Network Pharmacology Analysis Of Prof. Jisheng Zhao’s Composition Principle And Core Prescription For The Treatment Of Diabetic Kidney Disease

Research objectives:1.To summarize and analyze the composition principle and core prescription of Prof.Jisheng Zhao for the treatment of diabetic kidney disease(DKD)with the functions of pharmacological analysis and cluster analysis of the TCM heritage support platform(V2.5)and R studio software after collecting medical cases of DKD treated by Pro.Jisheng Zhao.2.To explore the active ingredients,targets involved,and related pathways of Prof.Zhao’s core prescription for the treatment of DKD by using network pharmacology and molecular docking methods,thus predicting the potential mechanisms of the core prescription for the treatment of DKD.Research methods:1.Data mining:The medical cases of DKD treated by Prof.Zhao were collected according to the inclusion and exclusion criteria,with the patient’s name and Chinese medicine prescriptions being entered into the WPS form and the TCM heritage support platform to establish a database and the basic information such as the patient’s age and gender and drug use frequency and sexual taste being counted by various functions of the platform.The Apriori algorithm was used for association rule analysis and the Ward method was used for cluster analysis in R studio to summarize and analyze the medication rule and core prescription of Prof.Jisheng Zhao for the treatment of DKD.2.Network pharmacology:The active ingredients of each drug of the core formula and their corresponding targets were obtained through the TCMSP database,the targets of DKD were obtained and the common targets were screened through Gene Cards and other databases.Then,the above information was collated and imported into Cytoscape 3.9 software to construct the herbal-component-target-disease network and protein interaction network,with the core targets being screened out through the topological analysis function,followed by the GO and KEGG enrichment analysis on the common targets,and molecular docking of key targets and active ingredients through MOE software,so as to explore the potential mechanism of core prescription for DKD treatment.Research results1.Study on Prof.Jisheng Zhao’s composition principle for the treatment of DKDIn this study,396 medical cases were collected from 132 patients,including 71 males and 61 females,with an average age of 60.7 years.There were 48 cases in DKD stage II,180 cases in DKD stage III,and 168 cases in DKD stage IV.A total of 130 herbal medicines,including tonic medicine(1096),heat-clearing and detoxicating herbs(627),antirheumatic medicine(694),and anti-water swelling drugs(528)were involved in the treatment.In terms of medicinal properties,cold,warm,and flat were the main three,accounting for 33.76%,35.64%,and 19.16%,respectively.The taste of medicine was mainly sweet,bitter,and pungent,accounting for 34.85%,30.19%,and 19.89%,respectively.The meridian distributions involved were kidney,liver,spleen,stomach,and lung.The top ten drugs in terms of frequency of use were Astragalus mongholicus(370),Cornus officinalis(351),Semen coicis(272),Ligusticum chuanxiong(265),Oldenlandia diffusa(249),Rhubarb(203),Dioscoreae nipponicae rhizoma(189),Erigeron breviscapus(189),Radix cynanchi paniculati(180),and Epimedium(165).The Apriori algorithm was used for association rule analysis for each prescription in each phase in R studio,and the parameters were adjusted to set the support and confidence of phase II and phase III prescriptions to 0.4 and 0.9,respectively,and the support and confidence of phase IV prescriptions to 0.35 and 0.9.151 association rules were obtained for the phase II prescription,containing drugs such as Astragalus mongholicus,Cornus officinalis,Poria cocos,Ligusticum chuanxiong,Erigeron breviscapus,Oldenlandia diffusa,Semen coicis,Radix cynanchi paniculati,Dioscoreae nipponicae rhizoma,Sinomenium acutum,Euonymus alatus,and Dried rehmannia root.92 association rules were obtained for the