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Resveratrol modulates the sFRP4/Wnt signaling Pathway and preserves blood-brain barrier integrity in rats with ischemic stroke
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DOI:10.1016/j.ejphar.2026.178951.png)
Abstract
En 中文
Resveratrol is a polyphenolic natural product. It has been demonstrated that resveratrol has protective effects on various neurological diseases. However, the mechanism by which resveratrol protects the neurological function in stroke remains unclear. In this study, we established a stroke rat via middle cerebral artery occlusion (MCAO). The MCAO rats were intraperitoneally administered with resveratrol (30 mg/kg) for 7 consecutive days. Neurological function scoring, cerebral infarct area assessment, tissue collection for subsequent assays, and pathological, neuroinflammatory, and oxidative stress analyses were performed at 24 h post-stroke, while the Morris water maze test for poststroke cognitive impairment (PSCI) was conducted from day 8 to day 14 post-stroke. The differentially expressed proteins (DEPs) were identified through proteomic analysis. The key regulatory pathways were verified through western blotting. Resveratrol significantly reduced the neurological function score, decreased the infarct area, and alleviated PSCI. Resveratrol significantly reduced the levels of inflammatory factors, lowered the malondialdehyde (MDA) level, and increased the levels of glutathione (GSH) and total antioxidant capacity (T-AOC). Proteomic analysis identified 263 DEPs. Protein‒protein interaction analysis suggested that secreted frizzled-related protein 4 (sFRP4)/Wnt pathway might be a potential target of resveratrol. Western blotting confirmed that resveratrol effectively reversed the stroke-induced upregulation of sFRP4, and also abrogated the stroke-induced downregulation of Wnt3a, Wnt4, Wnt5, Wnt11, and β-catenin levels. Additionally, resveratrol reversed the stroke-induced reduction in the levels of ZO-1, Occludin, and Claudin 5. It is concluded that resveratrol maintains the integrity of the blood-brain barrier and modulates the sFRP4/Wnt signaling pathway.
Keywords:
Resveratrol
sFRP4/Wnt signaling pathway
blood-brain barrier
ischemic stroke
neuroprotection
Journal
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4.7
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2.3W
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4.0W
