Neuroprotective effect of chrysin on hyperammonemia mediated neuroinflammatory responses and altered expression of astrocytic protein in the hippocampus.
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 (100mg/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.
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, India.
Renuka
R
Mani
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, India. Electronic address: nvkbiochem@yahoo.co.in.
Vijayakumar
V
Natesan
Department of Biochemistry and Biotechnology, Faculty of Science, Annamalai University, Annamalainagar 608002, India.
Ramakrishnan
R
Arumugam
D000643:Ammonium Chloride / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D005419:Flavonoids / Q000494:pharmacology*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D022124:Hyperammonemia / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D007249:Inflammation / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D062105:Molecular Docking Simulation; D009419:Nerve Tissue Proteins / Q000096:biosynthesis*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation / Q000187:drug effects
D016207:Cytokines; D005419:Flavonoids; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D000643:Ammonium Chloride; C043561:chrysin
Brain edema; Chrysin; Hyperammonemia; NH(4)Cl; Neuroinflammation