Alzheimer's disease (AD) is characterized by progressive cognitive decline and

memory dysfunction, with prominent roles in cholinergic deficits and synaptic plasticity

impairments. Vitisin B, a resveratrol tetramer derived from Vitis vinifera, exhibits potent

antioxidant and neuroprotective properties. However, its potential to influence cognitive

function in AD models remains inadequately explored. In this study, we first tested

vitisin B in an in vitro model using SH-SY5Y cells exposed to scopolamine-induced

cytotoxicity, where vitisin B significantly enhanced cell viability and promoted cell

survival. We evaluated its therapeutic potential in vivo using both systemic

administration and direct delivery into the third ventricle of the brain in a scopolamine-

induced AD mouse model. Across both administration routes, vitisin B exerted a broad

pro-cognitive effect, restoring multiple domains of learning and memory disrupted by

scopolamine. Vitisin B recovered spatial working memory in the Y-maze, normalized

exploratory activity in the open field, improved recognition memory in the novel object

recognition (NOR) test, and enhanced long-term memory retention in the passive

avoidance assay. This treatment restored cognitive function, alleviated cholinergic

deficits, increased hippocampal brain-derived neurotrophic factor (BDNF) levels, and

enhanced synaptic plasticity. These results suggest that vitisin B exerts reliable

cognitive and neuroprotective effects through both systemic and cerebral

administration, highlighting its potential as a promising therapeutic compound for

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restoring cholinergic function and enhancing hippocampal synaptic plasticity in AD.