基于网络药理学和分子对接技术的心可舒治疗冠心病的药效物质和作用机制研究  

Study on the effective substances and mechanism of Xinkeshu in treating coronary heart disease based on network pharmacology and molecular docking technology

作　　者：蔡晓凡 林明琴 CAI Xiao-fan;LIN Ming-qin(Hainan Medical University,Haikou 570100,Hainan,CHINA)

机构地区：[1]海南医科大学,海南海口570100

出　　处：《海南医学》2025年第8期1158-1167,共10页Hainan Medical Journal

基　　金：海南省自然科学基金高层次人才项目(编号:821RC573);大学生创新创业训练计划项目(编号:202311810004、X202211810111)。

摘　　要：目的探讨基于网络药理学和分子对接技术的心可舒治疗冠心病(CHD)的药效物质和作用机制。方法利用TCMSP数据库从建库至2024年8月31日筛选心可舒的化学成分,并借助PubChem、SwissTargetPrediction及SEA SearchServer数据库预测成分的靶点;通过GeneCards数据库获取CHD相关靶点;借助BioLadder平台筛选药物-疾病交集靶点;使用Cytoscape软件构建多元可视化网络,并进行拓扑分析;运用微生信平台对GO功能和KEGG通路进行富集分析;采用AutoDockVina软件进行分子对接验证。结果共筛选出心可舒化学成分84个,核心成分为2-(4-羟基-3-甲氧基苯基)-5-(3-羟丙基)-7-甲氧基-3-苯并呋喃甲醛、丹参醇B、丹参醛、隐丹参酮、丹参新酮Ⅱ、亚油酸乙酯、lappadilactone、紫丹参素C、表丹参螺缩酮内酯和香紫苏醇;获得CHD潜在治疗靶点506个,核心靶点为EGFR、MAPK14、CASP3、MAPK8、MAPK1、PRKCA、PTGS2、CHRM1、PIK3CA、MDM2、JAK2、STAT3、GSK3B和SRC;潜在靶点显著富集的通路达185条,核心通路为脂质和动脉粥样硬化通路、癌症中的蛋白聚糖通路、PI3K-Akt信号通路以及癌症中的MicroRNA通路;分子对接显示,MOL010839与PTGS2无法结合,MOL001494与CASP3、STAT3结合能较高,其余核心成分与靶点结合稳定(结合能≤-5kCal/mol)。结论心可舒通过“多成分-多靶点-多通路”协同调控炎症反应、脂质异常代谢、动脉粥样硬化斑块形成及细胞凋亡等病理过程,发挥治疗CHD的作用。Objective To investigate the pharmacodynamic substances and mechanism of Xinkeshu(XKS)in treat-ing coronary heart disease(CHD)based on network pharmacology and molecular docking technology.Methods Chemical components of XKS were screened from the TCMSP database(up to August 31,2024),and potential targets were predicted using PubChem,SwissTargetPrediction,and SEA Search Server databases.CHD-related targets were obtained from the GeneCards database.Drug-disease intersection targets were identified using the BioLadder platform.A multi-dimension-al visualization network was constructed using Cytoscape software,followed by topological analysis.GO functional and KEGG pathway enrichment analyses were performed using the Microbioinfo platform.Molecular docking validation was conducted using AutoDock Vina software.Results A total of 84 chemical components were identified in XKS,with core components including 2-(4-hydroxy-3-methoxyphenyl)-5-(3-hydroxypropyl)-7-methoxy-3-benzofurancar-boxaldehyde,tanshinol B,tanshinaldehyde,cryptotanshinone,neotanshinoneⅡ,ethyl linoleate,lappadilactone,przewal-skin C,epi-danshenspiroketallactone,and sclareol.There were 506 potential therapeutic targets for CHD,with core targets in-cluding EGFR,MAPK14,CASP3,MAPK8,MAPK1,PRKCA,PTGS2,CHRM1,PIK3CA,MDM2,JAK2,STAT3,GSK3B,and SRC.A total of 185 pathways were significantly enriched,with core pathways including lipid and atherosclerosis,proteo-glycans in cancer,PI3K-Akt signaling pathway,and microRNAs in cancer.Molecular docking revealed that MOL010839 could not bind to PTGS2,while MOL001494 exhibited high binding energy with CASP3 and STAT3.The remaining core components showed stable binding to their targets(binding energy≤-5 kCal/mol).Conclusion XKS exerts therapeutic ef-fects on CHD through a"multi-component,multi-target,multi-pathway"synergistic regulation of pathological processes such as inflammatory response,abnormal lipid metabolism,atherosclerotic plaque formation,and apoptosis.

关 键 词：冠心病 心可舒 网络药理学 分子对接 作用机制 

分 类 号：R541.4[医药卫生—心血管疾病]