2. Academic Validation
  3. Vitexin alleviates cerebral ischemia/reperfusion injury by regulating mitophagy via the SIRT1/PINK1/Parkin pathway

Vitexin alleviates cerebral ischemia/reperfusion injury by regulating mitophagy via the SIRT1/PINK1/Parkin pathway

  • Brain Res Bull. 2025 Jul:227:111404. doi: 10.1016/j.brainresbull.2025.111404.
Chao Chen 1,  Zhenzhong Zhang 2,  Baolin Du 3,  Chenling Lv 4
Affiliations

Affiliations

  • 1 Department of Cardiology, Hangzhou Hospital of Traditional Chinese Medicine, NO. 453 Stadium Road, Hangzhou, Zhejiang 310007, China.
  • 2 Department of Neurology, Tongde Hospital of Zhejiang Province, NO. 234 Gucui Road, Hangzhou, Zhejiang 310012, China.
  • 3 Department of Neurology, Urumqi Midong District Hospital of Traditional Chinese Medicine, NO. 1055 Fuqian Middle Road, Urumqi, Xinjiang Uygur 830063, China.
  • 4 Department of Neurology, Tongde Hospital of Zhejiang Province, NO. 234 Gucui Road, Hangzhou, Zhejiang 310012, China. Electronic address: piedaochuan321@163.com.
PMID: 40441663 DOI: 10.1016/j.brainresbull.2025.111404
Abstract

Objective: This study was conducted to elucidate vitexin's protective effects and underlying mechanism in ameliorating cerebral ischemia/reperfusion injury (CIRI) through regulation of Mitophagy.

Methods: Focal CIRI in mice was induced using the middle cerebral artery occlusion and reperfusion method. 2,3,5-triphenyltetrazolium chloride staining was performed for the evaluation of cerebral infarction. Neurological deficits and brain tissue damage were assessed by neurological deficit scores and hematoxylin-eosin staining, respectively. HT22 cells underwent oxygen-glucose deprivation/reoxygenation (OGD/R) exposure to develop an in vitro model. Prior to OGD/R, we pretreated the HT22 cells with vitexin, the Mitophagy inhibitor (Mdivi-1), or the SIRT1 Inhibitor (EX-527). Determination of cell viability and Apoptosis were carried out through the cell counting kit-8 assay and flow cytometry, respectively. JC-1 fluorescence staining and MitoSOX™ Red staining were respectively performed for assessing mitochondrial membrane potential (MMP) and detecting levels of mitochondrial Reactive Oxygen Species (mtROS). Expression of B-cell lymphoma 2 (Bcl-2), Bcl-2-associated X protein (Bax), microtubule-associated protein 1 A/1B-light chain 3 (LC3), sequestosome-1 (p62), PTEN-induced kinase 1 (PINK1), Parkin, as well as silent information regulator two 1 (SIRT1) was determined via Western blot.

Results: Vitexin was found to significantly alleviate CIRI in mice and mitigate HT22 cell injury due to OGD/R exposure, as confirmed by our in vivo and in vitro experiments, accompanied by activation of Mitophagy and the SIRT1/PINK1/Parkin pathway. The OGD/R+Vitexin+Mdivi-1 group (versus the OGD/R+Vitexin group) displayed decreased cell viability, increased Apoptosis, a reduced Bcl-2/Bax ratio, diminished MMP, elevated mtROS levels, downregulated PINK1, LC3-II, and Parkin expression, and upregulated p62 expression. Similarly, the OGD/R+Vitexin+EX-527 group showed reduced cell viability, increased Apoptosis, a decreased Bcl-2/Bax ratio, decreased MMP, elevated mtROS levels, downregulated SIRT1, PINK1, LC3-II, and Parkin expression, and upregulated p62 expression.

Conclusion: Vitexin ameliorates CIRI by activating Mitophagy via the SIRT1/PINK1/Parkin pathway.

Keywords

CIRI; Mitophagy; SIRT1/PINK1/Parkin pathway; Vitexin.

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