Beta-asarone attenuates ischemia-reperfusion-induced autophagy in rat brains via modulating JNK, p-JNK, Bcl-2 and Beclin 1
- 作者：Lin Liu ; Yong-Qi Fang ; fangyq2@163.com ; Zhong-Feng Xue ; Yu-Ping He ; Ruo-Ming Fang ; Ling Li
- 关键词：Autophagy ; 尾-asarone ; Ischemia&ndash ; reperfusion ; JNK ; Beclin 1
- 刊名：European Journal of Pharmacology
- 出版年：2012
- 期刊代码：24_00142999
- 类别：neu
- 出版时间：5 April, 2012
- 卷：680
- 期：1-3
- 页码：34-40
- 文件大小：801 K
摘要
Beta-asarone has significant pharmacological effects on the central nervous system. It can attenuate neuronal apoptosis, but its effects on the brain ischemia-reperfusion-induced autophagy have not been reported yet. Our study was a two-stage procedure: evaluation of 尾-asarone effects on the autophagy at first, and then analysis of the possible mechanism. The middle cerebral artery occlusion (MCAO) model was adopted to make the brain injure and Beclin 1 was used to evaluate the autophagy. We hypothesized that the mechanism might be related to c-Jun N-terminal kinases (JNK), phospho-JNK (p-JNK), Bcl-2 and Beclin 1. To test this hypothesis, we evaluated JNK, p-JNK, Bcl-2 and Beclin 1 levels with flow cytometry. Additionally, we divided the brain into three regions: ischemic region, ischemic penumbra, and normal region, and analyzed them respectively. We found, compared to both groups II (model control) and III (low dose), Beclin 1 levels in groups IV (medium dose) and V (high dose) were significantly decreased. Beclin 1, JNK and p-JNK levels in groups VII (尾-asarone) and VIII (JNK inhibitor) were significantly decreased, but Bcl-2 levels were significantly increased. Additionally, Beclin 1, JNK, p-JNK and Bcl-2 levels among the three regions had no significant differences. We conclude that 尾-asarone can attenuate the autophagy in a dose-dependent manner. The mechanism is likely that 尾-asarone can decrease JNK and p-JNK levels at first, and then increase Bcl-2 level, finally interfere with the functions of Beclin 1 during the execution of autophagy. Additionally, 尾-asarone can attenuate autophagy in a widespread manner.