Neuroprotective effect of chrysin on hyperammonemia mediated neuroinflammatory responses and altered expression of astrocytic protein in the hippocampus
| Autor: | Renuka Mani, Vijayakumar Natesan, Ramakrishnan Arumugam |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Central nervous system Nerve Tissue Proteins AMPA receptor Neuroprotection Hippocampus Ammonium Chloride Proinflammatory cytokine 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Glutamine synthetase Internal medicine medicine Animals Hyperammonemia Chrysin RNA Messenger Rats Wistar Neuroinflammation Pharmacology Brain Chemistry Flavonoids Inflammation General Medicine medicine.disease Rats Up-Regulation Molecular Docking Simulation 030104 developmental biology medicine.anatomical_structure Endocrinology Neuroprotective Agents chemistry Astrocytes Cytokines 030217 neurology & neurosurgery |
| Zdroj: | Biomedicinepharmacotherapy = Biomedecinepharmacotherapie. 88 |
| ISSN: | 1950-6007 |
| Popis: | Neuroinflammation is an innate immune response in the central nervous system (CNS) against metabolic and pathogenic toxic wastes. The main hypothesis implies that a state of hyperammonemia which is accountable for both direct and indirect modification in ammonia metabolism with an elevated production of inflammatory cytokines. This study was constructed to explore the modulating effect of chrysin on rudimentary pathophysiologic mechanisms of ammonium chloride (NH4Cl) mediated neuroinflammation in the experimental hyperammonemic rats. NH4Cl was injected intraperitonally (i.p) in male albino wistar rats for a time period of thrice a week for eight consecutive weeks. Initially, the levels of brain ammonia and water content were assessed. Immunohistochemical, RT-PCR and western blotting analysis revealed that the expression of glutamine synthetase (GS) activity and glial fibrillar acidic protein (GFAP) were down-regulated, whereas the expression of TNF-α, IL-1β, IL-6, p65 NF-κB, iNOS and COX-2 were up-regulated in brain tissue of hyperammonemic rats. Oral supplementation of chrysin (100 mg/kg b.w) to hyperammonemic rats considerably restored the levels of brain ammonia, water content, and the expressions of GS, GFAP, TNF-α, IL-1β, IL-6, p65 NF-κB, iNOS and COX-2. Our findings provided substantial evidence that the chrysin synergistically attenuating the neuroinflammatory mechanism by repressing the expression of proinflammatory cytokines and up-regulating the astrocytic protein expressions via ammonia-reducing strategies. This data suggests that chrysin effectively acts as a therapeutic agent to treat hyperammonemia mediated neuroinflammation. |
| Databáze: | OpenAIRE |
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