Asiaticoside attenuates memory impairment induced by transient cerebral ischemia-reperfusion in mice through anti-inflammatory mechanism
Asiaticoside attenuates memory impairment induced by transient cerebral ischemia-reperfusion in mice through anti-inflammatory mechanism
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DOI：
10.1016/j.pbb.2014.03.004
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发表时间：
2014-07-01
影响因子：
3.6
通讯作者：
Ma, Shi-Ping
中科院分区：
文献类型：
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作者：
Chen, She;Yin, Zhu-Jun;Ma, Shi-Ping
积雪草苷（AS）是从积雪草Centella asiatica（L.）这种药物在印度被用作增强记忆的药物已经有很长时间了。本研究旨在探讨AS对短暂性脑缺血再灌注所致小鼠记忆障碍和炎性细胞因子表达的影响及其可能的信号通路。根据Morris水迷宫任务和跳台被动回避实验，短暂双侧颈总动脉闭塞（tBCCAO）诱导小鼠严重的记忆障碍。同时，脑缺血再灌注小鼠海马区小胶质细胞活化及炎性细胞因子白细胞介素（IL）-1 β、白细胞介素（IL）-6和肿瘤坏死因子（TNE）-α的基因表达增加。术后第1天开始口服AS（40和60 mg/kg，1次/d，持续7 d）可明显改善记忆障碍和炎症反应。AS（20、40和60 mg/kg）可明显抑制海马小胶质细胞过度活化和p38 MAPK磷酸化。提示AS对小鼠短暂性脑缺血再灌注损伤具有神经保护作用，其机制可能与抑制p38 MAPK通路过度激活有关。(C)2014 Elsevier Inc. All rights reserved.
Asiaticoside (AS) is isolated from Centella asiatica (L.) which has been using for a long time as a memory enhancing drug in India. This study was to investigate the effects of AS on memory impairment and inflammatory cytokines expression induced by transient cerebral ischemia and reperfusion in mice, as well as the potential signaling pathway. Transient bilateral common carotid artery occlusion (tBCCAO) induced severe memory deficits in mice according to the Morris water maze task and the step-down passive avoidance test. Meanwhile the microglial activation and the gene expression of inflammatory cytokines including interleukin (IL)-1 beta, interleukin (IL)-6 and tumor necrosis factor (TNE)-alpha were increased in the hippocampus of the mice with cerebral ischemia and reperfusion. Oral administration of AS (40 and 60 mg/kg, once per day, started the day after surgery and lasted for 7 days) significantly ameliorated the memory impairment and the inflammation. Moreover, AS (20,40 and 60 mg/kg) markedly reduced the microglial overactivation and the phosphorylation of p38 MAPK in hippocampus compared with the transient cerebral ischemia and reperfusion group. These results suggested that AS showed the neuroprotective effect against transient cerebral ischemia and reperfusion in mice, and this effect might be associated with the anti-inflammation effect of AS via inhibiting overactivation of p38 MAPK pathway. (C) 2014 Elsevier Inc. All rights reserved.