The protective effects of a novel synthetic β-elemene derivative on human umbilical vein endothelial cells against oxidative stress-induced injury: Involvement of antioxidation and PI3k/Akt/eNOS/NO signaling pathways
The protective effects of a novel synthetic β-elemene derivative on human umbilical vein endothelial cells against oxidative stress-induced injury: Involvement of antioxidation and PI3k/Akt/eNOS/NO signaling pathways
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DOI：
10.1016/j.biopha.2018.07.107
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发表时间：
2018-10-01
影响因子：
7.5
通讯作者：
Ding Qilong
中科院分区：
文献类型：
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作者：
Ahmad, Khalil Ali;Ze, Hong;Ding Qilong
抗氧化治疗被认为是治疗氧化应激诱导的心血管疾病的有希望的策略。双（β-榄香烯-13-基）戊二酸酯（BEG）是一种新型β-榄香烯衍生物。本研究检测了BEG对过氧化氢（H2 O2）损伤的人脐静脉内皮细胞（HUVECs）的抗氧化活性，并探讨了其作用机制。HUVECs分为以下组：对照组（未处理细胞）;处理组（0.1、1、10 μ mol/L BEG处理细胞）;阳性对照组（0.1 mM Vitamin E处理细胞）;模型组（0.5 mM H2 O2单独处理细胞）。将细胞与或不与BEG预孵育24小时，然后与0.5 mMH（2）O（2）再孵育2小时。我们的研究结果表明，BEG显着降低过氧化氢诱导的内皮细胞活力，活性氧（ROS）的产生，减少乳酸脱氢酶（LDH）的释放，和丙二醛（MDA）水平的浓度依赖性的方式损失。BEG还能提高细胞超氧化物歧化酶（SOD）活性.此外，我们发现H2 O2降低Akt和eNOS磷酸化，这可能间接减少了一氧化氮（NO）的产生。然而，这些影响诱导的H2 O2，减少预处理与BEG。BEG的作用可被PI 3 K抑制剂wortmannin和eNOS抑制剂L-NAME抑制。因此，本研究表明，BEG具有抗氧化活性。BEG通过抗氧化和PI 3 K/Akt/eNOS/NO信号通路减轻H2 O2诱导的内皮细胞损伤。
Antioxidant therapy is considered as promising strategy for treating oxidative stress-induced cardiovascular disease. Bis (beta-elemene-13-yl) glutarate (BEG) is a novel beta-elemene derivative. Herein, we examined the antioxidant activity of BEG on human umbilical vein endothelial cells (HUVECs) after injury with hydrogen peroxide (H2O2) and investigated the mechanism involved. HUVECs were divided into the following groups: control group (untreated cells); treated groups (cells treated with 0.1, 1, 10 mu mol/L of BEG); positive control group (cells treated with 0.1 mM Vitamin E); model group (cells treated with 0.5 mM H2O2 alone). Cells were pre-incubated with or without BEG for 24 h and then incubated for a further 2 h with 0.5 mMH(2)O(2). Our results showed that BEG significantly reduced H2O2 induced loss in endothelial cell viability, reactive oxygen species (ROS) production, reduced lactate dehydrogenase (LDH) release, and malonyldialdehyde (MDA) level in a concentration-dependent manner. Also, BEG increased the cellular the superoxide dismutase (SOD) activity. Moreover, we found that H2O2 decreased Akt and eNOS phosphorylation, which perhaps, indirectly reduced nitric oxide (NO) production. These effects induced by H2O2, however, were reduced by pre-treatment with BEG. BEG effects were inhibited by a PI3K inhibitor (wortmannin) and eNOS inhibitor (L-NAME). In conclusion, the present study demonstrated that BEG has antioxidant activity. Furthermore, BEG reduced H2O2-induced endothelial cells injury by the involvement of antioxidation and PI3K/Akt/eNOS/NO signaling pathways.