A Preliminary Study On The Medication Law Of Professor Tan Zihu In The Treatment Of Insomnia Based On Data Mining And Network Pharmacology

Research objective: Based on the ancient and modern medical case platform V2.3.5 and IBM SPSS Modeler 18.0,excavated professor Tan Zihu’s experience in the treatment of insomnia.Based on network pharmacology technology,explored the mechanism of the core formula in the treatment of insomnia,so as to provide ideas and directions for later clinical and basic experiments.Research Methods:（1）extracted basic information of 789 patients with insomnia who first visited Tan Zihu’s clinic from January 2020 to December 2020 and their first prescription information;Standardized the drug names,nature,flavor return of menstruation and efficacy of 175 Chinese medicines involved,and use the ancient and modern medical case platform V2.3.5 to conduct statistical analysis of the patient’s general situation,frequency of single medicine,frequency of high-frequency drug types,and frequency of nature and flavor,menstruation;Use IBM SPSS Modeler 18.0 to analyze the association rules of the 789 prescriptions;Carried out clustering and complex network analysis of 789 first prescriptions according to the ancient and modern medical case platform V2.3.5;According to IBM SPSS Modeler 18.0,the association rules and network analysis of the corresponding drugs of each TCM certificate type were carried out.（2）The Pharmacological Analysis Platform of Chinese Medicine System（TCMSP）was used to obtain the active ingredients of drugs and their targets;according to the Gene Cards database,OMIM database,Drugbank database,TTD database,"Insomnia,Chronic Insomnia,Primary insomnia,Psychophysiological Insomnia" as the search term,to search for disease-related targets;used cytoscape 3.6.0 software to build a "Chinese medicine active ingredient-target" network,used the "Cyto NCA" function to analyze its topological properties;used string database to build a PPI network,and analyzed the PPI results with cytoscape 3.6.0 software,filtered the core network according to the topological analysis results such as degree values,mediat values,and centrality values;carried out the GO and KEGG analyse with the database.Research results:（1）Data mining analysis results:（1）General situation: The male to female ratio in 789 patients was 0.41:1.The age group with the highest incidence is 50-59 years old;（2）Single herb: a total of 175 traditional Chinese herbs are involved,The total frequency of herb is 12688 times.There are 7 drugs with a single drug use percentage greater than 50%,which were bupleurum,licorice,bighead,atractylodes,rhizome,Semen Ziziphi Spinosae,Poria with hostwood,paeony,angelica;（3）Four qi and five flavors: the drugs with flat、warm、mild cold are the most used,and the top three flavors types that were most used are sweet,bitter and spicy drugs;（4）Meridian analysis: In this study,the drug mainly involves the spleen,liver,heart and stomach meridian;（5）Types of high-frequency drugs: The top 3in the efficacy classification statistics are tonic drugs,tranquilizers,and qi regulating drugs;（6）Analysis of association rules: When Professor Tan Zihu treated insomnia,the commonly used two medicines compatibility was:bupleurum-paeony / Angelica / bighead atractylodes rhizome,bighead atractylodes rhizome-Angelica / Poria with hostwood,licorice-angelica / Poria with hostwood;The combination of three medicines: bighead atractylodes rhizome-bupleurum-Poria with hostwood / Semen Ziziphi Spinosae / licorice / paeony,Semen Ziziphi Spinosae-Poria with hostwood-licorice / bighead atractylodes rhizome,bighead atractylodes rhizome-Poria with hostwood-licorice;（7）Cluster analysis: Chinese medicines used at a high frequency are mainly clustered into five categories;（8）Complex network analysis: Through the complex network analysis of 789 prescriptions,the core prescription composition of Tan ’ s treatment of insomnia is obtained:bupleurum、 licorice、 bighead atractylodes rhizome、 Semen Ziziphi Spinosae、 Poria with hostwood、 paeony;（9）Through the correlation rules and network analysis of various types of drugs,combined with the results of cluster analysis,it is clear that the commonly used associated herb pairs as supplements for the 6 syndrome types are:Fructus Gardeniae,Gentianae Radix Et Rhizoma,Dendrobii Caulis,rose,dandelion;Semen Plantaginis,Chen-Pi,Pinelliae Rhizoma,Coix seed,Bambusae Caulis In Taenias;Codonopsis pilosula,Radix Astragali,Polygni Multiflori Caulis,Polygalae Radix,Fructus Amomi;Margaritifera Concha,Os Draconis,Ostreae Concha;Coptidis Rhizoma,Cinnamomi Cortex,Rehmanniae Radix Praeparata,Corni Fructus;Codonopsis pilosula,Radix Astragali,Radix Ophiopogonis,Glehniae Radix,Fructus Tritici Levis.（2）Results of network pharmacological analysis:（1）Chemical composition and action targets of the core formula: a total of116 species,a total of 414 candidate targets were obtained after removing duplicate values,The key chemical components of the core formula are quercetin,kaempferol,carotene,isorpentin,α-eauxinol,lycopene,β-sitosterol,and sterol;（2）Disease targets,intersection targets and core target screening: A total of 1052 insomnia targets were obtained.There were 110 intersection targets between the core prescription candidate targets and the Insomnia disease targets,and the key targets are TNF,AKT1,IL-6,IL-1β,MAPK3;（3）GO enrichment analysis results: GO enrichment analysis obtained a total of 606 entries,the core party mainly by regulating the genes of these biological processes which including cell’s response to drugs,chemical synapse transmission,cholinergic synaptic transmission,steroid metabolism,etc.And affected the cellular components such us the postsynaptic membrane,cell membrane,cell connection.By intervening in the activity of extracellular ligand-gated ion channel activity、drug binding、heme binding、enzyme binding and other molecular functions;（4）KEGG enrichment analysis results: A total of 107 KEGG pathways are involved,such us Neuroactive ligand-receptor interaction、Calcium signaling pathway 、 Serotonergic synapse 、 Cholinergic synapse 、 TNF signaling pathway、Steroid hormone biosynthesis、Dopaminergic synapse、Glutamatergic synapse、HIF-1 signaling pathway etc.Conclusions:（1）The data mining was carried out by using algorithms such as drug frequency analysis,cluster analysis,correlation rules,and network analysis,and the results showed Professor Tan Zihu’s clinical diagnosis and treatment ideas for insomnia and the law of drug prescription: the basic mechanisms of insomnia are liver qi depression,spleen and stomach disharmony,and heart loss.Therefore,liver thinning,spleen management,and heart nourishment should run through the treatment of insomnia.The medication is mainly to tonify the deficiency,rationalize the qi,and calm the spirit,pay attention to the homophony of the heart,liver and spleen,and take into account the qi,blood,yin and yang.（2）The core formula may act on key targets such as TNF,AKT1,IL-6,IL-1 β,MAPK3 through active ingredients such as quercetin,kaempferol,carotene,isolithrin,α-lycoperol,7-methyl-2-methoxyisoflavone,sylvestris anthracidin,naringen,β-sitosterol,and sterol to regulate Neuroactive ligand-receptor interaction pathway 、 Calcium signaling pathway、 Serotonergic synapse、 Cholinergic synapse、 TNF signaling pathway 、 Steroid hormone biosynthesis 、Dopaminergic synapse、 Glutamatergic synapse、 HIF-1 signaling pathway.Thus exerting the effects of anti-inflammatory,antioxidant stress,regulating synaptic plasticity,regulating sleep-wake mechanism.