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Background. Heart failure represents the terminal stage of various cardiovascular diseases. This study aims to explore the pharmacological mechanisms underlying the protective effect of Ginsenoside Rg3 against heart failure. Methods. Potential targets of Ginsenoside Rg3 were identified using SwissTargetPrediction and the Comparative Toxicogenomics Database, while heart failure-related genes were retrieved from the Comparative Toxicogenomics Database, Therapeutic Target Database, DisGeNET, and PharmGKB. Overlapping of Ginsenoside Rg3 targets with heart failure-related genes identified drug-disease interaction genes. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were conducted on the drug-disease interaction genes to elucidate their biological functions. A protein-protein interaction network was constructed using the drug-disease interaction genes, and the hub genes were identified by topological analysis. Additionally, we validate the expression of IL-6 and TNF by real-time PCR. Results. The intersection of Ginsenoside Rg3 targets and heart failure-related genes yielded 15 drug-disease interaction genes. Enrichment analysis highlighted the involvement of inflammation-related GO terms and KEGG pathways, such as positive regulation of interleukin-8 and -6 production, regulation of immune effector process, cytokine receptor binding, cytokine activity, adipocytokine signaling pathway, and IL-17 signaling pathway, which are implicated in the cardioprotective effect. Topological analysis revealed four hub genes: STAT3, CASP3, TNF, and IL-6. The application of Ginsenoside Rg3 significantly reversed the elevated levels of IL-6 and TNF in the isoproterenol-treated H9c2 cell line. Conclusions. Our findings suggest that the cardioprotective effect of Ginsenoside Rg3 may be mediated through its anti-inflammation properties. Further research is required to elucidate and validate the detailed cardioprotective mechanisms of Ginsenoside Rg3.

Background and Objectives: This study aims to illustrate the mechanisms underlying the therapeutic effect of Icariin after myocardial infarction (MI). Materials and Methods: Based on the network pharmacology strategy, we predict the therapeutic targets of Icariin against MI and investigate the pharmacological molecular mechanisms. A topological network was created. Biological process and Kyoto Encyclopedia of Genes and Genomes pathway enrichment were also performed. We also conducted the molecular docking analysis to stimulate the component–target interaction further and validate the direct bind effect. Results: Network pharmacology analysis identified 61 candidate genes related to the therapeutic effect of Icariin against MI. EGFR, AKT1, TP53, JUN, ESR1, PTGS2, TNF, RELA, HSP90AA1, and BCL2L1 were identified as hub genes. The biological processes of the candidate targets were significantly involved in the reactive oxygen species metabolic process, response to hypoxia, response to decreased oxygen levels, response to oxidative stress, regulation of reactive oxygen species metabolic process, and so forth. Overall, biological process enrichment analysis indicated that the protective effect of Icariin against MI might be associated with oxidative stress. Moreover, the pathway analysis showed that the candidate targets were closely associated with lipid and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, HIF-1 signaling pathway, etc. We identified the conformation with the lowest affinity score as the docking conformation. The simulated molecular docking was displayed to illustrate the topical details of the binding sites between Icariin and TNF protein. Conclusions: This study provides an overview of the mechanisms underlying the protective effect of Icariin against MI.

PEP 1-Cu/Zn superoxide dismutase (PEP-1-SOD1) fusion protein preconditioning has been reported to protect the myocardium from ischemia/reperfusion (I/R)-induced injury by decreasing the infarct size, reducing levels of cardiomyocyte apoptosis and reducing the release of myocardial-specific biomarkers. The aim of the present study was to examine the effects of PEP-1-SOD1 pretreatment on I/R-induced ventricular arrhythmias in Langendorff-perfused rat hearts. The isolated rat hearts were pretreated with PEP-1-SOD1 prior to I/R, and the I/R-induced hemodynamic parameters, infarct size and ventricular arrhythmias were then assessed. Compared with the unprotected hearts, PEP-1-SOD1 preconditioning significantly improved the hemodynamic parameters, decreased the cardiac lactate dehydrogenase and creatine kinase-MB (CK-MB) levels, reduced the infarct size and attenuated the ventricular arrhythmia. Further investigation showed that PEP-1-SOD1 preconditioning reduced both the incidence and duration of ventricular tachycardia/ventricular fibrillation. In addition, the intracellular reactive oxygen species (ROS) levels were decreased. The results of the present study suggest that PEP-1-SOD1 preconditioning can protect the heart against I/R injury and attenuate I/R-induced arrhythmia by downregulating the generation of ROS. [ABSTRACT FROM AUTHOR]