Discussion On The Medication Rules And Mechanisms Of Diarrhea In "Ancient And Modern Famous Medical Evidence Jinjian"

Objective: Based on data mining,this study aims to explore the medication rules for treating diarrhea in the book "Ancient and Modern Famous Doctors’ Clinical Guide to Diarrhea and Dysentery" and provide reference for clinical treatment of diarrhea.Using network pharmacology and molecular docking technology,this study aims to preliminarily elucidate the potential mechanism of the key Chinese herbal medicine combination in treating diarrhea,and provide evidence for clinical research.Methods: The internal prescription for the treatment of diarrhea in the book "Ancient and Modern Famous Doctors’ Clinical Guide to Diarrhea and Dysentery" was compiled and recorded in Microsoft Office Excel 2019 according to the inclusion criteria.The frequency of use,efficacy,taste,and meridian information of the Chinese herbal medicines were statistically analyzed using Microsoft Office Excel 2019 to identify the high-frequency Chinese herbal medicines.Meanwhile,a variable database of Chinese herbal medicines for the treatment of diarrhea was constructed using Microsoft Office Excel 2019 for further analysis.The association rule analysis was performed using IBM SPSS Modeler 18.0software,and the correlation between Chinese herbal medicines was measured by support and confidence levels.Cluster analysis,factor analysis,and decision tree model analysis were conducted using IBM SPSS Statistics 25.0 software.Systematic clustering was selected as the clustering method,and the Bartlett’s test of sphericity and Kaiser-Meyer-Olkin test were performed to test the feasibility of factor analysis.For the decision tree model analysis,the most frequently used Chinese herbal medicine was selected as the dependent variable,and the parent node was set to 10 and the child node was set to 2.The accuracy of the identification rules was verified using the 10-fold cross-validation method.The correlation between high-frequency Chinese herbal medicines was explored using the Pearson correlation bivariate model,and the strength of the correlation between Chinese herbal medicines was represented by the size of the Pearson correlation coefficient.A heatmap of the correlation between Chinese herbal medicines was created using Microsoft Office Excel2019.The components of the key Chinese herbal medicines and their corresponding protein targets were collected from the Chinese herbal medicine system pharmacology database and analysis platform.The targets related to diarrhea were collected from the GeneCards,CTD,and DisGeNET databases,and merged to obtain the disease targets related to diarrhea.Venny online platform was used to merge the component targets of Chinese herbal medicines with the disease targets to obtain the therapeutic targets of the key Chinese herbal medicines.The therapeutic targets were imported into the STRING database to construct a protein interaction network.The cyto Hubba plugin of Cytoscape software was used to screen the therapeutic targets to obtain the core targets of the key Chinese herbal medicines for the molecular docking.Finally,gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed using the therapeutic targets to determine the biological function and related signaling pathways of the key Chinese herbal medicines in treating diarrhea.Result: According to the discharge standard,a total of 147 prescriptions involving 194 traditional Chinese medicines were finally included,with a cumulative use of 1351 times.These traditional Chinese medicines were mainly classified as tonifying deficiency,regulating qi,promoting diuresis and relieving edema,clearing heat,and astringing.Frequency statistics identified 14 frequently used traditional Chinese medicines,including Poria,Glycyrrhizae Radlx Et Rhizoma,Atractylodis Macrocephalae Rhizoma,Paeoniae Radix Alba,Citri Reticulatae Pericarpium,and Coptidis Rhizome,which are commonly used in the treatment of diarrhea.The analysis of their nature,taste,and meridian distribution showed that traditional Chinese medicines for treating diarrhea are mainly warm in nature,sweet in taste,and mainly enter the spleen,stomach,and lung meridians.A total of 53 association rules were obtained between frequently used traditional Chinese medicines,including 24 combinations of two medicines,26 combinations of three medicines,and three combinations of four medicines.Cluster analysis yielded five clustering directions,and factor analysis extracted five common factors with a cumulative variance contribution rate of 56.647%.Using Poria as the dependent variable,the decision tree model identified Atractylodis Macrocephalae Rhizoma as the best identified traditional Chinese medicine,with a 10-fold cross-validation accuracy rate of 91.7% for all algorithms.Correlation analysis showed that the combination of Poria-Atractylodis Macrocephalae Rhizoma had the highest association,with a correlation coefficient of 0.629.Key traditional Chinese medicine combinations collected 97 active ingredients and 239 potential targets,with compounds such as quercetin,kaempferol,and 7-methoxy-2-methyl isoflavone having high degree values.The cyto Hubba screening yielded the top five protein targets by degree,namely TP53,VEGFA,AKT1,IL-6,and EGFR.Gene ontology and KEGG enrichment analysis showed that the key traditional Chinese medicines for treating diarrhea mainly involve biological processes such as the response to lipopolysaccharides,the response to bacterial-derived molecules,cytokine activity,cytokine receptor binding,membrane raft,and membrane microdomain.Their signal pathways mainly include the AGE-RAGE signal pathway,HIF-1 signal pathway,IL-17 signal pathway,Toll-like receptor signal pathway,and T-cell receptor signal pathway.The results of molecular docking showed that quercetin,kaempferol and 7-methoxy-2 methyl isoflavone had higher affinity with TP53,IL-6,AKT1 and EGFR.Conclusion: Through the use of data mining methods such as frequency analysis,association rule analysis,cluster analysis,factor analysis,decision tree modeling,and orrelation analysis,this study systematically analyzed and summarized the prescriptions and medication laws of ancient and modern medical practitioners for treating diarrhea in the book "Ancient and Modern Famous Doctors’ Clinical Practice Golden Mirror".It provides a certain reference for clinical prescription and medication for treating diarrhea.By using network pharmacology and molecular docking methods,this study systematically explored the mechanisms of key herbal medicines in the treatment of diarrhea,which may involve the AGE-RAGE signaling pathway,the HIF-1 signaling pathway,the IL-17 signaling pathway,the Toll-like receptor signaling pathway,and the T cell receptor signaling pathway.