Abstract
This study investigated the efficacy of a phlorotannin supplement (PS) in ameliorating scopolamine (SCO)-induced memory deficits in mice, focusing on synaptic function and the underlying molecular mechanisms. Male C57BL/6N mice were divided into six groups and treated with vehicle, donepezil (5 mg/kg body weight, (BW)), or PS (100, 250, or 500 mg/kg BW) for 6 weeks. Behavioral tests were conducted, followed by Golgi staining, immunofluorescence, and immunoblotting to assess synaptic protein expression and signaling pathways. Behavioral tests showed that PS administration significantly improved SCO-induced memory impairment and restored synaptic protein expression (synaptophysin, synapsin1, and postsynaptic density protein 95) in the hippocampus. Additionally, PS enhanced brain-derived neurotrophic factor (BDNF) signaling and activated the extracellular signal-regulated kinase/CAMP response element binding protein (ERK-CREB) pathway, essential for synaptic plasticity. Our findings demonstrate that PS mitigates SCO-induced memory dysfunction by protecting synaptic integrity and activating the BDNF-ERK-CREB signaling pathway, indicating the potential of PS as a natural intervention for treating memory deficits.