Pretreatment with schisandrin B attenuates heat stroke-induced myocardial injury and ferroptosis.

Heat stroke (HS) represents a severe public concern due to its high mortality rate, with cardiac injury recognized as a critical pathological process. Schisandra chinensis has been utilized in traditional Chinese prescription to prevent and treat heat stroke, but the underlying mechanism is unclear. The present study was designed to explore the cardioprotective effect of its main component, Schisandrin B (SchB). We analyzed cardiac RNA sequencing differentially expressed genes (DEGs) between HS and control mice to initially evaluate SchB's potential in attenuating HS-induced cardiac injury and its relation with ferroptosis. Using murine (core temperature reaching 42 °C) and cellular HS models (42 °C exposure for 5 h), we verified the cardiac preventive effects of SchB against HS-induced injury and its role in the modifying of ferroptosis. Bioinformatic analysis suggested SchB could modulate ferroptosis during HS. SchB pretreatment significantly prolonged time to reach HS in mice, alleviated cardiomyocyte injury, decreased Fe2+ and malondialdehyde (MDA) levels while elevated glutathione (GSH) levels. Additionally, SchB downregulated acyl-CoA synthetase long chain family member 4 (ACSL4) expression and upregulated solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in both murine and H9c2 cells HS models. Concurrently, SchB upregulated sirtuin 1 (SIRT1) expression while inhibiting the nuclear translocation of high mobility group box 1 (HMGB1). These findings suggest that SchB pretreatment may attenuate HS-induced cardiac ferroptosis and the associated myocardial injury through modulation of the SIRT1/HMGB1/ACSL4 pathway.