Inhibition of Iron Death by Lycium barbarum Polysaccharides Ameliorates Myocardial Injury in Sepsis: A Pharmacological Mechanism Study Based on the NRF2/HO-1 Pathway

Abstract

Sepsis remains a leading global cause of mortality, with sepsis-induced myocardial injury (SIMI) being a critical determinant of clinical outcomes. Lycium barbarum L. (goji berry), a traditional Chinese herb, has demonstrated therapeutic potential in sepsis-related organ injuries through multiple pathways. However, its role and mechanisms in SIMI remain unexplored. A network pharmacology approach identified candidate targets of Lycium barbarum via TCMSP and SwissTargetPrediction, intersected with sepsis/myocardial injury-related targets from GeneCards. Protein–protein interaction (PPI) networks were constructed using STRING and analyzed via Cytoscape's cytoHubba plugin. Enriched pathways were explored through KEGG/GO analyses. Transcription factor prediction, molecular docking (AutoDock Vina), and molecular dynamics (MD) simulations (GROMACS) were performed for key targets. Experimental validation included in vivo LPS-induced sepsis models and in vitro H9C2 cardiomyocyte assays. This study reveals that Lycium barbarum alleviates SIMI by modulating the NRF2/HO-1 signaling pathway, positioning it as a novel therapeutic candidate for sepsis-associated cardiac complications.