基于网络药理学、SMR及分子对接探讨昆仙胶囊治疗强直性脊柱炎的作用机制  

Mechanism of Kunxian Capsules in the Treatment of Ankylosing Spondylitis Based on Network Pharmacology,SMR and Molecular Docking

作　　者：廖威权 李禹莹 李志岭 郭盈澳 谢静静[2] 张剑勇[2] LIAO Weiquan;LI Yuying;LI Zhiling;GUO Ying’ao;XIE Jingjing;ZHANG Jianyong(The Fourth Clinical Medical School of Guangzhou University of Chinese Medicine,Shenzhen 518033 Guangdong,China;Shenzhen Traditional Chinese Medicine Hospital,Shenzhen 518033 Guangdong,China)

机构地区：[1]广州中医药大学第四临床医学院,广东深圳518033 [2]深圳市中医院,广东深圳518033

出　　处：《中药新药与临床药理》2025年第3期405-415,共11页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金资助项目(82174290);深圳市医疗三名工程项目(SZZYSM202311003)。

摘　　要：目的基于网络药理学、SMR及分子对接分析昆仙胶囊治疗强直性脊柱炎的作用机制。方法通过TCMSP、BATMAN-TCM、SwissTargetPrediction数据库收集昆仙胶囊的活性成分及作用靶点;检索GeneCards、OMIM、DrugBank、DisGeNet及TTD数据库获得强直性脊柱炎的相关靶点,使用Venny 2.1.0绘制韦恩图,得到昆仙胶囊治疗强直性脊柱炎的潜在作用靶点;利用Cytoscape 3.7.1构建“昆仙胶囊-活性成分-作用靶点-强直性脊柱炎”网络,根据拓扑参数筛选关键活性成分;将昆仙胶囊治疗强直性脊柱炎的潜在作用靶点上传至STRING平台构建蛋白互作网络,并导入Cytoscape 3.7.1筛选核心靶点;以核心靶点的表达数量性状位点(eQTL)作为工具变量、强直性脊柱炎为结局,使用基于汇总数据的孟德尔随机化分析(SMR)评估核心靶点表达水平与强直性脊柱炎发病风险的因果关系,探索强直性脊柱炎治疗的新靶点;使用Metascape进行GO及KEGG通路富集分析;使用AutoDockTools 1.5.7及QuickVina-W软件进行分子对接,并使用PyMOL 2.6.0软件进行可视化。结果昆仙胶囊治疗强直性脊柱炎的活性成分共179种,关键活性成分包括槲皮素(quercetin)、山柰酚(kaempferol)、胆固醇(CLR)、β-谷甾醇(beta-sitosterol)、甘草素(DFV)等;核心靶点包括TNF、IL1B、GAPDH、STAT3、EGFR等;SMR分析提示TNF、JAK2、ABHD16A与强直性脊柱炎显著关联,但TNF存在连锁效应;GO富集结果涉及炎症反应、细胞对氮化合物的反应、外源性刺激反应等,KEGG富集分析主要涉及Th17细胞分化、趋化因子信号通路、PI3K/Akt等信号通路;分子对接显示,核心靶点与关键活性成分对接活性良好。结论昆仙胶囊可能通过其所含的槲皮素、山柰酚、胆固醇、β-谷甾醇、甘草素等关键活性成分,作用于TNF、IL1B、GAPDH、STAT3、EGFR等核心靶点,调控Th17细胞分化、趋化因子、PI3K/Akt等信号通路治疗强直性脊柱炎,JAK2、ABHD16A基因表Objective To analyze the mechanism of Kunxian Capsules in the treatment of ankylosing spondylitis(AS)based on network pharmacology,SMR and molecular docking.Methods The active components and targets of Kunxian Capsules were collected by TCMSP,BATMAN and SwissTargetPrediction databases.GeneCards,OMIM,DrugBank,DisGeNet and TTD databases were screened to obtain the relevant targets of AS,and Venny 2.1.0 was used to draw the Venn diagram to obtain the potential targets of Kunxian Capsules in the treatment of AS.Cytoscape 3.7.1 was used to construct the‘Kunxian Capsules-active ingredients-targets of action-AS’network,and screening key active ingredients according to topological parameters.The potential targets of Kunxian Capsules for the treatment of AS were uploaded to the STRING platform to construct the protein-protein interaction(PPI)network,and imported into Cytoscape 3.7.1 to screen the core targets.The expression quantitative trait locus(eQTL)of core targets was used as an instrumental variable and AS as the outcome,the potential causal relationship between the expression levels of core targets and the risk of AS was assessed using Summary-data-based Mendelian Randomization(SMR)analysis to explore new targets for AS treatment.Metascape was used for GO and KEGG pathway enrichment analysis.Molecular docking was performed using AutoDockTools 1.5.7 and QuickVina-W software,and visualization was performed using PyMOL 2.6.0 software.Results A total of 179 active ingredients were identified in Kunxian Capsules for the treatment of AS.The key active ingredients included quercetin,kaempferol,cholesterol,β-sitosterol,liquiritigenin,magnoflorine,etc.The core targets include TNF,IL1B,GAPDH,STAT3,EGFR,etc.SMR analysis showed that TNF,JAK2 and ABHD16A were significantly associated with AS,but TNF had a linkage effect.GO enrichment results involved inflammatory response,cell response to nitrogen compounds,exogenous stimulation response,etc.KEGG enrichment analysis mainly involved Th17 cell differentiation,chemokine signa

关 键 词：昆仙胶囊 强直性脊柱炎 网络药理学 孟德尔随机化分析 分子对接 

分 类 号：R285.5[医药卫生—中药学]