Senolytic effects of Moringa oleifera leaf extract in an in vitro model of Alzheimer’s disease

Accumulation of senescent cells (SnCs) in the aging brain contributes to Alzheimer's disease (AD) progression through the secretion of 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 (MOL) extract in an in vitro AD-senescence model using SH-SY5Y cells exposed to amyloid-β (Aβ ₁₋₄₂ ) oligomers. SH-SY5Y cells exposed to Aβ oligomers exhibited senescent phenotype, characterised by increased senescence-associated β-galactosidase (SA-β-gal) positivity and upregulated nuclear expression of p21, p16, and γH2AX. Treatment with MOL extract significantly reduced the number of cells expressing senescence-associated molecular markers and induced apoptosis in senescent cells, 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.