School of Life Sciences, Jilin University, Changchun 130012, China.
Engineering Research Center of Chinese Ministry of Education for Edible and Medicinal Fungi, School of Plant Protection, Jilin Agricultural University, Changchun 130118, China.
Nutrients. 2022 Mar 29;14(7):1417. doi: 10.3390/nu14071417.
Verbascoside (VB) is a phenylethanoid glycoside extracted from the herbaceous plant and plays a neuroprotective role in Alzheimer's disease (AD). The goal of this study was to explore the neuroprotective mechanism of VB. Based on the proteomics analysis, immunohistochemistry, immunofluorescence, Western blot, and ELISA were utilized to explore the neuroprotective mechanism of VB in context of neuroinflammation in APP/PS1 mice, LPS-induced BV2 cells, and/or Aβ-stimulated N2a cells. Proteomic analysis demonstrated that the neuroprotection of VB correlated closely to its anti-inflammatory effect. VB significantly blocked microglia and astrocyte against activation in brains of APP/PS1 mice, suppressed the generation of IL-1β as well as IL-6, and boosted that of IL-4, IL-10 and TGF-β in vivo, which were analogous to results acquired in vitro. Furthermore, VB effectively restrained the phosphorylation of IKKα+β, IκBα, and NF-κB-p65 in APP/PS1 mice; LPS-induced BV2 cells, and Aβ-stimulated N2a cells and lowered the tendency of NF-κB-p65 translocation towards nucleus in vitro. These results demonstrate that the neuroprotective effect of VB correlates to the modulation of neuroinflammation via NF-κB-p65 pathway, making VB as a hopeful candidate drug for the prevention and treatment of AD.
毛蕊花糖苷(VB)是从草本植物中提取的苯乙醇苷类化合物,在阿尔茨海默病(AD)中发挥神经保护作用。本研究旨在探讨 VB 的神经保护机制。基于蛋白质组学分析,采用免疫组织化学、免疫荧光、Western blot 和 ELISA 等方法,探讨 VB 在 APP/PS1 小鼠、LPS 诱导的 BV2 细胞和/或 Aβ刺激的 N2a 细胞神经炎症中对神经的保护作用机制。蛋白质组学分析表明,VB 的神经保护作用与其抗炎作用密切相关。VB 可显著抑制 APP/PS1 小鼠脑内小胶质细胞和星形胶质细胞的活化,抑制 IL-1β和 IL-6 的产生,促进 IL-4、IL-10 和 TGF-β的产生,与体外结果相似。此外,VB 还能有效抑制 APP/PS1 小鼠、LPS 诱导的 BV2 细胞和 Aβ刺激的 N2a 细胞中 IKKα+β、IκBα和 NF-κB-p65 的磷酸化,并降低 NF-κB-p65 在体外向核内易位的趋势。这些结果表明,VB 的神经保护作用与 NF-κB-p65 通路对神经炎症的调节有关,使其成为预防和治疗 AD 的有希望的候选药物。