Chen Ruidan, Gao Hua, Zhu Tianshu, Zheng Ni, Jin Yan, Li Ming, Lu Zhiming
Department of Clinical Laboratory, Shandong Provincial Hospital, Shandong University, Jinan , Shandong, 250021, China.
Department of Clinical Laboratory, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Shandong, 250021, China.
Mol Neurobiol. 2025 Jul 25. doi: 10.1007/s12035-025-05227-3.
This study aimed to assess the therapeutic efficacy of syringaldehyde (SYD) in Alzheimer's disease (AD) and to investigate its potential underlying molecular mechanisms. The potential of SYD for AD treatment was first explored through a network pharmacology approach. APPswe/PS1dE9 (APP/PS1) transgenic mice were treated with SYD via intraperitoneal injection for 9 weeks, and cognitive and behavioral functions were evaluated using the Y-maze, Morris water maze, and novel object recognition tests. Histopathological analysis was conducted to assess neuronal changes and amyloid plaque deposition in the hippocampus using immunofluorescence, hematoxylin and eosin staining, Nissl staining, and Congo red staining. RNA sequencing and transcription factor prediction analyses were utilized to identify the potential molecular mechanisms underlying SYD's therapeutic effects. In addition, in vitro experiments were performed on HT22 hippocampal neuronal cells, including ROS assay, TUNEL assay, and quantitative reverse transcription PCR, to validate the mechanisms suggested by the in vivo results. The results demonstrated that SYD treatment significantly reduced amyloid plaque deposition in the hippocampus of APP/PS1 mice, promoted neuronal repair, and improved cognitive performance. Further analysis indicated that these therapeutic effects were mediated by SYD's ability to enhance resistance to oxidative stress, alleviate neuronal damage, and inhibit the NF-κB/IL-1β/NLRP3 inflammatory pathway, thereby counteracting neuroinflammation induced by neuronal activation. In conclusion, this study provides strong evidence for the potential of SYD to ameliorate cognitive impairment and reduce amyloid plaque deposition in AD, highlighting its promising role as a therapeutic agent in the treatment of Alzheimer's disease.
本研究旨在评估丁香醛（SYD）在阿尔茨海默病（AD）中的治疗效果，并探究其潜在的分子机制。首先通过网络药理学方法探索SYD治疗AD的潜力。对APPswe/PS1dE9（APP/PS1）转基因小鼠进行腹腔注射SYD治疗9周，使用Y迷宫、莫里斯水迷宫和新物体识别测试评估其认知和行为功能。采用免疫荧光、苏木精-伊红染色、尼氏染色和刚果红染色进行组织病理学分析，以评估海马区的神经元变化和淀粉样斑块沉积。利用RNA测序和转录因子预测分析来确定SYD治疗效果潜在的分子机制。此外，对HT22海马神经元细胞进行体外实验，包括活性氧检测、TUNEL检测和定量逆转录PCR，以验证体内实验结果所提示的机制。结果表明，SYD治疗显著减少了APP/PS1小鼠海马区的淀粉样斑块沉积，促进了神经元修复，并改善了认知表现。进一步分析表明，这些治疗效果是由SYD增强抗氧化应激能力、减轻神经元损伤以及抑制NF-κB/IL-1β/NLRP3炎症通路的能力介导的，从而抵消了神经元激活诱导的神经炎症。总之，本研究为SYD改善AD认知障碍和减少淀粉样斑块沉积的潜力提供了有力证据，突出了其作为治疗阿尔茨海默病治疗剂的潜在作用。
