Translational Potential of Baicalein in Mitigating RSL3-Induced Ferroptosis in Fibroblasts: Implications for Therapeutic Interventions.

Background: Ferroptosis is an iron-driven cell-death mechanism that plays a central role in various diseases. Recent studies have suggested that baicalein inhibits ferroptosis, making it a promising therapeutic candidate. Materials and Methods: Fibroblast cultures were treated with different agents to determine the effects of baicalein on ferroptosis. Ferroptosis-related gene expression, lipid peroxidation, and post-treatment cellular structural changes were measured using real-time quantitative polymerase chain reaction, C11-BODIPY dye, and transmission electron microscopy, respectively. Results: Baicalein significantly inhibited rat sarcoma virus selective lethal 3-induced ferroptosis in fibroblasts. Moreover, in baicalein-treated groups, reduced ferroptosis-related gene expression, decreased lipid peroxidation, and maintained cell structure was observed when compared with those of the controls. Discussion: The ability of baicalein to counteract RSL3-induced ferroptosis underscores its potential protective effects, especially in diseases characterized by oxidative stress and iron overload in fibroblasts. Conclusion: Baicalein may serve as a potent therapeutic agent against conditions in which ferroptosis is harmful. The compound's efficacy in halting RSL3-triggered ferroptosis in fibroblasts paves the way for further in vivo experiments and clinical trials.