Yang Xueping, Yv Qingyun, Ye Fanlong, Chen Sheng, He Zhang, Li Wenwei, Dong Fang
Laboratory of Neuropathology and Neuropharmacology, Department of Neurology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China.
Institute of Neurology, Institutes of Integrative Medicine, Fudan University, Shanghai, China.
Front Pharmacol. 2022 Feb 25;13:848813. doi: 10.3389/fphar.2022.848813. eCollection 2022.
Echinacoside (ECH), the major active constituent of , was found to exert neuroprotection through neurotrophic and anti-inflammatory functions in Parkinson's disease (PD) models. However, a clear intermediate molecule or pathway that unifies these two effects has to be found. In this study, our results demonstrate that ECH can protect DA neurons in PD mice with Western blot and immunohistochemistry staining. The quantitative real-time polymerase chain reaction was adapted to confirm its anti-inflammatory function with decreased cytokines (interleukin- (IL-) 6, IL-1β, and TNF-α) in PD mice and LPS-induced BV2 cells. Further studies found that ECH inhibited the IL-6/JAK2/STAT3 pathway and decreased phosphorylation of STAT3 on tyr705 by Western blot. It can also increase p-STAT3 (ser727) and brain-derived neurotrophic factor (BDNF) expression in PD mice and LPS-induced BV2 cells. This study revealed that ECH exerts neurotrophic and anti-inflammatory effects by regulating the IL-6/JAK2/STAT3 pathway and the phosphorylation of STAT3, promoting the mutually beneficial influence of the two effects to maximize its neuroprotective function.
紫锥菊苷（ECH）是[此处原文缺失相关植物名称]的主要活性成分，在帕金森病（PD）模型中，它通过神经营养和抗炎功能发挥神经保护作用。然而，必须找到一个统一这两种作用的明确中间分子或途径。在本研究中，我们的结果通过蛋白质印迹法和免疫组织化学染色证明ECH可以保护PD小鼠中的多巴胺能（DA）神经元。采用定量实时聚合酶链反应来证实其抗炎功能，在PD小鼠和脂多糖（LPS）诱导的BV2细胞中细胞因子（白细胞介素（IL）-6、IL-1β和肿瘤坏死因子-α）减少。进一步研究发现，通过蛋白质印迹法，ECH抑制IL-6/JAK2/STAT3途径并降低STAT3在酪氨酸705位点的磷酸化。它还可以增加PD小鼠和LPS诱导的BV2细胞中p-STAT3（丝氨酸727）和脑源性神经营养因子（BDNF）的表达。本研究表明，ECH通过调节IL-6/JAK2/STAT3途径和STAT3的磷酸化发挥神经营养和抗炎作用，促进两种作用的互利影响，以最大限度地发挥其神经保护功能。
