Antioxidant properties and PC12 cell protective effects of a novel curcumin analogue (2E,6E)-2,6-bis(3,5- dimethoxybenzylidene)cyclohexanone (MCH).

Antioxidant properties and PC12 cell protective effects of a novel curcumin analogue (2E,6E)-2,6-bis(3,5- dimethoxybenzylidene)cyclohexanone (MCH).
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DOI:
10.3390/ijms15033970
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发表时间:
2014-03-05
影响因子:
5.6
通讯作者:
Wang JW
Wang JW
中科院分区:
生物学2区
文献类型:
--
作者:
Ao GZ;Chu XJ;Ji YY;Wang JW

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通过体外抗氧化实验,研究了姜黄素类似物(2 E,6 E)-2,6-双(3,5-二甲氧基亚苄基)环己酮(MCH)对超氧阴离子、羟自由基和1,1-二苯基-2-苦基肼(DPPH)自由基的清除作用以及对H2 O2损伤的保护作用。与姜黄素和维生素C相比,MCH显示出优越的上级O2·−淬灭能力。与姜黄素相比,MCH的体外稳定性也有所提高。150 μM H2 O2可引起PC 12细胞抗氧化酶活性降低、谷胱甘肽(GSH)丢失、丙二醛(MDA)含量增加、乳酸脱氢酶(LDH)漏出、细胞凋亡和细胞活力下降。在H2 O2暴露前用0.63-5.00 μM MCH预处理细胞以剂量依赖性方式显著减弱这些变化。MCH在转录水平上增强转录因子NF-E2相关因子2(Nrf 2)的细胞表达。MCH还能减轻H2 O2诱导的细胞内活性氧(ROS)的积累、线粒体膜电位(MMP)的降低和caspase-3活性的升高。这些结果表明,MCH保护PC 12细胞免受H2 O2损伤,通过调节内源性抗氧化酶,清除ROS,激活Nrf 2细胞保护通路和防止凋亡。
The antioxidative properties of a novel curcumin analogue (2E,6E)-2,6-bis(3,5-dimethoxybenzylidene)cyclohexanone (MCH) were assessed by several in vitro models, including superoxide anion, hydroxyl radical and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging and PC12 cell protection from H2O2 damage. MCH displayed superior O2•− quenching abilities compared to curcumin and vitamin C. In vitro stability of MCH was also improved compared with curcumin. Exposure of PC12 cells to 150 μM H2O2 caused a decrease of antioxidant enzyme activities, glutathione (GSH) loss, an increase in malondialdehyde (MDA) level, and leakage of lactate dehydrogenase (LDH), cell apoptosis and reduction in cell viability. Pretreatment of the cells with MCH at 0.63–5.00 μM before H2O2 exposure significantly attenuated those changes in a dose-dependent manner. MCH enhanced cellular expression of transcription factor NF-E2-related factor 2 (Nrf2) at the transcriptional level. Moreover, MCH could mitigate intracellular accumulation of reactive oxygen species (ROS), the loss of mitochondrial membrane potential (MMP), and the increase of cleaved caspase-3 activity induced by H2O2. These results show that MCH protects PC12 cells from H2O2 injury by modulating endogenous antioxidant enzymes, scavenging ROS, activating the Nrf2 cytoprotective pathway and prevention of apoptosis.
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