Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Endodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
Institute of Stomatology, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China; Department of Prosthodontics, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, China.
Toxicol Appl Pharmacol. 2021 Apr 15;417:115482. doi: 10.1016/j.taap.2021.115482. Epub 2021 Mar 6.
Incomplete polymerization or biodegradation of dental resin materials results in the release of resin monomers such as triethylene glycol dimethacrylate (TEGDMA), causing severe injury of dental pulp cells. To date, there has been no efficient treatment option for this complication, in part due to the lack of understanding of the mechanism underlying these phenomena. Here, for the first time, we found that notoginsenoside R1 (NR1), a bioactive ingredient extracted from Panax notoginseng, exerted an obvious protective effect on TEGDMA-induced mitochondrial apoptosis in the preodontoblast mDPC6T cell line. In terms of the mechanism of action, NR1 enhanced the level of phosphorylated Akt (protein kinase B), resulting in the activation of a transcriptional factor, nuclear factor erythroid 2-related factor 2 (Nrf2), and eventually upregulating cellular ability to resist TEGDMA-related toxicity. Inhibiting the Akt/Nrf2 pathway by pharmaceutical inhibitors significantly decreased NR1-mediated cellular antioxidant properties and aggravated mitochondrial oxidative damage in TEGDMA-treated cells. Interestingly, NR1 also promoted mitophagy, which was identified as the potential downstream of the Akt/Nrf2 pathway. Blocking the Akt/Nrf2 pathway inhibited mitophagy and abolished the protection of NR1 on cells exposed to TEGDMA. In conclusion, these findings reveal that the activation of Akt/Nrf2 pathway-mediated mitophagy by NR1 might be a promising approach for preventing resin monomer-induced dental pulp injury.
未完全聚合或生物降解的牙科树脂材料会释放出树脂单体，如三甘醇二甲基丙烯酸酯（TEGDMA），导致牙髓细胞严重损伤。迄今为止，对于这种并发症还没有有效的治疗方法，部分原因是对这些现象背后的机制缺乏了解。在这里，我们首次发现，来自三七的活性成分人参皂苷 R1（NR1）对前成牙本质细胞系 mDPC6T 中的 TEGDMA 诱导的线粒体细胞凋亡具有明显的保护作用。就作用机制而言，NR1 增强了磷酸化 Akt（蛋白激酶 B）的水平，从而激活了转录因子，核因子红细胞 2 相关因子 2（Nrf2），最终上调了细胞抵抗 TEGDMA 相关毒性的能力。通过药物抑制剂抑制 Akt/Nrf2 通路，显著降低了 NR1 介导的细胞抗氧化特性，并加重了 TEGDMA 处理细胞的线粒体氧化损伤。有趣的是，NR1 还促进了自噬体的形成，这被认为是 Akt/Nrf2 通路的潜在下游机制。阻断 Akt/Nrf2 通路抑制了自噬体的形成，并取消了 NR1 对暴露于 TEGDMA 的细胞的保护作用。总之，这些发现表明，NR1 通过激活 Akt/Nrf2 通路介导的自噬可能是预防树脂单体诱导的牙髓损伤的一种有前途的方法。
