A single oral administration of flavanols enhances short-term memory in mice along with increased brain-derived neurotrophic factor.

Background: Flavanols (FLs), a group of polyphenols abundant in cocoa and red wine, have been associated with improved cognitive function, particularly hippocampus-dependent memory in older adults. However, their poor bioavailability has limited understanding of the mechanisms underlying their effects on the brain. This study aimed to investigate the cognitive and molecular responses following acute FLs administration in mice. Methods: Male C57BL/6J mice were orally administered FLs (25 mg/kg) or distilled water (DW) and subjected to a novel object recognition test. In one experiment, FLs were administered before training, in another, after training. Exploratory behavior and the discrimination index (DI) were analyzed. Hippocampal tissues were collected at 15 min to 4 h post-administration to assess levels of brain-derived neurotrophic factor (BDNF) and phosphorylated extracellular signal-regulated kinase, cAMP response element-binding protein (CREB), and tyrosine kinase receptor type 2 by western blotting. Results: Mice treated with FLs before training exhibited significantly longer exploration of the novel object and higher DI, whereas no enhancement was observed when FLs were administered after training. CREB phosphorylation increased at 30 min post-administration, and BDNF levels were elevated at 2 and 4 h. Conclusion: These findings suggest that FLs enhance short-term memory via hippocampal CREB activation and BDNF upregulation. Despite low systemic absorption, the rapid effects observed may involve sensory signaling pathways, potentially triggered by the astringent properties of FLs. This study provides mechanistic insight into the cognitive benefits of dietary FLs.