Lastly, blocking GPX4 abolishes the antidepressant effects of EDA, confirming the regulatory role of the Sirt1/Nrf2/HO-1/GPX4 signaling pathway in ferroptosis, with GPX4 serving as a crucial component in the treatment of depression and anxiety via ferroptosis mechanisms (Dang et al., 2022). This evidence concerns the gene NFE2L2 and major depressive disorder.