降脂通络软胶囊治疗高脂血症作用机制的网络药理学分析

Study on the Mechanism of Jiangzhi Tongluo Soft Capsules in the Treatment of Hyperlipidemia Based on Network Pharmacology

目的基于网络药理学和分子对接技术探讨降脂通络软胶囊治疗高脂血症的潜在作用机制。方法利用TCMSP及SwissADME数据库检索、筛选并结合相关文献查找降脂通络软胶囊的活性成分;通过SwissTargetPrediction数据库预测活性成分的作用靶点,构建“药物-活性成分-预测靶点”网络。利用Genecards、DisGeNET和OMIM数据库检索、筛选高脂血症的疾病相关靶点;将高脂血症的疾病相关靶点和降脂通络软胶囊活性成分预测靶点进行对比,取二者的交集,作为降脂通络软胶囊治疗高脂血症的潜在作用靶点;构建“活性成分-潜在作用靶点-疾病”网络。通过STRING数据库构建潜在作用靶点的蛋白相互作用(PPI)网络,筛选出降脂通络软胶囊治疗高脂血症的关键靶点,并对关键靶点进行GO功能及KEGG通路富集分析,筛选出核心通路。构建降脂通络软胶囊治疗高脂血症的“活性成分-关键靶点-核心通路-疾病”网络,筛选出核心活性成分及核心靶点。采用Autodock Tools 1.5.7软件对核心活性成分及核心靶点进行分子对接验证。结果检索、筛选到降脂通络软胶囊中姜黄素类活性成分共20个,预测得到412个作用靶点;共筛选出1734个高脂血症疾病相关靶点;得到139个降脂通络软胶囊治疗高脂血症的潜在作用靶点(共有靶点);通过潜在作用靶点PPI网络筛选得51个关键靶点。GO功能富集到2232个条目,其中涉及2013个生物过程、143个分子功能、76个细胞组成相关条目;KEGG通路富集分析共得到155条通路。3个核心靶点EGFR、RAF1、PIK3CA与8个核心活性成分姜黄素、去甲氧基姜黄素、双去甲氧基姜黄素等具有良好的结合活性。结论降脂通络软胶囊可能通过姜黄素、去甲氧基姜黄素等核心活性成分,作用于EGFR、RAF1、PIK3CA等核心靶点,通过PI3K-Akt通路、脂质和动脉粥样硬化通路等多条信号通路发挥对高脂血症的治疗作用。

Objective To investigate the potential mechanism of Jiangzhi Tongluo Soft Capsules in the treatment of hyperlipidaemia based on network pharmacology and molecular docking technology.Methods The TCMSP database was used to search,screen and combine with related literature to find out the active components of Jiangzhi Tongluo Soft Capsules;the SwissTargetPrediction database was used to predict the targets of the active components,and the network of drugs-active components-predicted targets was constructed.Genecards,DisGeNET and OMIM databases were used to search and screen the disease-related targets of hyperlipidaemia;the disease-related targets of hyperlipidemia and the prediction targets of Jiangzhi Tongluo Soft Capsules active components were compared,and the intersection was taken as the potential target of Jiangzhi Tongluo Soft Capsules in the treatment of hyperlipidemia.The network of"active components-potential targets-diseases"was constructed.The protein-protein interaction(PPI)network of potential targets was constructed by STRING database,and the key targets of Jiangzhi Tongluo Soft Capsules in the treatment of hyperlipidemia were screened,and the GO function and KEGG pathway enrichment analysis of the key targets were carried out to screen out the core pathway.The network of"active components-key targets-core pathways-diseases"for the treatment of hyperlipidaemia by Jiangzhi Tongluo Soft Capsules was constructed,and the core active components and core targets were screened out.Autodock Tools 1.5.7 software was used to verify the molecular docking of the core active components and core targets.Results A total of 20 active components of curcumin in Jiangzhi Tongluo Soft Capsules were retrieved and screened,and 412 targets were predicted;1734 hyperlipidaemia-related targets were screened;139 potential targets(common targets)for the treatment of hyperlipidaemia in Jiangzhi Tongluo Soft Capsules were obtained;51 key targets were screened by the PPI network of the potential targets.The GO function was enriched in 2232 entries,which involved 2013 biological processes,143 molecular functions,and 76 cellular components;the KEGG pathway enrichment analysis yielded a total of 155 pathways;the 3 core targets,EGFR,RAF1,and PIK3CA,had good binding activities with the 8 core active components,curcumin,desmethoxy curcumin,and bisdesmethoxy curcumin,and so on.Conclusion Jiangzhi Tongluo Soft Capsules may exert therapeutic effects on hyperlipidaemia through multiple signaling pathways such as PI3K-Akt pathway,lipid and atherosclerosis pathway by acting on the core targets of EGFR,RAF1 and PIK3CA through the core active components such as curcumin,demethoxy curcumin,and so on.