| Aim To screen the main active components for the treatment of coronary heart disease in Gualou Xiebai Banxia decoction,predict the targets of the active components,establish a drug-component-target-disease network,and explore the mechanism of the treatment of coronary heart disease with Gualou Xiebai Banxia decoctionMethod The active components and targets were screened from TCMSP database.The liuniprot database screens drugs for non-human targets and corrects them for official names.The TTD data,Gene Cards database and Dis Ge NET database were used to obtain the potential target of trichinoxiebetellia decoction in the treatment of coronary heart disease.Cytoscape was used to construct a compound-target-disease network for the treatment of coronary heart disease with fructus trichosanthis rhizome pinellia decoction.The Cyto NCA plug-in of Cytoscape software was used to analyze the topology of the network and to select the core active components of trichosanthis xiewhite pinellia decoction in the treatment of coronary heart disease.The high confidence interaction relation of intersection target proteins was obtained from String database,and the interaction network of intersection target proteins was constructed in Cytoscape software.Cyto NCA plug-in was used to analyze the topology of the network and to screen out the core target of trichosanthis xiebai pinellia decoction in the treatment of coronary heart disease.The structure of the target protein was obtained from the PDB database,and the Autodock software was used for molecular docking simulation and verification,and the results were visualized.The David database was used to conduct enrichment analysis of GO function and Up_Tissue distribution of KEGG pathway for potential targets,and the chemical-target-pathway network was constructed in Cytoscape software.Results 1.Active ingredients and targets of trichosanthis xiebai pinellia decoction: a total of 33 active ingredients meeting the requirements of OB>30% and DL>0.18 as well as the predicted targets were screened on the TCMSP platform.Fructus trichosanthis contains 10 active ingredients,stamponon stem contains 11 active ingredients,and pinellia bunge contains 13 active ingredients.Among them,amysterol(MOL000358)is distributed in both stamponon stem and pinellia bunge.A total of 137 predicted targets of active components were collected on the TCMSP platform,among which 30 were active components of trichosanthis,119 were active components of stemon and 83 were active components of pinellia.2.CHD related targets and intersection targets: a total of 1221 CHD related targets were screened based on TTD database,Gene Cards database and Dis Ge NET database.There are 68 targets of drug and disease intersection.3.Compound-target-disease network for the treatment of coronary heart disease with Gualou Xiebai Banxia decoction: a compound-target-disease network for the treatment of coronary heart disease with Gualou Xiebai Banxia decoction was constructed based on Cytoscape software.The network consists of 105 nodes and 390 edges,including 1 disease node,3 drug nodes,33 active ingredient nodes and 68 target nodes.Cyto NCA plug-in topology analysis of the results of the analysis show that,the median value Degree is 6,number of medium Degree of center BC a median of 24.706522,closely center for CC a median of 0.37313432,a total of six active ingredients meet the core active ingredient of the filter,quercetin(MOL000098)respectively,beta sitosterol(MOL000358),cytosine nucleoside(MOL002670),stigmasterol(MOL000449),pomelo peel(MOL004328),baicalin(MOL002714).4 Target protein PPI network: Based on the high confidence interaction information of the intersection target protein based on the feedback of String database,the target protein PPI network of trichosanthis xiewhite pinellia decoction in the treatment of coronary heart disease was constructed in Cytoscape software.After removing targets that do not interact with other target proteins,the network has a total of 67 nodes and 244 edges.The larger the diameter and the darker the color of the node are,the higher the Degree value of the node is,and the more target proteins interact with it.The thicker the edge and the darker the color are,the stronger the interaction between the two target proteins is.The results of topology analysis of Cyto NCA plugin are shown in table 3.The median Degree value is 5,the median BC value is 17.139444,and the median CC value is 0.15456675.A