Study On The Mechanism Of Xuefu Zhuyu Decoction In Treating Parkinson Disease Based On Network Pharmacology

ObjectiveThrough the information mining and analysis of various databases,the main active ingredients of Xuefu Zhuyu Decoction in the treatment of Parkinson disease are obtained,and the potential targets of Xuefu Zhuyu Decoction in the treatment of Parkinson disease are predicted,and a “drug-ingredient-target-pathway” is constructed.At the same time,the biological function enrichment analysis of the target is carried out to explore the mechanism of Xuefu Zhuyu Decoction in the treatment of Parkinson disease.MethodsThe TCMSP database was used to screen the active ingredients of Xuefu Zhuyu Decoction and the corresponding drug targets,and the Uniprot database was used to standardize the gene names of the corresponding targets.The target genes related to Parkinson disease were obtained by searching the Gene Cards database.After mapping the two genes,the intersection target was obtained as a potential target for the treatment of Parkinson disease by Xuefu Zhuyu Decoction.Use String database and Cytoscape software to construct the protein interaction network of potential targets and perform topological analysis to screen the core targets of Xuefu Zhuyu Decoction in the treatment of Parkinson disease.Using RStudio software,using R language and David v6.8 database to carry out biological function enrichment analysis of potential targets,and using Cytoscape software to construct a “drug-component-target-pathway” network.Results1.The active ingredients and drug targets of Xuefu Zhuyu Decoction: Through TCMSP platform,the screening conditions were set as Oral Bioavailability(OB)> 30%and Drug Likeness(DL)> 0.18.A total of 195 potential drug active ingredients of Xuefu Zhuyu Decoction were screened out.Through reverse matching,the drug targets of Xuefu Zhuyu Decoction were predicted,and all the predicted action targets of traditional Chinese medicine ingredients were input into Uniprot database for standardized annotation of gene names.A total of 245 drug action targets of Xuefu Zhuyu Decoction were obtained after annotation.2.Disease-related targets and intersection targets of Parkinson disease: A total of6854 disease-related target genes related to Parkinson disease were obtained through Genecards database retrieval with “Parkinson Disease” and “Paralysis Agitans” as key words.Then RStudio software mapped the drug targets of Xuefu Zhuyu Decoction to obtain the intersection targets as the potential targets of Xuefu Zhuyu Decoction in the treatment of Parkinson’s disease,with a total of 187.3.Protein interaction network and core targets: Use String database to construct and analyze the potential targets of Xuefu Zhuyu Decoction in the treatment of Parkinson disease,obtain the interaction network data between potential target proteins,and file the data After entering Cytoscape,use the Cyto NCA plug-in to analyze the network topology,and construct the protein interaction(PPI)network of the potential targets of Xuefu Zhuyu Decoction for the treatment of Parkinson disease,and visualize it and output it.The topological parameters of the root node set the screening conditions,and a total of 31 target gene nodes were screened as potential core targets for the treatment of Parkinson disease by Xuefu Zhuyu Decoction.The 31 targets are: STAT3,TP53,JUN,AKT1,MAPK1,MAPK3,MAPK14,RELA,IL6,MAPK8,FOS,EGFR,CCND1,CTNNB1,VEGFA,CXCL8,MYC,ESR1,RB1,CDKN1 A,CASP3,PRKCD,EGF,PRKCB,PRKCA,CASP8,IL1 B,BCL2L1,CREB1,CDK2.4.Biofunctional enrichment analysis of potential targets: Use RStudio software to perform GO functions on potential targets through the David v6.8 database,including Biological process,BP,Cellular component,CC,Molecular function,MF,enrichment Analysis and enrichment analysis of the KEGG pathway at the same time,a total of 1910 GO entries were obtained,including 1743 biological processes,49 cell components,and118 molecular functions,involving phosphatase binding、 RNA polymerase II-specific DNA-binding transcription factor binding 、 cytokine activity 、 protein phosphatase binding、DNA-binding transcription factor binding、amide binding、nuclear receptor activity,etc.A total of 163 KEGG pathways were enriched,including IL-17 signaling pathway、TNF signaling pathway、Apoptosis、PI3K-Akt signaling pathway、MAPK signaling pathway,etc.5.“Drug-component-target-pathway” network: Use Cytoscape software to draw the“drug-component-target-pathway” network relationship diagram of Xuefu Zhuyu Decoction for the treatment of Parkinson disease.There are 364 nodes and 2376 edges in the graph.It contains 11 traditional Chinese medicines,136 active ingredients,187 gene targets,and 30 KEGG pathways,reflecting that Xue Fu Zhuyu Decoction has an intervening effect on Parkinson disease through the combined action of multiple components,multiple targets,and multiple pathways.Conclusion1.Based on the theory that “blood stasis” is the pathological basis throughout Parkinson disease,this study explored the mechanism of action of Xuefu Zhuyu Decoction in treating Parkinson disease through the network pharmacological research method.The results showed that xuefu zhuyu decoction contains a variety of sterols and natural flavonoids,which have anti-inflammatory,anti-oxidative and anti-apoptotic effects,and some of them also have neuroprotective effects.At the same time,the study also found that Xuefu Zhuyu Decoction can be used to treat Parkinson’s disease through acting on multiple targets,such as STAT3,Akt1,MAPK1,MAPK3,MAPK14,IL6 and MAPK8,and participate in the regulation of cell proliferation,differentiation,apoptosis and inflammatory response during the occurrence and development of Parkinson’s disease.2.Through the enrichment analysis of biological function,it was found that the potential target of Xuefu Zhuyu Decoction for the treatment of Parkinson’s disease was related to a variety of biological functions,and involved in a variety of signaling pathways related to tumor,inflammation and apoptosis.Such as IL-17 signaling pathway,tumor necrosis factor signaling pathway,apoptosis,PI3K-Akt signaling pathway,MAPK signaling pathway,NF-κB signaling pathway,etc.Among them,PI3K-Akt signaling pathway and NF-κB signaling pathway are closely related to the mechanism of neuronal inflammation and apoptosis in Parkinson’s disease.It shows that Xuefu Zhuyu Decoction in treating Parkinson’s disease is the result of multi-component,multi-target and multi-channel synergistic effect.