Cyclocarya Polysaccharide Mitophagy-Mediated Periodontal Inflammation Therapy

This study aims to elucidate the molecular mechanisms by which Cyclocarya paliurus polysaccharide (CP) ameliorates LPS-induced oxidative damage and inflammatory responses in human periodontal ligament fibroblasts through modulation of the PINK1-OPTN/TBK1-mediated mitophagy pathway, thereby providing novel targeted therapeutic strategies for periodontitis. An LPS-induced hPDLF inflammation model was established to assess the therapeutic effects of Cyclocarya paliurus polysaccharide (CP, 0-100 μg/mL). Oxidative stress markers (ROS, MDA, SOD) and mitochondrial membrane potential (JC-1 staining) were analyzed alongside inflammatory cytokines (ELISA: IL-6, TNF-α). Mitophagy-related PINK1/OPTN/TBK1 expression was evaluated via qPCR and Western blotting. (1) CP exhibited no cytotoxicity toward hPDLFs at 0–25 μg/mL (P > 0.05), but significantly reduced cell viability at concentrations ≥50 μg/mL (P < 0.01). (2) Compared to the LPS group, CP dose-dependently attenuated oxidative stress markers (reduced ROS and MDA levels, enhanced SOD activity) and suppressed IL-6/TNF-α secretion (6.25–25 μg/mL, P < 0.05). (3) qPCR and Western blot analysis demonstrated CP significantly upregulated PINK1 mRNA expression and increased OPTN/TBK1 protein levels (P < 0.01), suggesting mitophagy modulation mediates its anti-inflammatory effects. (1) Cyclocarya paliurus polysaccharide mitigates LPS-induced oxidative damage in hPDLFs by scavenging free radicals and restoring redox homeostasis. (2) Its anti-inflammatory effects are mediated through activation of the PINK1-dependent TBK1/OPTN signaling pathway, which enhances mitophagy. These findings provide a mechanistic foundation for novel therapeutic strategies against periodontitis.