基于网络药理学研究苇茎汤治疗急性肺损伤机制

Mechanism of Weijing Decoction(苇茎汤)in the Treatment of Acute Lung Injury Based on Network Pharmacology

目的运用网络药理学方法分析苇茎汤治疗急性肺损伤(ALI)的潜在靶点和作用机制。方法通过中药系统药理学数据库和分析平台(TCMSP),检索苇茎、桃仁、薏苡仁、冬瓜子的有效活性成分及潜在靶点。以"acute lung injury"为关键词,通过人类基因数据库(GeneCard)检索获得急性肺损伤的相关靶基因,并与药物有效成分的靶点相映射得到共同靶点。利用Cytoscape3.7.1构建活性成分-靶点网络图,借助STRING在线数据库构建蛋白互作(PPI)网络。通过生物学信息注释数据库(DAVID)对靶点进行生物过程(GO-BP)富集分析和KEGG通路富集分析。结果共筛选出苇茎汤25个有效化合物及51个作用靶点,其中药物与疾病的共同靶点有51个,根据度值的大小确定MAOA、MAOB、CASP3、JUN、GABA、HTR2A为关键靶点;GO富集分析发现苇茎汤治疗ALI的生物过程主要富集在神经递质受体活动、细胞凋亡、氧化应激、炎症反应等方面。KEGG分析显示苇茎汤可能作用于p53信号通路、Ca^(2+)信号通路、cAMP信号通路、cGMP-PKG信号通路、VEGF信号通路、IL-17信号通路、TNF信号通路等以治疗ALI。结论苇茎汤在治疗ALI过程中具有"多靶点、多通路"的特点,苇茎汤中豆甾醇、β-谷甾醇、常春藤皂苷元等有效成分通过调控p53信号通路、Ca^(2+)信号通路、cAMP信号通路、cGMP-PKG信号通路、VEGF信号通路、IL-17信号通路、TNF信号通路治疗ALI。

Objective To explore the potential targets and mechanism of Weijing Decoction(苇茎汤)in the treatment of acute lung injury(ALI)based on the network pharmacology.Methods The active ingredients and potential targets of Weijing Decoction were searched via TCMSP database.The relevant targets genes of acute lung injury were retrieved through the human gene database(Gene Card)with the key word"acute lung injury",and mapped with the targets of the active constituent to obtain the common targets.The drug-active components-targets network was built by utilizing Cytoscape 3.7.1.The proteinprotein interaction(PPI)was acquired from the online STRING database.GO enrichment analysis and KEGG signaling pathway enrichment analysis were carried out on the targets through the biological information annotation database(DAVID).Results The 51 target gene names of 25 components were screened for Weijing Decoction,and 51 common target genes were obtained after crossing the ALI-related genes,among which the hub genes were MAOA,MAOB,CASP3,JUN,GABA,HTR2A.GO enrichment analysis demonstrated vividly that the biological processes of Weijing Decoction for ALI mainly focus on neurotransmitter receptor activity,extrinsic apoptotic signaling pathway,cellular oxidation and inflammation response.KEGG analysis illustrated that Weijing Decoction might have an influence on p53 signaling pathway,Ca^(2+)signaling pathway,c AMP signaling pathway,c GMP-PKG signaling pathway,VEGF signaling pathway,IL-17 signaling pathway,TNF signaling pathway and so on.Conclusion ALI can be treated by Weijing Decoction through"multi-target and multi-pathway",the Stigmasterol,beta-sitosterol,hederagenin and other active ingredients in Weijing Decoction may treat ALI by regulating p53 signaling pathway,Ca^(2+)signaling pathway,c AMP signaling pathway,c GMP-PKG signaling pathway,VEGF signaling pathway,IL-17 signaling pathway,TNF signaling pathway in vivo.