Investigation of Cardioprotective Activity of Silybin: Network Pharmacology, Molecular Docking, and In Vivo Studies

Abstract

AbstractThe abundant health benefits of silybin are known to benefit people with myocardial infarction (MI). However, their mechanisms of action are not precise. To address this problem, network pharmacology was used to identify the various components that can be utilized to treat this condition, and an in vivo study was conducted to evaluate the cardioprotective effect in MI rats. Genes associated with silybin and MI targets were extracted, and overlapping genes between silybin‐associated genes and MI targets were identified using Venn diagrams. Using Cytoscape, we built, visualized, and analyzed a network of compounds and genes with pathways. Protein‐protein interaction network (PPI), gene ontology (GO) function enrichment, and Kyoto Encyclopedia of Genes, and Genomes (KEGG) pathway enrichment analyses of the core targets were performed to predict its mechanism. A molecular docking study assessed the affinity between silybin and the top three genes. ECG pattern, serum CK‐MB, LDH, serum and heart tissue antioxidants, SOD and catalase in isoproterenol‐induced MI rats were used to test the cardioprotective effect of silybin. Silybin‐related genes (114) and MI‐related genes (1800) were identified, and 74 genes overlapped, in which the degrees of AKT1, TNF‐α and IL‐6 were higher than those of other targets are the disease target precisely. The enrichment of the gene set‐based indicated that the PI3K‐Akt, TNF‐α, IL‐17, VEGF, and HIF‐1 signaling pathways were significantly involved in the mechanisms of silybin against MI. The QRS complex of the ECG of silybin‐treated MI rats was restored to normal ECG and significantly increased serum (p<0.0001***) and heart tissue (p<0.0001***) SOD and serum (p<0.001**) and heart tissue (p<0.001**) catalase compared to MI rats. This study embodies the complex network relationship of multi‐target and multiple pathways of silybin in the treatment of MI and provides a novel method for further research on the mechanism of silybin. It has been suggested that silybin alleviates the symptoms of MI by improving antioxidant levels through the PI3K‐Akt/HIF‐1 pathway.