Analysis Of Medication Regularity And Mechanism Of Action During Asthma Attack In Children Based On Data Mining And Network Pharmacology

Objective: The aim of this study is to summarize the dosing pattern of TCM in the treatment of acute exacerbation of pediatric bronchial asthma through data mining and network pharmacology,apply the network pharmacology approach to the core drug combinations for the treatment of pediatric asthma exacerbation,predict the potential targets of action and select the active ingredients of core TCM,explore their mechanisms of action at the molecular level,construct a molecular network,and then validate them with molecular docking,and from the mechanism of action of Chinese herbal medicines in the treatment of pediatric asthma exacerbation was shown at the microscopic level with multiple pathways and multiple effects.Methods: 1.The computer searched CBM,CNKI,VIP,Wan fang and other databases to collect and organize the literature on TCM for pediatric asthma exacerbation,used Note Express related functions to eliminate duplicates,manually recorded the prescription information of pediatric asthma exacerbation and built the database,and then the data is preprocessed.Data mining mainly used R language,UCINET,Net Draw to do association rule analysis,frequency statistics,clustering analysis,complex network analysis on pediatric asthma exacerbation medication,and then mining the medication pattern of pediatric asthma exacerbation treated by TCM.2.Screening and searching the action targets and active ingredients of core TCM in BATMAN-TCM database,Traditional Chinese Medicine Systematic Pharmacology Analysis Platform(TCMSP),Traditional Chinese Medicine Encyclopedia database(ETCM),and disease targets related to pediatric asthma exacerbation were obtained in TTD,Gene Cards,Omim and other disease gene databases.The potential targets of the ingredients were mapped to the disease gene targets as the common potential targets of the core Chinese medicine for the treatment of pediatric asthma exacerbation,and the overall network topology analysis was performed.After the core targets and key ingredients were screened out,Kyoto gene analysis,genome encyclopedia(KEGG)pathway analysis and gene ontology(GO)enrichment analysis were performed on the potential targets of action using R language.3.Autodockd software was used to complete the docking of the target protein with the component small molecule semi-flexible molecules.The interaction patterns of receptor proteins and small molecules were analyzed and summarized based on the binding energy scores and the small molecules with high core target protein binding scores were used as examples.Results: 1.In this study,a total of 684 prescriptions were collected about pediatric asthma exacerbation period,and frequency analysis revealed that the 684 prescriptions included a total of 253 Chinese herbal medicines.Among them,Ziziphi,Dioscorea,Scutellaria,Ephedra,Glycyrrhiza,Bitter almond,Semen,Hesperidin,and Wu Wei Zi were used more frequently.From the results of association rules,complex networks,cluster analysis,and frequency statistical analysis,it was concluded that Ephedra-Glycyrrhiza-Bitter almond-Semen as the core drug combination,and based on this,this paper selected EphedraGlycyrrhiza-Bitter almond-Semen as atypical example to do the next study.2.There are 520 corresponding action targets and 127 active ingredients of EphedraGlycyrrhiza-Bitter Almond-Half-Half-Hsia screened in the public data platform,and 647 targets for pediatric asthma exacerbation were mined.The pediatric asthma targets were mapped to the component targets,yielding 131 intersecting targets.In the PPI network,CASP3,CXCL8,IL1 B,TP53,VEGFA,JUN,IL10 IL6,TNF,INS,etc.were obtained.Regarding the biofunctional enrichment analysis,the core targets were involved in several biological processes such as participation in cell differentiation and regulation of inflammatory response.On KEGG analysis,signaling pathways such as IL-17,PI3K-AKT,TNF,Toll,etc.were found to be highly correlated with pediatric asthma and were thus determined.Core targets with good binding pattern to major components can be shown by molecular results.Whether the target protein interacts with the small molecular ligands of the active ingredient of the herbal medicine and the identification of the site where the interaction occurs was confirmed from the results of target protein binding and active ingredient interaction patterns.Conclusion: 1.The analysis of the prescription of Chinese medicine for the treatment of pediatric asthma exacerbation period can be known that the core drug combination derived from cluster analysis,association rule analysis,complex network analysis,and frequency statistical analysis is ephedra-glycyrrhiza-bitter almond-half-xia.2.The effect of ephedra-glycyrrhiza-bitter almond-half-xia in the treatment of pediatric asthma exacerbation fully reflects the characteristics of multi-component,multi-target and multi-pathway of traditional Chinese medicine,which are closely related to various aspects such as the response of molecules of bacterial origin,positive regulation of cytokine production,positive regulation of inflammatory response secretion and neurotransmitter biosynthesis process.