Mechanism Of Pinellia Ternata-Chuanxiong In The Treatment Of Coronary Heart Disease Based On Network Pharmacology

Objective:To screen the effective components of Pinellia-Chuanxiong medicine for the treatment of coronary heart disease and the targets of its components,establish a drug-component-target-disease network,and explore the mechanism of Pinellia-Chuanxiong medicine for the treatment of coronary heart disease.Methods:The active ingredients and ingredient action targets of the drug were screened out in the TCMSP database.Non-human targets of drugs were screened and corrected to official names using the Uniprot database.Through the OMIM database,Gene Cards database,Dis Ge NET database and Drug Bank database,the related targets of Pinellia chuanxiong for the treatment of coronary heart disease were obtained.Cytoscape was used to construct the network diagram of "Chinese medicine-active ingredients-targets" and the network diagram of "Panxia,Chuanxiong herbal pair-coronary heart disease" for the treatment of coronary heart disease.Use the Network Analyzer tool to calculate the network graph,and filter out the core components according to the degree value.The high-confidence interaction relationship of the intersecting target proteins was obtained from the String database,the interaction network of the intersecting target proteins was constructed in Cytoscape software,and the core proteins were screened.The Metascape platform was used to analyze the GO function and KEGG pathway enrichment of potential targets,and the network map of "Panxia,Chuanxiong medicine pair-coronary heart disease-mechanism" was constructed in Cytoscape software.The core components and core proteins were selected for molecular docking,the core component structures were downloaded from the Pub Chem database,and the core protein structures were obtained from the PDB database,and Autodock software was used for molecular docking simulation verification,and the results were visualized.Results:1.Active ingredients and ingredient action targets of Pinellia and Chuanxiong medicine pairs: Using the TCMSP platform,a total of 20 active ingredients satisfying OB>30% and DL>0.18 were screened,and a total of 214 active ingredients were collected.indivual.Among them,2 components have no target,and the target of 1 component could not obtain a matching official name in the Uniprot database,so it was discarded.Finally,17 kinds of active ingredients of Pinellia-Chuanxiong medicine pair were obtained,11 kinds of active ingredients in Pinellia sinensis,and 6 kinds of active ingredients in Chuanxiong.The 214 components acted on the targets and the duplicates were deleted to obtain 101 components acting on the targets.2.Coronary heart disease-related targets and intersection targets: Based on the OMIM database,Gene Cards database,Dis Ge NET database and Drug Bank database to screen coronary heart disease-related targets,after sorting out the targets of these four databases and removing duplicates,coronary heart disease was finally obtained.There are a total of 3024 related targets.There are 48 intersection targets of drugs and diseases.3."Traditional Chinese medicine-active ingredients-targets" network diagram of Pinellia-Chuanxiong herbal pair in the treatment of coronary heart disease and "Panxia,Chuanxiong herbal pair-coronary heart disease" network diagram:Based on Cytoscape software to construct the treatment of Pinellia-Chuanxiong herbal pair Coronary heart disease "traditional Chinese medicine-active ingredients-target" network diagram,the network has 120 nodes and 214 edges.Based on Cytoscape software,the network diagram of "Panxia,Chuanxiong medicine pair-coronary heart disease" for the treatment of coronary heart disease was constructed.The network has a total of 121 nodes and 262 edges,including 1 disease node and 2 drug nodes.17 active ingredient nodes,101 target nodes.Using the Cyto NCA plug-in for topology analysis,the degree value is used as a reference.The top active ingredients are Beta-sitosterol(β-sitosterol),Baicalein(baicalein),Stigmasterol(stigmasterol),Caviidine(Cavidin),Myricanone(myricanone),Coniferin(coniferin)and other 6 active ingredients.Therefore,it is predicted thatβ-sitosterol,baicalein,stigmasterol,cavidin,myricetone and coniferoside are the core components of Pinellia chuanxiong for the treatment of coronary heart disease.4.Target protein PPI network: Based on the high-confidence interaction information of intersecting target proteins fed back by the String database,the PPI network of the target