Neuroinflammation plays a crucial role in the pathological process of Parkinson’s disease (PD). Nod-like receptor protein 3 (NLRP3) inflammasome was highly located in microglia and involved in the process of neuroinflammation. Activation of the NLRP3 inflammasome has been confirmed to contribute to the progression of PD. Thus, inhibition of NLRP3 inflammasome activation could be an important breakthrough point on PD therapy. Ellagic acid (EA) is a natural polyphenol that has been widely found in soft fruits, nuts, and other plant tissues with anti-inflammatory, antioxidant, and neuroprotective properties. However, the mechanisms underlying EA-mediated anti-inflammation and neuroprotection have not been fully elucidated. In this study, a lipopolysaccharide- (LPS-) induced rat dopamine (DA) neuronal damage model was performed to determine the effects of EA on the protection of DA neurons. In addition, the DA neuronal MN9D cell line and microglial BV-2 cell line were employed to explore whether EA-mediated neuroprotection was through an NLRP3-dependent mechanism. Results indicated that EA ameliorated LPS-induced DA neuronal loss in the rat substantia nigra. Further, inhibition of microglial NLRP3 inflammasome signaling activation was involved in EA-generated neuroprotection, as evidenced by the following observations. First, EA reduced NLRP3 inflammasome signaling activation in microglia and subsequent proinflammatory cytokines’ excretion. Second, EA-mediated antineuroinflammation and further DA neuroprotection from LPS-induced neurotoxicity were not shown upon microglial NLRP3 siRNA treatment. In conclusion, this study demonstrated that EA has a profound effect on protecting DA neurons against LPS-induced neurotoxicity via the suppression of microglial NLRP3 inflammasome activation.

中文翻译：

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鞣花酸通过抑制小胶质细胞中的NLRP3炎性体活化来保护多巴胺神经元。

神经炎症在帕金森氏病（PD）的病理过程中起着至关重要的作用。Nod样受体蛋白3（NLRP3）炎性小体高度位于小胶质细胞中，并参与神经炎症过程。已证实NLRP3炎性小体的激活有助于PD的发展。因此，抑制NLRP3炎性体的激活可能是PD治疗的重要突破点。鞣花酸（EA）是一种天然多酚，已在软果，坚果和其他植物组织中广泛发现，具有抗炎，抗氧化和神经保护的特性。但是，尚未完全阐明EA介导的抗炎和神经保护的机制。在这个研究中，脂多糖（LPS）诱导的大鼠多巴胺（DA）神经元损伤模型进行了确定EA对DA神经元保护的影响。此外，DA神经元MN9D细胞系和小胶质BV-2细胞系用于探讨EA介导的神经保护是否通过NLRP3依赖性机制。结果表明，EA改善了大鼠黑质中LPS诱导的DA神经元丢失。此外，小胶质NLRP3炎性体信号传导的抑制与EA产生的神经保护有关，如以下观察所证明的。首先，EA减少了小胶质细胞中NLRP3炎性体信号传导的激活以及随后的促炎细胞因子的排泄。第二，小胶质细胞NLRP3 siRNA处理未显示EA介导的抗神经炎和LPS诱导的神经毒性对DA的进一步神经保护。总之，这项研究表明，EA通过抑制小胶质NLRP3炎性体的活化，对保护DA神经元免受LPS诱导的神经毒性具有深远的影响。