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image of Computational Analysis and In Vitro Verification Insights into Quercetin’s Suppression of Neuroinflammation in BV2 Microglia through NF-κB Pathway Inhibition

Abstract

Introduction

Neuroinflammation, primarily mediated by activated microglia, is a significant contributor to neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Quercetin (QCT), a dietary flavonoid, has demonstrated anti-inflammatory and neuroprotective properties; however, the detailed molecular mechanisms behind these effects remain unclear. This study aimed to investigate the anti-inflammatory actions of QCT, particularly focusing on its potential to suppress the activation of microglia and subsequent neuroinflammation.

Methods

BV2 microglial cells were stimulated with lipopolysaccharide (LPS) to induce an inflammatory response and were subsequently treated with various concentrations of QCT. Cell viability was assessed using the MTT assay. Levels of pro-inflammatory cytokines (IL-6, TNF-α) and nitric oxide (NO) were quantified through ELISA and Griess reaction methods, respectively. Western blot analysis was conducted to examine inducible nitric oxide synthase (iNOS), NF-κB, IκBα, and phosphorylated IκBα protein expressions. approaches, including protein-protein interaction (PPI) network analysis and molecular docking, were employed to explore potential molecular mechanisms involving NF-κB signaling pathways.

Results

Treatment with QCT significantly reduced the secretion of IL-6 (96%) and TNF-α (87%), as well as NO production (42%), in a dose-dependent manner. Western blot results demonstrated a marked reduction in iNOS expression and inhibition of NF-κB activation through reduced phosphorylation of IκBα following QCT treatment. Molecular docking indicated a strong binding affinity between QCT and IKKβ, suggesting inhibition of the NF-κB pathway.

Discussion

The findings indicated QCT to exert potent anti-inflammatory effects in LPS-stimulated BV2 cells by modulating key proteins involved in the NF-κB signaling pathway. Specifically, the docking results implied QCT’s direct interaction with the catalytic subunit IKKβ, inhibiting IκBα phosphorylation and subsequent NF-κB activation. The results have been found to be consistent with previous literature, reinforcing QCT's role in reducing neuroinflammation through specific molecular targets and pathways. Further studies are necessary to validate the findings.

Conclusion

Quercetin effectively suppressed neuroinflammation in microglial cells through inhibition of the NF-κB signaling pathway, reducing levels of critical pro-inflammatory mediators. The outcomes have highlighted the potential of quercetin as a preventive nutraceutical for neurodegenerative diseases, necessitating future investigations to confirm its therapeutic efficacy.

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2025-10-08
2025-11-05

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Computational Analysis and In Vitro Verification Insights into Quercetin’s Suppression of Neuroinflammation in BV2 Microglia through NF-κB Pathway Inhibition
Bentham Science Publishers ; https://doi.org/10.2174/0109298673395813250901012530
/content/journals/cmc/10.2174/0109298673395813250901012530
/content/journals/cmc/10.2174/0109298673395813250901012530
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  • Article Type:     Research Article
Keywords: brain degeneration ; quercetin ; neuroinflammation ; BV2 cells ; anti-inflammation ; Microglia

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