Phlorotannin supplement mitigates cognitive impairment by enhancing synaptic plasticity in SAMP8 mice

Age–related cognitive decline is closely associated with impairments in synaptic structure and function, particularly in the hippocampus. Ecklonia cava, a brown seaweed rich in phlorotannins, has been suggested to possess neuroprotective properties; however, its effects on synaptic regulation and cognitive function in aging models remain unclear. In this study, we investigated the effects of phlorotannin supplement derived from E. cava (PS) on cognitive function and hippocampal synaptic integrity in senescence–accelerated mouse prone 8 (SAMP8) mice. In in vitro experiments, PS exerted neuroprotective effects in HT22 cells exposed to amyloid-β and L-glutamate. Moreover, PS inhibited the enzymatic activities of β-secretase and acetylcholinesterase, and exhibited notable ABTS-radical scavenging activity. Mice were orally administered PS at doses of 250 or 500 mg/kg/day for 17 weeks, and cognitive function was assessed using the Y-maze, passive avoidance, and Morris water maze tests. Hippocampal tissues were analyzed for dendritic spine density, synaptic protein expression, and activation of signaling pathways associated with synaptic plasticity and neurotrophic support. PS treatment significantly improved short–term, long–term, and spatial memory performance in SAMP8 mice. It also restored hippocampal spine density and upregulated synaptic proteins such as synapsin 1 and PSD95. Moreover, PS activated the NMDAR2B–CaMKII–CREB and BDNF–ERK pathway, accompanied by elevated BDNF immunoreactivity in the dentate gyrus. Collectively, these findings suggest that PS improves cognitive function during aging by restoring hippocampal synaptic density and reactivating key signaling pathways involved in synaptic plasticity and neurotrophic support. PS may serve as a promising dietary intervention for preventing or delaying age–related cognitive decline.