Medicial Experiment Education Department, Medical College of Nanchang University, No. 461 Bayi Road, Donghu District, Nanchang 330001, China.
Department of Neurology, The First Affiliated Hospital of Nanchang University, No.17 Yongwaizheng Street, Donghu District, Nanchang 330006, China.
Biomed Pharmacother. 2018 Jan;97:1011-1019. doi: 10.1016/j.biopha.2017.08.132. Epub 2017 Nov 8.
Parkinson's disease (PD) is a common neuro-degenerative disorder, and novel therapeutic targets are required for the treatment of PD. Juglanin is a natural compound extracted from the crude Polygonum aviculare, exhibiting anti-inflammatory, anti-oxidant and anti-cancer activities. In our study, PD in mice was induced by systemic LPS treatment as evidenced by enhanced α-synuclein and reduced tyrosine hydroxylase (TH), which were reversed by juglanin treatment. Moreover, juglanin administration attenuated LPS-caused behavioral and memory impairments and reduced LPS-induced enhancement of neuro-degenerative markers, including amyloid β (Aβ) and p-Tau. Additionally, juglanin ameliorated synaptic functionality through promoting the expression of synaptic markers, such as SYP, PSD-95 and SNAP-25. Toll-like receptor 4 (TLR4) signaling in brain regulates neuroinflammation, contributing to neurodegenerative diseases. Furthermore, LPS induced neuroinflammation through the acceleration of various pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), interleukin-18 (IL-18) and Cyclooxygenase-2 (COX-2), via activating TLR4/nuclear factor (NF)-κB pathway in hippocampus of mice and microglia cells. Juglanin significantly reduced LPS-induced production of pro-inflammatory cytokines and blocked TLR4/NF-κB pathway. We also found that LPS-induced astrocytes (AST) activity was prevented by juglanin through down-regulating glial fibrillary acidic protein (GFAP) and Iba1 in vivo and in vitro. Together, our results indicated that juglanin ameliorated neuroinflammation-related memory impairment, and neurodegeneration through impeding TLR4/NF-κB, indicating its potential for PD prevention.
帕金森病（PD）是一种常见的神经退行性疾病，需要寻找新的治疗靶点来治疗 PD。 Juglanin 是从粗制Polygonum aviculare 中提取的天然化合物，具有抗炎、抗氧化和抗癌作用。在我们的研究中，通过系统 LPS 处理诱导 PD，结果表明 α-突触核蛋白增加，酪氨酸羟化酶（TH）减少，而 Juglanin 处理可逆转这种情况。此外，Juglanin 给药可减轻 LPS 引起的行为和记忆障碍，并降低 LPS 引起的神经退行性标志物的增加，包括淀粉样β（Aβ）和 p-Tau。此外，Juglanin 通过促进突触标志物的表达改善突触功能，如 SYP、PSD-95 和 SNAP-25。大脑中的 Toll 样受体 4（TLR4）信号调节神经炎症，导致神经退行性疾病。此外，LPS 通过加速各种促炎细胞因子的产生，包括白细胞介素-1β（IL-1β）、肿瘤坏死因子-α（TNF-α）、白细胞介素-18（IL-18）和环加氧酶-2（COX-2），通过激活 TLR4/核因子（NF）-κB 通路，在小鼠海马和小胶质细胞中诱导神经炎症。Juglanin 可显著降低 LPS 诱导的促炎细胞因子的产生，并阻断 TLR4/NF-κB 通路。我们还发现，Juglanin 通过下调体内和体外的胶质纤维酸性蛋白（GFAP）和 Iba1 来阻止 LPS 诱导的星形胶质细胞（AST）活性。总之，我们的研究结果表明，Juglanin 通过抑制 TLR4/NF-κB 改善了与神经炎症相关的记忆障碍和神经退行性变，表明其在预防 PD 方面具有潜力。
