Based On Datamining To Explore The Distribution Characteristics Of Traditional Chinese Medicine Syndrome Elements And Medication Rules In Diabetes Mellitus And Osteoporosis

Objective:In this study,data mining method was used to collect the clinical research literature on the treatment of diabetes mellitus(DM)and osteoporosis(OP)by traditional Chinese medicine(TCM)or integrated Chinese and western medicine in the past 20 years to summarize the rules of modern TCM in the treatment of DM and OP.The network pharmacology method was used to further explore the potential mechanism of core prescription in the treatment of DM and OP,in order to provide theoretical support for the treatment of DM and OP with TCM.Methods:Clinical literatures on the treatment of DM and OP by TCM or integrated Chinese and Western medicine were retrieved from China National Knowledge Internet(CNKI),VIP Database for Chinese Technical Periodicals(VIP)and Wanfang Date from January 1,2000 to September 30,2022.According to the inclusion and exclusion criteria,the eligible literature was screened out.The basic information of literatures,TCM syndrome type,observation group prescription and name of Chinese medicine were extracted,and the Excel database was established after data standardization.Then,Microsoft Excel 2019 was used to conduct frequency statistics of TCM syndrome types,diseases-location syndrome elements and diseases-nature syndrome elements after standardization,and statistics of the frequency of Chinese medicine,attribute statistics of Chinese medicine,the association analysis of traditional Chinese medicine,high-frequency hierarchical cluster analysis of Chinese medicine and analysis of the complex network of Chinese medicine were carried out by the web version of the Ancient and Modern Medical Records Cloud Platform(website:https://www.yiankb.com/).Then,the core prescription was obtained.In the end,to explore the mechanism of core prescription in the treatment of DM and OP by network pharmacology.First of all,by searching the Traditional Chinese Medicine systems pharmacology database and analysis platform(TCMSP)to obtain the active ingredients and action targets of the core prescription.Cytoscape3.9.1 software was used to construct the network diagram of "core formula-active ingredient-action targets" Gene Cards and Drug Bank databases were used to obtain the disease targets of DM and OP.Venny2.1 platform was used to draw Venn diagram and obtain the intersection between core prescription action targets and disease targets.Cytoscape3.9.1 was used to construct the "disease-target-componentdrug" network diagram to obtain the main effective components of core prescription in the treatment of DM and OP.The protein interaction network of core formula-DM and OP was constructed using STRING database,and then Cytoscape3.9.1 was used for processing and topology analysis.Finally,Gene ontology(GO)function and Kyoto encyclopedia of genes and genomes(KEGG)pathway enrichment analysis of intersection targets were performed based on David database.Results:1.Literature search results: A total of 90 literatures were included in this study,including 96 prescriptions and 137 Chinese medicinal herbs.2.The statistics of syndrome type and syndrome element:a total of 33 TCM syndrome types were extracted from the included literatures,and highfrequency TCM syndrome types were syndrome of liver-kidney Yin deficiency,syndrome of kidney deficiency and blood stasis,syndrome of kidney Yang deficiency,syndrome of kidney Yin deficiency,syndrome of qi and Yin deficiency,syndrome of the blood stasis and meridian-collaterals obstruction,syndrome of spleen and stomach qi deficiency,syndrome of spleen and kidney deficiency and syndrome of blood stasis.Seven diseases-location syndrome elements and 12 diseases-nature syndrome elements were obtained.The diseases-location syndrome elements included kidney,spleen,liver,meridians,stomach,lung and bone collaterals.The top four diseases-location syndrome elements were kidney,spleen,liver and meridians.diseases-nature syndrome elements included blood stasis,Yin deficiency,qi deficiency,Yang deficiency,qi stagnation,essence deficiency,etc.Among them,blood stasis,Yin deficiency,qi deficiency,and Yang deficiency occur more frequently.3.The analysis of Chinese medicine:(1)the statistics of high-frequency Chinese medicines:Among 137 traditional Chinese medicines,32 traditional Chinese medicines appeare more than 10 times.In descending order of the occurrence frequency,the top 10 Chinese medicines were Ripe Rehmanniae,Cornus officinalis,Dioscoreae Rhizoma,Astragalus membranaceus,Salvia miltiorrhiza,Achyranthes niuxi,Wolfberry,Epimedium,Angelica sinensis,Bone broken tonic.