The Mechanism of Qishen Yixin Granules in Suppressing Myocardial Fibrosis: A Pharmacological Validation Based on Network Pharmacology

Background: Myocardial fibrosis (MF) is a condition that plays a crucial role in heart failure (HF) development and death, and current drugs for its treatment are limited. Qishen Yixin Granule (QSYXG) is a Traditional Chinese Medicine (TCM) that has been shown to be effective in treating chronic HF, but its mechanism of action is not yet fully understood. This study aimed to reveal the molecular mechanisms and bioactive compounds of QSYXG treating MF using an integrated network pharmacology and pharmacological validation pathway. Methods: The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) database, drug-target database and GeneCard database were used to screen active ingredients, drug targets and MF genes. The clusterProfiler package in R programming language was employed for functional and pathway enrichment analyses. Experimental validation was completed using hematoxylin-eosin staining, Massons trichrome staining, and immunohistochemistry in isoproterenol-induced MF rats. Western blot, phalloidin staining, and immunofluorescence staining were performed to elucidate the predicted mechanism on H9C2 cells. Results: In this study, 55 bioactive components and 59 putative targets were collected. Functional enrichment analysis revealed that responses to lipopolysaccharides, oxidative stress, and hypoxia constituted vital biological processes. Six targets, containing mitogen-activated protein kinase (MAPK) 14, prostaglandin-endoperoxide synthase 2 (PTGS2), serine/threonine kinase 1 (AKT1), MAPK8, Interleukin (IL)-6 and IL-1β, directly regulated these responses simultaneously. Five pathways were identified by the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. QSYXG could downregulate the expression of PTGS2, MAPK14 and MAPK8 and upregulate the expression of AKT1 in the treatment of MF. Conclusions: This study revealed that QSYXG could alleviate MF based on multiple components, targets and pathways.