Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro
Icariin Reduces Dopaminergic Neuronal Loss and Microglia-Mediated Inflammation in Vivo and in Vitro
复制标题
淫羊藿苷可减少体内外多巴胺能神经元损失和小胶质细胞介导的炎症
DOI：
10.3389/fnmol.2017.00441
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发表时间：
2018-01-09
影响因子：
4.8
通讯作者：
Zhang, Feng
中科院分区：
文献类型：
--
作者：
Wang, Guo-Qing;Li, Dai-Di;Zhang, Feng
帕金森病（Parkinson's disease，PD）是一种以中脑黑质（substantia nigra，SN）多巴胺（dopamine，DA）神经元逐渐丧失为特征的神经退行性疾病。大量证据表明小胶质细胞介导的炎症反应可能参与了PD的发病机制。因此，抑制神经炎症可能具有治疗PD的潜力。淫羊藿苷是从淫羊藿中提取的单一活性成分，具有抗炎、抗氧化、抗衰老等药理作用。最近的研究表明伊卡对脑功能障碍具有神经保护作用。然而，ICA发挥神经保护作用的机制已被充分阐明。本研究采用6-羟基多巴胺（6-OHDA）和脂多糖（LPS）两种不同的神经毒素致大鼠中脑DA能神经元损伤，探讨伊卡的神经保护作用。此外，还进行了原代大鼠中脑神经元-胶质细胞共培养，以探讨ICA介导的DA神经保护作用的机制。体外实验结果表明，伊卡通过抑制核因子-κ B（NF-κ B）通路的活化，保护DA神经元免受LPS/6-OHDA诱导的DA神经元损伤，抑制小胶质细胞活化和促炎因子的产生。在动物实验结果中，伊卡显著降低了小胶质细胞的活化，并显著减弱了LPS/6-OHDA诱导的DA神经元丢失和随后的动物行为变化。总之，伊卡可以保护DA神经元免受LPS和6-OHDA诱导的神经毒性在体内和体外。这些作用可能与抑制小胶质细胞介导的神经炎症密切相关。
Parkinson's disease (PD) is one of the most common neurodegenerative diseases characterized with a gradual loss of midbrain substantia nigra (SN) dopamine (DA) neurons. An excessive evidence demonstrated that microglia-mediated inflammation might be involved in the pathogenesis of PD. Thus, inhibition of neuroinflammation might possess a promising potential for PD treatment. Icariin (ICA), a single active component extracted from the Herba Epimedii, presents amounts of pharmacological properties, such as anti-inflammation, anti-oxidant, and anti-aging. Recent studies show ICA produced neuroprotection against brain dysfunction. However, the mechanisms underlying ICA-exerted neuroprotection are fully illuminated. In the present study, two different neurotoxins of 6-hydroxydopamine (6-OHDA) and lipopolysaccharide (LPS)-induced rat midbrain DA neuronal damage were applied to investigate the neuroprotective effects of ICA. In addition, primary rat midbrain neuron-glia co-cultures were performed to explore the mechanisms underlying ICA-mediated DA neuroprotection. In vitro data showed that ICA protected DA neurons from LPS/6-OHDA-induced DA neuronal damage and inhibited microglia activation and pro-inflammatory factors production via the suppression of nuclear factor-kappa B (NF-kappa B) pathway activation. In animal results, ICA significantly reduced microglia activation and significantly attenuated LPS/6-OHDA-induced DA neuronal loss and subsequent animal behavior changes. Together, ICA could protect DA neurons against LPS- and 6-OHDA-induced neurotoxicity both in vivo and in vitro. These actions might be closely associated with the inhibition of microglia-mediated neuroinflammation.