Screening And Optimization Of Prescriptions For Qi Deficiency And Blood Stasis Syndrome In Diabetic Peripheral Neuropathy Based On Network Pharmacology

The development of new Chinese medicines is not only the need for clinical treatment of diseases,but also the main driving force for the development of the medical and health industry.The formulation of traditional Chinese medicine is the first step in the research and development of a new Chinese medicine formula and is the key to determining the success and failure of the development of a new Chinese medicine formula.Diabetic Peripheral Neuropathy(DPN)refers to the complication of symptoms or signs of peripheral nerve dysfunction in diabetic patients when other causes are excluded,with a high incidence,long course of disease,and the rate of disability and death after onset is high.Relevant data shows that the number of diabetes patients in China ranks first in the world with 114 million person-times,and the incidence of DPN has reached more than 50%of the total number of diabetes.Qi deficiency and blood stasis syndrome is the most common type of syndrome with DPN in traditional Chinese medicine.The treatment of Chinese medicine is very abundant,but the only Chinese medicine used in clinical practice is Mudan granule.Therefore,this study aims to discover the rules of drug use from a large number of clinical treatment DPN literatures through a combination of literature mining and network pharmacology,and to screen out new formulas suitable for drug development to lay the foundation for further new drug research and development.Objective:Develop an automatic extraction system for TCM literature data to improve the efficiency of literature data mining.Discover the DPN medication rules of TCM treatment by literature data mining and network pharmacology.Screen and optimize new drug candidates,and establish a new method of TCM formulation based on TCM clinical literature.Methods:1.Establishment of automatic extraction system of Chinese medicine literature data.Formulate the data storage structure of the clinical literature extraction system,use the diabetic nephropathy clinical literature as the system data source for the extraction test system to collect the drug use results,and manually verify the extraction results to complete the software iteration.2.Analysis of DPN medication rules based on clinical literature of traditional Chinese medicine.Collected the articles published in China National Knowledge Infrastructure(CNKI),Wanfang Database,China Biomedical Literature Service System(SinoMed)and Vip Database from 2008 to 2019,with the subjects of "Diabetic Peripheral Neuropathy" and "Traditional Chinese Medicine" and searched in PubMed database The literature is(diabetic peripheral neuropathy)AND TCM.After screening,a database is established,using frequency statistics,association rules,and data analysis methods to build a complex network to analyze the efficacy,frequency,property,taste of the classics,common drug pairs and core prescriptions.3.Optimization of the formulation of DPN with qi deficiency and blood stasis syndrome based on network pharmacology for the treatment.Search the chemical composition of candidate drugs in the TSMSP,TCMID,ETCM databases and screen them through OB,DL,Caco-2.Predict the drug target in the SwissTargetPrediction database.Retrieve the relevant genes of DPN in the OMIM and GeneCards databases,and obtain the corresponding standard words of symptom of DPN with qi deficiency and blood stasis syndrome in the HSDN database.The related genes of DPN with qi deficiency and blood stasis symptom are enriched by network module using in DPN genes and the genes of DPN with qi deficiency and blood stasis syndrome.And Enrichment of KEGG pathway for drug candidates and genes of DPN with qi deficiency and blood stasis syndrome are carried out.Calculate the correlation coefficient and contribution value of the candidate drugs,and determine the group with the cumulative contribution value of 80.00%as the optimized group.4.Comparison of the efficacy between new formula and Mudan granules for the treatment of DPN with qi deficiency and blood stasis syndrome based on network pharmacologyCalculate the sum of the correlation coefficients between the optimization group and Mudan granules,compare the sum of correlation coefficients between the optimization group and Mudan granules,and confirm the difference in efficacy between them.Results:1.Successfully established an automatic extraction system of traditional Chinese medicine literature data,and completed the system improvement and iteration through manual correction of the extraction results of the system on the clinical literature of diabetic nephropathy.2.A total of 461 papers for treatment of DPN were included in this study,including 275 kinds of TCM and a total frequency of 6 361 times.Astragali Radix had the highest frequency.Among all kinds of medicinal materials,activating blood circulation and removing stasis was the most commonly used medicine,followed by Qi-invigorating medicine.Flavor of medicines was mainly sugariness and warm,and most of their meridian tropism was liver meridian.After the analysis by association rules,the couplet medicinals with the highest support was Astragali Radix-Angelicae Sinensis Radix.The core medicines obtained by complex network analysis were Astragali Radix,Angelicae Sinensis Radix,Chuanxiong Rhizoma,Spatholobi Caulis,Cinnamomi Ramulus,Carthami Flos,Pheretima,Paeoniae Radix Rubra,Salviae Miltiorrhizae Radix et Rhizoma and Persicae Semen3.The candidate groups were identified as Astragali Radix,Angelicae Sinensis Radix,Chuanxiong Rhizoma,Spatholobi Caulis,Cinnamomi Ramulus,Carthami Flos,Pheretima,Paeoniae Radix Rubra,Salviae Miltiorrhizae Radix et Rhizoma,Persicae Semen,Glycyrrhizae Radix et Rhizoma,Dioscoreae Rhizoma,Atractylodis Macrocephalae Rhizoma,Codonopsis Radix,Achyranthis Bidentatae Radix,Hirudo,Cyathulae Radix,Corydalis Rhizoma,Myrrha,Olibanum,Curcumae Longae Rhizoma,Eupolyphaga Steleophaga,Manis Squama and Sappan Lignum.There are 336 genes related to DPN with qi deficiency and blood stasis syndrome and 214 enrichment pathways.The Chinese medicine with the highest correlation coefficient is Carthami Flos.The optimized formula is Carthami Flos,Astragali Radix,Salviae Miltiorrhizae Radix et Rhizoma,Myrrha,Glycyrrhizae Radix et Rhizoma,Dioscoreae Rhizoma,Corydalis Rhizoma,Codonopsis Radix,Spatholobi Caulis and Achyranthis Bidentatae Radix,the cumulative contribution value of whose accounted for 83.47%of the total candidates.4.The sum of correlation coefficient of the Mudan granules was 2.61×106,which was lower than which of the optimized formula of 4.15 × 106.Conclusion:1.Developed a new system that can automatically extract the use of drugs in the clinical literature of traditional Chinese medicine.2.It is found that the law of TCM clinical medicine for DPN prevention and treatment is mainly to benefit qi and blood circulation,to dredge collaterals and relieve pain.3.The use of network pharmacology screening has optimized a candidate prescription for the treatment of DPN with qi deficiency and blood stasis syndrome,whose curative effect is better than Mudan granules.4.A new method for screening and optimizing traditional Chinese medicine formula based on data mining and network pharmacology has been initially established.