Enhancing cognitive memory function with kumquat (<i>Fortunella japonica Swingle</i>) polyphenol extract: mechanisms of action in <scp>d</scp>-galactose-induced aging model mice

Kumquat polyphenols, known for their antioxidant, anti-inflammatory, have been less studied for their potential to delay aging and enhance cognitive memory. This research involved extracting and analyzing free and bound phenols from oil-skinned kumquat (<i>Fortunella japonica Swingle</i>) for their antioxidant and anti-aging effects. Whole fruit free phenols (WFP) at low dose (WFP-L, 50 mg per kg per day) and high dose (WFP-H, 200 mg per kg per day) were administered to D-galactose-induced senescence model mice over six weeks, examining their impact on cognitive memory function and intestinal flora. Peel free phenols and seed-bound phenols displayed the strongest activities, with key compounds like quinic acid and <i>p</i>-hydroxybenzoic acid identified. WFP significantly reduced oxidative stress in aging mice, enhanced antioxidant capacity, lowered inflammatory markers and acetylcholinesterase activity in the hippocampus, and increased acetylcholine levels. By modulating the p53/SIRT1/NF-κB signaling pathway, WFP effectively delayed aging and cognitive decline. Furthermore, WFP improved intestinal microbial communities, regulating flora imbalances and enhancing the intestinal barrier by boosting beneficial bacteria and reducing harmful strains like <i>Bacteroides</i> and <i>Escherichia-Shigella</i>. These findings highlight kumquat polyphenols' therapeutic potential against age-related cognitive impairment.