Mechanism of Maimendong decoction in treating idiopathic pulmonary fibrosis based on network pharmacology and experimental validation
Objective:To investigate the therapeutic effect and mechanism of Maimendong decoction on idiopathic pulmonary fibrosis by utilizing network pharmacology methods and combining experimental research.Methods:TCMSP,ETCM and Swiss ADME were used to screen the active ingredients of Maimendong decoction.Through PubChem,SwissTargetPrediction and Uni-port databases,the action targets of various components of traditional Chinese medicine were screened.The GeneCards database and OMIN database were applied to obtain target genes of idiopathic pulmonary fibrosis.Venn diagrams drawing tool was used to screen the intersection targets of traditional Chinese medicine and diseases.The"traditional Chinese medicine active ingredient dis-ease target"network diagram was constructed by using the Cytoscape 3.9.1 software,and the protein interaction network(PPI)was constructed by using the CytoNCA plug-in to screen the core target proteins.DAVID was used for enrichment analysis of GO and KEGG pathways.Finally,we used bleomycin to establish a pulmonary fibrosis model in SD rats,observed the macroscopic specimens and pathological sections of rat lung tissue,and conducted real-time fluorescence quantitative PCR analysis to compare the mRNA expression levels of TGF-β1,α-SMA,IL-4,IFN-γ,LC3-Ⅱ,and beclin1 between the treatment group and the con-trol group.Results:A total of 402 therapeutic targets of Maimendong decoction for IPF were screened,including 50 core targets,corresponding to 159 active ingredients of 5 traditional Chinese medicines.GO enrichment analysis and KEGG enrichment analysis involved the PI3K-AKT signal pathway,MAPK signal pathway and other signal pathways to treat idiopathic pulmonary fibrosis.The animal experiment results showed that compared with the model group,the Maimendong decoction group could significantly reduce the relative expression level of TGF-β1,α-SMA and IL-4 mRNA(P<0.05),significantly upregulated the relative expres-sion level of mRNA LC3-Ⅱ,beclin1,IFN-γ(P<0.05).Conclusion:This study suggests that the key active components of Mai-mendong decoction may play a role in biological processes such as autophagy,inflammatory reaction,macrophage polarization,and improve pulmonary fibrosis.
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