Integrating Network Pharmacology and Pharmacological Validation for Deciphering the Mechanism of Qishen Yixin Granules in Suppressing myocardial fibrosis

The present study aimed to reveal the bioactive compounds and molecular mechanisms of Qishen Yixin Granules (QSYXG) in the treatment of MF using an integrated network pharmacology and pharmacological validation approach. All active ingredients, drug targets, MF genes were screened from the TCMSP database, drug-target databases, GeneCard database, respectively. Functional and pathway enrichment analyses were operated through the clusterProfiler package in R programming language. Experimental validation was performed using haematoxylin-eosin staining, Masson’s trichrome staining and immunohistochemistry in isoproterenol-induced MF rats, and western blot analysis, phalloidin staining and immunofluorescence staining were used to elucidate the predicted mechanism on H9C2 cells. In this study, 55 bioactive components and 59 putative targets were collected. Functional enrichment analysis revealed that responses to lipopolysaccharides, oxidative stress and hypoxia were the key biological processes and were regulated simultaneously by six direct targets, including PTGS2, MAPK14, AKT1, MAPK8, IL-6 and IL-1β. Five pathways were determined by KEGG pathway enrichment analysis. The experiment results indicate QSYXG could down-regulated expression of PTGS2, MAPK14 and MAPK8 and up-regulated expression of AKT1 in the treatment of MF. This study revealed QSYXG could alleviate MF based on multiple components, targets and pathways.