Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner
Icariin attenuates neuroinflammation and exerts dopamine neuroprotection via an Nrf2-dependent manner
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DOI：
10.1186/s12974-019-1472-x
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发表时间：
2019-04-22
影响因子：
9.3
通讯作者：
Zhang, Feng
中科院分区：
文献类型：
--
作者：
Zhang, Bei;Wang, Guoqing;Zhang, Feng
研究背景氧化应激和神经炎症被认为是帕金森病（Parkinson 'sdisease，PD）发病过程中的主要中枢事件。nrf 2是内源性防御系统的关键调节因子。新的发现将Nrf 2信号传导的激活与抗炎活性联系起来。因此，对神经炎症的显著抑制或有效的Nrf 2信号传导激活为PD治疗提供了有希望的策略。淫羊藿苷（伊卡）是从淫羊藿中提取的一种天然化合物，具有抗氧化、抗衰老、抗炎等药理作用。最近的研究证实伊卡对神经退行性疾病具有神经保护作用。然而，其潜在的机制尚未完全阐明。MethodsIn本研究中，小鼠黑质立体定向注射6-羟基多巴胺（6-OHDA）诱导的PD模型进行调查ICA赋予多巴胺（DA）的神经保护。此外，成年Nrf 2基因敲除小鼠和原代大鼠中脑神经元-胶质细胞共培养，以阐明是否ICA施加的神经保护是通过Nrf 2-dependent mechanism. Results. Results结果表明，伊卡衰减6-OHDA诱导的DA神经毒性和胶质细胞介导的神经炎症反应。此外，神经胶质细胞中Nrf 2信号通路的激活参与ICA产生的神经保护，如以下观察所揭示的。首先，伊卡增强了6-OHDA诱导的小鼠PD模型中的Nrf 2信号转导激活。第二，伊卡未能产生DA神经保护作用，并抑制神经胶质细胞介导的促炎因子在Nrf 2基因敲除小鼠的生产。第三，伊卡在原代神经元-神经胶质细胞共培养物中表现出神经保护作用，但在神经元富集培养物（不存在神经胶质细胞）中没有。无论是，ICA介导的神经保护没有察觉后Nrf 2 siRNA治疗神经胶质细胞co-culture.ConclusionsOur研究结果确定，伊卡衰减神经胶质细胞介导的神经炎症和诱发DA神经保护通过Nrf 2依赖的方式。
BackgroundOxidative stress and neuroinflammation are considered the major central events in the process of Parkinson's disease (PD). Nrf2 is a key regulator of endogenous defense systems. New finds have contacted activation of Nrf2 signaling with anti-inflammatory activities. Therefore, the outstanding inhibition of neuroinflammation or potent Nrf2 signaling activation holds a promising strategy for PD treatment. Icariin (ICA), a natural compound derived from Herba Epimedii, presents a number of pharmacological properties, including anti-oxidation, anti-aging and anti-inflammatory actions. Recent studies have confirmed ICA exerted neuroprotection against neurodegenerative disorders. However, the underlying mechanisms were not fully elucidated.MethodsIn the present study, mouse nigral stereotaxic injection of 6-hydroxydopamine (6-OHDA)-induced PD model was performed to investigate ICA-conferred dopamine (DA) neuroprotection. In addition, adult Nrf2 knockout mice and primary rat midbrain neuron-glia co-culture was applied to elucidate whether ICA-exerted neuroprotection was through an Nrf2-dependent mechanism.ResultsResults indicated that ICA attenuated 6-OHDA-induced DA neurotoxicity and glial cells-mediated neuroinflammatory response. Furtherly, activation of Nrf2 signaling pathway in glial cells participated in ICA-produced neuroprotection, as revealed by the following observations. First, ICA enhanced Nrf2 signaling activation in 6-OHDA-induced mouse PD model. Second, ICA failed to generate DA neuroprotection and suppress glial cells-mediated pro-inflammatory factors production in Nrf2 knockout mice. Third, ICA exhibited neuroprotection in primary neuron-glia co-cultures but not in neuron-enriched cultures (without glial cells presence). Either, ICA-mediated neuroprotection was not discerned after Nrf2 siRNA treatment in neuron-glia co-cultures.ConclusionsOur findings identify that ICA attenuated glial cells-mediated neuroinflammation and evoked DA neuroprotection via an Nrf2-dependent manner.