WITHDRAWN: Network Pharmacology and Molecular Docking Study of Jinwei Decoction for Enhancement of Glucocorticoid Anti-Inflammatory Effect in COPD through miR-21

Abstract

PurposeJinwei decoction can enhance the anti-inflammatory effect of glucocorticoid (GC) on chronic obstructive pulmonary disease (COPD) by restoring the activity of HDAC2. But the upstream mechanism of Jinwei decoction on HDAC2 expression is not clear. ObjectiveTo explore whether Jinwei decoction can enhance the anti-inflammatory effect of GC on COPD through microRNA21 (miR-21) by network pharmacology. MethodsThe TCMSP database was used to screen active ingredients and target genes of Jinwei decoction, and miRWalk2.0 was used to predict downstream target genes of miR-21. COPD-related genes were identified by searching GeneCards and OMIM databases; Venny 2.1 was used to screen intersection genes; Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways of intersection genes were analyzed by R software. Protein-protein interactions (PPIs) were analyzed by Cytoscape 3.7.2 software to identify core genes. Finally, interactions between main compounds and potential targets were verified by molecular docking. ResultsTwo hundred ninety-two active ingredients, 316 Jinwei drug targets, 10170 miR-21 target genes, 6617 COPD target genes, and 184 intersection gene were identified. Eleven core proteins of PPI networks may be involved. GO enrichment analysis showed that oxidative stress, regulation of inflammatory response, hormone transport, and histone modification were involved; KEGG pathway enrichment analysis concentrated in the PI3K-Akt, mitogen-activated protein kinase (MAPK), HIF-1, neutrophil extracellular bactericidal network, and other signaling pathways. ConclusionJinwei decoction can regulate histone deacetylase-2 activity and enhance the anti-inflammatory effect of GC on COPD by modulating miR-21. Its mechanism of action may be related to its effect on the PI3K Akt, MAPK, and TNF signaling pathways and neutrophil extracellular trap formation through miR-21.