Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway
Momordica charantia polysaccharides could protect against cerebral ischemia/reperfusion injury through inhibiting oxidative stress mediated c-Jun N-terminal kinase 3 signaling pathway
复制标题
苦瓜多糖可通过抑制氧化应激介导的c-Jun N端激酶3信号通路来预防脑缺血/再灌注损伤
DOI：
10.1016/j.neuropharm.2014.11.020
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发表时间：
2015-04-01
影响因子：
4.7
通讯作者：
Shen, Jiangang
中科院分区：
文献类型：
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作者：
Gong, Juanjuan;Sun, Fumou;Shen, Jiangang
苦瓜是一种治疗中风的中药，但其活性成分和作用靶点尚不清楚。苦瓜多糖（MCP）是苦瓜中重要的生物活性成分之一。本研究旨在验证MCP通过清除超氧阴离子（O-2（-））、一氧化氮（NO）和过氧亚硝基阴离子（ONOO-）以及抑制c-Jun N-末端蛋白激酶（JNK 3）信号通路对脑缺血/再灌注损伤具有神经保护作用的假说。本研究采用大鼠全脑和局灶性脑缺血/再灌注模型及体外培养的氧糖剥夺（OGD）神经细胞进行实验。观察MCP对凋亡细胞死亡和梗死体积的影响，清除O-2（-）、NO和ONOO-，抑制脂质过氧化和调节JNK 3信号通路的生物活性。主要结果如下：（1）MCP剂量依赖性地减轻OGD诱导的神经细胞凋亡和减少脑缺血体积，（2）MCP具有直接清除NO、O-2（-）和ONOO-的作用，并抑制脂质过氧化反应;（3）MCP可抑制JNK 3/c-Jun/Fas-L和JNK 3/CytC/Caspases-3信号通路的激活。综上所述，我们得出结论，MCP可能是一个有前途的神经保护成分的苦瓜和其机制可能至少部分归因于其抗氧化活性和抑制JNK 3信号级联在脑缺血/再灌注损伤。(C)2014爱思唯尔有限公司版权所有。
Momordica charantia (MC) is a medicinal plant for stroke treatment in Traditional Chinese Medicine, but its active compounds and molecular targets are unknown yet. Momordica charantia polysaccharide (MCP) is one of the important bioactive components in MC. In the present study, we tested the hypothesis that MCP has neuroprotective effects against cerebral ischemia/reperfusion injury through scavenging superoxide (O-2(-)), nitric oxide (NO) and peroxynitrite (ONOO-) and inhibiting c-Jun N-terminal protein kinase (JNK3) signaling cascades. We conducted experiments with in vivo global and focal cerebral ischemia/reperfusion rat models and in vitro oxygen glucose deprivation (OGD) neural cells. The effects of MCP on apoptotic cell death and infarction volume, the bioactivities of scavenging O-2(-), NO and ONOO-, inhibiting lipid peroxidation and modulating JNK3 signaling pathway were investigated. Major results are summarized as below: (1) MCP dose-dependently attenuated apoptotic cell death in neural cells under OGD condition in vitro and reduced infarction volume in ischemic brains in vivo; (2) MCP had directing scavenging effects on NO, O-2(-) and ONOO- and inhibited lipid peroxidation; (3) MCP inhibited the activations of JNK3/c-Jun/Fas-L and JNK3/cytochrome C/caspases-3 signaling cascades in ischemic brains in vivo. Taken together, we conclude that MCP could be a promising neuroprotective ingredient of Momordica charantia and its mechanisms could be at least in part attributed to its antioxidant activities and inhibiting JNK3 signaling cascades during cerebral ischemia/reperfusion injury. (C) 2014 Elsevier Ltd. All rights reserved.