proteins of Pinellia chuanxiong for the treatment of coronary heart disease was constructed in Cytoscape software,and there was no hidden network in the network.Contact node.According to the "degree" median 2 times as the card value,after excluding edge genes,the "connectivity(Degree),Betweenness(Betweenness)and closeness(Closeness)" median as the card value,the results were visualized,and a core network diagram of protein interactions was constructed.According to the core network diagram and the Cyto Hubba plug-in MCC algorithm in Cytoscape3.6.1 software,topological analysis was performed to calculate the top core proteins,and finally 12 core proteins were obtained,AKT1,TP53,VEGFA,MMP9,PTGS2,HIF1 A,PPARG,CASP3,FOS,ESR1,MAPK14,NR3C1.5.Enrichment analysis results: GO analysis and KEGG pathway analysis were performed on the Metascape platform.The GO analysis results showed that 83 molecular function entries were obtained,and the genes were mainly enriched in nuclear receptor activity,protein heterodimerization,and transcription factor binding.,cytokine activity,receptor binding,heme binding,protein binding,enzyme binding,etc.;483 biological process items were obtained,including blood circulation,cell response to organic compounds,cell response to external stimulation,and cell response to hypoxia.,response to inorganic substances,positive regulation of protein phosphorylation,positive regulation of RNA polymerase II promoter transcription,etc.;43 cell component entries were obtained,mainly in the nucleus,extracellular space and plasma membrane..KEGG analysis yielded186 items,mainly related to apoptosis,endocrine resistance,fluid shear stress and atherosclerosis,sphingolipid signaling pathway,adrenergic signaling pathway in cardiomyocytes,HIF-1 signaling pathway,PI3K-Akt Signal pathway,MAPK signal pathway,TNF signal pathway and NF-κB signal transduction pathway and other signal pathways to treat coronary heart disease.6.The network diagram of Pinellia,Chuanxiong medicine pair-coronary heart disease-mechanism: using Cyto Scape3.7.1 to build a network diagram of "Panxia,??Chuanxiong medicine pair-coronary heart disease-mechanism",the network involves 2 drugs,16 active ingredients,48 Targets of action,20 biological processes,and 19 pathways reflect that Pinellia-Chuanxiong medicine is composed of multiple effective components,multiple targets,and multiple pathways for the treatment of coronary heart disease.7.Molecular docking simulation test: Download the Pub Chem database to obtain the structure of the core components,download the PDB database to obtain the core protein structure,use Autodock Vina to perform molecular docking,and obtain the corresponding calculation results.Active ingredients and targets with better binding activity were screened by docking score Affinity.The results showed that the docking scores Affinity of all core components and core proteins were all ≤-5.0 kcal·mol-1,indicating that the conformation was relatively stable,and stable hydrogen bonds and hydrophobic interactions could be formed.All core components can combine with core protein to play a role,and achieve the effect of treating coronary heart disease by activating or inhibiting core protein-related pathways.Conclusions:1.For the treatment of coronary heart disease,Pinellia-Chuanxiong medicine embodies the simultaneous treatment of phlegm and blood stasis,the compatibility of the two drugs,resolves phlegm and disperses stagnation,activates blood and removes blood stasis.2.The treatment of coronary heart disease by Pinellia-Chuanxiong medicine is composed of a variety of active ingredients,among which β-sitosterol,baicalein,stigmasterol,cavitin,myricetone,coniferoside,etc.may become Pinellia-Chuanxiong medicine Core components for the treatment of coronary heart disease.3.The active ingredients of the Pinellia-Chuanxiong drug pair can act on multiple targets,and the Pinellia-Chuanxiong drug pair mainly through AKT1,TP53,VEGFA,MMP9,PTGS2,HIF1 A,PPARG,CASP3,FOS,ESR1,MAPK14,NR3C1 Equal targets for the treatment of coronary heart disease,the above targets can be used as the core targets of Pinellia chuanxiong for the treatment of coronary heart disease.4.Pinellia-Chuanxiong medicine pair plays a role in the treatment of coronary heart disease mainly through biological processes such as blood circulation,cell reaction to organic ring compounds,nuclear receptor activity,protein heterodimerization and other molecular functions.The signaling pathways involved include apoptosis,sphingolipids,HIF-1,PI3K-Akt,MAPK,TNF and NF-κB.