Zhang Baohui, Zhang Di, Chen Keyan, Wu Tengfei
Department of Neurobiology, China Medical University, Shenyang, 110122, China.
Journal Center, China Medical University, Shenyang, 110122, China.
Apoptosis. 2025 Apr;30(3-4):861-879. doi: 10.1007/s10495-024-02073-x. Epub 2025 Jan 20.
This study investigates silibinin's capacity to mitigate Alzheimer's disease (AD) pathologies with a particular emphasis on its effects on apoptosis and synaptic dysfunction in AD models. Employing APP/PS1 transgenic mice and SH-SY5Y neuroblastoma cell lines, our research assessed the efficacy of silibinin in reducing amyloid-beta (Aβ) deposition, neuroinflammation, and neuronal apoptosis. Our results demonstrate that silibinin significantly decreases Aβ accumulation and neuroinflammation and robustly inhibits apoptosis in neuronal cells. Additionally, silibinin enhances the expression of synaptic proteins, thereby supporting synaptic integrity. Through network pharmacology analysis, we identified potential targets of silibinin in Aβ metabolism and synaptic functions. Mechanistically, our findings suggest that silibinin promotes neuronal survival predominantly via the modulation of the Fyn/GluN2B/CaMKIIα signaling pathway, which protects against Aβ1-42-induced apoptosis. These insights highlight silibinin's potential as a therapeutic agent for AD, particularly its role in reducing neuronal apoptosis and maintaining synaptic function.
本研究调查了水飞蓟宾减轻阿尔茨海默病（AD）病理的能力，特别强调其对AD模型中细胞凋亡和突触功能障碍的影响。利用APP/PS1转基因小鼠和SH-SY5Y神经母细胞瘤细胞系，我们的研究评估了水飞蓟宾在减少淀粉样β蛋白（Aβ）沉积、神经炎症和神经元凋亡方面的功效。我们的结果表明，水飞蓟宾显著减少Aβ积累和神经炎症，并强烈抑制神经元细胞凋亡。此外，水飞蓟宾增强突触蛋白的表达，从而支持突触完整性。通过网络药理学分析，我们确定了水飞蓟宾在Aβ代谢和突触功能中的潜在靶点。从机制上讲，我们的研究结果表明，水飞蓟宾主要通过调节Fyn/GluN2B/CaMKIIα信号通路促进神经元存活，该信号通路可防止Aβ1-42诱导的细胞凋亡。这些见解突出了水飞蓟宾作为AD治疗药物的潜力，特别是其在减少神经元凋亡和维持突触功能方面的作用。
