Li Qiushi, Chen Long, Liu Xuewen, Li Xidong, Cao Yue, Bai Yang, Qi Fengjiao
Department of Neurology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, P.R. China.
Department of Anesthesiology, the First Affiliated Hospital of Jinzhou Medical University, Jinzhou, Liaoning, P.R. China.
J Cell Biochem. 2018 Aug;119(8):7053-7062. doi: 10.1002/jcb.27023. Epub 2018 May 8.
Neuroinflammation has been known as an important pathogenetic contributor of Alzheimer's disease (AD). Pterostilbene is a natural compound which has neuroprotective activity. However, the effect of pterostilbene on amyloid-β (Aβ)-induced neuroinflammation has not been clarified. The aim of the present study was to investigate the effect of pterostilbene on Aβ-induced neuroinflammation in microglia. The results indicated that pterostilbene attenuated Aβ -induced cytotoxicity of BV-2 cells. Aβ induced NO production and iNOS mRNA and protein expression, while pterostilbene inhibited the induction. The expression and secretion levels of IL-6, IL-1β, and TNF-α were enhanced by Aβ treatment, whereas pterostilbene decreased them. Aβ activated NLRP3/caspase-1 inflammasome, which was inactivated by pterostilbene. In addition, the inhibitor of caspase-1 Z-YVAD-FMK attenuated the Aβ -induced neuroinflammation in BV-2 cells. In conclusion, pterostilbene attenuated the neuroinflammatory response induced by Aβ in microglia through inhibiting the NLRP3/caspase-1 inflammasome pathway, indicating that pterostilbene might be an effective therapy for AD.
神经炎症被认为是阿尔茨海默病（AD）的重要发病机制因素。紫檀芪是一种具有神经保护活性的天然化合物。然而，紫檀芪对淀粉样β蛋白（Aβ）诱导的神经炎症的影响尚未阐明。本研究的目的是探讨紫檀芪对小胶质细胞中Aβ诱导的神经炎症的影响。结果表明，紫檀芪减轻了Aβ诱导的BV-2细胞的细胞毒性。Aβ诱导一氧化氮（NO）生成以及诱导型一氧化氮合酶（iNOS）mRNA和蛋白表达，而紫檀芪抑制了这种诱导作用。Aβ处理增强了白细胞介素-6（IL-6）、白细胞介素-1β（IL-1β）和肿瘤坏死因子-α（TNF-α）的表达和分泌水平，而紫檀芪降低了它们的水平。Aβ激活了NLRP3/半胱天冬酶-1炎性小体，而紫檀芪使其失活。此外，半胱天冬酶-1抑制剂Z-YVAD-FMK减轻了Aβ诱导的BV-2细胞神经炎症。总之，紫檀芪通过抑制NLRP3/半胱天冬酶-1炎性小体途径减轻了小胶质细胞中Aβ诱导的神经炎症反应，表明紫檀芪可能是治疗AD的有效药物。
