A network pharmacology-based study of the mechanism of Chuankezhi injection for the treatment of chronic obstructive pulmonary disease

Abstract

ObjectiveTo screen the active pharmaceutical ingredients (APIs) and primary targets of Chuankezhi for the treatment of chronic obstructive pulmonary disease (COPD) using a network pharmacology approach, and to investigate its potential mechanisms for the treatment of COPD. MethodsTo screen the APIs and primary targets of action of Morinda officinalis and epimedium from the TCMP (define the full name) and the Traditional Chinese Medicine Integrated Database (TCMID). The disease targets of COPD were obtained using the GeneCards and Online Mendelian Inheritance in Man (OMIM) databases. The intersections of disease targets and the acting targets of APIs were plotted into a Venn diagram. Protein-protein interaction (PPI) networks were constructed using the String database and analyzed with Cytoscape 3.7.1 to construct a “disease-active-ingredient-target” network. gene ontology (GO) enrichment analysis and KEGG pathway enrichment analysis were performed on the active small-molecule compounds using the DAVID6.8 database. The acting targets of Morinda officinalis and epimedium were analyzed to investigate the potential mechanisms of Chuankezhi in treatment on COPD. ResultsScreening produced 43 eligible active compounds, including 20 from Morinda officinalis and 23 from epimedium, with a total of 190 acting targets. The obtained APIs included quercetin, kaempferol, luteolin, icaritin, and β-sitosterol. There were 7 009 disease targets of COPD and 173 intersectional targets of the Chuankezhi treatment for COPD. The key acting targets, including AKT1, JUN, MAPK1, RELA, APP, and IL6, were obtained via screening the PPI network. GO enrichment analysis of biological processes mainly involved responses to drug treatments, positive regulation of transcription of the RNA polymerase II promoter, transcriptional regulation with DNA template, negative regulation of the apoptotic process, and responses to lipopolysaccharide. From the KEGG pathway enrichment analysis, the signaling pathways, including cancer pathways, the tumor necrosis factor (TNF) signaling pathway, the PI3K-Akt signaling pathway, and the hypoxia-inducible factor (HIF)-1 signaling pathway. ConclusionThe mechanism of the treatment of COPD with Chuankezhi mainly involves the PI3K-Akt signaling pathway to reduce the release of inflammatory factors.