基于网络药理学探讨柴胡-黄芩药对治疗病毒性肺炎的作用机制

Exploring the mechanism of Radix Bupleuri-Scutellariae Radix in the treatment of viral pneumonia based on network pharmacology

目的 通过数据库挖掘柴胡-黄芩有效成分及作用靶点,构建药对化学成分-作用靶点与病毒性肺炎靶点网络,探讨其治疗病毒性肺炎的机制。方法 从基因数据库GeneCards、OMIM、PharmGkb、TTD、DrugBank获取病毒性肺炎疾病靶点,通过中药系统药理学数据库(TCMSP)设置查询条件:口服生物利用度(OB)≥30%、类药性(DL)≥0.18查找柴胡-黄芩药对活性成分及靶点,通过Cytoscape3.8.0软件构建药物主要化学成分-作用靶点和疾病靶点网络,并利用PPI网络构建核心进行分析,同时利用基因功能(GO)和信号通路(KEGG)分析共同作用靶点及相关信号通路。结果 从TCMSP中筛选出柴胡(17个)-黄芩(36个)药对共有53种有效活性成分,从疾病基因数据库筛选出与病毒性肺炎密切相关的靶点共计4238个,通过比对分析药对-疾病作用靶点得出柴胡-黄芩药对与病毒性肺炎存在143个相同靶点。PPI、GO、KEGG分析显示柴胡-黄芩药对通过调控PI3K-Akt信号通路、MAPK信号通路、AGE-RAGE信号通路、TNF信号通路及IL-17等信号通路作用于FOS、TP53、TNF、JUN、IL6、MYC、RELA、HIF1A、CCND1、MAPK14、AKT1等关键靶点,通过抑制细胞增殖、应激、炎症、功能同步化、凋亡等途径从而发挥病毒性肺炎的作用。结论 本研究从网络药理学的角度揭示柴胡-黄芩药对治疗病毒性肺炎多靶点的机制,对于其临床应用具有翰要的理论意义。

Objective To constructed the network of drug-pair chemical components-targets and viral pneumonia targets and discuss the mechanism of its treatment of viral pneumonia,through the database mining of Radix Bupleuri-Scutellariae Radix effective components and targets.Methods Obtained viral pneumonia disease targets from gene databases Gene Cards,OMIM,PharmGkb,TTD,and DrugBank,and set query conditions through Traditional Chinese Medicine System Pharmacology Database(TCMSP) that oral bioavailability(OB)≥30%,drug-like properties(DL)≥ 0.18 Find the active ingredients and targets of Radix Bupleuri-Scutellariae Radix,Cytoscape 3.8.0 software was used to construct the main chemical components of drugs-targets and disease target networks,and the PPI network was used to construct the core for analysis.At the same time,gene function(GO) and signaling pathway(KEGG) were used to analyze common targets and related signaling pathway.Results A total of 53 active ingredients of Radix Bupleuri(17)-Scutellariae Radix(36) drug pairs were screened from TCMSP,and a total of 4238 targets closely related to viral pneumonia were screened from the disease gene database.Pair-disease action targets showed that there were 143 identical targets for the Bupleurum-Scutellaria baicalensis drug pair and viral pneumonia.PPI,GO,and KEGG analysis showed that Radix Bupleuri-Scutellariae Radix could act on FOS,TP53,TNF,JUN by regulating PI3K-Akt signaling pathway,MAPK signaling pathway,AGE-RAGE signaling pathway,TNF signaling pathway and IL-17 signaling pathway.IL6,MYC,RELA,HIF1A,CCND1,MAPK14,AKT1 and other key targets play the role of viral pneumonia by inhibiting cell proliferation,stress,inflammation,functional synchronization,apoptosis and other pathways.Conclusion This study reveals the multi-target mechanism of Radix Bupleuri-Scutellariae Radix in the treatment of viral pneumonia from the perspective of network pharmacology,which has important theoretical significance for its clinical application.