Exploring the Mechanisms of Huangkui(黄葵)Capsules in Treating Chronic Kidney Disease Based on Integrated Bioinformatics Analysis
Objective:To comprehensively analyze the mechanism of Huangkui(黄葵)Capsules in treating chronic kidney disease(CKD)by combining multiple bioinformatics methods.Methods:This study collected chemical ingredients of Huangkui Capsules from the literature,gathered CKD disease targets from Genecards,OMIM,and TTD databases,and used Cytoscape 3.8.0 software to construct a"drug-ingredient-target"network and a protein interaction network for screening core components and targets.The significantly differently expressed core genes(SDECGs)of Huangkui Capsules in treating CKD were obtained through differential analysis of clinical samples in the GEO database,and the expression and immune cell infiltration of these targets were analyzed.Then,CKD samples were clustered and expression analysis,immune cell analysis,and enrichment analysis of SDECGs between clusters were performed.The module key genes of the normal group and CKD group,and the clustering groups of CKD samples were obtained through weighted gene correlation network analysis(WGCNA).The intersec-tion of the key genes was selected,and these intersection genes were screened with four machine learning algorithms to construct a model,re-sulting in a column chart of the top five feature genes based on importance scores.Finally,the prediction results were validated using GEO dataset and molecular docking.Results:Huangkui Capsules were found to contain 43 chemical components and 393 targets,among which the core components were seven ingredients including myricetin,quercetin,and gossypetin.There were 247 intersection targets between CKD and Huangkui Capsules,25 of which were identified as core targets.Differential analysis using GEO unveiled 18 SDECGs,which were positively correlated with immune cell expression.Clustering of CKD samples resulted in two clusters(Cl and C2),and the expression of SDECGs,im-mune cell expression,and pathway enrichment of these two clusters basically corresponded to the normal group and CKD group.The mecha-nisms involved in the analysis mainly included immune inflammation,oxidative stress,cell pyroptosis and other processes.By combining WGCNA with support vector machine(SVM),a model was constructed and 5 feature genes(CCDC186,SMC5,SLC30A7,COIL,DMLX1)were obtained,which could predict the sensitivity of CKD patients to Huangkui capsules treatment and the risk of developing CKD.Conclu-sion:Huangkui capsules mainly treat CKD by acting on multiple targets(ALB,AKT1,GAPDH,etc.)and multiple pathways(immune in-flammation,oxidative stress,cell necrosis,autophagy,and tissue repair)through multiple components(myricetin,quercetin,gossypetin,etc.).This study provides guidance for the clinical treatment of CKD and the exploration of the mechanism of Huangkui capsules.
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