ArticleFluids and barriers of the CNS2025
Rutin ameliorates stress-induced blood‒brain barrier dysfunction and cognitive decline via the endothelial HDAC1‒Claudin-5 axis.
Article in Fluids and barriers of the CNS, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Chronic Administration of Carvone-RichPlants (Basel, Switzerland) · 2026Article
- Natural products and neurocognitive disorders: Mechanistic insights and research advances (Review).Molecular medicine reports · 2026Review
- Micro- and Nanoplastics in the Human Brain: Mechanistic Plausibility, Translational Challenges, and Links to Neurological Disease Trends.Molecular neurobiology · 2026Review
- Homocysteine Drives Hippocampal Blood-Brain Barrier Disruption and Cognitive Decline Under Chronic Stress via DNA Hypomethylation of Cav1.2.Brain sciences · 2026Article
- Serum Claudin-5 and Peripheral Inflammation in Major Depressive Disorder: A Case-Control Study with Focus on Suicidal Ideation.Alpha psychiatry · 2026Article
- Histone and non-histone (de)acetylation impact on the blood-brain barrier.Fluids and barriers of the CNS · 2026Review
- High-intensity interval training improves cognitive dysfunction in chronically stressed mice through alleviating homocysteine-induced transcriptional repression ofNeurobiology of stress · 2025Article
- Rutin Attenuates Virus Entry and Replication and Exerts Neuroprotection in Experimental Models of Japanese Encephalitis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Article
- Neuroprotective Effects of Qi Jing Wan and Its Active Ingredient Diosgenin Against Cognitive Impairment in Plateau Hypoxia.Pharmaceuticals (Basel, Switzerland) · 2025Article
- Molecular mechanisms of neuroprotective effect of rutin.Frontiers in pharmacology · 2025Review
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Abstract
backgroundEmerging evidence suggests that chronic stress compromises blood‒brain barrier (BBB) integrity by disrupting brain microvascular endothelial cells (BMECs), contributing to the development of cognitive impairments. Thus, targeting the BBB is expected to be a promising treatment strategy. The biological function of rutin has been investigated in neurological disorders; however, its regulatory role in stress-induced BBB damage and cognitive decline and the underlying mechanisms remain elusive.
methodsIn a chronic unpredictable mild stress (CUMS) mouse model, a fluorescent dye assay and behavioral tests, including a novel object recognition test and Morris water maze, were performed to evaluate the protective effects of rutin on BBB integrity and cognition. The effects of rutin on BMEC function were also investigated in hCMEC/D3 cells (a human brain microvascular endothelial cell line) in vitro. Furthermore, the molecular mechanisms by which rutin restores BBB endothelium dysfunction were explored via RNA-seq, quantitative real-time PCR, western blotting, immunofluorescence and chromatin immunoprecipitation. Finally, biotinylated tumor necrosis factor-α (TNF-α) was employed to test the influence of rutin on the ability of circulating TNF-α to cross the BBB.
resultsWe identified that rutin attenuated BBB hyperpermeability and cognitive impairment caused by the 8-week CUMS procedure. Moreover, rutin promoted the proliferation, migration and angiogenesis ability of BMECs, and the integrity of the cellular monolayer through positively regulating the expression of genes involved. Furthermore, rutin impeded histone deacetylase 1 (HDAC1) recruitment and stabilized H3K27ac to increase Claudin-5 protein levels. Ultimately, normalization of the hippocampal HDAC1‒Claudin-5 axis by rutin blocked the infiltration of circulating TNF-α into the brain parenchyma and alleviated neuroinflammation.
conclusionsThis work establishes a protective role of rutin in regulating BMEC function and BBB integrity, and reveals that rutin is a potential drug candidate for curing chronic stress-induced cognitive deficits.
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