基于网络药理学探讨苓甘五味姜辛汤治疗慢性阻塞性肺疾病有效成分及分子机制

Discussion on Effective Components and Molecular Mechanism of LingganWuweiJiangxin Decoction in Treating Chronic Obstructive Pulmonary Disease Based on Network Pharmacology

摘要: 目的：运用网络药理学方法探讨苓甘五味姜辛汤治疗慢性阻塞性肺疾病的有效成分及潜在分子机制。方法：通过TCMSP检索苓甘五味姜辛汤的活性成分得到各成分的作用靶点；通过OMIM和GeneCards疾病数据库检索慢性阻塞性肺疾病的相关靶点；将上述得到的药物和疾病靶点导入UNIPROT数据库进行基因的标准化处理，以Venn图展示药物与疾病的交集靶点。运用Cytoscape3.7.2软件构建“药物–成分–靶点–疾病”网络图；利用STRING在线平台构建PPI网络图，根据Degree值筛选核心靶点。利用DAVID在线数据库平台进行GO生物过程和KEGG通路富集分析。筛选得到苓甘五味姜辛汤活性成分130个，预测得到靶点143个，慢性阻塞性肺疾病相关靶点4717个，药物与疾病交集靶点122个。其中核心靶点包括VEGFA、CCL2、TP53、MAPK8、PTGS2、IL1B、IL6等。利用DAVID富集分析得到GO生物条目68条，KEGG通路15条(P < 0.05, FDR < 0.05)，其中生物过程(biological process, BP) 47条，分子功能(molecular function, MF) 13条，细胞组分(cell composition, CC) 8条，主要涉及对药物的反应、酶结合和药物结合过程等；主要涉及癌症通路、钙离子信号通路、肿瘤坏死因子信号通路、非小细胞肺癌等信号通路。结论：苓甘五味姜辛汤中的活性成分可以作用于VEGFA、CCL2、TP53、MAPK8、PTGS2、IL1B、IL6等关键靶点，通过调控钙离子信号通路、肿瘤坏死因子信号通路等参与治疗慢性阻塞性肺疾病。

Abstract: Objective: To explore the effective components and potential molecular mechanism of LingganWuweiJiangxin Decoction in treating chronic obstructive pulmonary disease by network pharmacology. Methods: The active components of LingganWuweiJiangxin Decoction were searched by TCMSP and the action targets of each component were searched by this database. Search the related targets of chronic obstructive pulmonary disease through OMIM and GeneCards disease database; Import the drug and disease targets obtained above into UNIPROT database for gene standardization, and show the intersection target of drug and disease by Venn diagram. The network diagram of “drug-component-target-disease” was constructed by using Cytoscape3.7.2 software. PPI network diagram is constructed by using STRING online platform, and core targets are screened according to Degree value. Enrichment analysis of GO biological process and KEGG pathway using DAVID online database platform. Results: Through TCMSP screening, 130 active ingredients of LingganWuwei-Jiangxin Decoction and 143 predicted targets, 4717 targets related to chronic obstructive pulmonary disease and 122 targets mapped by drugs and diseases were obtained. Among them, vascular endothelial growth factor A (VEGFA), C-C motif chemokine ligand 2 (CCL2), tumor protein P53 (TP53), mitogen-activated protein kinase 8 (MAPK8), prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin 1 beta (IL1B), interleukin 6 (IL6), tumor necrosis factoe (TNF), mitogen-activated protein kinase 1 (MAPK1) and other nodes have higher degree values, which may be the core targets of drug treatment. According to DAVID enrichment analysis, there are 68 GO biological items (P < 0.05, FDR < 0.05), including 47 biological processes (BP), 13 molecular functions (MF), and 8 cell compositions (CC), which mainly involve the reaction to drugs, positive regulation of cell proliferation, extracellular space, etc. Fifteen KEGG pathways (P < 0.05, FDR < 0.05) were obtained by the same method, mainly involving cancer pathway, calcium signaling pathway, neuroactive ligand-receptor interaction, tumor necrosis factor signaling pathway, hypoxia necrosis factor signaling pathway, non-small cell lung cancer and other signaling pathways. The active components in LingganWuweiJiangxin decoction can act on key targets such as VEGFA, CCL2, TP53, MAPK8, PTGS2, IL1B, IL6, etc., and participate in the treatment of chronic obstructive pulmonary disease by regulating calcium signal pathway, tumor necrosis factor signal pathway and hypoxia necrosis factor signal pathway.