phase III prescription,containing drugs such as Astragalus mongholicus,Cornus officinalis,Poria cocos,Ligusticum chuanxiong,Erigeron breviscapus,Oldenlandia diffusa,Semen coicis,Radix cynanchi paniculati,Dioscoreae nipponicae rhizoma,Euonymus alatus,and Dried rehmannia root.237 association rules were obtained for phase IV prescriptions,containing drugs like Astragalus mongholicus,Cornus officinalis,Glabrous greenbrier rhizome,Rhubarb,Ligusticum chuanxiong,Epimedium,Semen coicis,Oldenlandia diffusa,Radix cynanchi paniculati,and Dioscoreae nipponicae rhizoma.The parameters were adjusted to set the support and confidence of the phase II prescription to 0.45 and 0.9,respectively,which at this point contained the herbs like Astragalus mongholicus,Cornus officinalis,Poria cocos,Erigeron breviscapus,Ligusticum chuanxiong,Oldenlandia diffusa,Semen coicis,and Radix cynanchi paniculati.The herbs obtained in the prescription for the stage III case were Astragalus mongholicus,Cornus officinalis,Ligusticum chuanxiong,Erigeron breviscapus,Oldenlandia diffusa,Semen coicis,and Radix cynanchi paniculati.The herbs obtained in the prescription of stage IV cases were Astragalus mongholicus,Cornus officinalis,Rhubarb,Glabrous greenbrier rhizome,Ligusticum chuanxiong,Oldenlandia diffusa,Semen coicis,Dioscoreae nipponicae rhizoma,and Epimedium.The ward method was used for hierarchical cluster analysis,with 50 Chinese herbal medicines with a frequency greater than 20 being selected and clustered into 5 categories with a contour coefficient of 0.40.The potential prescriptions obtained from the cluster analysis were:(1)Astragalus mongholicus,Cornus officinalis,Ligusticum chuanxiong,Semen coicis,and Oldenlandia diffusa;(2)Rhubarb,Glabrous greenbrier rhizome;(3)Radix scrophulariae,Radix ophiopogonis,Epimedium,and Euonymus alatus;(4)Erigeron breviscapus;(5)Dioscoreae nipponicae rhizoma,Sinomenium acutum,and Radix cynanchi paniculati.Based on the above results and Prof.Zhao’s medication habit,the core formula was formulated as Astragalus mongholicus,Cornus officinalis,Poria cocos,Erigeron breviscapus,Ligusticum chuanxiong,Semen coicis,Oldenlandia diffusa,Dioscoreae nipponicae rhizoma.2.Study on the exploration of the core prescription for the treatment of DKD based on network pharmacologyThe active ingredients involved in the core prescription for the treatment of DKD included quercitrin,luteolin,formononetin,Baicalein,β-sitosterol and others,with transcription factor AP-1,tumor protein p53,mitogen-associated protein kinase 1,estrogen receptor 1,and hypoxia inducible factor 1-α as the key targets,which involved lipids and atherosclerosis,AGE-RAGE signaling pathway in diabetic complications,fluid shear stress and atherosclerosis,IL-17 and other signaling pathways.Research conclusions:1.This study summarizes and analyzes the common medical pair and composition principle applied by Professor Jisheng Zhao in the treatment of DKD by using data mining methods.Professor Zhao believes that DKD is developed from the development of prolonged thirst disease involving the kidneys,with the disease character being asthenia in origin and asthenia in superficiality,the disease mechanism being five internal organs weakness with weakness mainly in the spleen and kidney,and combination of dampness and stagnant blood with blood stasis throughout the DKD.Therefore,the treatment for it should be based on reinforcing spleen and kidney as well as eliminating dampness and activating blood.The core formula for the treatment of DKD is Astragalus mongholicus,Cornus officinalis,Poria cocos,Erigeron breviscapus,Ligusticum chuanxiong,Semen coicis,Oldenlandia diffusa,Dioscoreae nipponicae rhizoma.2.The potential targets and pathways of the core prescriptions for the treatment of DKD were explored using network pharmacology,showing that the core prescription treats DKD by acting on targets such as JUN,MYC,and MAPK1 through components such as quercetin,lignocaine,and baicalin,and by regulating signaling pathways such as AGE-RAGE and IL-17.