Unsaponifiable matter from walnut oil ameliorate memory deficits and mitochondrial dysfunction in aging mice via activating Nrf2 signaling pathway

Aging is an inevitable biological phenomenon that involves a multitude of physiological alterations. Dietary interventions are being considered as potential strategies for delaying age-related dysfunction. Unsaponifiable matter (USM), a composition of highly active ingredients found in walnut oil, has demonstrated antioxidant effects. This study aims to explore the neuroprotective effects of USM on D-galactose-treated C57BL/6 mice and elucidate its underlying mechanism, which was validated in PC12 cells treated with D-galactose. The results of behavioral tests demonstrated that USM significantly improved cognitive deficits associated with aging. The morphological analysis demonstrated that USM effectively alleviated hippocampal neuronal damage, synaptic impairment, and mitochondrial dysfunction induced by D-galactose. Furthermore, USM significantly increases the antioxidant enzymes activity while reducing the malondialdehyde and reactive oxygen species levels. The results suggest that USM can mitigate age-related symptoms caused by D-galactose by activating the nuclear factor erythroid-2-related factor 2 signaling pathway, which enhances the expression of antioxidant enzymes, restore redox balance, and improves synaptic and mitochondrial functions. This has a positive on improving cognition and memory disorders in elderly mice.