Neuroinflammation is a principal element in Alzheimer’s disease (AD) pathogenesis, so anti-inflammation may be a promising therapeutic strategy. Forsythoside B (FTS•B), a phenylethanoid glycoside isolated from Forsythiae fructus, has been reported to exert anti-inflammatory effects. However, no studies have reported whether the anti-inflammatory properties of FTS•B have a neuroprotective effect in AD. In the present study, these effects of FTS•B were investigated using amyloid precursor protein/presenilin 1 (APP/PS1) mice, BV-2 cells, and HT22 cells. APP/PS1 mice were administered FTS•B intragastrically for 36 days. Behavioral tests were then carried out to examine cognitive functions, including the Morris water maze, Y maze, and open field experiment. Immunohistochemistry was used to analyze the deposition of amyloid-beta (Aβ), the phosphorylation of tau protein, and the levels of 4-hydroxynonenal, glial fibrillary acidic protein, and ionized calcium-binding adapter molecule 1 in the hippocampus. Proteins that showed marked changes in levels related to neuroinflammation were identified using proteomics and verified using enzyme-linked immunosorbent assay and western blot. BV-2 and HT22 cells were also used to confirm the anti-neuroinflammatory effects of FTS•B. In APP/PS1 mice, FTS•B counteracted cognitive decline, ameliorated the deposition of Aβ and the phosphorylation of tau protein, and attenuated the activation of microglia and astrocytes in the cortex and hippocampus. FTS•B affected vital signaling, particularly by decreasing the activation of JNK-interacting protein 3/C-Jun NH2-terminal kinase and suppressing WD-repeat and FYVE-domain-containing protein 1/toll-like receptor 3 (WDFY1/TLR3), further suppressing the activation of nuclear factor-κB (NF-κB) signaling. In BV-2 and HT22 cells, FTS•B prevented lipopolysaccharide-induced neuroinflammation and reduced the microglia-mediated neurotoxicity. FTS•B effectively counteracted cognitive decline by regulating neuroinflammation via NF-κB signaling in APP/PS1 mice, providing preliminary experimental evidence that FTS•B is a promising therapeutic agent in AD treatment.

中文翻译：

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连翘苷 B 通过抑制阿尔茨海默病中的 NF-κB 信号传导来减轻记忆障碍和神经炎症

神经炎症是阿尔茨海默病 (AD) 发病机制的主要因素，因此抗炎可能是一种很有前景的治疗策略。连翘苷 B (FTS•B) 是一种从连翘中分离出的苯乙醇苷，据报道具有抗炎作用。然而，没有研究报告 FTS•B 的抗炎特性是否对 AD 具有神经保护作用。在本研究中，使用淀粉样前体蛋白/早老素 1 (APP/PS1) 小鼠、BV-2 细胞和 HT22 细胞研究了 FTS•B 的这些影响。APP/PS1 小鼠灌胃 FTS•B 36 天。然后进行行为测试以检查认知功能，包括莫里斯水迷宫、Y 迷宫和野外实验。免疫组织化学用于分析淀粉样蛋白-β (Aβ) 的沉积，tau 蛋白的磷酸化，以及海马中 4-羟基壬烯醛、神经胶质纤维酸性蛋白和离子钙结合接头分子 1 的水平。使用蛋白质组学鉴定与神经炎症相关的水平显着变化的蛋白质，并使用酶联免疫吸附测定和蛋白质印迹进行验证。BV-2 和 HT22 细胞也用于证实 FTS•B 的抗神经炎症作用。在APP/PS1小鼠中，FTS•B对抗认知能力下降，改善Aβ沉积和tau蛋白磷酸化，减弱皮层和海马小胶质细胞和星形胶质细胞的活化。FTS•B 影响重要信号，特别是通过降低 JNK 相互作用蛋白 3/C-Jun NH2 末端激酶的激活和抑制 WD 重复和含有 FYVE 结构域的蛋白 1/toll 样受体 3 (WDFY1/TLR3)，进一步抑制核的激活因子-κB (NF-κB) 信号。在 BV-2 和 HT22 细胞中，FTS•B 可阻止脂多糖诱导的神经炎症并降低小胶质细胞介导的神经毒性。FTS•B 通过在 APP/PS1 小鼠中通过 NF-κB 信号传导调节神经炎症，有效地抵消了认知能力下降，提供了初步实验证据表明 FTS•B 是一种很有前途的 AD 治疗剂。FTS•B 可防止脂多糖诱导的神经炎症并降低小胶质细胞介导的神经毒性。FTS•B 通过在 APP/PS1 小鼠中通过 NF-κB 信号传导调节神经炎症，有效地抵消了认知能力下降，提供了初步实验证据表明 FTS•B 是一种很有前途的 AD 治疗剂。FTS•B 可防止脂多糖诱导的神经炎症并降低小胶质细胞介导的神经毒性。FTS•B 通过在 APP/PS1 小鼠中通过 NF-κB 信号传导调节神经炎症，有效地抵消了认知能力下降，提供了初步实验证据表明 FTS•B 是一种很有前途的 AD 治疗剂。