ArticleCNS neuroscience & therapeutics2022
Fisetin ameliorates cognitive impairment by activating mitophagy and suppressing neuroinflammation in rats with sepsis-associated encephalopathy.
Article in CNS neuroscience & therapeutics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.
- The Neuroprotective Role of Fisetin in Different Neurological Diseases: a Systematic Review.Molecular neurobiology · 2023Pooled it
- Fisetin Attenuates Amyloid-Beta-Induced Neurotoxicity in Human Neuroblastoma SH-SY5Y Cells: Integrating In Silico Target Prediction and In Vitro Validation.Journal of biochemical and molecular toxicology · 2026Article
- PINK1-Parkin pathway-mediated mitophagy in sepsis: friend or foe?Molecular biology reports · 2026Review
- Intermittent Hypoxia Exacerbates Lipopolysaccharide-Induced Neurobehavioral Abnormalities: The Role of Neuroinflammation and Synaptic-Related Proteins.Brain and behavior · 2026Article
- Microglial mitophagy as an immunometabolic checkpoint in alzheimer's disease: linking mitochondrial quality control to neuroinflammation.Journal of neuroinflammation · 2026Review
- Hydrogen alleviates sepsis-associated encephalopathy via ATG9B-dependent mitophagy.Molecular medicine (Cambridge, Mass.) · 2026Article
- Gut‑brain axis in anesthesia and critical illness: Molecular crosstalk and its impact on delirium and outcome (Review).International journal of molecular medicine · 2026Review
- Research Advances in the Pathogenesis of Sepsis-Associated Encephalopathy.International journal of molecular sciences · 2026Review
- Fisetin Attenuates D-Gal-Induced Ovarian Aging by Modulating Mitophagy via the AMPK/mTOR Pathway.Antioxidants (Basel, Switzerland) · 2026Article
- Restricting intracellularAutophagy · 2026Article
- Endothelial miR-7052 Safeguards Blood-Brain Barrier Integrity During Endotoxemia by Co-repressing ANGPT2 and PDE5A.Molecular neurobiology · 2026Article
- Mitochondrial dysfunction, neuroinflammation, and associated mechanisms in sepsis-associated encephalopathy: from pathogenesis to emerging therapeutics.Frontiers in neuroscience · 2026Review
- Traditional Chinese botanical medicines and plant-derived bioactive compounds in amyotrophic lateral sclerosis: mechanistic evidence, translational challenges, and therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Natural products targeting programmed cell death: a novel therapeutic strategy for intervertebral disc degeneration.International journal of surgery (London, England) · 2026Review
- Fisetin carbon dots alleviate periodontitis by enhancing mitophagy through regulation of sirtuin 3 SUMOylation.Journal of nanobiotechnology · 2025Article
- Molecular hydrogen-mediated SIRT1 activation alleviates sepsis-associated encephalopathy by promoting mitophagy.European journal of medical research · 2025Article
- Review
- Integrated multi omics and machine learning reveal mitochondrial immunometabolic networks in sepsis associated encephalopathy.Scientific reports · 2025Article
- Neuronutrition and Nrf2 Brain Resilience Signaling: Epigenomics and Metabolomics for Personalized Medicine in Nervous System Disorders from Bench to Clinic.International journal of molecular sciences · 2025Review
- Fisetin Augments OEC Neuroprotection Through Modulating Neurotrophin/Cytokine Signaling and Activating PI3K/Akt/CREB Pathway in an In Vitro Neurodegenerative Injury.Neuromolecular medicine · 2025Article
9 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundFisetin, the effective ingredient of the traditional Chinese medicine named Cotinus coggygria, is recommended to be active therapeutic in many disorders. However, its role in sepsis-associated encephalopathy (SAE) remains unclarified.
methodsCecal ligation and puncture (CLP) operation was performed to establish a rat model of SAE. Rats were grouped according to the surgery operation and fisetin administration. Cognitive impairment was assessed by Morris water maze test. Disruption of blood-brain barrier (BBB) integrity was detected by Evan's blue staining. The mitophagy, reactive oxygen species (ROS) generation, NLRP3 inflammasome activation, and pro-inflammatory cytokines levels were measured through western blot and double immunofluorescence labeling. A transmission electron microscope was applied for the observation of mitochondrial autophagosomes.
resultsRats in the CLP group presented increased expression of IL-1R1, pNF-κB, TNF-α, and iNOS in microglial cells, indicating severe inflammation in the central nervous system (CNS). Nevertheless, there was no increase in BBB permeability. Meanwhile, NLRP3 inflammasome was activated in cerebral microvascular endothelial cells (CMECs), presented with an elevation of caspase-1 expression and IL-1β secretion into CNS. In addition, we found fisetin significantly improved cognitive dysfunction in rats with SAE. Neuroprotective effects of fisetin might be associated with inhibition of neuroinflammation, represented with decreased expression of IL-1R1, pNF-κB, TNF-α, and iNOS in microglia. Furthermore, fisetin induced mitophagy, scavenged ROS, blocked NLRP3 inflammasome activation of CMECs, as evidenced by decreased expression of caspase-1 and reduced release of IL-1β into CNS.
conclusionCollectively, fisetin-blocked NLRP3 inflammasome activation via promoting mitophagy in CMECs may suppress the secretion of IL-1β into CNS, reduce neuroinflammation, and contribute to the amelioration of cognitive impairment.
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