%0 Journal Article
%T Inhibition of TNF-α/NF-κB Signaling Underlies the Protective Effect of Gypenosides Against CORT-Induced Ferroptosis in PC12 Cells
%A Ahmed Mansour
%A Omar Saeed
%J Bulletin of Pioneering Researches of Medical and Clinical Science
%@ 3006-2659
%D 2024
%V 4
%N 2
%R 10.51847/nBFetxR4X2
%P 186-202
%X Persistent psychological strain may trigger malfunction of the nervous system, together with behaviors resembling depression in animals. Gypenosides can relieve neuronal damage caused by sustained stress, though the protective pathway remains inadequately characterized. The current work set out to probe the influence and operational mechanisms of gypenosides on neuronal ferroptosis induced by chronic stress. To this end, an in vitro model of sustained stress-induced neuronal impairment was created by applying corticosterone to induce injury in PC12 cells. We established that the ferroptosis blockers DFO and Ferrostatin-1 reduced corticosterone-driven cell death in PC12 cells by lowering iron deposition and lipid peroxidation and by boosting cellular survival. At the same time, gypenosides lessened ferroptosis induced by the ferroptosis inducer Erastin in PC12 cells. Subsequently, gypenosides prevented corticosterone-elicited ferroptosis in PC12 cells. At the molecular level, gypenosides reduced the abundance of Hepcidin and DMT1 and increased the abundance of Ferritin and FPN1, thereby restoring the corticosterone-disturbed iron equilibrium and alleviating iron overload. In parallel, gypenosides alleviated corticosterone-driven lipid peroxidation by restraining GLS2 expression, increasing SLC7A11 and glutathione peroxidase 4 levels, and curtailing glutamate accumulation and GSH exhaustion. Gypenosides also reduced corticosterone-induced secretion of inflammatory mediators, TNFR1 levels, and NF-κB and p53 phosphorylation in PC12 cells. Altogether, these results imply that gypenosides ease corticosterone-elicited ferroptosis via suppressing the TNF-α/NF-κB signaling cascade in PC12 cells.
%U https://bprmcs.com/article/inhibition-of-tnf-anf-kb-signaling-underlies-the-protective-effect-of-gypenosides-against-cort-indu-cyk3klzgqanwtxp