Mechanistic Study On The Treatment Of COPD With Tongfei Huatan Decoction Based On Network Pharmacology And Molecular Docking

Objective: Predicting the molecular basis and mechanism of action of Tongfei Huatan Decoction in the treatment of COPD based on network pharmacology and molecular docking.Methods: The TCMSP database was used to obtain the effective chemical components and their corresponding targets in Tongfei Huatan Decoction,and then the Uni Prot database was used for gene annotation of the targets to obtain names of the genes encoding the targets.Gene Cards database and GEO gene microarray were used to obtain COPD disease-related genes.The corresponding targets of Tongfei Huatan Decoction were intersected with the COPD-related genes obtained by Gene Cards and GEO to obtain the targets of Tongfei Huatan Decoction for COPD.The PPI network was constructed by importing the targets of Tongfei Huatan Decoction for COPD into STRING database,and then the topological parameters of the PPI network were calculated by using Cytohubba plugin in Cytoscape software.Based on the topological parameters,the core targets in the PPI network were screened.Based on R software,KEGG and GO enrichment analyses were performed on the targets of Tongfei Huatan Decoction for COPD,and some of the enrichment results obtained were visualized in the form of bar plots and bubble plots.Cytoscape was used to construct the herbalcomponent-target-network diagram,based on which the core components of Tongfei Huatan Decoction were analyzed.Auto Dock Vina was used to dock the core components with proteins in the key pathways to predict their affinity.Results:(1)Based on the TCMSP,233 active chemical components and 257 target proteins corresponding to the active chemical components were obtained for Tongfei Huatan Decoction.(2)Based on the Gene Cards database,3672 COPD-related genes were obtained.Based on the GSE5058 microarray,we analyzed the gene expression in bronchial epithelial cells of 12 COPD patients and 6 non-smoking healthy volunteers,and obtained 15,800 differentially expressed genes.(3)The 257 target proteins corresponding to the active chemical components of Tongfei Huatan Decoction were intersected with3672 COPD-related genes obtained from Gene Cards and 15800 differentially expressed genes obtained from GSE5058,and 130 intersected targets were obtained,which were the targets of Tongfei Huatan Decoction for COPD treatment.In the GSE5058 microarray,all 130 intersecting targets were up-regulated in the airway epithelial cells of 12 COPD patients.(4)The PPI network is obtained by importing 130 intersection targets into the STRING database.130 nodes and 443 edges are included in the PPI network,and the average node degree value is6.82.In Cytoscape,the MCC,Degree,Closeness,Betweenness of the whole PPI network are calculated by using the plug-in Cytohubba.The mean values were 402.47,15.28,46.72,and 219.38,respectively.based on these 4 mean values,10 core targets were obtained,which were JUN,HIF1 A,RELA,ESR1,TP53,STAT3,MAPK1,AKT1,CTNNB1,and CREB1.(5)In R language,KEGG and GO enrichment analysis was performed on 130 intersection targets,and 142 KEGG enrichment entries were obtained,including key pathways closely related to COPD disease development,such as PI3K-Akt signaling pathway,IL-17 signaling pathway,HIF-1 signaling pathway,TNF signaling pathway,p53 signaling pathway,etc.GO enrichment analysis yielded a total of 1559 results were obtained,including 1428 results for biological processes,31 results for cellular components and 100 results for molecular functions.The first 30 BP enrichment results include entries on response to oxidative stress,epithelial cell proliferation,response to hypoxia,regulation of smooth muscle cell proliferation,senescence,fibroblast proliferation,regulation of apoptotic signaling pathways,and regulation of epithelial cell proliferation,which are inextricably linked to COPD pathophysiology.The first 30 CC enrichment results include entries for RNA polymerase II transcriptional regulatory complex,serine/threonine protein kinase complex,etc.The first 30 MF enrichment results nuclear include entries for nuclear receptor activity,cytokine activity,etc.(6)Based on Cytoscape,eight core components of Tongfei Huatan Decoction were analyzed,including quercetin,kaempferol,luteolin,wogonin,tanshinone IIA,naringenin,baicalein,and nobiletin.There are more than 20 targets of these 8 core components.(7)Molecular docking results showed that the eight core components docked well with PI3 K,IL-17 A,IL17-RA,TNF-α and p53.the binding energy of PI3 K docked with the eight core active ingredients was lower,indicating a stronger affinity with the core active ingredients.Conclusion:(1)In Tongfei Huatan Decoction,the core components Quercetin,kaempferol,luteolin,wogonin,tanshinone IIA,naringenin,baicalein,and nobiletin have the most targets of action and dock well with PI3 K,IL-17 A,IL-17 AR,TNF-α and p53 in the key pathways,suggesting that these core components may be the molecular basis of Tongfei Huatan Decoction in the treatment of COPD.(2)The treatment of COPD with Tongfei Huatan Decoction may be related to its ingredients of Quercetin,kaempferol,luteolin,wogonin,tanshinone IIA,naringenin,baicalein,and nobiletin.These core components may play a therapeutic role in antiinflammatory,anti-oxidative stress and inhibition of mucus hypersecretion.The specific mechanism may be related to the regulation of PI3K-Akt signalling pathway,IL-17 signalling pathway,HIF-1 signalling pathway,TNF signalling pathway and p53 signalling pathway.