| Objective: To predict the potential active components of XKY and its potential target and mechanism of action in the treatment of Chronic Heart Failure(CHF).Methods:(1)Drug composition and target analysis: ?)The constituents of XKY were searched by TCMSP and literature,and the active constituents were screened by TCMSP and Swiss ADME.The screening rates of TCM components were counted respectively,and the potential factors affecting the activity of TCM components were analyzed combined with the properties of TCM.The distribution of active components of XKY in different medicines was analyzed by TBtools.ii)TCMSP and Swiss Target Prediction were used to predict potential targets,and TBtools was used to analyze the distribution of potential targets in each Chinese medicine.(2)Correlation analysis of drug targets and disease targets :i)The disease-related genes of CHF were queried in Gene Cards,and the genes were grouped according to the quartile and the 2000 th digit of Relevance Scores,and the GO and KEGG results of each group of genes were analyzed to select the disease targets of CHF in this study.ii)The therapeutic targets for XKY-CHF in this study were determined after analysis of potential XKY targets and CHF disease-related genes using TBstool.(3)Network construction and analysis :i)PPI analysis of CHF disease targets,XKY potential targets and XKY-CHF treatment targets was conducted by STRING.ii)"TCM-component-target","TCM-component-therapeutic target" networks and PPI networks were established and analyzed by Cytoscape.(4)Go and KEGG analysis and molecular docking :i)R was used for GO and KEGG analysis.ii)Use Auto Dock Vina for molecular docking and Discovery Studio 2020 Client to view and analyze docking results.Results:(1)Analysis of components of Chinese medicine:XKY has207 potential active components,most of which are unique to traditional Chinese medicines.Whether it has the effect of invigorating the spleen or not may be a factor affecting the activity of chemical components in XKY.(2)Target analysis:There were1152 potential targets of XKY,among which 328 targets were unique to each drug,and 7 targets were common to all drugs.10,352CHF-related genes were obtained,and the first 2000 genes were selected as CHF disease targets in this study.There were 344 therapeutic targets for XKY-CHF.(3)Network analysis: ?)The Degree value of dehydrotumoic acid,glingoic acid C,vanehorin B is the highest in the network of "Chinese medicine-ingredient-therapeutic target".ii)29 targets,such as APP,BDKRB2 and CASR,were the key targets of XKY-CHF.iii)There were 40 components,such as astragaloside IV,astragalus isoflavanoside,ginsenosides,chaihusenoside A,aconitoside,cohositol and naringin,which acted on the first 5 HUB targets in the PPI network of XKY-CHF treatment targets.(4)GO and KEGG analysis :XKY regulates a wide range of BP and KEGG pathways related to CHF,such as cardiac systolic regulation,tissue remoremoing,regulation of lipid metabolism,glucose homeostasis,cellular calcium homeostasis,regulation of cytokine secretion,as well as RAS,adrenergic signaling,apoptosis,dilated cardiomyopathy and other signaling pathways.(5)Molecular docking: the selected 10Hub targets of XKY-CHF and their corresponding components,most of the receptor-ligand binding energy is less than-5 k Al /mol,showing good binding activity and conformation.Conclusion: XKY treat CHF may be through astragaloside IV,ginsenoside Re,cohositol,chaihusenoside A,aconitrin,naringin and other key components;APP,BDKRB2,CASR,AGTR2,ADORA1,ADCY5 and other key targets;r egulation of cardiac contraction,myocardial energy metabolism,cellular calcium homeostasis,apoptosis,chronic inflammation,RAS,adrenergic signaling,dilated cardiomyopathy and other biological processes and signaling pathways.It has the characteristics of multi-component,multi-target and multi-mechanism. |
PDF Full Text Request