厚朴酚通过减轻线粒体凋亡和抑制核因子κB信号通路减轻小鼠中寡聚淀粉样β1-42诱导的阿尔茨海默病。
Honokiol Attenuates Oligomeric Amyloid β1-42-Induced Alzheimer's Disease in Mice Through Attenuating Mitochondrial Apoptosis and Inhibiting the Nuclear Factor Kappa-B Signaling Pathway.
作者信息
Wang Mo, Li Yu, Ni Changwei, Song Guijun
机构信息
Department of Nuclear Medicine, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
Third Department of Neurology, The Second Affiliated Hospital of Dalian Medical University, Dalian, China.
出版信息
Cell Physiol Biochem. 2017;43(1):69-81. doi: 10.1159/000480320. Epub 2017 Aug 25.
BACKGROUND
Increasing evidence indicates that amyloid β oligomer (AβO) is toxic to neurons in Alzheimer's disease (AD) brain. The aim of the present study is to evaluate the effects of honokiol on AβO-induced learning and memory dysfunction in mice.
METHODS
AD mice model was established by AβO intrahippocampal injection. The cognitive function was evaluated using Morris water maze (MWM). Nissl staining was used to examine the hippocampal neuron damage. Primary hippocampal neurons were exposed to AβO. The apoptosis in the hippocampal tissues and primary neurons was assessed using terminal dexynucleotidyl transferase-mediated dUTP nick end labeling-neuronal nuclei (NeuN) and Hoechst staining, respectively. The mitochondrial membrane potential and radical oxygen species were detected using standard methods. Western blotting assay was used to check the expression levels of apoptotic and nuclear factor kappa-B (NF-κB) signaling-associated proteins and electrophoretic mobility shift assay was used to detect NF-κB-DNA binding.
RESULTS
Honokiol increased the time spend in the target zone of the AD mice in the MWM. In addition, honokiol dose-dependently attenuated AβO-induced hippocampal neuronal apoptosis, reactive oxygen species production and loss of mitochondrial membrane potential. Furthermore, AβO-induced NF-κB activation was inhibited by honokiol, as well as the upregulated amyloid precursor protein and β-secretase.
CONCLUSION
Honokiol attenuates AβO-induced learning and memory dysfunction in mice and it may be a potential candidate in AD therapy.
背景
越来越多的证据表明,淀粉样β寡聚体(AβO)对阿尔茨海默病(AD)大脑中的神经元有毒性。本研究旨在评估厚朴酚对AβO诱导的小鼠学习和记忆功能障碍的影响。
方法
通过海马内注射AβO建立AD小鼠模型。使用莫里斯水迷宫(MWM)评估认知功能。采用尼氏染色检查海马神经元损伤。将原代海马神经元暴露于AβO。分别使用末端脱氧核苷酸转移酶介导的dUTP缺口末端标记-神经元细胞核(NeuN)和Hoechst染色评估海马组织和原代神经元中的细胞凋亡。使用标准方法检测线粒体膜电位和活性氧。采用蛋白质免疫印迹法检测凋亡相关蛋白和核因子κB(NF-κB)信号通路相关蛋白的表达水平,采用电泳迁移率变动分析法检测NF-κB与DNA的结合。
结果
厚朴酚增加了AD小鼠在MWM目标区域的停留时间。此外,厚朴酚剂量依赖性地减轻了AβO诱导的海马神经元凋亡、活性氧生成和线粒体膜电位丧失。此外,厚朴酚抑制了AβO诱导的NF-κB激活,以及淀粉样前体蛋白和β-分泌酶的上调。
结论
厚朴酚减轻了AβO诱导的小鼠学习和记忆功能障碍,可能是AD治疗的潜在候选药物。