Abstract
The gradual loss of cognitive function, manifested by impaired learning and spatial memory, is a hallmark of brain senescence during aging. However, effective natural interventions targeting multiple mechanisms involved in aging-related neurodegeneration remain limited. This study assessed the possible protective efficacy of quinoa seed powder (QSP) against D-galactose (D-gal)- and γ-radiation-induced brain senescence in rats. Fifty male albino rats (n = 10/group) were randomly allocated into five experimental groups. Aging was induced by D-gal administration and fractionated whole-body γ-radiation (1.5 Gy/week for four consecutive weeks; total dose 6 Gy). Behavioral performance, oxidative stress biomarkers, telomerase activity, autophagy markers, neurodegenerative proteins, histopathological alterations, antioxidant activity of quinoa ethanolic extract (QEE), and molecular docking were evaluated. QSP significantly (P 50 value of 5.91 mg/mL against DPPH radicals. Docking analysis showed that kaempferol exhibited the most favorable binding affinities among the tested quinoa constituents toward mTOR (- 7.579 kcal/mol) and catalase (- 7.286 kcal/mol), with short-timescale molecular dynamics analyses providing additional structural support for the predicted interaction profiles. These findings suggest that QSP exerts multi-target neuroprotective effects through attenuation of oxidative stress and modulation of autophagy-related pathways, supporting its potential as a natural strategy for mitigating aging-associated neurodegenerative changes.