Beta-asarone attenuates ischemia-reperfusion-induced autophagy in rat brains via modulating JNK, p-JNK, Bcl-2 and Beclin 1.
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 β-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 (β-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 β-asarone can attenuate the autophagy in a dose-dependent manner. The mechanism is likely that β-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, β-asarone can attenuate autophagy in a widespread manner.
The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China.
Lin
L
Liu
Yong-Qi
YQ
Fang
Zhong-Feng
ZF
Xue
Yu-Ping
YP
He
Ruo-Ming
RM
Fang
Ling
L
Li
D000081248:Allylbenzene Derivatives; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects*; D000071186:Beclin-1; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism*; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000378:metabolism; D010751:Phosphopyruvate Hydratase / Q000097:blood; D010766:Phosphorylation / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism
D000081248:Allylbenzene Derivatives; D000840:Anisoles; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; C012195:asarone; D048031:JNK Mitogen-Activated Protein Kinases; D010751:Phosphopyruvate Hydratase