Based On Data Mining And Network Pharmacology Methods, A Preliminary Study On The Prescription Rules Of Professor Mao Lijun For Treating Depression

Purpose:Through the use of modern data mining methods such as cluster analysis and association analysis to conduct retrospective research on Professor Maolijun’s prescriptions for treating depression patients,her systematically integrated the basic prescriptions and commonly used drug pairs for Professor Maolijun’s syndrome differentiation and treatment of various syndrome types,and analyzed relevant drug experience.Improve the accuracy of clinical medication.Professor Maolijun’s basic core prescription for the treatment of depression based on data mining expounds its intervention mechanism through the network pharmacology model method,and clarifies the molecular biological mechanism.Methods:1.Strictly screen the patients who were diagnosed as "depressed" by Professor Maolijun in the Xiyuan Hospital,China Academy of Chinese Medical Sciences according to the acceptance criteria.A total of 851 prescriptions were used.Office was used to establish a database of patient prescriptions for Chinese medicine,and then IBM SPSS was adopted.Statistic 25.0 and SPSS Modeler 18.0 software perform descriptive statistical analysis,cluster analysis and association rule analysis of patients on the database.2.Use the TCMSP and BATMAN-TCM databases to mine the active ingredients in rose,turmeric,rot,mother-of-pearl and Albizia bark through the TCM system pharmacology analysis platform,and use the PharmMapper pharmacophore database to predict potential targets;through GeneCards/OMIM database to obtain currently known disease targets related to depression;then use R language software to screen out the intersection of traditional Chinese medicine and depression targets,create a Venn diagram and use Cytoscape 3.8.0 software to build protein-protein interactions Relation network diagram,and then screen the core targets according to the degree algorithm,and finally use the R software to conduct biological process enrichment analysis and metabolic pathway enrichment analysis on the key targets.Result:1.Judging from the distribution of TCM syndrome types,234 cases were syndrome of heart-yin deficiency,accounting for 28%;213 cases of liver and kidney yin deficiency,accounting for 25%;197 cases of phlegm-heat disturbance,accounting for 23%;There were 130 cases of liver qi stagnation syndrome,accounting for 15%;77 cases of heart and spleen deficiency syndrome,accounting for 9%.From the perspective of the frequency distribution of medicines,the 20 Chinese medicines with the highest frequency and frequency are mother-of-pearl,turmeric,xiangfu,rose,albizia bark,shouwu vine,bleu,wild jujube seed,peony bark,amethyst,and raw Dragon Tooth,Angelica,Gardenia,Taizi Ginseng,Rehmannia glutinosa,Scrophulariaceae,Tangerine Peel,Baiziren,Radix Adenophora,Poria.It is mainly based on Qi regulating,tranquilizing and nourishing yin drugs.2.Based on the results of cluster analysis,combined with clinical practice,it is clear that the drug composition of the five basic prescriptions of syndrome types are:①Stagnation of liver qi:Chenpi,Bupleurum,Chuanxiong,Zhishi,Turmeric,Cyperus rot,Rose,Mother-of-pearl,Muxiang,Magnolia officinalis,Inula,Perilla stalk;②Phlegm-heat disturbance syndrome:Pinellia,Zhuru,Dannanxing,Mother-of-pearl,Citrus aurantium,Acorus calamus,Polygala,tangerine peel,Poria;③Heart Deficiency of the spleen:Codonopsis,Radix Atractylodes,Poria,Astragalus,Suanzaoren,Muxiang,Angelica,Salvia,Polygala,Fushen;④Insufficiency of heart and yin:Taizishen,Scrophulariaceae,Radix Poly gala,Poly gala,Poria Shen,Ophiopogon,Schisandra,Bozi kernel,Sour date kernel,Shouwu vine,Albizia bark,Rehmannia glutinosa,Gardenia,Moutan cortex;⑤Deficiency of liver and kidney yin:Chinese wolfberry,chrysanthemum,Rehmannia glutinosa,Cornus,Chinese yam,Moutan bark,Alisma,Poria,Ligustrum lucidum,Eclipta prostrata,Angelica,Digu Bark,Sour date kernel.3.Based on the results of association rules and clinical practice,it is clear that the commonly used associated drug pairs for the 5 syndrome types are:①Stagnation of liver