Astragaloside IV Protects Primary Cerebral Cortical Neurons from Oxygen and Glucose Deprivation/Reoxygenation by Activating the PKA/CREB Pathway
Astragaloside IV Protects Primary Cerebral Cortical Neurons from Oxygen and Glucose Deprivation/Reoxygenation by Activating the PKA/CREB Pathway
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黄芪甲苷 IV 通过激活 PKA/CREB 通路保护原代大脑皮质神经元免受缺氧和葡萄糖剥夺/复氧的影响
DOI：
10.1016/j.neuroscience.2019.01.040
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发表时间：
2019-04-15
期刊：
影响因子：
3.3
通讯作者：
Liu, Jianxun
中科院分区：
文献类型：
--
作者：
Xue, Bingjie;Huang, Jisheng;Liu, Jianxun
中风是全球死亡和残疾的主要原因之一，中风后认知障碍是导致这种残疾的主要原因。黄芪甲苷（Astragaloside IV，AST-IV）是黄芪的主要活性成分，广泛应用于治疗中风病。AST-IV被发现具有抗缺血性中风的认知增强特性;然而，这种作用的机制在很大程度上仍然难以捉摸。线粒体健康对缺血性损伤后的细胞活力至关重要。环磷酸腺苷反应元件结合蛋白（CREB）是一种转录因子，可被蛋白激酶A（PKA）激活，以保护线粒体，调节记忆和认知功能。我们使用了一种体外缺血性损伤模型，通过氧和葡萄糖剥夺（OGD）培养的神经元，导致PKA失活和减少CREB磷酸化，降低细胞活力，增加神经元凋亡。我们假设AST-IV可以通过调节PKA/CREB信号通路和保护线粒体功能来保护OGD暴露的大脑皮层神经元。我们发现，AST-IV治疗后，OGD诱导的线粒体和细胞损伤被逆转。通过测定线粒体电位、活性氧（ROS）和三磷酸腺苷（ATP）水平来评价神经元线粒体的活性。AST-IV显著增强PKA和CREB磷酸化，并防止OGD诱导的线粒体功能障碍，从而保护暴露于OGD的神经元免受损伤和死亡。此外，AST-IV的作用被PKA抑制剂部分阻断。总的来说，这些数据阐明了AST-IV对皮质神经元缺血性损伤的保护作用的分子机制。(C)2019作者由Elsevier Ltd代表IBRO出版。
Stroke is one of the major leading causes of death and disability worldwide, and post-stroke cognitive impairment is a major contributor to this disability. Astragaloside IV (AST-IV) is a primary bioactive compound of Radix Astragali, which is widely used in traditional Chinese medicine to treat stroke. AST-IV was found to possess cognition-enhancing properties against ischemic stroke; however, the mechanisms underlying this effect remain largely elusive. Mitochondrial health is critical to cell viability after ischemic injury. Cyclic AMP response element-binding protein (CREB) is a transcription factor that can be activated by protein kinase A (PKA) to preserve mitochondria, regulate memory and cognitive functions. We used an in vitro model of ischemic injury via oxygen and glucose deprivation (OGD) of cultured neurons, which led to PKA inactivation and decreased CREB phosphorylation, reduced cell viability, and increased neuronal apoptosis. We hypothesized that AST-IV could protect OGD-exposed cerebral cortical neurons by modulating the PKA/CREB signaling pathway and preserving mitochondrial function. We found that the mitochondrial and cellular injuries induced by OGD were reversed following treatment with AST-IV. The activity of neuronal mitochondria was evaluated by measuring the mitochondrial potential and the levels of reactive oxygen species (ROS) and adenosine triphosphate (ATP). AST-IV significantly enhanced PKA and CREB phosphorylation and prevented OGD-induced mitochondrial dysfunction, thereby protecting neurons exposed to OGD from injury and death. Furthermore, the effects of AST-IV were partially blocked by a PKA inhibitor. Collectively, these data elucidated the molecular mechanisms underlying the protective effects of AST-IV against ischemic injury in cortical neurons. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of IBRO.