Neuroprotection by acetyl-11-keto-β-Boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway.
Neuroprotection by acetyl-11-keto-β-Boswellic acid, in ischemic brain injury involves the Nrf2/HO-1 defense pathway.
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DOI：
10.1038/srep07002
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发表时间：
2014-11-11
影响因子：
4.6
通讯作者：
Wen A
中科院分区：
文献类型：
--
作者：
Ding Y;Chen M;Wang M;Wang M;Zhang T;Park J;Zhu Y;Guo C;Jia Y;Li Y;Wen A
脑卒中是一种复杂的疾病，其发病机制涉及氧化应激相关通路。核因子红细胞-2相关因子2（Nrf 2）/血红素加氧酶-1（HO-1）通路被认为是脑卒中神经保护的潜在靶点。乙酰基-11-酮基-β-乳香酸（AKBA）是从乳香树（Boswellia serrate）提取物中分离得到的一种活性三萜类化合物。本研究旨在探讨新型Nrf 2激活剂AKBA对脑缺血损伤的保护作用。通过大脑中动脉闭塞在Sprague-Dawley大鼠中产生中风模型。为了模拟体外缺血样条件，将原代培养的皮层神经元暴露于短暂的氧和葡萄糖剥夺（OGD）。AKBA治疗显著减少了再灌注后48小时大脑中动脉闭塞（MCAO）大鼠脑组织中Nrf 2和HO-1表达的梗死体积和凋亡细胞，并增加了神经学评分。 在原代培养的神经元中，AKBA增加了Nrf 2和HO-1的表达，这提供了对OGD诱导的氧化损伤的保护。此外，AKBA处理增加了Nrf 2与抗氧化剂反应元件（ARE）的结合活性。AKBA的保护作用因Nrf 2或HO-1的敲除而减弱。总之，这些发现提供了AKBA保护神经元免受缺血性损伤的证据，并且这种神经保护作用涉及Nrf 2/HO-1途径。
Stroke is a complex disease involved oxidative stress-related pathways in its pathogenesis. The nuclear factor erythroid-2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway has been considered a potential target for neuroprotection in stroke. Acetyl-11-Keto-β-Boswellic Acid (AKBA) is an active triterpenoid compound from the extract of Boswellia serrate. The present study was to determine whether AKBA, a novel Nrf2 activator, can protect against cerebral ischemic injury. The stroke model was produced in Sprague–Dawley rats via middle cerebral artery occlusion. To model ischemia-like conditions in vitro, primary cultured cortical neurons were exposed to transient oxygen and glucose deprivation (OGD). Treatment of AKBA significantly reduced infarct volumes and apoptotic cells, and also increased neurologic scores by elevating the Nrf2 and HO-1 expression in brain tissues in middle cerebral artery occlusion (MCAO) rats at 48 hours post reperfusion. In primary cultured neurons, AKBA increased the Nrf2 and HO-1 expression, which provided protection against OGD-induced oxidative insult. Additionally, AKBA treatment increased Nrf2 binding activity to antioxidant-response elements (ARE). The protective effect of AKBA was attenuated by knockdown of Nrf2 or HO-1. In conclusion, these findings provide evidence that AKBA protects neurons against ischemic injury, and this neuroprotective effect involves the Nrf2/HO-1 pathway.
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影响因子：
3.6
作者：
Elshazly, Shimaa M.;Abd El Motteleb, Dalia M.;Nassar, Noha N.
通讯作者：
Nassar, Noha N.
影响因子：
7.4
作者：
Stepkowski, Tomasz M.;Kruszewski, Marcin K.
通讯作者：
Kruszewski, Marcin K.
DOI：
10.1097/00004647-200203000-00012
发表时间：
2002-03-01
影响因子：
6.3
作者：
Serkova, N;Donohoe, P;Christians, U
通讯作者：
Christians, U
影响因子：
3.2
作者：
Durante W
通讯作者：
Durante W
DOI：
10.1016/0169-328x(95)00315-j
发表时间：
1996-04-01
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Nimura, T;Weinstein, PR;Sharp, FR
通讯作者：
Sharp, FR