Image 2_Gastrodin inhibits neuronal ferroptosis by regulating mir-455–5p/ACSL4 pathway after stroke via exosome.tif

Compared with the model group, the levels of ACSL4, TFR1, and MBL-2 proteins were markedly decreased, while GPX4 expression was significantly upregulated in the ischemic hemisphere of the gastrodin-treated rats. These results suggest that gastrodin exerts neuroprotective effects by inhibiting ferroptosis following cerebral infarction. In an oxygen-glucose deprivation model using Neuro-2a cells, we further observed that GSE enhanced cell viability by suppressing ferroptosis.

Using RNA immunoprecipitation dual-luciferase reporter assays, and fluorescence in situ hybridization we confirmed colocalization between miR-455–5p and ACSL4. Subsequently, we manipulated miR-455–5p expression in Neuro-2a cells through transfection and assessed cell viability using CCK-8 and Live/Dead assays. The results demonstrated that GSE inhibited OGD-induced ferroptosis and improved cell viability by modulating the miR-455–5p/ACSL4 signaling pathway.

In conclusion, our study indicates that gastrodin can suppress neuronal ferroptosis probably through an exosome-mediated mechanism involving the miR-455–5p/ACSL4 pathway, thereby exerting neuroprotective effects after ischemic injury. In addition, exosomal delivery represents a promising strategy to treat stroke.</p>