Evaluation the role of quinoa seeds in attenuation the brain cellular senescence and aging induced by D-galactose and γ-radiation in rats: insights into autophagy, telomerase activity, amyloid-β and tau proteins.

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 < 0.05) attenuated oxidative stress, as evidenced by decreased malondialdehyde levels and increased catalase activity and reduced glutathione content. Furthermore, QSP significantly reduced amyloid-β 1-42 (Aβ42) and Tau protein accumulation, increased telomerase activity, and enhanced autophagy-related modulation through upregulation of microtubule-associated protein 1 light chain 3 beta (LC3B) and downregulation of mammalian target of rapamycin (mTOR) expression. In vitro analysis showed that QEE exhibited potent antioxidant activity, with EC50 values of 16.67 and 23.01 mg/mL for TAC and FRAP, respectively, and an IC50 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.