Study On The Medication Rules And Mechanism Of Action Of Traditional Chinese Medicine In The Treatment Of Phlegm-fire Disturbance Of Heart Type Ventricular Premature Beat

Objective:1.Using data mining technology,establish a database of prescriptions for modern clinical treatment of phlegm and disturbing ventricular premature beats,conduct statistical analysis of medication rules,and mine core therapeutic drugs.2.Using network pharmacology methods,the mechanism of action of core drug formulas in the treatment of sputum and disturbing ventricular premature beats was discussed,and the targets and pathways involved in the treatment were predicted,so as to provide ideas for clinical streamlining medication and follow-up research.Methods:1.Retrieve literature on traditional Chinese medicine treatment for phlegm-fire disturbing the heart type ventricular premature contractions(VPC)from the databases including China National Knowledge Infrastructure(CNKI),Chinese Biomedical Literature Database(CBM),Wanfang Data,and VIP database.The search period is from the establishment of the database to December 31,2022.Chinese search terms include "premature beats," "ventricular premature contractions," "ventricular premature beats," "ventricular ectopic beats,""ventricular extrasystoles," "ventricular premature complex," as well as "clearing heat and resolving phlegm," "phlegm-fire disturbing the heart," and "phlegm-heat disturbing the heart."Based on these terms,construct search strategies for each platform,then screen the literature information that meets the inclusion and exclusion criteria,and standardize the data to establish a database.Use the TCM Inheritance Calculation Platform V3.0 for statistical analysis.Set the "support number" to 27 and the "confidence" to 0.9 for association rule analysis.Set the number of clusters to 4,and use the K-means clustering algorithm for cluster analysis to summarize the medication rules.2.We used the TCMSP database to search for effective ingredients of core drugs,setting OB(oral bioavailability)≥ 30%and DL(drug-likeness)≥0.18.For compounds not included in TCMSP,we supplemented data from the ETCM database.The protein targets were standardized using the STRING and UniProt databases and converted to their corresponding human gene target names(genesymbol)to construct a database of drug activity targets.Disease-related targets were searched in the GeneCards database to establish a gene target database related to ventricular premature contractions.The VennDiagram tool 2.1.0 was used to find the intersection of drug activity targets and disease targets and to draw a Venn diagram.Using Cytoscape 3.9.1,a "drug-active ingredient-target" network was constructed.The intersection targets were imported into the STRING database to construct a PPI network.GO and KEGG enrichment analysis was performed using the DAVID database.Finally,we predicted the key effective ingredients,key targets,and possible pathways involved in the treatment of phlegm-fire disturbing the heart type ventricular premature contractions by constructing graphs using bioinformatics tools.Results:1.A preliminary search yielded 217 articles,which were screened according to inclusion and exclusion criteria,resulting in the inclusion of 53 articles and 53 formulae involving 79 Chinese herbs with a total frequency of 597.Huanglian,Fuling,Zhuru,Chenpi,Banxia,and Gancao were the top six herbs used by frequency,with the use of cold and warm-natured herbs being dominant,and bitter,sweet,and pungent tastes being the main flavors used.The selection of herbs was mainly based on their effect on the heart meridian,spleen meridian,and lung meridian,with consideration given to the stomach meridian.The combination of herbs mainly focused on the efficacy of clearing heat,regulating qi,tonifying deficiency,and resolving phlegm.The most commonly used combinations of herbs were "Fuling,Zhuru,""Fuling,Chenpi," and "Zhuru,Chenpi," and the highest confidence association combinations were "Zhishi → Fuling," "Huanglian,Chenpi → Zhuru," and "Huanglian,Zhuru→Chenpi." Cluster analysis yielded four core formulae,and data mining identified a core group of herbs for treating phlegm-fire disturbing the heart type ventricular premature contractions:Huanglian,Banxia,Gancao,Zhishi,Zhuru,Chenpi,and Fuling.2.Analysis of the core formula showed a total of 143 effective ingredients corresponding to 272 targets,5570 ventricular premature contraction-related targets,and 212 intersection targets between drugs and diseases.In the "drug-active ingredient-ventricular premature contraction target" network,quercetin,naringenin,hesperetin,7-methoxy-2-methyl isoflavone,and hesperidin were the effective ingredients with the highest Degree value.In the PPI network,AKT1,ALB,TP53,IL6,and VEGFA were the top 5 targets ranked by Degree value.The main pathways involved in drug regulation were cancer pathways,lipid and atherosclerosis pathways,AGE-RAGE signaling pathway,IL-17 signaling pathway,and TNF signaling pathway,etc.Conclusion:1.The core prescription for modern doctors to treat phlegm-heat disturbing heart type ventricular premature beats is Huanglian,Banxia,Gancao,Zhishi,Zhuru,Chenpi,and Fuling.In treatment,emphasis is placed on regulating the functions of the heart and spleen,clearing heat from the heart channel,and simultaneously using methods to "regulate the spleen" and"treat qi" to dispel phlegm-heat and external pathogenic factors,targeting the pathological processes of phlegm syndrome with targeted treatment.2.The results of network pharmacology studies show that the most likely effective ingredients of the core prescription are quercetin,naringenin,acteoside,7-methoxy-2-methyl isoflavone,and hesperidin.By regulating the targets such as AKT1,ALB,TP53,IL6,VEGFA,etc.,they participate in signal pathways such as cancer pathway,lipid and atherosclerosis pathway,AGE-RAGE,IL-17,TNF,etc.,producing anti-inflammatory,antioxidant,and cardioprotective effects,and achieving the treatment of ventricular premature beats.