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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

Hsieh CY, Chuang CH, Gomez MC, Tayo LL, Huang SM, Tsai PW

Current medicinal chemistry, 2026

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 (i- NOS), NF-κB, IκBα, and phosphorylated IκBα protein expressions. In silico 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…

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