Analysis Of The Medication Laws And Network Pharmacology Of Traditional Chinese Medicine In Treating Chronic Pulmonary Heart Disease(acute Stage)

ObjectiveTo explore the regularity of traditional Chinese medicine in the treatment of acute phase of chronic pulmonary heart disease to guide clinical treatment,and to preliminarily discuss the possible target and signal pathway of traditional Chinese medicine in the treatment of this disease.MethodsFirst of all,the randomized controlled studies,experience of famous doctors,proved case,and case reports of traditional Chinese medicine(including Chinese patent medicine)in the treatment of acute stage of chronic pulmonary heart disease(CPHD)were searched from Chinese databases such as CNKI,Wanfang,VIP,and China Biology Medicine disc(CBM disc).prescribing information was Extracted from the relevant literature,and was summarized in Excel sheets.The prescribing information was introduced into the TCMISS2.5 software to dig out the medication laws including the syndrome of the prescription,frequency of drug use,character,taste,and channel tropism.Apriori algorithm and entropy clustering method of complex system were used to obtain the core association rules between herbs and the new possible combination of prescriptions for the treatment of this disease.Then,Traditional Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP),Universal Protein database(Uniprot)and Genecards database(Genecards)were used to find out the active ingredients that were contained in the core herbs of association rules and the corresponding target genes,as well as CPHD related genes.The same part of the genes between the target gene of the herbs and CPHD’s genes was taken as the core target genes of Chinese medicine for CPHD.After that,Cytoscape software and STRING Database were used to construct "active ingredient-core target genes" network diagrams and "Protein-Protein interactions(PPI)" network diagrams.Finally,M etascape Database was used for KEGG signaling pathway enrichment analysis of co re target genes,and the network diagram of "core target genes-signaling pathway" wa s constructed again with Cytoscape software.Results(1)In terms of data mining of medication laws.A total of 123 prescriptions(con taining Chinese patent medicine)for the treatment of acute stage of CPHD were in cluded,of which 93 were obtained from randomized controlled studies,16,6 and 8were respectively obtained from proved case,famous doctors’ experience and case rep orts,covering 174 TCM prescriptions in total.The main syndromic types are Yang de ficiency and water flooding(20 percent),phlegm and blood stasis obstructing the lun g(11 percent),phlegm and heat obstructing the lung(percent),phlegm and dampness a ccumulate the lung(6 percent),etc.Fuling,Baizhu,Tinglizi,Danshen,Guizhi,Kuxingren,Ga ncao,Taoren,Huangqi,Fuzi were the top ten in frequency of all herbs.Among them,wa rm herbs are the most common,followed by cold and flat.The flavors of the herbs were mainly bitter,sweet and spicy,and they are mainly belong to the lungs,spleen and heart in terms of the channel tropism.The drug association rules based on Ap riori algorithm mainly include Baizhu,Chenpi,Danshen,Guizhi,Fuzi,Fuling,Tinglizi,Gan cao,etc.A total of 13 new prescriptions were generated based on the entropy clusteri ng method of complex system.In order:Baishao-Huangqin-Shengjiang-Sangbaipi;Maido ng-Wuweizi-Xiyangshen-Taizishen;Fabanxia-Huangqi-Mahuang-Danggui;Dangshen-Tingl izi-Shuizhi-Renshen-Fangji;Kuxingren-Jiegeng-Gualou-Baishao-Shengjiang;Yiyiren-Yuxin gcao-Dongguazi-Taizishen-Huangjing;Cheqianzi-Yimucao-Zhebeimu-Paojiang;Zhishi-Dah uang-Houpo-Huangjing;Niuxi-Chaihu-Gangmeigen-Zicao;Taoren-Chishao-Pugongying-Da nggui-Chuanxiong-Honghua;Fuzi-Guizhi-Baizhu-Kuxingren-Gualou;Baishao-Kuxingren-S hengjiang-Fuzi-Sangbaipi;Danggui-Shengdihaung-Chaihu-Chishao-Taizishen-Mudanpi.(2)In terms of network pharmacological of action mechanism.On the basis of the medication laws,the 7 herbs of the core association rules in which Gancao was not included(Baizhu,Chenpi,Danshen,Guizhi,Fuzi,Fuling,Tinglizi)were selected for a network pharmacological analysis.A total of 87 active ingredients with pharmacological significance were found,and 182 core target genes were identified,among which the top 13 were STAT3,Akt1,TP53,Jun,MAPK1,MAPK3,TNF,Rela,MAPK14,IL6,MAPK8,EGFR,ED N1 and so on.The enrichment analysis of these 182 core target genes mainly involves the signal pathways including PI3K-Akt,MAPK,AGE-RAGE,TNF,Cellular Senescence.These pathways are mainly related to inflammatory response,oxidative stress and pulmonary vascular remodeling.Conclusion(1)In the acute stage of CPHD,the main syndromic types were Yang deficiency and water flooding,phlegm and blood stasis obstructing the lung,phlegm and heat obstructing the lung,phlegm and dampness accumulate the lung.The main pathological factors were Yang deficiency,phlegm drinking,blood stasis and heat toxicity.the herbs that can increase Qi(warm Yang),promote diuresis,eliminate phlegm,activate blood were often used to treat this disease.Among them,the most relevant herbs are: Baizhu,Chenpi,Danshen,Guizhi,Fuzi,Fuling,Tinglizi.This is a prescription that combines many effects in one,such as increasing Qi(warm Yang),promoting diuresis,eliminating phlegm,activating blood.This well reflects the pathological characteristics of the acute phase of CPHD,which is characterized by deficiency in origin and enrichment in symptom mixing deficiency and excessiveness.(2)Traditional Chinese medicine may act on STAT3,Akt1,TP53,Jun,MAPK1,MAPK3,TNF,Rela,MAPK14,IL6,MAPK8,EGFR,EDN1 and other targets.It regulates PI3K-Akt,MAPK,AGE-RAGE,TNF,Cellular Senescence and other signaling pathways,thereby inhibiting inflammation,anti-oxidation,improving pulmonary vascular remodeling,and playing a therapeutic role in the treatment of CPHD in the acute attack stage,which provides a scientific basis for the treatment of CPHD by traditional Chinese medicine.