Director Cui Xiangning's Medication Rule And Network Pharmacology In The Treatment Of Hypertension Complicated With Insomnia

Objective:1.Using the TCM Inheritance Auxiliary Platform to explore the medication rule of chief physician Cui Xiangning for treatment of hypertension combined with insomnia,screen out the core drugs and combine her clinical experience.2.Using the network pharmacological method to analyze the mechanism of treating different diseases with same method" of core drugs in treatment of hypertension and insomnia.Methods:1.Collect clinical records of cases with hypertension and insomnia treated by chief physician Cui Xiangning in cardiology department at China Academy Medical Sciences Guang'an men hospital from September 2018 to September 2020,enter the data to the TCM Inheritance Auxiliary Platform(V2.5),standardize the data and establish the data base;The medication rule was analyzed by function of frequency statistics,association rules,and complex entropy clustering;Combining clinical followup study,summarize the clinical experience of chief physician Cui Xiangning.2.Screen out the active ingredients and targets,then obtain the common targets of hypertension and insomnia,then the intersection of drug target and disease target was mapped as the "treating different diseases with same method" targets of core drugs in treatment of hypertension and insomnia;The "core drugs-ingredients-targets" map was constructed based on Cytoscape software and the protein interaction network diagram based on String database;Use the Metascape platform to analyze the ontology of gene Kyoto encyclopedia of gene,and genomes enrichment of the "treating different diseases with same method" targets;Prodict and explore the potential mechanism of "treating different diseases with same method" of core drugs in treatment of hypertension and insomnia.Results:l.Totally 383 medical records were included,there are 242 females and 141 males,the average age is 58.07years old.Old-aged people accounted for the largestproportion(42.56%),followed by middle-aged people(35.25%)and young people(13.84%).The top 3 syndrome types are yin-deficiency and yang excess,liver-fire hyperactivity and phlegm-dampness syndromes;The top three syndrome elements are fire-heat,phlegm-dampness and yin-deficiency;Involving 212 Chinese traditional medicines,the properties are largely cold,most of tastes are bitter,sweet,pungent;the mainly meridian tropism are liver,heart,spleen and kidneys;The top ten commontraditional Chinese medicines were oyster,fossil fragment,common jujube seed,chinesethorowax root,baikal skullcap root,root of herbaceous peony,magnet,ternate pinellia rhizome,immature bitter orange and tuckahoe;Common efficacy of the main medicine are tranquilization,clearing heat and regulating qi;The common drug combination include fossil fragments-oyster,fossil fragments-common jujube seed-oyster,and chinese thorowax root-fossilfragments-common jujube seed-oyster etc.;Confidence-based association rules are "fossilfragments?oyster","baikal skullcap root,fossil fragments?oyste","root of herbaceous peony,fossil frag-ments?oyste",etc.;Totally twelve core drug combinations and 10 newprescriptions are obtained by using entropy clustering method.2.Select the drugs whose frequency?70%(oyster,fossil fragments,common jujube seed,chinese thorowax root,baikal skullcap root,herbaceous peony root as the core medicine.There are 57 active components,121 drug targets,190 disease targets and 52 common targets of "treating different diseases with same method".The key ingredients include quercetin,kaempferol,?-sitosterol,Stigmasterol,wogonin,etc.The network of protein interaction has 52 nodes and 432 edges.14 key targets can be screened,like IL6,CXCL8,NOS3,TNF,IL1B,FOS,AKT1,VEGFA,REN,PTGS2,etc.;GO function enrichment analysis obtained 18 biological process(BP)items,6 cellular component(CC)items,cell composition,and 13 molecular function(MF)items.KEGG pathway enrichment analysis include 106 signal pathways,of which the key pathways are AGE-RAGE in diabetic complications,fluid shear stress and atherosclerosis,TNF signaling pathway,Neuroactive ligand-receptor interaction,Calcium signaling pathway,etc.Conclusion:1.Data mining on prescription medication rule shows that main meridian tropism of hypertension combined with insomnia are the liver and heart,the spleen and kidneys were involved,the core pathogenesis is "liver dysfunction,yinand yang imbalance";The core prescription of Chief physician Cui treatmenting include oyster,fossil fragments,common jujube seed,chinese thorowax root,baikal skullcap root,root of herbaceous peony,magnet,ternate pinellia rhizome,immature bitter orangeand tuckahoe.The main prescription is similar to "Bupleurum plus Fossil fragments and Oyster Decoction",and the different prescriptions are selected according to the specific syndrome elements.The Cui's clinical experiences include the harmonization of qi and blood,the simultaneous treatment of heart and liver,care for the spleen and stomach,and combination of body differentiation and syndrome differentiation2.Network pharmacology studies have shown that the core drug "treating different diseases with same treatment" mechanism of hypertension and insomnia may be active ingredients(such as quercetin,kaempferol,?-sitosterol,phytosterol,and wogonin)via influencing IL6,CXCL8,NOS3,TNF,IL1B,FOS,AKT1,VEGFA,REN,PTGS2 and other targets to regulate the pathways like AGE-RAGE signaling pathway in diabetic complications,Fluid shear stress and atherosclerosis,TNF signaling pathway,Neuroactive ligand-receptor interaction,Calcium signaling pathway,etc.