Gastrodin inhibits neuronal ferroptosis by regulating mir-455–5p/ACSL4 pathway after stroke via exosome
- 1China-Japan Friendship Hospital , ,
- 2ZiBo Hospital of Traditional Chinese Medicine , ,
- 3Beijing Tiantan Hospital Affiliated to Capital Medical University , ,
Abstract
Recent studies have demonstrated that ferroptosis plays a crucial role in neuronal cell death following cerebral infarction. Our previous research showed that gastrodin (GAS) significantly improved neurological function in rats subjected to middle cerebral artery occlusion (MCAO); however, the underlying mechanisms remain unclear. In the present study, we employed Western blotting, quantitative PCR (qPCR), and immunofluorescence assays to investigate the changes in the expression levels of ferroptosis-related regulatory proteins (ACSL4, TFR1, GPX4, and MBL-2) in both in vivo and in vitro models following ischemic-hypoxic injury, as well as the modulatory effects of gastrodin on these proteins. We also conducted an in-depth exploration of an innovative therapeutic approach involving exosomes. Specifically, we constructed gastrodin-treated serum exosomes (GSE) to assess their role in neuroprotection. Our findings revealed that gastrodin significantly reduced infarct volume in middle cerebral artery occlusion rats. 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.
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BibTeX
@article{nan2026gastrodin,
title = {{Gastrodin inhibits neuronal ferroptosis by regulating mir-455–5p/ACSL4 pathway after stroke via exosome}},
author = {Yinan Nan and Wenhao Zhu and Shaoqing Wang},
journal = {Frontiers in pharmacology},
year = {2026},
month = oct,
doi = {10.3389/fphar.2026.1882367},
url = {https://europepmc.org/article/PMC/PMC13670028},
note = {CC BY},
}
RIS
TY - JOUR
TI - Gastrodin inhibits neuronal ferroptosis by regulating mir-455–5p/ACSL4 pathway after stroke via exosome
AU - Yinan Nan
AU - Wenhao Zhu
AU - Shaoqing Wang
PY - 2026
DA - 2026/10/01
JO - Frontiers in pharmacology
DO - 10.3389/fphar.2026.1882367
UR - https://europepmc.org/article/PMC/PMC13670028
AB - Recent studies have demonstrated that ferroptosis plays a crucial role in neuronal cell death following cerebral infarction. Our previous research showed that gastrodin (GAS) significantly improved neurological function in rats subjected to middle cerebral artery occlusion (MCAO); however, the underlying mechanisms remain unclear. In the present study, we employed Western blotting, quantitative PCR (qPCR), and immunofluorescence assays to investigate the changes in the expression levels of ferroptosis-related regulatory proteins (ACSL4, TFR1, GPX4, and MBL-2) in both in vivo and in vitro models following ischemic-hypoxic injury, as well as the modulatory effects of gastrodin on these proteins. We also conducted an in-depth exploration of an innovative therapeutic approach involving exosomes. Specifically, we constructed gastrodin-treated serum exosomes (GSE) to assess their role in neuroprotection. Our findings revealed that gastrodin significantly reduced infarct volume in middle cerebral artery occlusion rats. 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.
SN - 1663-9812
ER -