Notoginsenoside R1 alleviates TEGDMA-induced mitochondrial apoptosis in preodontoblasts through activation of Akt/Nrf2 pathway-dependent mitophagy.
Notoginsenoside R1 alleviates TEGDMA-induced mitochondrial apoptosis in preodontoblasts through activation of Akt/Nrf2 pathway-dependent mitophagy.
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DOI：
10.1016/j.taap.2021.115482
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发表时间：
2021-03
影响因子：
3.8
通讯作者：
Konghuai Wang;Danni Wu;Xuekun Ren;Qihao Yu;Ruona Liu;Sheng-Bing Huang;Yihuai Pan;Shufan Zhao-Shufan
中科院分区：
文献类型：
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作者：
Konghuai Wang;Danni Wu;Xuekun Ren;Qihao Yu;Ruona Liu;Sheng-Bing Huang;Yihuai Pan;Shufan Zhao-Shufan
牙科树脂材料的不完全聚合或生物降解导致树脂单体如三甘醇二甲基丙烯酸酯（TEGDMA）的释放，造成牙髓细胞的严重损伤。迄今为止，这种并发症还没有有效的治疗方案，部分原因是缺乏对这些现象背后机制的了解。本研究首次发现三七中提取的活性成分三七皂苷R1（NR 1）对TEGDMA诱导的前成牙本质细胞mDPC 6 T细胞线粒体凋亡具有明显的保护作用。在作用机制方面，NR 1增强磷酸化Akt（蛋白激酶B）的水平，导致转录因子核因子红细胞2相关因子2（Nrf 2）的激活，并最终上调细胞抵抗TEGDMA相关毒性的能力。通过药物抑制剂抑制Akt/Nrf 2通路显著降低了NR 1介导的细胞抗氧化特性，并加重了TEGDMA处理的细胞中的线粒体氧化损伤。有趣的是，NR 1也促进线粒体自噬，这被确定为Akt/Nrf 2途径的潜在下游。阻断Akt/Nrf 2通路可抑制线粒体自噬，并消除NR 1对TEGDMA暴露的细胞的保护作用。总之，这些研究结果表明，Akt/Nrf 2通路介导的线粒体自噬激活NR 1可能是一个有前途的方法，防止树脂单体诱导的牙髓损伤。
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 fromPanax 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.