Quercetin-induced metabolic reprogramming in LPS-stimulated BV-2 microglia: Untargeted LC–MS metabolomic profiling with molecular docking and molecular dynamics simulations
Records of Natural Products, cilt.20, sa.6, 2026 (SCI-Expanded, Scopus)
- Yayın Türü: Makale / Tam Makale
- Cilt numarası: 20 Sayı: 6
- Basım Tarihi: 2026
- Doi Numarası: 10.25135/rnp.2603.3766
- Dergi Adı: Records of Natural Products
- Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, ABI/INFORM, EMBASE, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO)
- Anahtar Kelimeler: BV-2 microglia, molecular docking, molecular dynamics simulation, neuroinflammation, nitric oxide, Quercetin, untargeted metabolomics
- Açık Arşiv Koleksiyonu: AVESİS Açık Erişim Koleksiyonu
- Hacettepe Üniversitesi Adresli: Evet
Özet
Neuroinflammation is characterized by microglial activation, excessive nitric oxide (NO) and reactive oxygen species (ROS) production. Although quercetin is widely reported to attenuate microglial inflammation, its accompanying metabolic adaptations remain incompletely defined. In this study, the effect of quercetin on LPS-induced BV-2 cells was examined together with quercetin-associated metabolic remodeling using an integrated experimental and in silico strategy. LPS-stimulated BV-2 cells were co-treated with quercetin (1.25–10 μM) and cell viability and NO production were quantified. Untargeted LC–MS metabolomics was conducted on the control, LPS, and LPS+quercetin groups (n = 6), followed by multivariate and pathway enrichment analysis. Quercetin was found to be non-cytotoxic and to significantly reduce LPS-induced NO levels in a concentration-dependent manner. Metabolomic profiling demonstrated clear group separation, with quercetin inducing a distinct metabolic phenotype intermediate between inflamed and basal states. Differential metabolites indicated remodeling of nucleotide sugars, purine intermediates, amino acid pools, and sphingolipid-related features. Pathway analysis identified glutamate metabolism as the dominant signal, alongside nitrogen-handling routes, including the urea cycle and ammonia recycling. Complementary docking and molecular dynamics simulations targeting NADPH oxidase 2 (NOX2) supported a stable interaction with quercetin. Overall, quercetin-mediated NO suppression is coupled to coordinated redox-linked metabolic remodeling in activated microglia.