Silibinin's role in counteracting neuronal apoptosis and synaptic dysfunction in Alzheimer's disease models.

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.