Corylin ameliorates inflammaging and pyroptosis in diabetic periodontitis

Background/purpose: Diabetic periodontitis (DP) is a severe oral disease characterized by hyperinflammation and impaired wound healing, with inflammaging and pyroptosis playing key roles in its pathogenesis. Corylin, an isoflavone compound, has shown promising anti-inflammatory and anti-pyroptotic properties, but its specific effects on DP remain largely unexplored. This study aimed to evaluate the effects of Corylin on inflammaging and pyroptosis in an in vitro model of DP, potentially offering novel insights into therapeutic strategies for this challenging condition. Materials and methods: This in vitro study evaluated the effects of Corylin on inflammaging and pyroptosis in human gingival fibroblasts (HGFs) exposed to advanced glycation end products (AGEs) to mimic the diabetic environment. We then examined the reactive oxygen species (ROS) generation and wound healing ability in the cells. To assess the inflammaging, we probed into cell senescence activity and senescence marker p16 as well as its senescence associated secretory phenotype (SASP) such as interleukins (IL)-6 and IL-8. Next, we measured the levels of pyroptosis markers including nucleotide-binding domain, leucine-rich–containing family, pyrin domain–containing-3 (NLRP3), apoptosis-associated speck-like protein containing a CARD (ASC), caspase-1 in cells with and without Corylin. Results: Corylin reduced ROS production and enhanced wound healing in AGEs-treated HGFs in a dose-dependent manner. Furthermore, Corylin attenuated the heightened inflammaging markers, which included cellular senescence and the secretion of SASP, IL-6 and IL-8. Additionally, Corylin downregulated the expression of pyroptosis-related components, including NLRP3, ASC, and caspase-1, in AGEs-treated HGFs. Conclusion: These findings suggest that Corylin may have therapeutic potential in DP by mitigating AGE-induced inflammaging and pyroptosis. Corylin's ability to promote wound healing and inhibit both cellular senescence and pyroptosis highlights its potential as a novel therapeutic agent for DP.