Analysis Of The Medication Rules And Mechanisms Of Classical Prescriptions Used In The Treatment Of EH Based On Data Mining And Network Pharmacolog

Objective: To explore the Chinese clinical research literature on classical prescriptions for the treatment of essential hypertension since the establishment of the database through data mining methods,and to analyse the data on the classical prescriptions and prescriptions involved,so as to provide new ideas for clinical formulation and drug use.To screen the core drugs in TCM for the treatment of essential hypertension,conduct network pharmacology analysis,construct complex biological networks,explore the main TCM components,targets and pathways of the core drugs at the molecular level,lay the theoretical foundation for further basic experimental studies,and provide new ideas and methods for clinical use and new drug development.Method:1.Through China Knowledge Network(CNKI),Wanfang Data(Wanfang Data),and VIP Chinese Journal Full Text Database(VIP),we searched the relevant literature from the date of establishment to 15 June 2022,using "Topic=hypertension" as the search term,after limiting the relevant TCM disciplines.The relevant literature consistent with the study was searched,reviewed and screened,and the database of TCM prescriptions was established by using an Excel sheet,and frequency analysis,cluster analysis and association rule analysis were conducted using SPSS 25.0 software to summarize the pattern of TCM prescriptions for the treatment of essential hypertension and to screen out the core drugs for their prescriptions.2.Using the Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform(TCMSP)to find the active chemical components and targets of the drugs in the new formula,the Genecards database was used to retrieve the target proteins related to essential hypertension,and the intersection of the two was taken to obtain the key target proteins,and the targets were converted into gene names with the help of the joint protein sequence database Uni Prot,using Cytoscape 3.9.1 software to visualize the complex drug-active ingredient-target protein interactions,upload the potential key-acting targets to STRING 11.5,database to construct PPI networks,obtain core-acting targets,perform GO functional enrichment analysis and KEGG pathway enrichment analysis on the obtained targets through Metascape database,obtain The main signaling pathways were analyzed by the Metascape database to obtain the main effects and to explore the mechanism of action of the new formula for the treatment of essential hypertension.Results:1.235 papers were obtained after data mining,including 197 journal papers and38 dissertations.A total of 263 doses were prescribed in the prescription-level literature,and the classical prescriptions contained a total of 307 doses.Among them,the top five in use were Ban Xia Bai Zhu Tian Ma Tang,Wen Dan Tang,Zhen Gan Xi Feng Tang,Liu Wei Di Huang Wan,and Chai Hu Jia Long Gu Mu Li Tang.At the Chinese medicine level,the top 5 herbs in terms of frequency of use were Fu Ling,Licorice,Atractylodes Macrocephala,Rhizoma Atractylodis Macrocephala and Radix et Rhizoma.The types of herbs were the most deficiency tonic,the most cold herbs,the most sweet herbs among the five flavours,and the most liver meridians among the meridians.The analysis of drug association rules showed that the confidence level of Poria→Tianma and Atractylodes,and Poria→Gan Cao and Atractylodes was 100%.The drug clustering analysis was performed on the herbs used ≥32 times,and three new drug clusters were obtained.C1: Dragon bone,oyster,cow knee,white peony,Chai Hu,scutellaria,cinnamon stick,angelica,dihuang,chuanxiong;C2: rehmannia,dogwood,yam,peony skin,zedoary,danshen,hooked vine;C3: ginger,semen,jujube,tianma,chenpi,atractylodes,poring,bamboo,heliotrope,roasted licorice and licorice.The core drugs of the new prescription were ginger,half asia,jujube,tianma,peel,atractylodes,poria,bamboo rhizome,hedgehog and licorice.2.Network pharmacological analysis: the key targets of drug active ingredients interacting with primary hypertension disease.All active ingredients of drugs in the new prescription obtained from the cluster analysis were screened according to OB≥30% and DL≥0.18,and a total of 145 active ingredients were obtained after de-weighting,with β-sitosterol,dousterol,naringenin and Chuan Chen Piin as the core ingredients.A total of 109 key gene targets shared by drug and disease were obtained after de-weighting,with PTGS2,ESR1,PTGS1,PPARG and NOS2 as the more important targets.The potential mechanism of action situation of the drug,the target proteins predicted by PPI network construction were IL6,TNF,AKT1,IL1 B,VEGFA;the GO enrichment analysis showed that the core drug active ingredients mainly involved the activity of signalling receptor regulators,heme binding,protease binding,adrenergic receptor activity,phosphodiesterase binding and other molecular functions,affecting the cellular response to organic nitrogen compounds,positive regulation of cell motility,responses to inorganic substances,biological processes in response to oxygen content and action at sites such as cell membrane rafts and endoplasmic reticulum lumen.A total of 198 pathways were obtained using KEGG enrichment analysis,mainly involving AGE-RAGE signalling pathways,cancer signalling pathways,tumour necrosis factor signalling pathways,and cellular senescence.Conclusion: 1.From an analysis of the clinical literature,we conclude that there is a wide range of classical formulas that can effectively treat essential hypertension,but the main applications are those based on the principles of tonifying the spleen,drying dampness,combining tonics and diarrhoea,and moving qi to dispel phlegm,such as Ban Xia Bai Zhu Tian Ma Tang and Wen Dan Tang.2.The core drugs of the new prescription have multi-component,multi-target and multipathway action characteristics.The main mechanism may be related to anti-oxidative stress and reduction of inflammatory response.It is hypothesized that the core ingredients of the new prescription are mainly involved in the regulation of AGE-RAGE signalling pathway,tumour necrosis factor signalling pathway and cancer signalling pathway in diabetic complications.