Exploring the protective mechanisms of syringaresinol against myocardial infarction by experimental validation and network pharmacology

Abstract

Myocardial Infarction (MI) is a leading cause of mortality worldwide. Currently, effective treatments are still lacking. Increasing evidence supports the benefits of Syringaresinol (SYR) for the treatment of cardiovascular disease is accumulating. Nevertheless, whether SYR can alleviate MI is unknown. The study aims to investigate the protective effect of SYR against MI and elucidate its potential molecular mechanism. We found that SYR ameliorate MI-induced cardiac dysfunction, reduce infarct size, and alleviate myocardial hypertrophy, fibrosis, inflammation, as well as apoptosis. In addition, we collected targets related to SYR and MI through multiple databases, and obtained 281 potential therapeutic targets after intersection. GO and KEGG enrichment analysis found that these therapeutic targets were concentrated on inflammation, fibrosis, and apoptosis pathways. Based on the PPI network and combined with Centiscape2.2 and cytoHubba analysis, we obtained 10 hub proteins. The molecular docking results showed that SYR has strong bindings with 10 hub proteins. snRNA-seq data showed that CASP3 and NFKB1 were expressed in all cell types. In addition, the therapeutic targets of SYR are also mainly distributed in all cell types. Finally, we found that SYR could alleviate MI by partially reversing the expression of AKT1, EGFR, CASP3, SRC, NFKB1, HSP90AA1, HIF1A, MMP9 and ESR1 both in vivo and in vitro. Our findings suggested that SYR may protect against MI by reducing inflammatory, fibrotic and apoptotic effects via multiple targets and pathways, which provides a new theoretical foundation for the clinical therapy of MI.