Neuroprotective properties of icariin in MPTP-induced mouse model of Parkinson's disease: Involvement of PI3K/Akt and MEK/ERK signaling pathways
Neuroprotective properties of icariin in MPTP-induced mouse model of Parkinson's disease: Involvement of PI3K/Akt and MEK/ERK signaling pathways
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DOI：
10.1016/j.phymed.2016.12.017
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发表时间：
2017-02-15
期刊：
影响因子：
7.9
通讯作者：
Wong, Man-Sau
中科院分区：
文献类型：
--
作者：
Chen, Wen-Fang;Wu, Lin;Wong, Man-Sau
工作背景：箭叶淫羊藿在中国、韩国、日本等国家被广泛用于治疗骨质疏松、心血管功能障碍、改善神经功能和性功能。淫羊藿苷是箭叶淫羊藿的主要活性成分。在本研究中，我们研究了淫羊藿苷对帕金森病（PD）小鼠模型多巴胺能神经元的保护作用及其可能的机制。卵巢切除的PD小鼠用载体或淫羊藿苷（MPTP注射前3天）处理，有或没有磷脂酰肌醇3-激酶（PI 3 K）抑制剂LY 294002或促分裂原活化蛋白激酶激酶（MEK）抑制剂PD 98059。用高效液相色谱法测定纹状体多巴胺（DA）含量。Western blot检测纹状体Bcl-2、Bax和Caspase 3蛋白表达。用免疫组织化学方法检测黑质核内酪氨酸羟化酶免疫反应（TH-IR）神经元的数量。结果：淫羊藿苷预处理可改善MPTP引起的纹状体DA含量下降和黑质致密核TH阳性神经元的丢失。淫羊藿苷可逆转MPTP诱导的纹状体Bcl-2、Bax和caspase 3蛋白表达的变化。LY 294002或PD 98059阻断PI 3 K/Akt或MEK/ERK信号通路可减轻淫羊藿苷引起的PD小鼠纹状体DA含量和SNpc TH-IR的增加。此外，单独的淫羊藿苷处理在多巴胺能MES 23.5细胞中以时间依赖性模式显著诱导Akt和ERK的磷酸化。结论：淫羊藿苷对PD小鼠模型多巴胺能神经元具有保护作用，其机制可能与PI 3 K/Akt和MEK/ERK通路有关。(C)2016年爱思唯尔有限公司。
Background: Epimedium sagittatum is a traditional Chinese herb normally which is used to treat the osteoporosis, cardiovascular dysfunction, and to improve neurological and sexual function in China, Korea and Japan. Icariin is the major active ingredient in Epimedium sagittatum. In the present research, we examined the neuroprotective effects of icariin on dopaminergic neurons and the possible mechanisms in a mouse model of Parkinson's disease (PD).Methods: Ovariectomized PD mice were treated with vehicle or icariin (3 days before MPTP injections) with or without the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 or mitogen-activated protein kinase kinase (MEK) inhibitor PD98059. The dopamine (DA) content in the striatum was studied by HPLC. Western blot was used to determine the protein expressions of Bcl-2, Bax and Caspase 3 in the striatum. The numbers of tyrosine hydroxylase-immunoreactive (TH-IR) neurons in the substantial nigra pars compacta (SNpc) were assessed by immunohistochemistry. The activation of Akt and ERK by icariin were detected in doparminergic MES23.5 cells.Results: Icariin pretreatment could ameliorate the decreased striatum DA content and the loss of TH-IR neurons in the SNpc induced by MPTP. The MPTP-induced changes of Bcl-2, Bax and caspase 3 protein expressions in the striatum could be reversed by icariin pretreatment. Blockade of PI3K/Akt or MEK/ERK signaling pathway by LY294002 or PD98059 could attenuate the increase of DA content in the striatum and TH-IR in the SNpc induced by icariin in PD mice model. Additionally, icariin treatment alone significantly induced the phosphorylation of Akt and ERK in a time dependent pattern in dopaminergic MES 23.5 cells. These effects were abolished by co-treatment with LY294002 or PD98059.Conclusion: These data demonstrated that icariin has neuroprotective effect on dopaminergic neurons in PD mice model and the potential mechanisms might be related to PI3K/Akt and MEK/ERK pathways. (C) 2016 Elsevier GmbH.