Analysis Of Medication Rules And Mechanisms Of Chinese Medicines In Treatment Of Primary Liver Carcinoma And Ascites Based On Data Mining And Network Pharmacology

OBJECTIVE:To explore the dosing patterns in the literature of Chinese medicine compound prescriptions for the treatment of Primary Liver Carcinoma combined with Ascites by using data mining techniques,to construct a new formula for the treatment combined with modern pharmacological basis,and to explore the possible molecular mechanisms of the new prescription by using network pharmacology,in the hope of benefiting clinical practice.METHODS:(1)To search for the literature on the treatment of Primary Liver Carcinoma combined with Ascites by internal compound prescriptions of traditional Chinese medicine from SINOMED,CNKI,WANFANG Data,and VIP Network since its establishment to December 31,2021.Then to collect prescriptions which meet standards and standardize them.To investigate frequency analyses of the single herbs,category,efficacy,Four Qi,Five Flavors,and attribution by using Microsoft Excel 2010 software.To analyze the association principle of herbs in prescriptions by using Apriori algorithm in IBM SPSS Modeler 18.0 software.To cluster the herbs(frequency≥9)by using IBM SPSS Statistics 25.0 software.(2)To construct a herb collection of Primary Liver Carcinoma and Ascites based on the SymMap database and further to construct a new formula.(3)To search for the herb-related components and targets in the new formula from the TCMSP database.To search for the disease targets from Genecards,OMIM and other databases.To obtain the core targets by intersecting the drug targets and disease targets.To build a PPI network so as to discover the dominant targets by entering the core targets into the STRING platform.To discover the major biological functions and pathways by performing GO and KEGG enrichment analyses by entering core targets into the Bioinformatics platform.To construct a network model of "Herb-active ingredient-core target-disease" by using Cytoscape 3.9.1 software.To verify the stability of the network by using RStudio program.To verify the molecular docking of active ingredient and core target by using AutoDock software and to visualization key compounds by using PyMol 2.5 software.RESULTS:(1)A total of 35 articles containing 36 prescriptions involving 114 Chinese herbs were included in this study.We found that the most frequently used Chinese herb was the most frequently used category was Polyporaceae,the most frequently used herb efficacy was a tonic for deficiency,the most frequently used Qi was warm,the most frequently used Flavor was sweet and the most frequently used herb belonged to the spleen meridian.Analysis of the association principle suggested that the most supportive association rule for pair herbs was "Poria Cocos(Schw.)Wolf.-Atractylodes Macrocephala Koidz",and the association rule for corner herbs was"Polyporus Umbellatus(Pers)Fries,Atractylodes Macrocephala Koidz-Alisma Orientale(Sam.)Juzep.".The clustering analysis suggested that the herbs could be grouped into five categories:harmonizing the liver and spleen,tonifying the spleen and inducing diuresis,eliminating phlegm and softening firmness,tonifying the spleen and promoting diuresis,and warming the Yang and resolving Qi.(2)A new TCM formula named "Qi-Yuan Formula" was constructed,which consists of Hedysarum Multijugum Maxim.,Citri Fructus,Fritillariae Thunbrgii Bulbus,Radix Salviae,Scutelariae Barbatae Herba and Plantaginis Semen.(3)"Qi-Yuan Formula" involves 129 active ingredients and 120 herb targets.There are 3508 targets of "Primary Liver Carcinoma",869 targets of "Ascites" and 40 core targets at the intersection of herb targets and disease targets.The PPI network suggested that the core targets are IL6,VEGFA,PTGS2 and etc.The core targets are mainly participating in the regulation of inflammatory response,cellular response to chemical stress and other biological processes and mainly participating in signal pathways such as Fluid shear stress and atherosclerosis.The "Herb-active ingredient-core target-disease"interaction network model suggests that the key active ingredients of "Qi-Yuan Formula" are quercetin,luteolin,kaempferol and etc.,and the main targets are ESR1,AR,PTGS2,and etc.The network model is stable.The molecular docking validation suggested that the binding of Iuteolin-NOS2 was optimal.CONCLUSION:The clinical medication pattern of Primary Liver Carcinoma combined with Ascites is consistent with its pathogenesis.As a treatment formula,"Qi-Yuan Formula" has the characteristics of multi-component,multi-target and multi-pathway.