Network pharmacology-based mechanistic investigation of Jinshui Huanxian formula acing on idiopathic pulmonary fibrosis

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a chronic respiratory disease with high incidence rate, morbidity and mortality. Jinshui Huanxian formula (JHF) is an empirical formula for the pathogenesis of lung-kidney qi deficiency and phlegm-blood stasis in pulmonary fibrosis. The purpose of this study is to explore the pharmacological mechanism of JHF action in IPF therapy by network interaction analysis. Methods The main active components and corresponding target genes of JHF were predicted using various databases. Two sets of IPF disease genes were obtained from the DisGeNET database and GEO database. Two sets of drug targets for IPF treatment were collected and the overlapping genes between disease genes and drug targets were analyzed. The target genes of JHF were intersected with the differentially expressed genes of IPF to obtain the predicted targets of JHF acting on IPF. The functions and pathways of predicted targets acting on IPF were analyzed by using DAVID and KEGG pathway database. Finally, the resulting drug target mechanisms were validated in a rat model of pulmonary fibrosis. Results 494 active compounds and 1304 corresponding targets were screened. Intersection analysis showed that 4 genes were common genes of JHF targets, IPF disease genes and anti-IPF drugs in KEGG database, and these genes were targeted by several compounds of JHF respectively. 72 JHF targets were closely related with IPF, and were thus considered therapeutically relevant. The targets were screened and participated in the regulation of IPF through 18 pathways. The molecular functions of targets included regulation of oxidoreductase activity, kinase regulator activity, phosphotransferase activity and transmembrane receptor protein kinase activity. In vivo experiments showed that JHF could alleviate the degree of pulmonary fibrosis, including the decrease of collagen deposition and epithelial-mesenchymal transition. Conclusions This study explored the mechanisms of JHF from a systematic point of view, trying to identify the specific target pathways acing on IPF. Pharmacological network with in vivo validation explained the potential roles and mechanisms of JHF in IPF therapy.