Medication Rules And Mechanism Analysis Of Diabetes With Anxiety Based On Data Mining And Network Pharmacology

Objective:Through the analysis of 137 cases of patients with type 2 diabetes mellitus(T2DM)with anxiety,to summarize the common TCM syndrome types and medication rules of clinical patients,and through the network pharmacology method,to analyze the core drugs,in order to explore the mechanism of treatment of T2DM with anxiety.Methods:Patients with type 2 diabetes mellitus and anxiety were collected from December 2021 to December 2022 in the Department of Endocrinology,the First Affiliated Hospital of Heilongjiang University of Chinese Medicine.According to the inclusion and exclusion criteria,the basic information of the patients,the four diagnosis data and Chinese medicine prescriptions were entered into EXCEL software to establish a patient medical record information database.Statistical analysis,association rule analysis and clustering analysis were performed using the auxiliary platform of TCM inheritance V3.0 to summarize the distribution of TCM syndrome types and medication rules of type 2 diabetes patients with anxiety in our hospital.Then,network pharmacology analysis was performed on the core medication prescriptions obtained by data mining.The active components and action targets of the drugs were screened by TCMSP,and the common targets of type 2 diabetes and anxiety were obtained at the same time.The intersection targets of drugs and diseases were selected and imported into the String database to obtain protein relationships.The drug-component-target diagram and PPI diagram were constructed using Cytoscape v3.9.1 Finally,GO and KEGG enrichment analysis was performed through the Meta-scape database.Results:1.General data:137 cases,79 cases were female,58 cases were male;The age was mainly concentrated in 50-59 years old and 60-69 years old,each accounting for 45 cases;The distribution of TCM syndrome types were as follows:3 5 cases(25.55%)of liver depression and qi stagnation,33 cases(24.09%)of phlegm-heat stagnation,29 cases(21.17%)of deficiency of liver and kidney,21 cases(15.33%)of deficiency of both heart and spleen,19 cases(13.87%)of blood stasis and venation.2.Medication frequency and drug classification statistics:A total of 199 Chinese medicinals were included in the 137 prescriptions,with the total medication frequency of 2501,and the Chinese medicinals with the usage frequency of not less than 55 times,including Poria,Rhizoma Coptidis,Radix Astragali seu Hedysari,Radix Salviae Miltiorrhizae,Radix Bupleuri,Radix Angelicae Sinensis,Rhizoma Ligustici Chuanxiong,Radix Paeoniae Alba,Radix Scutellariae,Rhizoma Pinelliae,and Pericarpium Citri Reticulatae.Analysis of four-qi and five-taste:Among the four-qi,cold drugs were the most frequently used,followed by warm drugs,neutral drugs,cold drugs,and heat drugs.The first three most frequently used ones of the five flavors were bitter,sweet and pungent;The descending order of meridian tropism frequency of drugs was spleen meridian,liver meridian,lung meridian,and heart meridian.The ones with the frequency of more than 50 times in the analysis of Chinese medicine association rules included Poria and Radix Astragali seu Hedysari.Rhizoma Coptidis and Radix Salviae Miltiorrhizae;Radix Bupleuri and Radix Paeoniae Alba;Poria and Rhizoma Coptidis;Poria and Radix Salviae Miltiorrhizae;Rhizoma Coptidis and Radix Bupleuri;Rhizoma Coptidis and Radix Scutellariae.The top three of the association rules were Rhizoma Coptidis-Pericarpium Citri Reticulatae-Rhizoma Pinelliae,Rhizoma Pinelliae-Pericarpium Citri Reticulatae-Rhizoma Coptidis,and Radix Scutellariae-Rhizoma Coptidis.According to clustering analysis,the