The Traditional Japanese Herbal Medicine Hachimijiogan Elicits Neurite Outgrowth Effects in PC12 Cells and Improves Cognitive in AD Model Rats via Phosphorylation of CREB.
The Traditional Japanese Herbal Medicine Hachimijiogan Elicits Neurite Outgrowth Effects in PC12 Cells and Improves Cognitive in AD Model Rats via Phosphorylation of CREB.
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DOI：
10.3389/fphar.2017.00850
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发表时间：
2017
影响因子：
5.6
通讯作者：
Iwasaki K
中科院分区：
文献类型：
--
作者：
Kubota K;Fukue H;Sato H;Hashimoto K;Fujikane A;Moriyama H;Watanabe T;Katsurabayashi S;Kainuma M;Iwasaki K
Hachimijiogan(HJG)是一种传统草药，可以改善痴呆症患者的焦虑症。在这项研究中，我们验证了HJG发挥神经营养因子样效应以改善阿尔茨海默病(AD)模型大鼠记忆障碍的假设。首先，我们描述了HJG以浓度依赖的方式(3μg/mlHJG，p<0.05；10-500μg/mlHJG，p<；0.001)诱导PC12细胞(一种大鼠嗜铬细胞瘤细胞系)突起生长。生地黄、山药、泽泻、菌核、牡丹皮、桂皮等6种中草药成分均可诱导轴突生长，其中以500μg/ml的作用最强。第二，我们证明了cAMP反应元件结合蛋白的抑制剂KG-501(10μM，p<；0.001)可以阻断hJG诱导的轴突生长。此外，HJG可诱导PC12细胞CREB的磷酸化(20min，2.5±0.58倍)和Cre介导的转录(500μg/ml，p<；0.01；1000μg/ml，p<；0.001)。这些结果表明，HJG的神经营养作用是通过CREB依赖机制实现的。最后，我们使用Morris水迷宫对AD模型动物(CI+Aβ大鼠)进行了HJG治疗后记忆障碍的改善。HJG反复口服可改善记忆障碍(300 mg/kg，p<；0.05；1000 mg/kg，p<；0.001)，并诱导海马区CREB磷酸化(1000 mg/kg，p<；0.01)。综上所述，我们的结果表明，和健颗粒具有与NGF相似的神经营养作用，并可以通过激活CREB来改善痴呆大鼠的认知功能障碍。因此，HJG有可能成为治疗痴呆症的神经营养因子的替代品。
Hachimijiogan (HJG) is a traditional herbal medicine that improves anxiety disorders in patients with dementia. In this study, we tested the hypothesis that HJG exerts neurotrophic factor-like effects to ameliorate memory impairment in Alzheimer disease (AD) model rats. First, we describe that HJG acts to induce neurite outgrowth in PC12 cells (a rat pheochromocytoma cell line) like nerve growth factor (NGF) in a concentration-dependent manner (3 μg/ml HJG, p < 0.05; 10–500 μg/ml HJG, p < 0.001). While six herbal constituents of HJG, Rehmannia root, Dioscorea rhizome, Rhizoma Alismatis, Poria sclerotium, Moutan bark, and Cinnamon bark, could induce neurite outgrowth effects, the effect was strongest with HJG (500 μg/ml). Second, we demonstrated that HJG-induced neurite outgrowth was blocked by an inhibitor of cAMP response element binding protein (CREB), KG-501 (10 μM, p < 0.001). Moreover, HJG was observed to induce CREB phosphorylation 20–90 min after treatment (20 min, 2.50 ± 0.58-fold) and CRE-mediated transcription in cultured PC12 cells (500 μg/ml, p < 0.01; 1000 μg/ml, p < 0.001). These results suggest a CREB-dependent mechanism underlies the neurotrophic effects of HJG. Finally, we examined improvements of memory impairment following HJG treatment using a Morris water maze in AD model animals (CI + Aβ rats). Repeated oral administration of HJG improved memory impairment (300 mg/kg, p < 0.05; 1000 mg/kg, p < 0.001) and induced CREB phosphorylation within the hippocampus (1000 mg/kg, p < 0.01). Together, our results suggest that HJG possesses neurotrophic effects similar to those of NGF, and can ameliorate cognitive dysfunction in a rat dementia model via CREB activation. Thus, HJG could potentially be a substitute for neurotrophic factors as a treatment for dementia.
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影响因子：
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作者：
Manning CE;Williams ES;Robison AJ
通讯作者：
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作者：
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通讯作者：
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AYERLELIEVRE, C;OLSON, L;PERSSON, H
通讯作者：
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