Professor Mao Lijun's Medication Rules And Network Pharmacology Research For Insomni

Objective:To explore the medication rules of Professor Mao Lijun’s treatment of insomnia through data mining methods,and to analyze the core prescriptions by network pharmacology methods,and to explore the biological mechanism of treating insomnia,laying a foundation for later clinical and basic research.Methods:Collect medical record information of 423 insomnia patients who were treated at Professor MaoLijun’s outpatient clinic from 2020 to 2022 according to the inclusion and exclusion criteria,and standardize the clinical manifestations,names of traditional Chinese medicines,properties and meridians,and efficacy involved in the prescriptions.Then create a standardized medical record database in Excel,and use the Ancient and Modern Medical Case Cloud Platform to perform frequency analysis on patient basic information,clinical manifestations,and frequency,properties,meridian distributions,effect of the drugs.Then perform association rule analysis,clustering analysis,and complex network analysis on the drugs in the collected prescriptions to obtain medication rules and extract the core prescriptions.Use the BATMAN-TCM database to predict the effective ingredients and related targets of core prescriptions.Obtain disease-related targets from OMIN,GeneCards,DisGeNET,PharmGKB,TTD,and DrugBank databases,intersect disease targets with drug targets to obtain intersection target genes,and use Cytoscape3.91 software to build a"Medicine-Ingredient-Target" network to analyze the key ingredients involved in the intervention of insomnia in the core prescription.Build a protein interaction network through the STRING database and import the protein interaction results into Cytoscape to select core targets.Use the DAVID database to conduct GO and KEGG enrichment analysis of intersection genes to obtain possible biological mechanisms of the core prescription for treating insomnia.Resrults:The 423 patients included in the study were mainly middle-aged and elderly,with the most concentrated age group being 40-59 years old.There were more females than males,and the main insomnia-related symptoms were difficulty falling asleep,followed by light sleep,early waking,and difficulty sleeping after waking up.Associated symptoms mainly included anxiety,palpitations,and low mood.The efficacy of high-frequency drugs mainly focused on calming the mind,relieving depression,sedation,nourishing yin,supplementing deficiency,and clearing heat.The nature of the drugs was mainly cold and neutral,with few involving extremely cold or hot drugs,and the taste was mainly sweet and bitter.The drug pairs extracted through association rules were Ligustrum Lucidum paired with Ecliptae Herba,Rhizoma Pinelliae paired with Caulis Bambusae,Rhizoma Pinelliae paired with Citri Reticulatae Pericarpium,Radix Bupleuri paired with Cyperi Rhizoma,Ziziphi Spinosae Semen paired with Platycladi Semen,Os Draconis paired with Calcined Oyster,Lycii Cortex paired with Radix Stellariae,Radix Curcumae paired with Rosae Rugosae Flos,Rehmannia Glutinosag paired with Radix Scrophulariae,Dens Draconis paired with Nacres,etc.By conducting cluster analysis,high-frequency drugs are grouped into eleven categories:Radix Pseudostellariae,Atractylodes Macrocephala Rhizoma,Poria Cocos;Calcined Oyster,OsDraconis,Liliums,Albiziae Flos;Polygni Multiflori Caulis;Radix Bupleuri,Cyperi Rhizoma,Radix Curcumae,Rosae Rugosae Flos;Nacres,Albiziae Cortex,Ziziphi Spinosae Semen;Gardenia Jasminoides,Moutan Cortex;Dens Draconis,Fluoritum;Radix Scutellariae,Citri Reticulatae Pericarpiumi,Caulis Bambusae,Rhizoma Pinelliae;Radix Angelicae Sinensis,Rehmannia glutinosag,Schisandrae Chinensis Fructus,Radix Scrophulariae,Radix Glehniae;Anemarrhenae Rhizoma,Radix Stellariae,Cortex Lycii;Radix Ophiopogonis,Ligustrum lucidumi,Ecliptae Herba.The core prescription composition obtained through complex network analysis was Ziziphi Spinosae Semen,Albiziae Cortex,Nacres,Radix Curcumae,Cyperi Rhizoma,and Rosae Rugosae Flos.Through network pharmacology research,the top 10 ranked components obtained are:betulin,isoamyl alcohol,patchoulenone,carvone,curcumene,rotundone,curdione,turmerone,isoamylamine,norepinephrine,betulinic acid,and N-methylcorydaldine.The key target points in the core prescription for treating insomnia include BDNF,ALB,INS,DRD2,TH,GRIN2B,TAC1,IL6,IL1B,CRH,TNF,GRIN2A,MAPK3,GRIA1.The top 10 entries enriched in GO BP include Chemical synaptic transmission,excitatory postsynaptic potential,neurological system process,regulation of membrane potential,ion transmembrane transport,G protein-coupled receptor signaling pathway(coupling nucleotide second messenger),regulation of postsynaptic membrane potential,response to drug,gamma-aminobutyric acid signaling pathway,and G protein-coupled serotonin receptor signaling pathway.The top 10 entries enriched in GO CC cell component analysis include postsynaptic membrane,integral component of plasma membrane,synapse,neuronal projection,dendrite,GABA-A receptor complex,plasma membrane,integral component of presynaptic membrane,presynaptic membrane,and chloride channel complex.The top 10 entries enriched in GO MF analysis include neurotransmitter receptor activity,transmitter-gated ion channel activity involved in regulation of postsynaptic membrane potential,Excitatory extracellular ligand-gated ion channel activity,extracellular ligand-gated ion channel activity,GABA-A receptor activity,G protein-coupled serotonin receptor activity,GABA-gated chloride ion channel activity,inhibitory extracellular ligand-gated ion channel activity,benzodiazepine receptor activity,and acetylcholine-gated cation-selective channel activity.The top 20 pathways enriched in KEGG analysis are as follows:neuroactive ligand-receptor interaction,nicotine addiction,cAMP signaling pathway,retrograde endocannabinoid signaling,morphine addiction,calcium signaling pathway,amphetamine addiction,serotonergic synapse,dopaminergic synapse,GABAergic synapse,cocaine addiction,circadian entrainment,taste transduction,pathways of neurodegeneration-multiple diseases,cholinergic synapse,chemical carcinogenesis-receptor activation,cGMP-PKG signaling pathway,long-term potentiation,renin secretion and alcoholism.Conclusions:Professor MaoLijun emphasizes the influence of emotional abnormalities on the occurrence and development of insomnia in clinical treatment of insomnia.The treatment emphasizes the interaction between organs and advocates the use of dynamic perspective based on the concept of "five organs integrated" to prescribe medicine.The prescription should be determined based on the degree of deficiency and excess in different diseases.The core prescription for treating insomnia may involve intervention in various neurochemical transmissions,nutrition and remodeling of nerve cells,regulation of hormone levels,secretion of cell inflammatory factors,circadian rhythm entrainment,cAMP signaling pathway,cGMP-PKG signaling pathway,calcium signaling pathway,neurodegenerative pathways,etc.The intervention of the core prescription in treating insomnia is a result of the complex interactions of multiple targets and pathways.