Calycosin treats acute myocardial infarction via NLRP3 inflammasome: Bioinformatics, network pharmacology and experimental validation

Abstract

Background: Calycosin (CA) is a flavonoid natural product that may effectively treats acute myocardial infarction (AMI), but its mechanism is unclear.

Methods: Targets related to AMI and CA were identified using the GEO database, SwissTargetPrediction, PharmMapper and literature searches. Protein-protein interactions analysis and Cytoscape were used to screen the core targets of CA for AMI treatment. Enrichment analysis identified biological pathways linked to AMI and potential mechanisms of CA. Immune infiltration analysis was used to explore the role of immune cells in AMI and the correlation between core targets and immune cells. And further validated in AMI rats with ligated left anterior descending.

Results: Bioinformatics identified relevant targets and biological mechanisms of AMI, and network pharmacology revealed 31 potential targets affected by CA, with NLRP3, IL-18, IL-1β, MMP9, and TLR4 as core targets. Enrichment analysis demonstrated the biological roles of these potential targets and NLRP3, IL1β and IL18 were selected for further analysis. Immune infiltration analysis showed that both NLRP3 and IL-1β were closely associated with monocytes, mast cells activated and neutrophils, and IL-18 was closely associated with monocytes. CA exerted cardioprotective effects in AMI rats by inhibiting NLRP3 inflammasome activation and reducing IL-18 and IL-1β levels, improving cardiac function and attenuating myocardial injury and fibrosis.

Conclusion: CA effectively protects cardiac function and mitigates myocardial injury in post-AMI rats, probably through NLRP3 inflammasome inhibition.

Keywords: Acute myocardial infarction; Calycosin; IL-18; IL-1β; NLRP3 inflammasome.