The Efficacy And Mechanism Of Salvianolate Injection In The Treatment Of Stable Angina Pectoris Based On Metaanalysis And Network Pharmacology

Objective: Based on meta-analysis and network pharmacology to explore the efficacy and potential mechanism of salvianolate injection in the treatment of stable angina pectoris,to provide high-level evidence-based medical evidence and dosing reference for clinical application.Methods:(1)Randomized controlled trials of treatment of stable angina pectoris with salvianolate injection were collected by computer searches of the China Knowledge Network(CNKI),Wanfang Data Knowledge Service Platform(Wanfang Data),VIP,Chinese Biomedical Literature(CBM),Pub Med,Cochrane Library,and EMBase databases.The search time frame was established until October 2022.The literature was screened according to inclusion and exclusion criteria,and extracted for Meta-analysis using Review Manager 5.4 software,and the GRADE criteria were used to evaluate the evidence level of the outcome indicators.(2)The chemical structure formulae of the six main components of salvianolate injection were obtained from the Pub Chem database and imported into the Swiss Target Prediction analysis platform to predict their targets of action,with "Stable angina" was used as the search term to search Gene Cards,OMIM and other databases to collect information on the targets of stable angina.After obtaining the intersection targets of the two,a correlation network map was constructed with Cytoscape 3.9.0 and topological analysis was performed.The intersecting targets were analysed with the String database to analyse the key targets for stable angina pectoris intervention with salvianolate injection.Gene ontology enrichment analysis and Kyoto encyclopedia of genes and genomes enrichment analysis were performed through the DAVID database and the results were visualized through the bioinformatics platform.Results:(1)A total of 18 randomised controlled clinical trials with 2038 patients were included in the Meta-analysis.The results showed that the total effective rate of angina pectoris efficacy(RR=1.24,95% CI=[1.09,1.40],P<0.001),total effective rate of ECG improvement(RR=1.34,95% CI=[1.21,1.50],P<0.001)and nitroglycerin discontinuation rate(RR=1.35,95% CI=[1.16,1.58],P<0.001)in the trial group were better than the control group,and all differences were statistically significant.The results of subgroup analysis showed that salvianolate injection combined with conventional therapy was superior to compound danshen injection combined with conventional therapy in improving the efficacy of angina pectoris(RR=1.35,95% CI=[1.16,1.58],P<0.001).The results of funnel plots plotting the total effective rate of angina pectoris efficacy and the effective rate of ECG improvement showed a lack of symmetry in the scatter distribution,suggesting a possible publication bias.The GRADE classification results showed moderate quality evidence for ECG improvement efficiency,low quality evidence for nitroglycerin discontinuation reduction rate,and very low quality evidence for total angina efficiency.(2)A total of 102 drug predicted targets and3871 disease targets were collected by network pharmacology,and topological analysis by constructing protein-protein interactions network revealed that multiple bioactive components of salvianolate injection may regulate lipid and atherosclerosis,bladder cancer,through targets such as EGFR,CASP3,JUN,ESR1,MMP9,ERBB2,ITGB1,MMMP2 IL-17,AGE-RAGE and other signaling pathways for the treatment of stable angina pectoris.Conclusions: The combination of salvianolate injection with conventional treatment is superior to conventional treatment alone or the addition of danshen injection to conventional treatment in terms of clinical efficacy.The potential mechanism may be related to its multiple active ingredients interfering with inflammatory response,regulating lipid metabolism,anti-atherosclerosis,regulating oxidative stress,pro-angiogenesis,and regulating cardiomyocyte apoptosis through multi-target and multi-pathway.