Neuroprotection by genipin against reactive oxygen and reactive nitrogen species-mediated injury in organotypic hippocampal slice cultures
Neuroprotection by genipin against reactive oxygen and reactive nitrogen species-mediated injury in organotypic hippocampal slice cultures
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DOI：
10.1016/j.brainres.2013.11.020
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发表时间：
2014-01-16
期刊：
影响因子：
2.9
通讯作者：
Morrison, Barclay, III
中科院分区：
文献类型：
--
作者：
Hughes, Rebecca H.;Silva, Victoria A.;Morrison, Barclay, III
栀子籽提取物（GFE）中含有的Genipin是治疗脑卒中或创伤性脑损伤（TBI）的有效候选成分。继发性损伤包括活性氧（ROS）和活性氮（RNS）介导的损伤，它们可以改变细胞关键结构的生物学功能，最终导致细胞死亡。在这项工作中，我们研究了genipin对器官型海马切片培养（OHSC）中ROS和RNS产生的损伤的神经保护潜力，以及它作为直接自由基清除剂的潜力。50 μ M剂量的吉尼平对过氧化叔丁基氢（tBHP）（一种有害的有机过氧化物）具有显著的保护作用。该剂量的genipin在添加thbhp后0、1、6和24小时，与对照（0.1% DMSO）相比，显著降低了48小时的细胞死亡。同样，在添加鱼藤酮后0、1、2和6小时，genipin显著降低了48小时的细胞死亡，鱼藤酮通过更生理相关的机制产生活性氧。此外，genipin显著降低了一氧化氮（NO）直接供体s -亚硝基-n -乙酰青霉胺（SNAP）引起的细胞死亡和24 h时亚硝酸盐水平，并成功猝灭了稳定的自由基1,1-二苯基-2-picryl-hydrazyl (DPPH)，表明genipin可能具有直接自由基清除剂的作用。我们令人鼓舞的发现表明，genipin应该在具有ROS和rns介导的损伤（如TBI和卒中）的动物模型中进行测试，以评估其体内疗效。(C) 2013 Elsevier B.V.版权所有
Genipin, the multipotent ingredient in Gardenia jasmenoides fruit extract (GFE), may be an effective candidate for treatment following stroke or traumatic brain injury (TBI). Secondary injury includes damage mediated by reactive oxygen species (ROS) and reactive nitrogen species (RNS), which can alter the biological function of key cellular structures and eventually lead to cell death. In this work, we studied the neuroprotective potential of genipin against damage stemming from ROS and RNS production in organotypic hippocampal slice cultures (OHSC), as well as its potential as a direct free radical scavenger. A 50 mu M dose of genipin provided significant protection against tert-butyl hydroperoxide (tBHP), a damaging organic peroxide. This dosage of genipin significantly reduced cell death at 48 h compared to vehicle control (0.1% DMSO) when administered 0, 1, 6, and 24 h after addition of tBHP. Similarly, genipin significantly reduced cell death at 48 h when administered 0, 1, 2, and 6 h after addition of rotenone, which generates reactive oxygen species via a more physiologically relevant mechanism. Furthermore, genipin significantly reduced both cell death and nitrite levels at 24 h caused by S-nitroso-N-acetylpenicillamine (SNAP), a direct nitric oxide (NO) donor, and successfully quenched 1,1-Diphenyl-2-picryl-hydrazyl (DPPH), a stable free radical, suggesting that genipin may act as a direct free radical scavenger. Our encouraging findings suggest that genipin should be tested in animal models of CNS injury with a significant component of ROS- and RNS-mediated damage, such as TBI and stroke, to assess its in vivo efficacy. (C) 2013 Elsevier B.V. All rights reserved.