Network Pharmacology and Experimental Verification Revealed the Mechanism of Yiqi Jianpi Recipe on Chronic Obstructive Pulmonary Disease

Abstract

Objective. The study aimed to explore the active ingredients, targets, and mechanism of action of Yiqi Jianpi recipe (YQJPR) in the treatment of COPD based on the network pharmacology and COPD rat models. Methods. The active ingredients and targets of YQJPR were collected by TCMSP. Disease-related protein targets were obtained from GeneCards. The Venn diagram was used to show the key therapeutic targets of COPD in YQJPR. The PPI network was established by STRING, and cytoHubba plug-in was used to screen the core targets within the network. GO functional enrichment and KEGG pathway enrichment analysis were performed to describe the functions and pathways of the core targets. Cytoscape software was used to construct the ingredient-target network and the core target-enrichment pathway network. The chemical constituents of YQJPR were analyzed by HPLC-MS/MS. Results. The network pharmacology showed 152 active ingredients and 225 targets in YQJPR for the treatment of COPD. The key active ingredients were quercetin, luteolin, kaempferol, tanshinone IIA, and baicalein. The contents of quercetin and luteolin in YQJPR were quantitatively measured by HPLC-MS/MS. 22 core genes were screened, including AKT1, IL-6, JUN, VEGFA, and CASP3, which were mainly involved in BPs such as cell proliferation and differentiation, oxidative/chemical stress, and regulation of DNA-binding transcription factor activity and regulated viral infection, tumor, HIF-1, MAPK, TNF, and IL-17 pathways. Animal experiments showed that YQJPR could significantly reduce the expression of p-ERK1/2, p-Akt, c-Myc, cleaved caspase-3, and p-Stat3 in lung tissue ( $p<0.05$ ). HE staining showed that, compared with the model group, YQJPR significantly improved lung tissue morphology and reduced lung inflammation in rats. Conclusion. The effects of YQJPR on COPD may involve multiple components, pathways, and targets. This study provides new ideas for further and more comprehensive exploration of the therapeutic effect of YQJPR on COPD in the future.