Exploring The Medication Rules And Mechanism Of Action For Functional Constipation Based On Data Mining And Network Pharmacolog

Purpose: This study aims to input,analyze,summarize,and draw conclusions on the medication rules and compatibility relationships of functional constipation based on nearly a decade of literature from databases such as CNKI.This was done through the assistance of the "Traditional Chinese Medicine Inheritance Assistance Platform(V2.5)",which explores new combinations of drugs and provides more data support for clinical medication guidance.Using network pharmacology,the molecular basis and mechanism of the "Fructus AurantiiAtractylodes Macrocephala-Angelica sinensis" drug combination for the treatment of functional constipation was speculated to provide data support for future experimental research.Materials and methods:Study 1: By searching Chinese literature in the three major databases,VIP,CNKI,and Wan Fang,from January 1,2012,to December 12,2022,on the clinical study of functional constipation treated with oral traditional Chinese medicine decoctions,selecting literature according to the inclusion and exclusion criteria,and inputting the selected traditional Chinese medicine formulae into the "Traditional Chinese Medicine Inheritance Auxiliary Platform(V2.5)" for data mining and analysis,using frequency statistics to analyze the four properties,five flavors,and meridian tropism of the core and high-frequency Chinese herbal medicines,and mining association rules to obtain key herbal combinations,high-frequency herbal combinations,and new formula combinations.Study 2: Based on network pharmacology,a core Chinese herbal medicine combination for treating functional constipation "Fructus Aurantii-Atractylodes Macrocephala-Angelica sinensis" screened a total of 24 active ingredients,including chenpiol,stigmasterol,verbascoside,luteolin,β-sitosterol and other core active ingredients,corresponding to 113 target genes of Chinese herbal medicine and disease,mainly including serine/threonine kinase1,tumor necrosis factor,tumor protein,interleukin-6,cysteine protease 3,etc.The GO enrichment analysis showed reactions to drugs,steroids,nutrition level,and cellular response to chemical stress.The KEGG pathway enrichment analysis showed relevance to prostate cancer restricted signaling pathway,hepatitis B signaling pathway,endocrine resistance signaling pathway,diabetic complications AGE-RAGE signaling pathway,IL-17 signaling pathway,and so on.Results:1.In this study,a total of 174 traditional Chinese medicine prescriptions were screened,involving 141 different herbs.Frequency analysis revealed that the most frequently used herbs for treating functional constipation were Fructus Aurantii Immaturus,Rhizoma Atractylodis Macrocephalae,and Radix Angelicae Sinensis.Warm-natured herbs were the most commonly used among the four natures,while the spleen was the most frequently targeted meridian.Through association rule analysis,25 high-frequency herb combinations,9core herbs,and 5 pairs of core herb combinations were identified.In addition,11 new formulas were discovered through entropy-based hierarchical clustering.2.Based on network pharmacology,the core herb combination for treating functional constipation,which consists of Fructus Aurantii Immaturus,Rhizoma Atractylodis Macrocephalae,and Radix Angelicae Sinensis,was found to contain 24 active ingredients,including neohesperidin,beta-sitosterol,verbascoside,hesperidin,and beta-sitosterol.The corresponding target genes for the herbs and disease totaled 113 and mainly included serine/threonine kinase 1,tumor necrosis factor,tumor protein,interleukin-6,and cathepsin L.GO enrichment analysis revealed that the response to drug,response to steroid hormone,response to nutrient levels,and response to chemical stress were the major biological processes involved.KEGG pathway analysis indicated that the signaling pathways for prostate cancer,hepatitis B,endocrine resistance,AGE-RAGE,and IL-17 were all related.Conclusion:1.The main treatment principles for functional constipation in clinical practice identified through data mining are to tonify qi and nourish blood,regulate qi and relieve stagnation,and nourish yin and moisturize dryness.2.Network pharmacology analysis of the core drug combination "Fructus AurantiiAtractylodes Macrocephala-Angelica sinensis" shows that the treatment of functional constipation is related to the multi-target,multi-drug active ingredients,and multi-signal pathways of the core drug combination "Fructus Aurantii-Atractylodes MacrocephalaAngelica sinensis".