2-O-methylmagnolol mitigates the generation of reactive oxidative stress and inflammaging in human gingival epithelial cells and fibroblasts with advanced glycation end products stimulation

Background/purpose: Individuals with diabetes mellitus (DM) are more susceptible to periodontitis, largely due to the accumulation of advanced glycation end-products (AGEs), which drive oxidative stress and inflammaging. Inflammaging is a state of chronic low-grade inflammation and accelerated cellular aging that contributes to periodontal degradation, mediated by AGEs-induced cellular senescence and senescence-associated secretory phenotype (SASP). 2-O-methylmagnolol (2-MG), a bioactive compound with antioxidant and anti-inflammatory properties, remains underexplored in DM-associated periodontal degeneration. This study investigated the effects of 2-MG on AGE-induced oxidative stress and inflammaging in human gingival epithelial cells (HGEs) and human gingival fibroblasts (HGFs). Materials and methods: The study assessed the effects of 2-MG on AGE-stimulated HGEs and HGFs by evaluating cell proliferation, wound healing capacity, reactive oxygen species (ROS) accumulation, cellular senescence markers, and the secretion of SASP factors, including interleukin (IL)-6 and IL-8. Additionally, Western blot analysis was performed to examine the protein expression of a senescence marker p16. Results: Treatment with 2-MG at concentrations up to 10 μM did not significantly affect HGEs and HGFs cell proliferation (P > 0.05). However, 2-MG effectively improved AGEs-induced wound healing impairment and significantly attenuated ROS production in a dose-dependent manner (P < 0.05). Furthermore, 2-MG reduced cellular senescence and suppressed the secretion of IL-6 and IL-8 (P < 0.05). Western blot analysis demonstrated that 2-MG inhibited AGEs-induced p16 expression (P < 0.05). Conclusion: The findings indicate that 2-MG mitigates AGEs-induced oxidative stress and inflammaging in HGEs and HGFs. These results suggest that 2-MG may have therapeutic potential in preventing or attenuating DM-associated periodontal degeneration.