Professor Zhang Hongchun's Drug Use In The Treatment Of Chronic Obstructive Pulmonary Disease In Stable Period And Network Pharmacology Analysis

Objective:Using network pharmacology methods,this paper aims to analyze the medication rule,core prescriptions and core drugs of Professor Zhang Hongchun in treating patients with chronic obstructive pulmonary diseases(COPD)in stable period.Then,the network pharmacology analysis of core drugs was carried out to explore the target,signal pathway and mechanism of core drugs in the treatment of COPD,which can lay a foundation for the screening and experimental verification of core drugs in treating stable COPD.Methods:(1)First,we collected and sorted out the prescriptions of Professor Zhang Hongchun from January,2015 to May,2019 for patients with COPD in stable stage.The age,gender,taste,meridian tropism,frequency of use and dosage of drugs were analyzed based on the frequency statistical method by using Traditional Chinese Medicine Inheritance Support System(TCMISS).The combination and rules of drugs commonly used in prescriptions were obtained based on the association rules,and then the core prescriptions and core drugs were obtained.And the new prescriptions were obtained based on the entropy clustering method of complex system.(2)The active components and targets of core drugs were found and and screened in TCMSP database.After standardized the name of COPD in PubMed,we used genecards,TTD,DrugBank,DisgeNET,Digsee and other databases to retrieve COPD targets,and intersect drug targets with disease targets.Then the network of "drug compound target disease" was drawn by using the software of Cytoscape 3.7.2,and the PPI network was constructed by using String database,and the key genes in the network were obtained.Finally,the Bioinformation package and R software were used to analyze the GO function enrichment and KEGG pathway enrichment of the targets.Results:(1)The section of prescription analysis included a total of 27 patients and 111 prescriptions.Most of the patients were male(16:11 for male:female),and most of them were over 60 years old(85%).The prescription contains hundred and six traditional Chinese medicines,which are mainly warm,cold and plain in drug property,mainly sweet,bitter and pungent in drug flavor,and most of them belong to lung,spleen,liver and kidney meridians.The top ten drugs used frequently are Licorice,Angelicae Sinensis Radix,Pseudostellariae Radix,Farfarae Flos,Cornus Officinalis Sieb Et Zucc,Schisandrae Chinensis Fructus,Poria Cocos(Schw.)Wolf,Perillae Fructus,Perilla Frutescens,Asteris Radix Et Rhizoma.Thirty-four core combinations of drugs were extracted,and thirty-eight association rules with a confidence level of one were extracted,and three new prescriptions were obtained through the analysis of drug use rules.The core prescriptions of Professor Zhang Hongchun in treating COPD are:Angelicae Sinensis Radix(15g),Pseudostellariae Radix(30g),Cornus Officinalis Sieb Et Zuce(15g),Schisandrae Chinensis Fructus(15g),Farfarae Flos(15g),Asteris Radix Et Rhizoma(15g),Poria Cocos(Schw.)Wolf(15g),Perillae Fructus(15g),Perilla Frutescens(15g),Ephedra Herba(10g),Licorice(3g).Then we selected five drags,including Licorice,Angelicae Sinensis Radix,Pseudostellariae Radix,Farfarae Flos,Comus Officinalis Sieb Et Zucc,to do network pharmacology analysis.(2)In the part of network pharmacology analysis,with OB≥30%and DL≥0.18 as the screening conditions,55 chemical components and 182 corresponding targets of five traditional Chinese medicines,including Licorice,Angelicae Sinensis Radix,Pseudostellariae Radix,Farfarae Flos,Cornus Officinalis Sieb Et Zucc,were found in TCMSP database.And 647 COPD related targets were found in multiple disease databases.93 key targets were obtained by intersecting the target of core drugs with that of COPD.The analysis of "drug-compound-target-disease" network shows that quercetin,β-sitosterol,luteolin,kaempferol,stigmasterol,Acacia and other active compounds play a key role in the network by connecting more targets.Through the analysis of PPI network map constructed by String platform,it was found that the targets of IL-1β,IL-6,IL-8,IL-10,AKT1,VEGFA,MMP-2 and MMP-9 were connected with many nodes in the network,which are the key targets of core drug therapy for COPD.A total of 127 functional items(P<0.05)were obtained by GO functional enrichment analysis.The items with higher enrichment were mostly related to the activation of cytokines and enzymes.A total of 141 signal pathways(P<0.05)were obtained by the enrichment analysis of KEGG pathway.The pathways with higher enrichment were mostly related to the infection of pathogenic microorganism and inflammatory reaction.Conclusion:Professor Zhang considers that the stable COPD is located in the lung and kidney,mainly due to deficiency syndrome,mostly manifested as one or more viscera deficiency syndrome of lung,spleen and kidney.During the treatment,the basic treatment is mainly to invigorate lung,spleen and kidney,and it is also to stop cough,eliminate phlegm and asthma,promote qi,activate blood circulation and dissipate blood stasis.The core prescription obtained from the analysis conforms to the above treatment ideas,mainly including the drugs of tonifying lung and kidney(Angelicae Sinensis Radix,Pseudostellariae Radix,Cornus Officinalis Sieb Et Zucc,Schisandrae Chinensis F ructus,),relieving cough and asthma(Farfarae Flos,Perillae Fructus,Perilla Frutescens,Asteris Radix Et Rhizoma,Ephedra Herba),and Invigorating the spleen and Qi(Pseudostellariae Radix,Poria Cocos(Schw.)Wolf).The core drugs are mainly composed of tonic drugs,which are in line with the characteristics of deficiency syndrome in the stable COPD,and should be mainly treated by regulating the lung and kidney.The three new prescriptions can be used according to the syndromes,which have some reference value for the treatment of COPD,but need further clinical and experimental verification.Through the analysis of network pharmacology,it can be concluded that the potential mechanism of core drugs in the treatment of COPD is the active components of quercetin,β-sitosterol,luteolin,kaempferol,stigmasterol,acacia,which may act on the targets of IL-1β,IL-6,IL-8,IL-10,AKT1,VEGFA,MMP-2,MMP-9,and so on,and through the regulation of IL-17,TNF and other signals,play an important role in the process of immunity,inflammation and oxidative stress.