(2)The attribute statistics of Chinese medicine:The main natures of Chinese medicine used in clinical practice are warmth and smooth,and its main medicinal flavor is sweet,followed by bitter and pungent.Its chief meridian tropism is kidney meridian,liver meridian and spleen meridian.4.The analysis of association rules of Chinese medicine:A total of 11 herb pairs were obtained.According to the descending order of co-occurrence,the top 5 herb pairs were Cornus officinalis-Prepared Rehmannia Root,Dioscoreae Rhizoma-Prepared Rehmannia Root,Dioscoreae Rhizoma-Cornus officinalis,Cornus officinalis-Dioscoreae Rhizoma,Lycium barbarum-Prepared Rehmannia Root.5.High-frequency hierarchical cluster analysis of Chinese medicine:Hierarchical cluster analysis is performed on 32 Chinese medicines with frequency ≥10,and 5 cluster combinations were obtained:A1: Cornus officinalis,Dioscoreae Rhizoma,Prepared Rehmannia Root,Lycium barbarum;A2: Epimedium,Astragalus,Salvia;A3: Eucommia,Angelica,Drynaria,Achyranthes;A4: Antler glue,Sichuan Achyranthes,Polygonati Rhizoma,Dodder,Aconite;A5: Rhizoma Anemarrhenae,Rhizoma Chuanxiong,Fructus Schisandrae Chinensis,Radix Ophiopogonis,Oyster,Radix Paeoniae Alba,Radix Rehmanniae,Radix Dipsaci,Earthworm,Rhizoma Atractylodis Macrocephalae,Herba Taxilli,Fructus Psoraleae,Rhizoma Alismatis,Cortex Moutan,Poria,Radix Glycyrrhizae.6.Analysis of the complex network of Chinese medicine:A complex network analysis of 137 Chinese medicines were performed to obtain the core prescription for clinical treatment of DM and OP.Including Prepared Rehmannia Root,Dioscoreae Rhizoma,Cornus Officinalis,Lycium Barbarum and Twotooth Achyranthes Root.7.Network pharmacology of core prescriptions:(1)The core prescription contained 91 active ingredients and 205 targets.(2)There were 1158 disease targets in DM and OP,and 94 intersecting targets with core prescription action targets.(3)In the “disease-target-component-drug” network,the active components with higher degree values were quercetin,stigmasterol,kaempferol,wogonin and β-sitosterol,ect.(4)There are 25 key targets in the treatment of DM and OP with core prescription.,including catalase、interleukin1β、Caveolin 1,Protein Kinase B1,prostaglandin-endoperoxide synthase 2,ect.(5)GO biological process and KEGG pathway enrichment analysis were performed for potential targets.GO biological processes were mainly including positive regulation of gene expression,positive regulation of transcription,DNA-templated and positive regulation of transcription from RNA polymerase II promoter,ect.Cellular Component were mainly including extracellular space、extracellular region and macromolecular complex,ect.;Molecular Function were mainly including enzyme binding,identical protein binding,steroid hormone receptor activity,ect.Conclusion(s):1.Clinical DM and OP was more common in 7 types of syndromes such as liver and kidney yin deficiency syndrome,kidney deficiency and blood stasis syndrome,and kidney yang deficiency syndrome,kidney yin deficiency syndrome,Qi and Yin deficiency and blood stasis syndrome.Its main disease locations were kidney,spleen,liver and meridians,and blood stasis is the most vital pathological factor.2.Ripe Rehmanniae,Cornus Officinalis,Dioscoreae Rhizoma,Astragalus Membranaceus,Salvia Miltiorrhiza,Achyranthes Niuxi,Wolfberry,Epimedium,Angelica Sinensis,Bone Broken Tonic were commonly used Chinese medicines in clinic.The main nature of Chinese medicine used in clinical practice are warmth and smooth,and its main medicinal flavor wassweet,followed by bitter and pungent.Its major meridian tropism was kidney meridian,liver meridian and spleen meridian and the efficacy focused on tonifying liver and kidney,strengthening muscles and bones and replenishing yin and blood.3.The main principle of Chinese medicine compatibility was “nourishing liver and kidney,invigorating spleen and qi,removing blood stasis and clear meridians”.Treating deficiency and excess syndrome at the same time and achieving dredge by tonification,which make bones strong,tendons soft,blood and qi unblocked.4.The active ingredients such as quercetin,stigmasterol,kaempferol,wogonin and β-sitosterol in the core prescription may act on the targets such as catalase,interleukin-1β,caveolin 1,protein kinase B1,and prostaglandin endoperoxidase 2.,affecting AGE-RAGE signaling pathway in diabetic complications、Lipid and atherosclerosis、Fluid shear stress and atherosclerosis、IL-17 signaling pathway、TNF signaling pathway other metabolic and inflammatory signaling pathways,intervening in the proliferation and differentiation of skeletal cells,improve chronic inflammation and glucose and lipid metabolism disorder to achieve the purpose of treating DM and OP.