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Vitexin Improves Cerebral ischemia‑reperfusion Injury by Attenuating Oxidative Injury and Ferroptosis via Keap1/Nrf2/HO-1signaling

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Abstract

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.

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Data availability

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

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  1. Department of Neurology, Yantaishan Hospital, Yantai, Shandong, China

    Lei Guo

  2. Department of Neurology, Yantai Laiyang Central Hospital, 111 Changshan Road, 265200, Laiyang, Yantai, Shandong, P.R. China

    Lei Shi

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Guo, L., Shi, L. Vitexin Improves Cerebral ischemia‑reperfusion Injury by Attenuating Oxidative Injury and Ferroptosis via Keap1/Nrf2/HO-1signaling. Neurochem Res 48, 980–995 (2023). https://doi.org/10.1007/s11064-022-03829-0

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