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ORIGINAL RESEARCH article
Front. Pharmacol.
Sec. Neuropharmacology
Volume 16 - 2025 | doi: 10.3389/fphar.2025.1581320
Edaravone dexborneol protected neurological function by targeting NRF2/ARE and NF-κB/AIM2 pathways in cerebral ischemia/reperfusion injury
Provisionally accepted- Changsha Medical University, Changsha, China
Edaravone dexborneol (Eda-Dex), a promising neuroprotectant composed of edaravone and (+)-borneol, has been clinically applied in stroke treatment. However, the mechanism of action of Eda-Dex remains unclear. We created a rat model of cerebral ischemia/reperfusion injury (CIRI) through middle cerebral artery occlusion.Neurological scoring, TTC staining, and laser speckle imaging were used to assess neurological deficits, infarct size and cerebral blood flow (CBF). Behavioral tests, including the open field test, the elevated plus maze, the sucrose preference test, and the novel object recognition test, were conducted to assess cognitive functionanimal behavior. Western blotting and ELISA were employed to assess levels of expression of components of the NRF2/ARE and NF-κB/AIM2 pathways and of specific cytokines.The levels of oxidative stress markers were analyzed via commercially available kits. HE staining, Nissl staining, and immunohistochemistry were used to assess pathological alterations in the brain. Our results showed that Eda-Dex dramatically reduced the neurological deficit score and cerebral infarct size, increased CBF, and attenuated anxiety-like behavior and improved cognitive function in CIRI rats. Eda-Dex significantly reduced oxidative stress and relieved inflammatory response and it significantly upregulated NRF2, NQO1, HO-1, and SLC7A11 and significantly downregulated NF-κB, AIM2, ASC and caspase 1 in the infarcted brain. Moreover, Eda-Dex clearly reduced pathological damage, rescued neurons, and reduced the activation of microglia and astrocytes. In summary, the results of this study confirm that Eda-Dex exerts neuroprotective effects by synergistically inhibiting oxidative stress and inflammation via the NRF2/ARE and NF-κB/AIM2 pathways in CIRI rats.
Keywords: edaravone dexborneol, Neuroprotection, Nrf2/ARE pathway, NF-κB/AIM2 pathway, Cerebral ischemia/reperfusion injury
Received: 22 Feb 2025; Accepted: 28 Mar 2025.
Copyright: © 2025 Zhang, Zhu, Zhou, Wang, Demg, He and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Hui Zhang, Changsha Medical University, Changsha, China
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