Astaxanthin Inhibits Ferroptosis of Hippocampal Neurons in Kainic Acid‐Induced Epileptic Mice by Activating the Nrf2/ GPX4 Signaling Pathway

作者：Shihao Chen, Linqian Zhao, Xing Jin, Qichang Liu, Yuqing Xiao, Huiqin Xu · 发表于：CNS Neuroscience & Therapeutics · 年份：2025 · DOI：10.1111/cns.70238 · 被引用次数：18 · 研究领域：Ferroptosis and cancer prognosis、Inflammasome and immune disorders、Cholesterol and Lipid Metabolism

BACKGROUND: Epilepsy, a prevalent neurological disorder, is distinguished by episodic abnormal discharges of neurons within the brain, resulting in transient brain dysfunction. Prior research has identified a novel form of cell death termed ferroptosis, which is intricately linked to the initiation and progression of epilepsy. It has been demonstrated that astaxanthin (AST) can inhibit ferroptosis by enhancing the activity of nuclear factor erythroid 2-related factor 2 (Nrf2), thereby providing cytoprotection. Therefore, this study aims to investigate whether AST can alleviate neuronal ferroptosis in epilepsy by activating the Nrf2/GPX4 pathway, thereby exerting a neuroprotective effect. METHODS: By constructing a kainic acid (KA)-induced epilepsy mouse model and a KA-induced HT22 cell model, we employed behavioral testing, Western blot analysis, quantitative real-time reverse transcription qRT-PCR, ferroptosis-related assay kits, immunofluorescence staining, and other methods. These methodologies were utilized to investigate the protective effects and underlying mechanisms of AST on ferroptosis in KA-induced epileptic mice and HT22 neurons. RESULTS: Our results demonstrate that AST pretreatment alleviates KA-induced epileptic behaviors and cognitive impairments in mice and mitigates ferroptosis indicators such as lipid peroxidation and mitochondrial morphological alterations. This neuroprotective effect appears to be mediated by the activation of the Nrf2/GPX4 signaling axis...