Dietary Theogallin Enhances Cognitive Function and Neuronal Activation via Immediate-Early Gene Activation in Aged Mice

Theogallin, a tea-derived polyphenol
enriched in newly developed
cultivars such as MK5601, has been shown to have cognitive benefits.
However, its biological and mechanistic effects of theogallin remain
unclear. Herein, we investigated the transcriptomic profiles of six
mouse tissues after oral theogallin administration. Theogallin induced
tissue-enriched transcriptional responses, particularly in the brain,
where it activated memory-related and neuronal activity-related pathways
through the upregulation of immediate-early genes (IEGs). These transcriptional
changes closely resembled brain-derived neurotrophic factor (BDNF)-induced
neuronal activation and contrasted with gene expression patterns associated
with Alzheimer’s disease. In aged mice, theogallin improved
recognition memory and increased the expression of IEGs-associated
proteins, while reducing neurodegeneration-linked markers. Theogallin
also enhanced neuronal gene expression in SH-SY5Y cells, supporting
a direct neuromodulatory role and further promoting neurite outgrowth.
Therefore, theogallin is a functional enhancer of neuronal activation
with potential therapeutic relevance for age-related cognitive decline
and neurodegenerative disorders.