ScholarWorks@경상국립대학교

초록

Introduction Quercetin, a naturally occurring flavonoid, has been reported to possess several pharmacological activities including neuroprotective properties. Chronic alcohol exposure is known to cause apoptotic neurodegeneration. In this study, docking studies were used to investigate the ligand-protein affinity against various neuroinflammatory targets like ChAt, TNF, IL-6, and IL-1 beta. Next, molecular studies were performed to determine quercetin activity against chronic ethanol-induced neurodegeneration in the adult rat cortex.Methods Adult rats were treated with ethanol for 3 months while quercetin was treated for the last 20 days along with ethanol to the respective experimental groups. Elements of the mitochondrial apoptotic pathway i.e. pro-apoptotic protein Bax, cytochrome C release, and activation of caspase-9 and caspase-3 were determined after respective drug treatment. Our docking results revealed that quercetin possesses neuroprotective potential by targeting neuroinflammatory proteins inhibiting neurodegeneration.Results Western blot results showed that ethanol administration increased the protein expressions of Bax, cytochrome C, caspase-9, and caspase-3. Furthermore, DNA damage was also observed by chronic ethanol treatment with increased expression of PARP-1. Quercetin treatment offered neuroprotection in the cortex against ethanol-induced neurodegeneration. Quercetin reversed the ethanol-induced apoptotic trend via down-regulating Bax, preventing cytochrome C release and inhibition of caspase cascade.Conclusion Immunohistological findings i.e. caspase-3 immunoreactivity, Nissl staining, and Fluoro-Jade B staining also revealed significant neuronal survival with quercetin treatment against ethanol-induced neuronal cell death. Our in-silico and in-vivo findings suggest that quercetin has the potential capability to be used as a neuroprotective agent against alcoholic neurotoxicity.

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