Selective elimination of amyloid-β-induced senescent neuroblastoma cells by Moringa oleifera leaf extract

Accumulation of senescent cells (SnCs) in the ageing brain contributes to Alzheimer's disease (AD) progression by secreting a senescence-associated secretory phenotype (SASP) that exacerbates neuroinflammation and neurodegeneration. Senolytic agents that selectively eliminate SnCs have emerged as a potential therapeutic strategy; however, safer natural alternatives remain underexplored. In this study, we aimed to investigate the senolytic potential of Moringa oleifera leaf extract (MOL) in an in vitro AD-senescence model using SH-SY5Y cells exposed to amyloid-β (Aβ_1-42) oligomers. SH-SY5Y cells exposed to 20 µM Aβ oligomers exhibited a senescent phenotype, characterised by increased senescence-associated β-galactosidase (SA-β-gal) positivity and upregulated nuclear expression of p21, p16, and γH2AX. Treatment with 300 µg/mL MOL significantly reduced the number of cells expressing senescence-associated molecular markers and induced apoptosis in SnCs, while attenuating the secretion of pro-inflammatory SASP cytokines, including IL-8 and TNF-α. Overall findings suggest that MOL extract preferentially targets SnCs and mitigates SASP-associated inflammation. These results support the potential of MOL as a natural compound with senolytic activity and provide a foundation for further development into its therapeutic relevance in AD.