drugs were grouped into six categories,as follows:Prescription 1:Poria,Radix Astragali seu Hedysari,Radix Salviae Miltiorrhizae,Radix Rehmanniae Preparata,Radix Ophiopogonis,Rhizoma Dioscoreae,Rhizoma Alismatis,and Rhizoma Coptidis;Prescription 2:Radix Astragali seu Hedysari,Radix Angelicae Sinensis,Rhizoma Atractylodis Macrocephalae,Rhizoma Coptidis,Rhizoma Pinelliae,Poria,Radix Salviae Miltiorrhizae,and Radix Codonopsis;Prescription 3:Radix Scutellariae,Rhizoma Coptidis,Radix Bupleuri,Rhizoma Ligustici Chuanxiong,Radix Paeoniae Alba,Fructus Gardeniae,Radix Angelicae Sinensis,and Poria;Prescription 4:Pericarpium Citri Reticulatae,Rhizoma Coptidis,Radix Angelicae Sinensis,Poria,Rhizoma Pinelliae,Radix Bupleuri,Fructus Aurantii,and Radix Paeoniae Alba;Prescription 5:Poria,Radix et Rhizoma Polygalae,Cortex Moutan,Rhizoma Dioscoreae,Radix Ophiopogonis,Rhizoma Ligustici Chuanxiong,Fructus Schisandrae Chinensis,and Radix Astragali seu Hedysari;Prescription 6:Radix Salviae Miltiorrhizae,Radix Paeoniae Alba,Radix Bupleuri,Radix Scutellariae,Rhizoma Coptidis,Rhizoma Atractylodis,Cortex Eucommiae,and Fructus Aurantii.3.Through data mining,we found that Poria,Rhizoma Coptidis,Pericarpium Citri Reticulatae,and Rhizoma Pinelliae were commonly used drugs,and they showed strong correlation in association rules and clustering analysis.Therefore,these four drugs were used for network pharmacology analysis as the core drug group of type 2 diabetes with anxiety.Through the retrieval of TCMSP database,a total of 33 active components and 205 action targets in the core drug groups were obtained.A total of 893 disease targets for type 2 diabetes with anxiety status were obtained through disease database retrieval,and the intersection of drug targets and disease targets was selected,yielding a total of 95 drug-disease targets.Among them,quercetin,berberine,baicalein,naringenin,hederagenin,nobiletin and stigmasterol are the core components,which have the effects of improving diabetes and anti-anxiety.They may act through such targets as IL6,AKT1,TNF,VEGFA,IL1B,TP53,and CASP3,as well as through AGE-RAGE signaling pathway,HIF-1 signaling pathway,TNF signaling pathway and PI3K-Akt signaling pathway.Conclusion:1.In this study,the majority of patients with type 2 diabetes mellitus and anxiety were women,and the majority of the population were middle-aged and elderly.The clinical syndrome types were liver stagnation and qi stagnation and phlegm-heat mutual accumulation.2.The lesion site of the disease is mainly in the spleen and liver meridians.The main treatment drugs were bitter and cold herbs and pungent and warm herbs.The commonly used drugs were Poria,Rhizoma Coptidis,Radix Astragali,Radix Salviae Miltiorrhizae,Radix Bupleuri,Radix Angelicae Sinensis,Rhizoma Ligustici Chuanxiong,Radix Paeoniae Alba,Radix Scutellariae,Rhizoma Pinelliae,and Pericarpium Citri Reticulatae.The drug combination with high confidence was Rhizoma Coptidis-Pericarpium Citri Reticulatae-Rhizoma Pinelliae,and six new formula combinations were obtained through software analysis and the principles of their formula were analyzed,which can be used as basic prescriptions for clinical treatment of this disease.3.Pericarpium Citri Reticulatae,Rhizoma Pinelliae,Rhizoma Coptidis,and Poria contain quercetin,berberine,baicalein,naringenin,hederagenin,nobiletin,and stigmasterol,which may activate relevant pathways such as AGE-RAGE signaling pathway,HIF-1 signaling pathway,TNF signaling pathway,and P13K-Akt signaling pathway by targeting IL6,AKT1,TNF,VEGFA,IL1B,TP53,and CASP3,to exert the effects of improving diabetes and anti-anxiety by regulating inflammatory response,oxidative stress response,apoptosis,and improving insulin resistance.