Cerebral ischemia/reperfusion involves multiple pathological processes and ferroptosis played a crucial role in the disease progression. Nevertheless, whether Vitexin could ameliorate ischemia/reperfusion injury via meditate the ferroptosis still remains unknown. In this study, we established the oxygen-glucose deprivation and reoxygenation (OGD/R) neuron cell and middle cerebral artery occlusion/reperfusion (MCAO/R) rat model. The cell viability, cell apoptosis and reactive oxygen species (ROS) levels were tested by CCK-8 assay and Flow cytometry, respectively. Hematoxylin-eosin staining, TTC, TEM, immunofluorescence analysis and western blot were used to investigate the effects of Vitexin. The results demonstrated that Vitexin could enhanced the cell viability and decreased the cell apoptosis in OGD/R cell model. Meanwhile, incubation with Vitexin maintained the neuroprotective effects in OGD/R induced generation of lipid ROS and neuronal cell ferroptosis via regulated the expressions of Keap1/Nrf2/HO-1 relative protein levels. Moreover, treatment with Vitexin reversed brain infracted volume, the normal histopathology and mitochondrial function in MCAO/R rat model. Vitexin significantly decreased the Nrf2 transfer ration from nuclear to cytosol and regulated the expression of Keap1/Nrf2/HO-1 signaling both in vitro and in vivo. Nevertheless, the protective effects of Vitexin were blocked with the Nrf2 inhibitor ML385. Vitexin could protect the neuron cell and brain related with the Keap1/Nrf2/HO-1 signaling pathway. Vitexin was a useful candidate for stroke therapy and our research may provide an attractive therapeutic target for the treatment of stroke.

脑缺血/再灌注涉及多个病理过程，铁死亡在疾病进展中起着至关重要的作用。尽管如此，牡荆素是否可以通过调节铁死亡来改善缺血/再灌注损伤仍然未知。在本研究中，我们建立了氧糖剥夺和复氧（OGD/R）神经元细胞和大脑中动脉闭塞/再灌注（MCAO/R）大鼠模型。分别通过CCK-8法和流式细胞仪检测细胞活力、细胞凋亡和活性氧（ROS）水平。苏木精-伊红染色、TTC、TEM、免疫荧光分析和蛋白质印迹用于研究牡荆素的作用。结果表明牡荆素可以增强OGD/R细胞模型中的细胞活力并减少细胞凋亡。同时，与 Vitexin 孵育通过调节 Keap1/Nrf2/HO-1 相关蛋白水平的表达，在 OGD/R 诱导的脂质 ROS 产生和神经元细胞铁死亡中保持神经保护作用。此外，牡荆素治疗可逆转 MCAO/R 大鼠模型中的脑梗塞体积、正常组织病理学和线粒体功能。Vitexin 显着降低 Nrf2 从核转移到胞质溶胶的比率，并在体外和体内调节 Keap1/Nrf2/HO-1 信号的表达。然而，牡荆素的保护作用被 Nrf2 抑制剂 ML385 阻断。牡荆素可以保护与Keap1/Nrf2/HO-1信号通路相关的神经元细胞和大脑。Vitexin 是中风治疗的有用候选物，我们的研究可能为中风的治疗提供有吸引力的治疗靶点。