Isoquercitrin alleviates sepsis-induced myocardial injury via the EGFR/PI3K/AKT signaling pathway.
TL;DR
Isoquercitrin mitigates sepsis-induced myocardial injury by targeting the EGFR/PI3K/AKT pathway, thereby inhibiting inflammation and apoptosis and represents a promising therapeutic candidate for sepsis-related cardiac damage.
Abstract
Background
Sepsis-induced myocardial injury is a life-threatening complication. Isoquercitrin (IQC), a natural flavonoid glycoside, exhibits anti-inflammatory and anti-apoptotic properties, yet its role in septic cardiomyopathy remains unclear.
Methods
IQC targets were predicted via transcriptomics and molecular docking. LPS-induced AC16 cardiomyocyte injury and cecal ligation puncture (CLP) rat models were established. Cell viability and apoptosis were assessed by CCK-8 and flow cytometry. Inflammatory cytokines were measured using ELISA. Myocardial injury and fibrosis were evaluated via HE and Masson staining. Protein expression was analyzed by Western blot. EGFR knockdown and inhibitor (MTX-531) were applied for mechanistic validation.
Results
EGFR was identified as a high-affinity target of IQC, with PI3K-AKT being the most enriched pathway. In vitro, IQC restored cell viability, suppressed apoptosis, and reduced inflammation in LPS-stimulated AC16 cells-effects reversed by EGFR knockdown or PI3K/AKT inhibition. In vivo, IQC alleviated myocardial injury, fibrosis, and apoptosis in septic rats, accompanied by reduced inflammation and activated EGFR/PI3K/AKT signaling. These benefits were abolished by MTX-531.
Conclusion
Isoquercitrin mitigates sepsis-induced myocardial injury by targeting the EGFR/PI3K/AKT pathway, thereby inhibiting inflammation and apoptosis. IQC represents a promising therapeutic candidate for sepsis-related cardiac damage.