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Updated: Jan 14, 2026
Robust Ligature-Induced Model of Murine Periodontitis for the Evaluation of Oral Neutrophils
Published on: January 21, 2020
Luteolin as a multi-target agent against periodontitis: integrating Nrf2-mediated antioxidant defense and quorum
Zixin Fan1, Pengzhou Tang2, Yuluan Bu1
1Department of Periodontics, Affiliated Stomatological Hospital of Nanjing Medical University, Nanjing, 210029, China; State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases(Nanjing Medical University), China; Jiangsu Province Engineering Research Center of Stomatological Translational Medicine(Nanjing Medical University), China.
Aim Of The Study:
This study integrated in vivo and in vitro approaches to elucidate the molecular mechanisms of luteolin against periodontitis, which involved activating the PI3K/AKT/Nrf2 pathway to restore mitochondrial function and alleviate oxidative stress, as well as inhibiting biofilm formation by disrupting the quorum sensing (QS) system.
Materials And Methods:
Active components of luteolin were sourced from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database, and target prediction was performed using ChemMapper. Periodontitis-related genes were retrieved from DisGeNET and GeneCards. A "herb-active component-candidate target" network was constructed via protein-protein interaction (PPI) analysis and GO/KEGG enrichment. Molecular docking and dynamics simulations validated luteolin's binding affinity to core targets. In vitro, luteolin's effects on oxidative stress and inflammation were assessed in Porphyromonas gingivalis (P. g)-LPS-induced human gingival fibroblasts (HGFs). In vivo, its therapeutic potential was evaluated in a C57BL/6 mouse periodontitis model.
Results:
Network pharmacology identified EGFR, SRC, MMP9, AKT1, and ESR1 as key targets of luteolin. KEGG analysis highlighted the PI3K/AKT and VEGF pathways as critical for luteolin's anti-inflammatory effects. Molecular docking confirmed strong binding between luteolin and PI3K/AKT (binding energies: 5.5318 and -6.4241 kcal/mol, respectively). In vitro, luteolin reduced ROS and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α, iNOS) by activating the PI3K/AKT/Nrf2 pathway. It also restored mitochondrial function and inhibited biofilm formation in multispecies bacterial cultures. In vivo, luteolin significantly attenuated alveolar bone loss and inflammation in mice, as evidenced by Micro-CT and histology.
Conclusion:
Luteolin mitigates periodontitis by targeting oxidative stress, inflammation, and bacterial QS, offering a novel multi-target therapeutic strategy. Its dual action on host immune modulation and biofilm disruption underscores its potential as an adjunct to conventional periodontal therapy.
