Thymol mitigates monosodium glutamate-induced neurotoxic cerebral and hippocampal injury in rats via overexpression of nuclear erythroid 2-related factor 2 signaling pathway as well as altering nuclear factor- kappa β and glial fibrillary acidic protein expression

Abstract Monosodium glutamate (MSG) is commonly used in various food industries as a flavor enhancer. MSG is reported to cause many toxic effects, including increased neurotoxicity. The study investigates the molecular mechanisms underlying thymol's neuroprotective effect against MSG-induced neurotoxic cerebral and hippocampal injury in rats. Brain injury was induced by MSG (2 g/kg; i.p.) for 15 days. Thymol (400 & 800 mg/kg/day; p.o.) was administered along with MSG. MSG control rats showed a significant reduction in behavioral activity, elevated brain tissue oxidative stress, inflammatory parameters, Nrf2 gene up-regulation, overexpression of nuclear factor-kappa β (NF-kβ), glial fibrillary acidic protein (GFAP) as well as neuronal damage in the cerebral cortex & hippocampus. Thymol ameliorated MSG-induced brain injury via overexpression of the Nrf2 gene, thus increasing the cellular defense and organizing antioxidant & anti-inflammatory effects. Thymol improved behavioral activity and brain tissue GSH content. Thymol also decreased brain contents of MDA, NO, TNF-α & IL-6. Moreover, Thymol improved NF-kβ & GFAP immunohistochemical expression and histopathological picture in the cerebral cortex & hippocampus compared to MSG control rats. The aforementioned results suggest that thymol exhibits promising neuroprotective effects. The study elucidates the molecular mechanisms linking Nrf2 pathway signaling to oxidative stress, inflammation & NF-kβ expression underlying thymol’s protection against MSG-induced neurotoxicity. The study also highlights the role of GFAP expression in MSG-induced astrocyte injury of cerebrum & hippocampus of rats and the promising protective effects of thymol in ameliorating astrocyte injury.