Research On The Regularity Of Prescription And Dialectics In The Treatment Of Schizophrenia Based On Data Mining

Objective:Through the excavation of literatures related to the clinical trials of traditional Chinese medicine in the treatment of schizophrenia,this study analyzed the syndrome differentiation and medication rules of TCM in the treatment of schizophrenia,and discussed the core combination and effective prescription composition of TCM in the treatment of schizophrenia.Based on network pharmacology,the mechanism of core TCM combination in the treatment of schizophrenia was discussed.And the mechanism was verified by molecular docking.The purpose was to provide a reference for the prescriptions of TCM in the treatment of schizophrenia,and to provide ideas for new drug development.Methods:The clinical research literature for schizophrenia treatment was collected from China National Knowledge Infrastructure Database,Wanfang Database,China Science and Technology Journal Database and Pub Med websites.The papers were published from January 1st,2000 to June30th,2022.Effective papers were screened by inclusion and exclusion criteria.And then,the information of effective papers was extracted.The database was established after standardized processing.Microsoft Office Excel 2016 was used to describe the general information,diagnostic information,case information and herb,property and flavor and meridian of the literature.The association regularity of high-frequency traditional Chinese medicine was analyzed,and the core combination of TCM was obtained with the help of IBM SPSS Modeler 18.0.The cluster analysis of high frequency Chinese medicine was carried out by IBM SPSS Statistics 29.0,the regularity of herb use was summarized,and effective prescriptions were obtained.Based on Traditional Chinese Medicine Systematic Pharmacology Database and Analysis Platform（TCMSP）and Sym Map platform,the chemical components of the core combination of traditional Chinese medicine were searched.The active components and related target proteins were screened according to OB and DL.At the same time,genes related to schizophrenia were searched in Gene Cards database.The intersection genes of the core combination of traditional Chinese medicine and schizophrenia were uploaded to the STRING platform to get the Chinese medicinal material components-schizophrenia targets PPI network model.And then,GO and KEGG enrichment analysis were performed by Metascape platform.The important pathways of core Chinese medicine combination in the treatment of schizophrenia were screened out.With the help of Cyto Scape 3.8.0,the core TCM combination components-schizophrenia targets-signaling pathways network was constructed,and the network topology parameters were analyzed to further judge the main active components,the core targets and the mechanism of action.Finally,Molecular docking was performed by Auto Dock 1.5.7 to verify the reliability of the mechanism prediction.Results:1 Statistical resultsA total of 142 articles were included.The age distribution showed that64.79%of the literature were published in recent ten years.The regional distribution showed that there were more studies in the eastern region than in the western region.The articles with funds support accounted for 19.01%.And papers published in key periodicals accounted for 29.58%.The diagnosis of disease name was mainly madness.And the stagnation of phlegm and qi,phlegm and fire internal disturbance,and qi and blood stasis were the most common types in the diagnosis of symptom type.The number of cases included in the literature was more than 50,accounting for 90.85%.And the treatment response rate≥80%accounted for 88.73%.The top three duration of therapy were 8 weeks,12 weeks and 6 weeks.The drug most commonly used in the control group was Risperidone.The most commonly used evaluation index of curative effect was PANSS.In this study,there were 260 prescriptions and 188 kinds of Chinese medicinal materials were included,and the total frequency of drug use was2972.The top three drugs with the highest frequency were Liquorice Root,Grassleaf Sweetflag Rhizome and Indian Bread.The main meridians were heart,lung and spleen.The main properties were warm,plain and cold.And the main flavors were bitter,sweet,pungent.The frequency of toxic drugs was172.2 Data mining resultsAccording to the analysis of association rules,the core drug combination with the strongest relationship was"Grassleaf Sweetflag Rhizome-Bile Arisaema".And five kinds of prescriptions were obtained by cluster analysis.The first category included Peach Seed,Red Peony Root,Chinese Thorowax Root,Nutgrass Galingale Rhizome,Danshen Root.The second category included Grassleaf Sweetflag Rhizome,Bile Arisaema,Turmeric Root Tuber,Immature Orange Fruit,Bamboo shavings,Pinellia Tuber,Dried Tangerine Peel,Indian Bread,Common Aucklandia Root.The third category included Baical Skullcap Root,Cape Jasmine Fruit,Rhubarb,Golden Thread,Bone Fossil of Big Mammals.The fourth category included Largehead Atractylodes Rhizome,Tangshen.The fifth category included Dried Rehmannia Root,Dwarf Lilyturf Tuber,Thinleaf Milkwort Root,Indian Bread with Pine,Chinese Angelica,Szechwan Lovage Rhizome,Milkvetch Root,Chinese Magnoliavine Fruit,Spine Date Seed,Liquorice Root,White Peony Root.3 Network pharmacological analysis resultsIn this study,there were 10 active components in the core drug combination"Grassleaf Sweetflag Rhizome-Bile Arisaema".151 drug targets and 1056 potential targets for schizophrenia were obtained.There were 48intersection targets.The results of topological analysis showed that the main active components of"Grassleaf Sweetflag Rhizome-Bile Arisaema"in the treatment of schizophrenia were phorbol,kaempferol and so on,and RELA,IL-6 and TNF were the core targets.GO and KEGG enrichment analysis showed that cellular components or structures of"Grassleaf Sweetflag R h i zo m e-B i l e A ri s a em a"in the treatment of schizophrenia mainly were postsynaptic,synaptic membrane,postsynaptic membrane,and the targets were mainly concentrated in cancer pathway and PI3K/Akt pathway.4 Molecular docking resultsThe molecular docking results showed that there were 13 kinds with binding energy<-5.0 k J·mol^-1,accounting for 86.67%.Among them,TNF had the best binding activity with phorbol,whose binding energy was-7.09k J·mol^-1.Conclusions:1、The stagnation of phlegm and qi was the most common in schizophrenia which was diagnosed as epilepsy in TCM,phlegm and fire internal disturbance was more common in mania,and qi and blood stasis was more common in schizophrenia with a long course of disease.The principles of TCM treatment for schizophrenia was to consciousness restor resuscitat,resolving phlegm,and regulating yin and yang.Liquorice Root,Grassleaf Sweetflag Rhizome and Indian Bread were often used.The drugs of regulating qi and resolving phlegm were used for the stagnation of phlegm and qi.Removing pathogenic fire and resolving phlegm drugs were used for phlegm and fire internal disturbance.And regulating qi and activating blood drugs were used for qi and blood stasis.2、The core combination of traditional Chinese medicine in the treatment of schizophrenia was"Grassleaf Sweetflag Rhizome-Bile Arisaema".3、Five prescriptions of Chinese medicine for the treatment of schizophrenia were drawn.The first category was suitable for qi and blood stasis schizophrenia.The second category was suitable for the stagnation of p h l e g m an d q i schizophrenia.The third category was suitable for schizophrenia such as phlegm and fire internal disturbance and liver fire exuberance.The fourth category was the basic drugs for deficiency of vital energy schizophrenia.The fifth category was suitable for schizophrenia with heart and spleen deficiency,spleen and kidney deficiency.4、It was predicted that the main active components of core drugs in the treatment of schizophrenia were phorbol,kaempferol and so on,which acted on RELA,IL-6,TNF and other targets to affect the signal transduction of neurotransmitters through cancer pathway and PI3K/Akt pathway.