qi:mother-of-pearl-rose-xiangfu-bupleurum-turmeric;②phlegm-heat disturbs the spirit Syndrome:Zhuru-Yujin-Bupleurum-pinellia;③Deficiency of heart and spleen:Astragalus/Angelica-muxiang-Bupleurum-Bleu-Bai Ziren;⑤syndrome of liver and kidney yin deficiency:Rehmannia glutinosa-Eclipta prostrata-Ligustrum lucidum-Moutan cortex.4.Comprehensive analysis of the composition of the basic prescriptions of each syndrome type,combined with the overall taste frequency statistics of 851 prescriptions,confirmed by Professor Mao Lijun,it is clear that the final core prescription drugs are set as:mother-of-pearl,xiangfu,turmeric,rose,albiziabark.5.Analyze the molecular biological mechanism of core drug interventions in the treatment of depression through network pharmacology:①The main active ingredients of core drugs:norepinephrine(NE),lycopene LYC,flavonoids quercetin,naringenin,luteolin,kaempferol,isorhamnetin,etc.and alkaloid β-gluten Sterols,stigmasterol,etc.②Core targets:AKT1,TP53,MAPK1,CASP3,IL6,EGFR,TNF,ESR1,CCND1,EGF;types:transcription factors,kinases,inflammatory factors,growth factors,etc.③GO enrichment analysis result:compound target-depression target is analyzed by biologcal process(BP),and the key target is mainly involved in cytochemical stress reaction,reactive oxygen reaction,oxidative stress reaction,inorganic reaction,lipid Regulation of polysaccharide response,etc.Cellular component(CC)analysis found that the target protein is mainly regulated in the cell membrane,plasma membrane protein complex,receptor complex,membrane surface,vesicle cavity,secretory granule cavity,and cytoplasmic vesicle cavity.Molecular function(MF)analysis shows that the target is mainly involved in protein kinase activity,RNA polymerase II specific DNA binding transcription factor,protein phosphatase binding,phosphatase binding,kinase regulatory activity,DNA binding transcription factor binding,peptide Regulation of binding,protein kinase regulatory activity,ubiquitin-like protein ligase binding,transmembrane receptor protein tyrosine kinase activity,etc.④KEGG enrichment analysis results:tumor,PI3K-Akt,AGE-RAGE,MicroRNAs,HIF-1,MAPK,C-type lectin receptor and other signaling pathways.Summary:1.The first part of the study uses algorithms such as drug frequency analysis,cluster analysis,and association rules to conduct data mining one by one.The results obtained show Professor Maolijun’s clinical differentiation and treatment ideas and prescription rules for depression:depression is mostly based on yin deficiency Pathogenesis,yin and blood dark consumption are often the final pathological result.The treatment is to nourish yin,nourish blood and invigorate the spleen,soothe the liver,nourish the heart and calm the nerves;liver depression is a pathological process of depression,and it is also the pathogenesis from beginning to end.The method of relieving depression of the liver should be used throughout the whole course of treatment;for new patients,the main method is to invigorate the spleen and soothing the liver,and for chronic patients,to nourish yin and blood,nourish the heart and calm the nerves.Medications are mainly based on regulating qi and soothe the nerves,nourishing yin and clearing away heat;the course of depression is relatively slow,and medication should not be severe.At the same time,attention should be paid to nourishing the heart and spleen without being too dry,and nourishing the liver and kidney without being too greasy.2.The network pharmacology part of the research systematically analyzed the molecular mechanism of Professor Maolijun’s core drugs for treating depression,and obtained 65 active ingredients and 93 core drugs for the treatment of depression.Among them,the more critical ones can be more effective in treating depression.The most influential active ingredients include norepinephrine(NE),lycopene LYC,flavonoids quercetin,naringenin,luteolin,kaempferol,isorhamnetin,etc.and the alkaloidβ-sitosterol,Stigmasterol,etc.The core prescription drugs pass on the core targets AKT1,MAPK1,IL6,TNF,and EGF.And PI3K-Akt signaling pathway,MAPK signaling pathway,and effective regulation of microRNA signaling pathway to treat depression.