Dietary Magnolia kobus DC. Attenuates Age-Associated Hippocampal Alterations in Mice in Association with Modulation of Iron Metabolism- and Ferroptosis-Related Markers.

Brain aging is a major contributor to cognitive decline and neurodegenerative disorders. Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has emerged as a key mechanism associated with age-related hippocampal dysfunction. Here, we investigated whether dietary supplementation of Magnolia kobus DC. (MO) attenuates age-related hippocampal alterations in mice in association with changes in iron metabolism- and ferroptosis-related markers. Behavioral tests combined with molecular and histological analyses of hippocampal tissues from young and aged mice demonstrated that MO significantly attenuated age-associated behavioral alterations, including Y-maze spontaneous alternation performance, and modulated age-related molecular and histological alterations in the hippocampus. MO supplementation was associated with reduced expression of cellular senescence and neuroinflammatory markers and modulation of blood-brain barrier-associated tight junction proteins. Furthermore, MO supplementation was associated with partial normalization of age-associated alterations in iron metabolism-related proteins and modulation of ferroptosis-related markers, including lipid peroxidation-related markers. MO supplementation was also associated with increased cholinergic and synaptic protein expression and lower β-amyloid-related immunoreactivity and p-Tau (Ser404) levels in the aged hippocampus. These findings suggest that dietary MO attenuates age-associated hippocampal dysfunction in association with modulation of iron metabolism- and ferroptosis-related markers, highlighting its potential as a functional dietary intervention for promoting healthy brain aging.