Luteolin ameliorates periodontitis by modulating mitochondrial dynamics and macrophage polarization via the JAK2/STAT3 pathway.

Background: Periodontal disease (PD) is a chronic inflammatory condition affecting oral and systemic health. Luteolin (LUT), a natural flavonoid, has shown anti-inflammatory effects, but its therapeutic potential and mechanisms in PD remain unclear.

Objective: This study aimed to investigate the effects of LUT on PD, focusing on its impact on mitochondrial dynamics, macrophage polarization, and the JAK2/STAT3 signaling pathway.

Methods: A combination of network pharmacology analysis and in vivo and in vitro experiments was employed. The efficacy of LUT was evaluated using a ligature-induced rat PD model and LPS-stimulated THP-1-derived macrophages. Key assessments included micro-CT for bone loss, flow cytometry for macrophage polarization, and Western blot for pathway analysis.

Results: LUT significantly reduced alveolar bone loss and enhanced M2 macrophage polarization, as indicated by increased CD206 and Arg1 expression. Additionally, it improved mitochondrial function by reducing ROS and restoring membrane potential, decreasing mitochondrial fission, and promoting mitochondrial fusion. Mechanistically, LUT inhibited JAK2/STAT3 phosphorylation, promoting anti-inflammatory effects.

Conclusion: These findings suggest that LUT ameliorates periodontal inflammation and bone loss by modulating mitochondrial dynamics, promoting M2 macrophage polarization, and suppressing the JAK2/STAT3 signaling pathway. This highlights LUT as a promising multitarget candidate for PD treatment.