total of 16 targets meet the screening criteria for core targets,including IL6,MAPK1,VEGFA,TP53,BC,IL1 B,PTGS2,CCL2,EGF,EGFR,HMOX1,NOS3,MAPK14,ESR1,MMP2,CAT and AR.5.Molecular docking simulation verification: obtain target protein information from PDB database.The lowest binding energy between the target protein and the active component calculated by Autodock_vina software,all the results of the lowest binding energy are less than-5kj ?mol-1,indicating that the receptor protein has binding activity with the active component and can form a relatively stable conformation.The lowest binding energy of the core active component and the receptor protein was higher than that of the aspirin molecule and the receptor protein,which verified the rationality of the target protein receptor and ligand selection.Molecular docking simulation shows that the active component molecules and surrounding molecules form stable conformation through intermolecular forces such as hydrogen bond.6.Enrichment analysis results: some enrichment analysis results were obtained through David database.The GO Biological enrichment analysis enriched 307 GO entries,including 219 Biological Processes(BP)entries,36 Cellular Component(CC)entries and 52 Molecular Function(MF)entries.It involves positive regulation of nitric oxide biosynthetic process,response to hypoxia,and activation of MAPK activity.A total of 30 pathways were enriched by KEGG pathway enrichment analysis,involving hypoxia-inducing factor-1 signaling pathway(hif-1 signaling pathway),tumor necrosis factor signaling pathway(TNF signaling pathway),Estrogen signaling pathway(Estrogen signaling pathway),and pi3k-akt signaling pathway(pi3k-akt signaling pathway).The tissue distribution enrichment analysis was carried out to 10 items,mainly involving fibroblasts,liver,platelets,heart,peripheral blood,white blood cells,blood and other parts.7.Compound-target-pathway network: the compound-target-pathway network for the treatment of coronary heart disease with fructus Gualou Xiebai Banxia decoction was constructed in Cytoscape software,as shown in FIG.8.Orange yellow nodes represent drugs in this diagram,nodes represent fructus scallions white pinellia active ingredient soup,red nodes represent fructus scallions white soup of pinellia tuber core active ingredient,the blue nodes represent fructus scallions white soup of pinellia tuber potential targets for treatment of coronary heart disease(CHD),dark blue nodes represent fructus scallions core target pinellia decoction treatment of coronary heart disease,white green nodes represent filtering through the analysis of the enrichment of KEGG pathways.The compound-target-pathway network has 122 nodes and 437 edges,involving 3 drugs,33 active ingredients,56 potential targets and 30 KEGG pathways,which reflects the characteristics of multiple components,multiple targets and multiple pathways in the treatment of coronary heart disease.Conclusion(1)through database retrieval,it was found that there were a variety of compounds in fructus trichinolifolia decoction,and the treatment of coronary heart disease by fructus trichinolifolia decoction was a combination of various active ingredients,among which quercetin,pomelino,baicalin and baicalin may be the core components in the treatment of coronary heart disease by fructus trichinolifolia decoction.(2)through the target prediction and screening of active components,it was found that the active components of fructus trichosanthis xiebai pinellia decoction could act on multiple targets.Trichosanthes scallions white pinellia soup primarily through IL6,MAPK1 crack the original activated protein kinase 1,TP53 p53 tumor antigen,VEGFA,IL1 B,PTGS2 the CCL2,EGF,HMOX1 heme oxygenase,NOS3 targets,such as fructus scallions white soup of pinellia tuber core targets for the treatment of coronary heart disease(CHD)(3)through GO analysis and KEGG analysis,it was found that trichosanthis xiebai banxia decoction mainly regulated the nitric oxide biosynthetic process,response to hypoxia,heme binding,angiogenesis and positive regulation of vasodilation Vasodilation and other biological processes and molecular functions play a role in the treatment of coronary heart disease.The signaling pathways involved include hif-1 signaling pathway,Estrogen signaling pathway,pi3k-akt signaling pathway,Calcium signaling pathway,and vascular endothelial growth factor signaling pathway. |
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