[Salidroside suppresses ferroptosis in HT22 cells following oxygen-glucose deprivation/reoxygenation through regulation of non-ubiquitinated FUNDC1-dependent mitophagy pathway].

This study aims to investigate whether the mitophagy receptor FUN14 domain-containing 1(FUNDC1) serves as a molecular link between mitophagy and neuronal ferroptosis, and to determine whether salidroside(Sal) can inhibit neuronal ferroptosis after oxygen-glucose deprivation/reoxygenation(OGD/R) by inducing FUNDC1 expression and regulating mitophagy, thereby exerting neuroprotective effects. An in vitro model of neuronal ischemia-reperfusion injury was established with HT22 cells subjected to OGD/R. The experiment consisted of three parts:(1) control, OGD/R, ferrostatin-1(Fer-1), FUNDC1 overexpression(OV-FUNDC1), and OV-FUNDC1+Fer-1 groups;(2) control, OGD/R, 3-methyladenine(3MA, an autophagy inhibitor), Sal, and Sal+3MA groups;(3) control, OGD/R, Sal, FUNDC1 silencing(Si-FUNDC1), and Sal+Si-FUNDC1 groups. In the first part of the experiment, the survival rate of cells in each group was detected by the CCK-8 assay, and the protein levels of p62, microtubule-associated protein light chain 3(LC3), acyl-CoA synthetase long-chain family 4(ACSL4), and glutathione peroxidase 4(GPX4) were measured by Western blot. The results showed that compared with the control group, the OGD/R group had down-regulated protein levels of p62 and GPX4(P