| Objective:The potential components and mechanism of Tongxinluo capsule in treating heart failure were identified by network pharmacology-molecular docking technology.On this basis,cross-sectional clinical study design was used to analyze the association between Tongxinluo Capsule and inflammation-related indicators in patients with heart failure.Methods:1.First,the main components of Tongxinluo Capsule were found using Chinese Pharmacopoeia,then the active components and target information were extracted using TCMSP database and BATMAN-TCM database system,and the "TCM-Active IngredientTarget" diagram was constructed using Cytoscape-3.8.2 software system.Target data of heart failure mainly come from Gene Cards,OMIM and TTD databases.The intersection of the active ingredient target of Tongxinluo capsule and the disease target of heart failure is adopted.The network information of protein interaction is constructed using STRING platform and Cytoscape software.Gene ontology(GO)analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis were carried out in David database,mainly targeting targets with potential therapeutic effects.The top 20 pathways and corresponding target information obtained from enrichment studies and the top 20 active components were formed into a "compositional target-pathway" relationship graph.Online molecular docking at DockThor.2.A cross-sectional clinical study was conducted to collect the demographic characteristics,lifestyle,disease history,cardiac color ultrasound and laboratory indicators of heart failure patients admitted to the Department of Cardiovascular Medicine,the Second Hospital of Shanxi Medical University from December 2020 to November 2022.A total of 406 patients who met the inclusion criteria and qualified after screening for exclusion criteria were statistically analyzed.Neutrophil/lymphocyte ratio(NLR)and platelet/lymphocyte ratio(PLR)were calculated.Nonparametric test of relevant samples was used to analyze the changes of inflammatory indicators in patients with heart failure before and after treatment with Tongxinluo Capsule,and generalized linear regression model was used to analyze the association between the use of Tongxinluo capsule and changes in inflammatory indicators in patients with heart failure.Model 1 was adjusted for age,sex,and BMI.Model 2 further adjusted for smoking,alcohol consumption,length of hospital stay,and disease history.In order to better identify the therapeutic effect of Tongxinluo capsule on different populations,we conducted stratified analysis of age,gender,BMI,smoking,alcohol consumption and disease history,and calculated the interaction effect.Results:1.The active ingredients of Tongxinluo capsule,such as crocin,isoxanthopterin,Dmannitol and ursolic acid,may pass through calcium ion signaling pathway,cAMP signaling pathway,IL-17 signaling pathway,TNF signaling pathway and C-type lectin receptor signaling pathway,among which the inflammatory pathway is of special significance.Finally,the expression of AKT1,RELA,PTGS2,MAPK14,MAPK1,NFKB1,JUN,MAPK10,MAPK8,MAPK9 and other key targets are activated or inhibited,so as to achieve the purpose of treating HF.2.Clinical studies based on cross-sectional design(1)Compared with heart failure patients who did not use Tongxinluo capsule,there were no differences in age,gender,BMI,smoking history,drinking history,coronary heart disease,dilated cardiomyopathy,hypertension,diabetes,hyperlipidemia and pulmonary infection among patients in the Tongxinluo group(P>0.05).(2)Comparison of cardiac color ultrasound indicators between the group without Tongxinluo Capsule and the group using Tongxinluo Capsule on admission showed that There was no significant difference in left atrial inner diameter(LAD),left ventricular enddiastolic inner diameter(LVEDD),ejection fraction(LVEF)and other indexes between the two groups(P>0.05).In addition,the comparison of biochemical and inflammatory indicators between the two groups showed that there was no statistical significance in the ratios of BNP,white blood cells,platelets,neutrophils,lymphocytes,NLR and PLR between the two groups at admission,indicating that there was no significant difference in the observed indicators between the two groups and they were comparable.(3)Association between Tongxinluo Capsule and patients with heart failure The study found that,without adjusting for any confounding factors,patients with heart failure using Tongxinluo capsule had lower inflammation-related indicators than those without Tongxinluo capsule,among which NLR was decreased by 0.50(95%CI:-0.05,1.06)and PLR was decreased by 8.33(95%CI:1.92,14.74).After adjusting for age,gender and BMI,it was found that the use of Tongxinluo capsule reduced NLR by 0.50(95%CI:-0.05,1.05)and PLR by 8.64(95%CI:2.22,15.06)in patients with heart failure compared with those who did not use Tongxinluo capsule.Model 2 After further adjusting for potential confounding factors such as smoking,alcohol consumption,length of stay,coronary heart disease,hypertension,diabetes,hyperlipidemia,lung infection,etc.,using Tongxinluo capsule reduced NLR of inflammation-related indicators in patients with heart failure by 0.35(95%CI:-0.01,0.71),PLR decreased by 8.23(95%CI:1.94,14.44).(4)Stratified analysis showed that Tongxinluo capsule had no difference in the association with inflammation-related indicators of heart failure patients in terms of age,gender,BMI,length of stay,smoking,hypertension,diabetes,hyperlipidemia,and lung infection.The association of Tongxinluo capsule on inflammation-related indicators NLR in patients with heart failure may be different in terms of coronary heart disease history,and the improvement of inflammation-related indicators in patients with heart failure without coronary heart disease history is more significant.Compared with patients who did not use Tongxinluo capsule,the use of Tongxinluo capsule in patients with heart failure without a history of coronary heart disease showed a significant difference in the improvement of inflammation-related indicators NLR.Compared with patients who did not use Tongxinluo capsule,the use of Tongxinluo capsule in patients with heart failure without a history of coronary heart disease could reduce by 0.80(95%CI:0.18,1.42).Conclusion:1.Through network pharmacology and molecular docking technology,it is verified that Tongxinluo capsule may achieve the purpose of treating heart failure through multiple signaling pathways,among which inflammation pathway plays a significant role in Tongxinluo Capsule’s treatment of heart failure.2.Combined with clinical studies,it is found that Tongxinluo capsule may treat heart failure by reducing inflammation-related indicators,and it is more significant to improve the level of inflammation-related indicators NLR in heart failure patients without a history of coronary heart disease. |
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