Dietary Supplementation with Whole Propolis Differentially Modulates Cognitive and Anxiety-like Behaviors in Male and Female Mice

Propolis is a complex bee-derived natural product with reported neuroprotective properties, largely based on studies using solvent extracts or isolated bioactive constituents. However, the neurobehavioral effects of consuming whole propolis as a dietary component remain poorly understood. In this study, we investigated the impact of dietary supplementation with whole propolis on cognitive and anxiety-like behaviors in male and female mice. Adult mice (8-10 week old) received standard chow or chow supplemented with 5% whole propolis for 14 days, after which behavioral assessments were conducted using the Novel Object Recognition test, Y-maze, and the zero plus maze. Whole propolis supplementation enhanced recognition memory in both male and female mice, as indicated by increased exploration of the novel object. In contrast, spatial working memory assessed by spontaneous alternation in the Y-maze was impaired in male mice but unchanged in females. Anxiety-like behavior, evaluated using the zero plus maze, was increased in both sexes, as reflected by reduced open-arm exploration. These findings demonstrate that whole propolis consumption differentially modulates neurobehavioral outcomes in a sex-dependent manner. The study highlights the importance of evaluating natural products in their unrefined dietary form and underscores the need to consider sex as a biological variable when assessing the neurobehavioral impact of dietary bioactive compounds.

Key Words: propolis, memory, anxiety, locomotion, mice