathway enrichment analysis using the Metascape database.Cytoscape 3.10.2 software was used to create a“drug-compound-target”network,and NetworkAnalyzer was applied for topological analysis of key compounds and targets.Results Ten key active compounds,including rutin,5,7,4’-trimethylapigenin,and eucalyptol,as well as ten key targets,including prostaglandin-endoperoxide synthase 2(PTGS2)and heat shock proteinβ(HSPCB),were identified.Pathway enrichment analysis suggested that Dachengqi decoction could improve the subjective symptoms of DLSS patients through the PI3K-Akt signaling pathway,AGE-RAGE signaling pathway,neurodegeneration pathway,and various cellular activities.Conclusion Dachengqi decoction can not only alleviate constipation and related symptom exacerbation in DLSS patients,but also modulate inflammation,oxidative stress,and nerve cell tissue repair through its active compounds,targets,and pathways.
作者
甘叶娜
韩晟
苑艺
薛丽娟
黄昊雯
李欢欣
张心慈
奎思怡
孟博斐
李奇霏
阿那古·吐地
刘志凤
秦灵灵
李多多
GAN Yena;HAN Sheng;YUAN Yi;XUE Lijuan;HUANG Haowen;LI Huanxin;ZHANG Xinci;KUI Siyi;MENG Bofei;LI Qifei;ANARGUL Tudi;LIU Zhifeng;QIN Lingling;LI Duoduo(School of Pharmaceutical Science,Peking University,Beijing 100191,China;International Research Center for Medicinal Administration,Peking University,Beijing 100191,China;Centre for Evidence-Based Medicine,Beijing University of Chinese Medicine,Beijing 100029,China;Department of Tuina and Pain,Dongzhimen Hospital,Beijing University of Chinese Medicine,Beijing 100700,China)
出处
《中国药物警戒》
2025年第2期162-168,I0004-I0007,共11页
Chinese Journal of Pharmacovigilance
基金
国家自然科学基金资助项目(82305427)
北京中医药薪火传承“3+3”工程刘寿山名家研究室(2022-SZ-A-50)。
