Supercritical CO2 extraction of fermented soybean lipids against erastin-induced ferroptosis in rat pheochromocytoma cells

• Optimum extraction of FSE-C was achieved at 35 °C, 30 MPa, and 2.40 ± 0.19% moisture content. • Concentrations of minor active components in FSE-C were higher than those in unfermented soybean lipids. • FSE-C significantly inhibited erastin-induced ferroptosis in PC12 cells. • Potential mechanisms of FSE-C were revealed in key pathways and biomarkers of ferroptosis. The optimum supercritical carbon dioxide (SC-CO 2 ) extraction of fermented soybean lipids (FSE-C) was as follows: 35 °C, 30 MPa, and 2.40 ± 0.19% moisture content using response surface methodology. The fatty acid composition of FSE-C contained more palmitic acid and α-linolenic acid and less linoleic acid than unfermented soybean lipids (SE-C). FSE-C had higher contents of minor active components (phytosterols, squalene, total flavonoid, and total polyphenol) than SE-C. The protective effects of FSE-C on erastin-induced ferroptosis were investigated to reveal the potential mechanisms of action characterized by increasing cell viability and glutathione concentrations, attenuating levels of intracellular Fe 2+ ion, lipid peroxidation, and ROS, as well as modifying mRNA expression (GPx4, SLC7A11, ACSL4, and LPCAT3) and lipid metabolism. These findings suggest that FSE-C is a class of active ingredients against erastin-induced ferroptosis and warrants further exploration and utilization as a functional food.