| The China Cardiovascular Health and Disease report 2019 pointed out that there are 330 million people suffering from cardiovascular disease,of which 11 million are coronary heart disease(CHD).Cardiovascular mortality is the first.With the aging of the population,the situation of CHD will be more severe.The prevention and treatment of CHD is still an important research direction.The theory of Cardiosplenic Concurrent Treatment(CSCT)in traditional Chinese medicine(TCM)has a good basis for clinical application and plays an important clinical value.In this study,network pharmacology,systematic review and data mining methods were used to further evaluate the mechanism,clinical efficacy and compatibility of CSCT for CHD.Study 1:To explore the mechanism of CSCT Prescription for CHD based on network pharmacologyObjective To study the effective components and main targets of CSCT Prescription for CHD,and to predict its mechanism.Methods The compounds and targets of CSCT Prescription were collected by TCMSP database,and its compound-target network diagram was constructed by Cytoscape3.7.2.The disease targets of CHD were obtained by OMIM,DrugBank and GeneCards databases.The drug targets and disease targets were calibrated by Uniprot database and the Venny analysis tool was used to obtain the intersection target.The intersection target was imported into String database to analyze the protein-protein interaction(PPI),and the PPI network text file was imported into Cytoscape3.7.2 to screen out core target.The drug-disease common target was imported into Metascape database,and Gene Ontology(GO)and Kyoto Encyclopedia of Genes and genomes(KEGG)enrichment analysis were carried out.The network map of active component-disease target-action pathway was constructed by Cytoscape3.7.2,and the core components,core targets and core action pathways were inferred by Network Analyzer tools in the software.Results After screening by absorption,distribution,metabolism and excretion(ADME),20 kinds of active ingredients of Astragalus,7 kinds of Baizhu,2 kinds of Angelica sinensis,64 kinds of Salvia miltiorrhiza,14 kinds of Coptis and 3 kinds of Zedoary,which acting on 224 target genes,were extracted.1990 CHD disease target genes were obtained by searching OMIM,DrugBank and GeneCards databases.The intersection target was introduced into String database to analyze PPI,and finally 15 core targets were screened,including STAT3,JUN,AKT1,MAPK1,TNF,TP53,RELA,MAPK14,MAPK8,IL6,APP,VEGFA,CXCL8,EGFR and FOS.The results of GO enrichment analysis and KEGG pathway enrichment analysis showed that CSCT Prescription played a role in regulating CHD based on 2209 biological processes,148 molecular functions,96 cellular components and 193 signal pathways.Conclusion It was predicted that CSCT Prescription can regulate FSS,AGE-RAGE,PI3K-Akt,MAPK and other signal pathways through key targets such as PTGS2,PTGS1,SCN5A,ADRB2,so as to exert its effect from multiple dimensions,such as anti-atherosclerosis(AS),anti-platelet aggregation,inhibition of inflammatory reaction,increase of myocardial energy metabolism,reduction of myocardial cell apoptosis and so on.Study 2:The efficacy and safety of CSCT for CHD:a Meta analysis of randomized controlled trialsObjective To use Meta analysis to evaluate the efficacy and safety of CSCT for CHD systematically and scientifically,so as to provide more medical evidence-based support.Method 1.Screening criteria:The type of study was a randomized controlled trial.The subjects were CHD patients including stable angina pectoris,unstable angina pectoris(UA),non-ST segment elevation myocardial infarction(NST-EMI),old myocardial infarction and patients after percutaneous coronary intervention(PCI),with unlimited sex,age and course of disease.The intervention measures were as follows:the experimental group was treated with TCM on the basis of conventional treatment,the control group was only treated with conventional treatment for CHD,the course of treatment was ≥14 days,the outcome observation indexes included the curative effect of angina pectoris symptoms,electrocardiogram,TCM syndrome and high sensitivity C-reactive protein(hs-CRP).2.Retrieval strategy:four Chinese and four foreign language databases were searched,namely:China knowledge net database(CNKI),Wanfang database(WanFang),VIP Chinese sci-tech periodical database(VIP),Chinese biomedical literature database(CBM)and PubMed,EMbase,Cochrane library,Web of science.The search time is dated from the establishment of the database to March 2020.3.The included literature was obtained and its data were extracted,including the general data of the literature,the characteristics of the research objects,intervention measures,curative