ArticleAntioxidants (Basel, Switzerland)2020
Yuzu and Hesperidin Ameliorate Blood-Brain Barrier Disruption during Hypoxia via Antioxidant Activity.
Article in Antioxidants (Basel, Switzerland), 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Hesperidin Attenuates H₂O₂-Induced Neurotoxicity via Modulation of Inflammatory Pathways and MMP Activity in Differentiated SH-SY5Y Cells: In Vitro and In Silico Models.Journal of biochemical and molecular toxicology · 2026Article
- Neuroprotective effects of hesperidin on cerebral vasospasm after subarachnoid hemorrhage in rats: an experimental study.Ulusal travma ve acil cerrahi dergisi = Turkish journal of trauma & emergency surgery : TJTES · 2025Article
- Neuroactive Phytochemicals as Multi-Target Modulators of Mental Health and Cognitive Function: An Integrative Review.International journal of molecular sciences · 2025Review
- Cardiovascular protective effects of natural flavonoids on intestinal barrier injury.Molecular and cellular biochemistry · 2025Review
- Much More than Nutrients: The Protective Effects of Nutraceuticals on the Blood-Brain Barrier in Diseases.Nutrients · 2025Review
- Advances in understanding the role of inflammatory factors and immune cells in the pathology of epilepsy, mediated by neuroimmune interactions within the gut-brain axis.Frontiers in cell and developmental biology · 2025Review
- Traditional, complementary, and integrative medicine in the management of ischemic stroke: a narrative review.Frontiers in pharmacology · 2025Review
- Review
- Harnessing the Power of Polyphenols: A New Frontier in Disease Prevention and Therapy.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Phenolic Compounds of Therapeutic Interest in Neuroprotection.Journal of xenobiotics · 2024Review
- P2X7 receptor: A receptor closely linked with sepsis-associated encephalopathy.Open life sciences · 2024Review
- Formulation and Characterization of Hesperidin-Loaded Transethosomal Gel for Dermal Delivery to Enhance Antibacterial Activity: Comprehension of In Vitro, Ex Vivo, and Dermatokinetic Analysis.Gels (Basel, Switzerland) · 2023Article
- Neuroprotective Potentials of Flavonoids: Experimental Studies and Mechanisms of Action.Antioxidants (Basel, Switzerland) · 2023Review
- Methanol extract of Iraqi Kurdistan RegionFrontiers in chemistry · 2023Article
- Caveolin-1 accelerates hypoxia-induced endothelial dysfunction in high-altitude cerebral edema.Cell communication and signaling : CCS · 2022Article
- Natural Antioxidant in Cardiovascular and Cerebrovascular Diseases.Antioxidants (Basel, Switzerland) · 2022Article
- Effects of Natural Polyphenols on Oxidative Stress-Mediated Blood-Brain Barrier Dysfunction.Antioxidants (Basel, Switzerland) · 2022Review
- Editorial: Polyphenols' action on the brain.Frontiers in neuroscience · 2022Article
- Electroacupuncture Increases the Hippocampal Synaptic Transmission Efficiency and Long-Term Plasticity to Improve Vascular Cognitive Impairment.Mediators of inflammation · 2022Article
- Erythrocytes, a New Contributor to Age-Associated Loss of Blood-Brain Barrier Integrity.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2021Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Yuzu and its main component, hesperidin (HSP), have several health benefits owing to their anti-inflammatory and antioxidant properties. We examined the effects of yuzu and HSP on blood-brain barrier (BBB) dysfunction during ischemia/hypoxia in an in vivo animal model and an in vitro BBB endothelial cell model, and also investigated the underlying mechanisms. In an in vitro BBB endothelial cell model, BBB permeability was determined by measurement of Evans blue extravasation in vivo and in vitro. The expression of tight junction proteins, such as claudin-5 and zonula occludens-1 (ZO-1), was detected by immunochemistry and western blotting, and the reactive oxygen species (ROS) level was measured by 2'7'-dichlorofluorescein diacetate intensity. Yuzu and HSP significantly ameliorated the increase in BBB permeability and the disruption of claudin-5 and ZO-1 in both in vivo and in vitro models. In bEnd.3 cells, yuzu and HSP were shown to inhibit the disruption of claudin-5 and ZO-1 during hypoxia, and the protective effects of yuzu and HSP on claudin-5 degradation seemed to be mediated by Forkhead box O 3a (FoxO3a) and matrix metalloproteinase (MMP)-3/9. In addition, well-known antioxidants, trolox and N-acetyl cysteine, significantly attenuated the BBB permeability increase, disruption of claudin-5 and ZO-1, and FoxO3a activation during hypoxia, suggesting that ROS are important mediators of BBB dysfunction during hypoxia. Collectively, these results indicate that yuzu and HSP protect the BBB against dysfunction via maintaining integrity of claudin-5 and ZO-1, and these effects of yuzu and HSP appear to be a facet of their antioxidant properties. Our findings may contribute to therapeutic strategies for BBB-associated neurodegenerative diseases.
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Registered trials
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