Lin Taichen, Ng Min Yee, Ho Chun-Te, Liao Yi-Wen, Yu Cheng-Chia, Chen Chun-Jung
School of Dentistry, Chung Shan Medical University, Taichung, Taiwan.
Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan.
J Dent Sci. 2025 Jul;20(3):1615-1621. doi: 10.1016/j.jds.2025.02.014. Epub 2025 Feb 27.
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.
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.
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.
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.
背景/目的：糖尿病性牙周炎（DP）是一种严重的口腔疾病，其特征为炎症反应过度和伤口愈合受损，炎症衰老和细胞焦亡在其发病机制中起关键作用。柯里拉京是一种异黄酮化合物，已显示出有前景的抗炎和抗细胞焦亡特性，但其对DP的具体作用在很大程度上仍未得到探索。本研究旨在评估柯里拉京在DP体外模型中对炎症衰老和细胞焦亡的影响，可能为这种具有挑战性的病症的治疗策略提供新的见解。
本体外研究评估了柯里拉京对暴露于晚期糖基化终产物（AGEs）以模拟糖尿病环境的人牙龈成纤维细胞（HGFs）中炎症衰老和细胞焦亡的影响。然后我们检测了细胞中的活性氧（ROS）生成和伤口愈合能力。为了评估炎症衰老，我们探究了细胞衰老活性和衰老标志物p16以及其衰老相关分泌表型（SASP），如白细胞介素（IL）-6和IL-8。接下来，我们测量了有或没有柯里拉京的细胞中细胞焦亡标志物的水平，包括核苷酸结合寡聚化结构域样受体蛋白3（NLRP3）、含CARD结构域的凋亡相关斑点样蛋白（ASC）、半胱天冬酶-1。
柯里拉京以剂量依赖性方式减少了AGEs处理的HGFs中的ROS产生并增强了伤口愈合。此外，柯里拉京减弱了升高的炎症衰老标志物，包括细胞衰老和SASP、IL-6和IL-8的分泌。此外，柯里拉京下调了AGEs处理的HGFs中细胞焦亡相关成分的表达，包括NLRP3、ASC和半胱天冬酶-1。
这些发现表明，柯里拉京可能通过减轻AGE诱导的炎症衰老和细胞焦亡而在DP中具有治疗潜力。柯里拉京促进伤口愈合以及抑制细胞衰老和细胞焦亡的能力突出了其作为DP新型治疗剂的潜力。