effect indicators,literature quality evaluation and other related information.4.RevMan5.3 software was used for methodology quality evaluation and Meta analysis.5.The safety of the included research was analyzed.Results A total of 3424 articles were screened,and finally 17 articles were included.The total sample size was 1460 cases,including the experimental group(n=748)and the control group(n=712).The results of Meta analysis showed that applying CSCT with conventional treatment is more effective than simple conventional treatment in the angina pectoris symptom curative effect(RR=0.22,95%Cl=[0.17,0.26],P<0.00001),electrocardiogram curative effect(RR=1.34,95%Cl=[1.25,1.44],P<0.00001),TCM syndrome curative effect(RR=1.27,95%Cl=[1.13,1.42],P<0.00001)and hs-CRP(MD=-2.29,95%Cl=[-2.80,-1.77],P<0.00001).In the analysis of electrocardiogram curative effect,the scattered points are basically asymmetrically distributed,suggesting that there may be a certain degree of publication bias.The related adverse reactions were observed in 8 studies,of which 3 studies showed adverse reactions.The experimental group developed mild stomach discomfort,diarrhea and dizziness,and the symptoms disappeared after continuing treatment.Mild dizziness and diarrhea occurred in the control group,which relieved spontaneously in a short time.In both groups,liver function abnormalities occurred.The liver function returned to normal after discontinuing the statins,and the patients with stomach discomfort improved after the usage of acid suppressants,suggesting that it may be related to statins and aspirin.All GRADE evidence rating of outcomes are low.Conclusion There is a certain efficacy and good safety in angina pectoris symptom,electrocardiogram,TCM syndrome and hs-CRP when apply CSCT with conventional treatment for CHD.However,due to the low quality of the included studies,more high-quality evidence is still needed to prove.Study 3:Study on the compatibility rules of CSCT based on the Inheritance Auxiliary Platform of TCMObjective To explore the compatibility rules of CSCT for CHD through a small sample of CSCT prescriptions.Methods The database was established based on the CSCT prescriptions in the previous meta-analysis.The data were preprocessed to be standardized and were inputted into the Inheritance Auxiliary Platform of TCM(V2.5)on the basis of the secondary verification.The "statistical report" module was used to count the drug frequency,four characters,five tastes,meridian tropism and so on.The "data analysis" module was used to analyze the frequency and correlation of drugs.On the basis of "data analysis" module,high-frequency drug combinations and their associated characteristics were screened and analyzed by setting support and confidence levels.This study didn’t performed new prescription and combination analysis.Results 40 kinds of Chinese medicine were founded in 17 prescriptions,and the top 10 Chinese medicine were Astragalus,Salvia,Codonopsis,Licorice,Ligusticum chuanxiong,Atractylodes macrocephala,Poria,Safflower,Angelica,Red Peony.The four characters of the medicine for CSCT are mainly warm and mild,and the five tastes are mainly sweet,bitter and pungent.The meridian tropism of spleen and heart are used most frequently.Taking support degrees as 6,a total of 57 commonly used drug combinations were obtained,including 27 pairs medicines,22 corner medicines,and 7 groups medicines,involving a total of 9 Chinese medicines.Taking support degrees as 6 and the confidence level as 0.9,18 drug combinations were screened.Conclusion The damage to the spleen and lack of vitality,which lead to qi deficiency,dampness,phlegm obstruction,and blood stasis,are important pathogenesis of CHD.Therefore,CHD can be treated from the point of spleen.In this study,a small sample of CSCT prescription were analyzed to explore the compatibility rules of CSCT for CHD.The characteristics of CSCT can be summarized as:basing on the heart and spleen,it use both cold and warm Chinese medicine to invigorate the spleen,dry out dampness and promote blood circulation.The four herbs of Astragalus,Codonopsis,Atractylodes and Poria are the main ingredients to invigorate qi,strengthen the spleen and dry out dampness.Salvia,Ligusticum chuanxiong,Safflower and Angelica can be described as the masters of activating blood and removing blood stasis in CSCT.Astragalus and Salvia miltiorrhiza are often used as major medicine in CSCT,with a relatively large dosage."Astragalus-Salvia miltiorrhiza" is the most classic drug pair in CSCT.However,due to the small sample size,multi-center and large-sample clinical research is still needed for further practical verification. |
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