Wang Guo-Qing, Li Dai-Di, Huang Chun, Lu Di-Sheng, Zhang Chao, Zhou Shao-Yu, Liu Jie, Zhang Feng
Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, China.
Front Mol Neurosci. 2018 Jan 9;10:441. doi: 10.3389/fnmol.2017.00441. eCollection 2017.
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. 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-κB (NF-κB) 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 and These actions might be closely associated with the inhibition of microglia-mediated neuroinflammation.
帕金森病(PD)是最常见的神经退行性疾病之一,其特征是中脑黑质(SN)多巴胺(DA)神经元逐渐丧失。大量证据表明,小胶质细胞介导的炎症可能参与了PD的发病机制。因此,抑制神经炎症可能为PD治疗提供有前景的潜力。淫羊藿苷(ICA)是从淫羊藿中提取的单一活性成分,具有多种药理特性,如抗炎、抗氧化和抗衰老。最近的研究表明ICA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尚未完全阐明。在本研究中,应用两种不同的神经毒素6-羟基多巴胺(6-OHDA)和脂多糖(LPS)诱导大鼠中脑DA神经元损伤,以研究ICA的神经保护作用。此外,进行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。数据显示,ICA通过抑制核因子-κB(NF-κB)通路的激活,保护DA神经元免受LPS/6-OHDA诱导的DA神经元损伤,并抑制小胶质细胞激活和促炎因子的产生。在动物实验结果中,ICA显著降低小胶质细胞激活,并显著减轻LPS/6-OHDA诱导的DA神经元丢失及随后的动物行为变化。总之,ICA可以保护DA神经元免受LPS和6-OHDA诱导的神经毒性,体内和体外均如此。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。