Differential Cognitive Profiles Induced by Hexanic Fractions of Rubus fruticosus in a Transgenic Alzheimer’s Disease Model

Cognitive decline in AD extends beyond global memory impairment, encompassing deficits in working memory, cognitive flexibility, recognition processes, and the integration of exploratory strategies. Dissecting these components in transgenic models offers an opportunity to refine our understanding of how distinct neurobiological perturbations shape cognitive architecture under neurodegenerative conditions.

This study presents a comparative cognitive analysis of six hexanic fractions derived from Rubus fruticosus in the 5xFAD mouse model of AD. Transgenic mice were assigned to treatment groups receiving individual fractions at two concentrations (50mg/kg and 100mg/kg; n=10 per fraction) alongside control groups (NaCl,n=5; galantamine, n=5). All treatments were administered orally for seven consecutive days, one hour prior to behavioral assessment.

Cognitive performance was evaluated using a battery of tasks designed to probe complementary domains of cognition: spontaneous alternation (Y-Maze), recognition memory and encoding efficiency (Novel Object Recognition), and working and reference memory organization (Radial Arm Maze). Additional measures of exploratory behavior and emotional modulation were obtained using the Open Field, Elevated Plus Maze, and the Forced Swimming Test to contextualize cognitive outcomes within broader behavioral states. In silico pharmacokinetic and target-prediction analyses were conducted to support interpretation of behavioral variability across fractions.

Comparative behavioral profiling revealed fraction-specific cognitive signatures, indicating that distinct fractions differentially modulate cognitive subdomains rather than producing uniform enhancements across tasks. Several fractions exhibited non-linear dose–response relationships, with lower doses preferentially influencing memory accuracy and task-specific strategies, while higher doses primarily affected locomotor or exploratory parameters. These dissociations suggest that cognitive outcomes in the 5xFAD model reflect complex interactions between fraction-specific phytochemical composition and disease-related alterations in neural circuitry.

This study underscores the value of comparative cognitive phenotyping in transgenic models of AD. Integrating in silico predictions with multidimensional behavioral analysis provides a framework for interpreting divergent cognitive effects across chemically related fractions.