Based On Data Mining And Network Pharmacology Patterns To Explore TCM Drugs For The Treatment Of Influenza

Objective:This study collected oral Chinese medicine to treat influenza related data and literature research in the past 20 years.With the help of data mining technology,to study the nature flavor and channel tropism and the rule of prescription medication,so as to the provide reference for the clinical treatment of influenza with prescription of traditional Chinese medicine.With the help of network pharmacology technology to explore the feasible mechanism of action of the core drug group in the process of influenza treatment,in order to accumulate more experience and obtain more research data for traditional Chinese medicine in the treatment of influenza.Methods:1.Data mining: Using electronic retrieval to collect China National Knowledge Infrastructure(CNKI),Wangfang Data Service Platform(Wangfang),VIP database recorded that relevant literature with traditional Chinese medicine treatment of influenza in the course of 2000-2020.According to the relevant standards,a total of 197 valid literatures was obtained.The effective information from the obtained literature was extracted to create a database,and the data had sorted out and summarized through standardized processing.What is more,prescription information was input into Excel2010.SPSS statistical software was used to analyze the frequency of all traditional Chinese medicines,and 40 Chinese medicines with medication frequency ≥22 were screened out.Cluster analysis,association rule analysis,principal component factor analysis and the decision tree algorithm analysis was carried out for high-frequency drugs.2.Network pharmacology : According to the drug combinations with 100%confidence in association rules,cluster analysis results and the decision tree algorithm,the core drug group for the treatment of influenza was deduced.And on this basis,the effective components and action targets of "honeysuckle,forsythia,rhizoma phragmitis,platycodon grandiflorum,fructus arctii" were searched relying on the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP).At the same time,to construct the network analysis of core drug group active component-target-influenza disease,and GO function enrichment analysis and KEGG pathway analysis were performed.To investigate the possible mechanism of the core drug group in the treatment of influenza.Results:1.Data mining:1.1 The general information results represent that 197 effective literatures meeting the exclusion and inclusion criteria are selected,and a total of 317 prescriptions for the treatment of influenza are summarized and sorted out,involving 224 traditional Chinese medicines.1.2 All the traditional Chinese medicines have 224 flavors and the accumulative total frequency of drug use is 3444 times.There were 40 kinds of traditional Chinese medicine with frequency ≥22,and the top five(excluding licorice)are forsythia(55.52%),honeysuckle(50.79%),Platycodon grandiflorum(41.64%),radix scutellariae(40.38%),and bitter apricot seed(37.85%).In the drug category,frequency of the top ten in the drug has heat-clearing drug,diaphoretic drug,expectorant cough suppressant and anti-asthmatic drug,tonify deficiency medicine,dampness-transforming medicinal,damp-clearing drug,qi-regulating drug,purgative medicinal,blood-activating and stasis-eliminating drug,drug for suppressing hyperactive liver for calming endogenous wind.The frequency analysis of all TCM property and flavor and channel tropism in the treatment of influenza showed that the frequency of four-qi from high to low was cold,warm,flat,cool and hot.The frequency of five-flavor from high to low was bitter,pungent,sweet,salty,sour and astringent.The proportion of channel tropism from major to minor is lungs,stomachs,hearts,spleens,livers,large intestines,small intestines and so on.1.3 The results of association rule demonstrated that two drug combinations were ranked according to confidence and support degree,and the binomial association of drug pairs in order of confidence from high to low was forsythia & mint compatibility and forsythia & fructus arctii compatibility.The three correlations were honeysuckle &forsythia & platycodon grandiflorum characteristics of compatibility and the compatibility of honeysuckle & forsythia and fructus arctii.To support degree from high to low sequence that the top 2 drugs of binomial correlation were honeysuckle and forsythia.The three correlations were honeysuckle & forsythia & licorice