Methylglyoxal (MGO), a cytotoxic metabolite of glycolysis, can cause endothelial cells impairment, which is tightly associated with diabetic vascular complication. Umbelliferone, a derivative of coumarin, participates in various pharmacological activities. This study aimed to determine the effectiveness of umbelliferone in MGO-induced apoptosis and oxidative stress in endothelial cells. In this study, it has been indicated that umbelliferone inhibited MGO-induced human umbilical vein endothelial cells (HUVECs) cytotoxicity, apoptosis, Bax/Bcl-2 protein ratio, the activity of cleaved-caspase-3, and mitochondrial membrane potential loss. Furthermore, we found that umbelliferone inhibited MGO-induced activation of mitogen-activated protein kinases and nuclear factor-κB signaling pathways in HUVECs. In addition, umbelliferone could suppress oxidative stress, as evidenced by decrease of reactive oxygen species and malondialdehyde (MDA) generation, and increase of superoxide dismutase and glutathione peroxidase contents. Moreover, we found that umbelliferone can activate Nrf2/HO-1 signaling. Importantly, silencing of Nrf2 signaling clearly eliminated the anti-oxidative stress of umbelliferone, whereas umbelliferone pretreatment had no effect on Nrf2 overexpressing HUVECs. Altogether, this study suggested that umbelliferone pretreatment has a protective effect on MGO-induced endothelial cell dysfunction through inhibiting apoptosis and oxidative stress.

中文翻译：

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伞形酮通过抑制细胞凋亡和氧化应激来防止甲基乙二醛诱导的 HUVEC 功能障碍

甲基乙二醛 (MGO) 是一种糖酵解的细胞毒性代谢物，可引起内皮细胞损伤，这与糖尿病血管并发症密切相关。伞形酮是香豆素的衍生物，参与多种药理活性。本研究旨在确定伞形酮对 MGO 诱导的内皮细胞凋亡和氧化应激的有效性。在这项研究中，已表明伞形酮抑制 MGO 诱导的人脐静脉内皮细胞 (HUVEC) 的细胞毒性、细胞凋亡、Bax/Bcl-2 蛋白比率、cleaved-caspase-3 的活性和线粒体膜电位损失。此外，我们发现伞形酮抑制 MGO 诱导的 HUVEC 中丝裂原活化蛋白激酶和核因子-κB 信号通路的激活。此外，伞形酮可以抑制氧化应激，表现为活性氧和丙二醛 (MDA) 生成减少，超氧化物歧化酶和谷胱甘肽过氧化物酶含量增加。此外，我们发现伞形酮可以激活 Nrf2/HO-1 信号。重要的是，Nrf2 信号的沉默明显消除了伞形酮的抗氧化应激，而伞形酮预处理对 Nrf2 过表达的 HUVEC 没有影响。总而言之，这项研究表明，伞形酮预处理通过抑制细胞凋亡和氧化应激，对 MGO 诱导的内皮细胞功能障碍具有保护作用。我们发现伞形酮可以激活 Nrf2/HO-1 信号。重要的是，Nrf2 信号的沉默明显消除了伞形酮的抗氧化应激，而伞形酮预处理对 Nrf2 过表达的 HUVEC 没有影响。总而言之，这项研究表明，伞形酮预处理通过抑制细胞凋亡和氧化应激，对 MGO 诱导的内皮细胞功能障碍具有保护作用。我们发现伞形酮可以激活 Nrf2/HO-1 信号。重要的是，Nrf2 信号的沉默明显消除了伞形酮的抗氧化应激，而伞形酮预处理对 Nrf2 过表达的 HUVEC 没有影响。总而言之，这项研究表明，伞形酮预处理通过抑制细胞凋亡和氧化应激，对 MGO 诱导的内皮细胞功能障碍具有保护作用。