Integrating network pharmacology and molecular docking to explore the pharmacological mechanism of tanshinone IIA in improving chronic obstructive pulmonary disease.

Abstract

This study explores the mechanism of action of tanshinone IIA in the treatment of chronic obstructive pulmonary disease (COPD) using network pharmacology and molecular docking. The targets of tanshinone IIA were searched by Swiss Target Prediction Database, PharmMapper Database, SuperPred Database, and TargetNet Database. The targets of COPD were obtained by Genecards Database, OMIM Database, and Therapeutic Target Database, then the intersection targets were selected as the targets of tanshinone IIA in the treatment of COPD. The intersecting targets were imported into the STRING database to obtain the PPI network and the top10 relevant targets, and GO enrichment and KEGG signaling pathway analysis were performed by R language. Core targets were obtained by taking the intersection of Top5 GO and KEGG corresponding targets with Top10 targets in PPI. Then tanshinone IIA was molecularly docked to the screened core target protein receptors by AutoDock Vina software. Tanshinone IIA included 442 potential targets and 979 COPD-associated targets, and 104 intersecting targets were obtained by taking the intersection of the two. The PPI network showed that ALB, EGFR, CASP3, MMP9, PTGS2, NFKB1, ESR1, SRC, PPARG, and HSP90AA1 were the top 10 relevant targets. GO enrichment analyses showed that the main components involved were the response to response to lipopolysaccharide, response to molecule of bacterial origin, positive regulation of cytokine production, positive regulation of MAPK cascade, and positive regulation of kinase activity. KEGG signaling pathway analysis revealed major involvement in prostate cancer, AGE-RAGE signaling pathway in diabetic complications, Hepatitis B, PI3K-Akt signaling pathway, relaxin signaling pathway. EGFR, CASP3, MMP9, NFKB1, SRC, and HSP90AA1 were the 6 core targets. Molecular docking showed that the binding energies of tanshinone IIA and the core target were all less than ≤-5.0 kcal/mol, demonstrating good affinity. The treatment of COPD with tanshinone IIA involves multiple signaling pathways and biological processes, and its binding to the key targets of EGFR, CASP3, MMP9, NFKB1, SRC, and HSP90AA1 may be one of the important mechanisms of its action, which provides new theoretical ideas for the subsequent treatment of COPD with tanshinone IIA.