1. Neuroprotective potential of fisetin in an experimental model of spinal cord injury: via modulation of NF-κB/IκBα pathway
- Author
-
Jinku Zhang, Huan-Xia Li, Jing Cui, Jing-Shi Fan, and Jian-Zhou Tong
- Subjects
Male ,0301 basic medicine ,Necrosis ,Flavonols ,fisetin ,Neural Conduction ,Nitric Oxide Synthase Type II ,IκBα ,Pharmacology ,Neuroprotection ,NF-κB ,Proinflammatory cytokine ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,NF-KappaB Inhibitor alpha ,medicine ,Animals ,Degeneration and Repair ,Spinal Cord Injuries ,bcl-2-Associated X Protein ,biology ,Caspase 3 ,Tumor Necrosis Factor-alpha ,General Neuroscience ,NF-kappa B ,apoptosis ,spinal cord injury ,Rats ,Nitric oxide synthase ,Neuroprotective Agents ,030104 developmental biology ,Spinal Cord ,chemistry ,Cyclooxygenase 2 ,Hyperalgesia ,ComputingMethodologies_DOCUMENTANDTEXTPROCESSING ,biology.protein ,Tumor necrosis factor alpha ,medicine.symptom ,Locomotion ,030217 neurology & neurosurgery ,Fisetin - Abstract
Supplemental Digital Content is available in the text., Aim To evaluate neuroprotective efficacy of fisetin against the experimental model of spinal cord injury (SCI). Materials and methods SCI was induced in male Sprague-Dawley rats by placing an aneurysm clip extradurally. Rats were treated either with vehicle or fisetin for 28 days after SCI. Results Treatment with fisetin significantly attenuated SCI-induced alternations in mechano-tactile and thermal allodynia, hyperalgesia and nerve conduction velocities. SCI-induced upregulated tumor necrosis factor-alpha, interleukins, inducible nitric oxide synthase, cyclooxygenase-II, Bcl-2-associated X protein and caspase-3 mRNA expressions in the spinal cord and these were markedly reduced by fisetin. Spinal nuclear factor kappa B and nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha protein levels were also significantly downregulated by fisetin. Hematoxylin and eosin staining of spinal cord suggested that fisetin significantly ameliorated histological aberrations such as neuronal degeneration, necrosis and inflammatory infiltration induced in it. Conclusion Fisetin exerts neuroprotection via modulation of nuclear factor kappa B/nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor-alpha pathway by inhibiting release of inflammatory mediators (inducible nitric oxide synthase and cyclooxygenase-II), proinflammatory cytokines (tumor necrosis factor-alpha and interleukins), apoptotic mediators (Bcl-2-associated X protein and caspase-3).
- Published
- 2021