The Drug Rules And Mechanism Of Action Of Professor Zhang Xiaoke In The Treatment Of Prediabetes Mellitus Based On Data Mining And Network Pharmacology

Objective: To summarize the medication rules and academic ideas of Professor Zhang Xiaoke in the treatment of prediabetes mellitus based on data mining analysis,to identify core drugs,to explore the potential mechanism of action of prediabetes mellitus through network pharmacology,to provide clinical ideas and scientific basis for the promotion and development of traditional Chinese medicine in the treatment of prediabetes mellitus,and to strengthen the exchange and inheritance of academic ideas of traditional Chinese medicine.Methods: A total of 124 doses of the first prescription of prediabetes mellitus patients treated by Professor Zhang Xiaoke in the Second Department of Endocrinology Clinic of the Affiliated Hospital of Shaanxi University of Chinese Medicine and the Jinqiu Clinic of Shaanxi University of Chinese Medicine were collected from October 2020 to December2022,and a total of 124 doses were collected for data processing and standardization.Through the TCM inheritance assistance platform,the frequency,efficacy classification,four qi and five flavor classification,association rules and cluster analysis of the data were summarized to summarize the core drugs,drug pairs and commonly used drug combinations.Based on network pharmacology,TCMSP database was used to screen the active ingredients and targets of core drugs,the target names were unified by Uni Prot database,disease targets of prediabetes mellitus were screened by Disgenet and Gene Cards databases,the intersection genes of core drugs and disease targets were obtained with Veney(2.1.0),and the core drug-active ingredient-target-target-disease network map was constructed through Cytoscape(3.7.2).The intersecting genes were imported into the String database for protein network interaction analysis and visualized by Cytoscape(3.7.2).GO and KEGG enrichment analysis of intersecting genes was performed using the Matescape database,and Micro Letter visualization was performed.Results:(1)A total of 124 doses of the first prescription of pre-diabetic patients were collected in this study,involving 135 flavors of traditional Chinese medicine,among which the top 10 flavors were Coptis chinensis,Dried ginger,Mulberry white skin,Zhimu,Yam,Yinchen,Mulberry leaves,Smallpox powder,Lychee kernel,and Milk thistle,and the frequency of use of the first 6 flavors was > 50%,which can be regarded as the core drug of Professor Zhang Xiaoke for the treatment of prediabetes mellitus.The most used are antipyretic drugs,deficiency medicines,and moisture-reducing drugs;The four qi of the drug are mainly cold,warm and flat;The five flavors are mainly bitter,sweet and bitter,and most of them are attributed to the spleen,stomach,lungs,kidneys and liver,of which the spleen and stomach are the main ones;The core drug pair was Coptis chinensis-dried ginger.Cluster analysis yielded 3 commonly used drug combinations.(2)A total of 94 core drug active ingredients for the treatment of prediabetes mellitus were screened,with a total of 222 targets,and a total of 1745 disease targets for prediabetes mellitus were screened,and 146 intersection genes were obtained by intersecting the two,of which AKT1,TP53,IL6,TNF,JUN,VEGFA,CASP3,IL1 B,HIF1A,PTGS2 were the core targets.The main components of core drug treatment for pre-diabetes are quercetin,kaempferol,β-sitanol,dioscin,stigmasterol and so on.GO(BP)5234 was obtained by analyzing the intersection genes,mainly involving the response of cells to lipids,the response of cells to hormones,and the response of cells to inorganic substances.GO(CC)486,mainly involving membrane rafts,transcriptional regulatory complexes,receptor complexes,etc.;GO(MF)825 articles,mainly involving DNA binding transcription factor binding,nuclear receptor activity,kinase binding,etc.KEGG analyzed a total of 259 pathways,among which AGE-RAGE signaling pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,and insulin resistance were the main pathways for core drugs to treat prediabetes mellitus.Conclusions:(1)Professor Zhang Xiaoke believes that the basic pathogenesis of PDM is medium full internal heat,spleen deficiency and dampness,and its progress is transmitted in the mode of three and four meridians,and the basic treatment is determined to clear heat and replenish deficiency,dissolve dampness and stagnation,and the medication is mainly to clear heat,replenish deficiency and dissolve dampness,cold,warm and flat coregulation,bitter,sweet and bitter together,treatment focuses on the spleen and stomach,often taking into account the lungs,kidneys and liver,the core drug pair is huanglian-dried ginger,and the core drugs are Coptis chinensis,Dried ginger,Mulberry white peel,Zhimu,Yam,and Yinchen.(2)The mechanism of action of core drug treatment of PDM may regulate the AGE-RAGE signaling pathway,PI3K-Akt signaling pathway,MAPK signaling pathway,IR,etc.in diabetic complications through its active ingredients,thereby affecting AKT1,TP53,IL6,TNF,JUN,VEGFA,CASP3,IL1 B,HIF1A,PTGS2 and other related protein activities to reduce blood glucose and improve the clinical symptoms of PDM.