characteristics of compatibility and the compatibility of forsythia & platycodon grandiflorum &licorice.When confidence was 100% the drug combination was forsythia+fructus arctii+ honeysuckle + Platycodon grandiflorum.1.4 Cluster analysis shows that the drugs can be divided into 9 groups: C1: mulberry leaf and chrysanthemum.C2: forsythia,honeysuckle,mint,fructus arctii,rhizoma phragmitis,bamboo leaves,licorice,platycodon grandiflorum.C3: radix scrophulariae,periostracum cicada,gardenia.C4: schizonepeta,saposhnicovia divaricata,radix peucedani,notopterygium root.C5: isatidis root,folium isatidis,cyrtomium rhizome.C6: poria cocos,pericarpium citri reticulatae,pinellia ternata,magnolia officinalis,fructus aurantii immaturus.C7: radix puerariae,coptidis rhizoma.C8: radix scutellariae,bupleurum,herba houttuyniae.C9: Gypsum,rhizoma anemarrhenae,semen armeniacae amarae,ephedra,fritillary bulb,sweet wormwood,rhubarb.1.5 The results of principal component factor analysis demonstrate that 14 common factors are extracted.To display of former three common factor,F1 mainly contains the following drugs: licorice,platycodon grandiflorum,mint,fructus arctii,rhizoma phragmitis and bamboo leaves;F2 mainly contains drugs: pinellia ternata,poria cocos,fructus aurantii immaturus,pericarpium citri reticulatae and magnolia officinalis;The main drugs in F3 are: semen armeniacae amarae,gypsum,ephedra,rhizoma anemarrhenae and fritillary bulb.1.6 The decision tree algorithm analysis results demonstrate that: Based on the analysis of CHAID decision tree algorithm,six traditional Chinese medicines,including honeysuckle,Platycodon grandiflorum,rhizoma phragmitis,licorice,sweet wormwood and folium isatidis are selected to form decision tree model.The CRT decision tree algorithm was analyzed,and four traditional Chinese medicines(honeysuckle,Platycodon grandiflorum,rhizoma phragmitis,sweet wormwood)are selected to form decision tree model.QUEST decision tree algorithm is used to select three traditional Chinese medicines(honeysuckle,Platycodon grandiflorum and Rhizoma phragmitis)to form decision tree model.2.Network pharmacology2.1 A total of 62 active ingredients are included in the core drug portfolio,and 29 chemical components that might be effective for influenza are quercetin,kaempferol,luteolin,baicalein,and acacia.Effective targets for the treatment of influenza may include peroxisome proliferator activated receptor gamma γ(PPARG),cell apoptosis regulating the Bcl-2(Bcl-2),Caspase＿3(CASP3),Caspase＿8(CASP8),nitric oxide synthase-induction(NOS2),and prostaglandin G/H synthase 1(PTGS1),prostaglandin G/H synthase 2(PTGS2)et al.And construct the core drug group active component-target-influenza disease network diagram.2.2 A total of 408 GO items are enriched in the core drug group for the treatment of influenza,including 332 BP items,27 CC items and 49 MF items.The biological processes mainly involve cellular response to chemical stress,cellular response to lipopolysaccharide,response to oxidative stress,reactive oxygen species metabolic process etc.The cell components are mainly relevant to the membrane region,fossa and secretory granule lumen.The molecular functions are mainly cytokine,growth factor receptor binding,enzyme binding,receptor ligand activity,etc.There are 30 important signaling pathways,such as AGE-RAGE signaling pathway,tumor necrosis factor signaling pathway,Chagas disease,IL-17 signaling pathway,which is closely related to influenza disease.Conclusion: 1.Traditional Chinese medicine treatment of influenza mainly from clearing heat,relieving phlegm,relieving asthma and relieving cough to strengthen the principle.Therefore,drugs are mainly used to detoxify the surface and remove wind,and to clear heat and detoxify honeysuckle,forsythia,platycodon grandiflorum,fructus arctii,rhizoma phragmitis and mint,etc.It is supplemented supplemented by gypsum,rhizoma anemarrhenae,semen armeniacae amarae,etc,and Radix ophiopogonis,white peony and fructus jujubae,etc.2.Through the complex network analysis of "honeysuckle,forsythia,ructus root,platycodon grandiflorum and burdock" with multiple components,multiple pathways and multiple targets,it is preliminary speculated that the mechanism of action of traditional Chinese medicine in the treatment of influenza disease may be through the regulation of AGE-RAGE signaling pathway,TNF signaling pathway and other signaling pathways by PPARG,Bcl-2,CASP3,CASP8,NOS2,PTGS1,PTGS2 and other targets,which provides a basis for further discussion.