Hexahydrocurcumin protects against cerebral ischemia/reperfusion injury, attenuates inflammation, and improves antioxidant defenses in a rat stroke model.
Hexahydrocurcumin protects against cerebral ischemia/reperfusion injury, attenuates inflammation, and improves antioxidant defenses in a rat stroke model.
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DOI：
10.1371/journal.pone.0189211
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发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Tocharus C
中科院分区：
文献类型：
--
作者：
Wicha P;Tocharus J;Janyou A;Jittiwat J;Changtam C;Suksamrarn A;Tocharus C
本实验的目的是研究六氢姜黄素（HHC）是否通过激活脑缺血/再灌注（I/R）后的抗氧化活性、抗炎症和抗凋亡来减轻脑损伤并改善功能结局。本研究采用脑I/R损伤大鼠暂时性大脑中动脉闭塞（MCAO） 2 h后再灌注。雄性Wistar大鼠随机分为5组，分别为假手术组、载药组、hhc - 10 mg/kg组、hhc - 20 mg/kg组、hhc - 40 mg/kg组。这些动物在脑再灌注开始时立即通过腹腔注射HHC。再灌注24h后，采用2,3,5-三苯基四氯化氮（TTC）染色、苏木精伊红（H&E）染色、末端脱氧核苷酸转移酶缺口末端标记（TUNEL）染色观察大鼠神经功能缺损情况。此外，制备脑组织进行蛋白质提取，用于Western blot分析、丙二醛（MDA）检测、一氧化氮（NO）检测、超氧化物歧化酶（SOD）检测、谷胱甘肽（GSH）检测和谷胱甘肽过氧化物酶（GSH- px）检测。数据显示，与载药组相比，所有剂量的hhc治疗大鼠的神经功能缺损评分和梗死体积均显著降低。HHC治疗可显著减轻I/R大鼠的氧化应激和炎症，降低MDA和NO水平，降低NF-κB （p65）和环氧合酶-2 （COX-2）的表达。HHC还显著提高了Nrf2（细胞核）蛋白表达、血红素氧化酶-1 （HO-1）蛋白表达、抗氧化酶和超氧化物歧化酶（SOD）活性。此外，HHC处理也显著减少了凋亡，Bax和cleaved caspase-3减少，Bcl-XL增加，这与凋亡神经元细胞减少一致。因此，HHC治疗通过减少氧化应激、炎症和细胞凋亡来保护大脑免受脑I/R损伤。HHC的抗氧化特性可能在改善功能结果中发挥重要作用，并可能对I/R损伤提供重要的神经保护。
The purpose of the present experiment was to investigate whether hexahydrocurcumin (HHC) attenuates brain damage and improves functional outcome via the activation of antioxidative activities, anti-inflammation, and anti-apoptosis following cerebral ischemia/reperfusion (I/R). In this study, rats with cerebral I/R injury were induced by a transient middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. The male Wistar rats were randomly divided into five groups, including the sham-operated, vehicle-treated, 10 mg/kg HHC-treated, 20 mg/kg HHC-treated, and 40 mg/kg HHC-treated I/R groups. The animals were immediately injected with HHC by an intraperitoneal administration at the onset of cerebral reperfusion. After 24 h of reperfusion, the rats were tested for neurological deficits, and the pathology of the brain was studied by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyltransferase UTP nick end labeling (TUNEL) staining. In addition, the brain tissues were prepared for protein extraction for Western blot analysis, a malondialdehyde (MDA) assay, a nitric oxide (NO) assay, a superoxide dismutase (SOD) assay, a glutathione (GSH) assay, and a glutathione peroxidase (GSH-Px) assay. The data revealed that the neurological deficit scores and the infarct volume were significantly reduced in the HHC-treated rats at all doses compared to the vehicle group. Treatment with HHC significantly attenuated oxidative stress and inflammation, with a decreased level of MDA and NO and a decreased expression of NF-κB (p65) and cyclooxygenase-2 (COX-2) in the I/R rats. HHC also evidently increased Nrf2 (nucleus) protein expression, heme oxygenase-1 (HO-1) protein expression, the antioxidative enzymes, and the superoxide dismutase (SOD) activity. Moreover, the HHC treatment also significantly decreased apoptosis, with a decrease in Bax and cleaved caspase-3 and an increase in Bcl-XL, which was in accordance with a decrease in the apoptotic neuronal cells. Therefore, the HHC treatment protects the brain from cerebral I/R injury by diminishing oxidative stress, inflammation, and apoptosis. The antioxidant properties of HHC may play an important role in improving functional outcomes and may offer significant neuroprotection against I/R damage.
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影响因子：
3.7
作者：
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通讯作者：
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