Akademik Veri Yönetim Sistemi
FRONTIERS IN PHARMACOLOGY, cilt.1, sa.1, ss.1-12, 2026 (SCI-Expanded, Scopus)
Rosmarinic acid (RA), gallic acid (GA), and 3-hydroxytyrosol (3-HT) are phenolic compounds abundant in medicinal plants traditionally used to support cognitive function and neurological well-being. Although their antioxidant and neuroprotective properties are well documented in mammalian systems, their behavioral effects remain insufficiently explored in alternative in vivo models relevant for ethnopharmacological screening. In this study, we investigated the anxiolytic and cognitive-enhancing potential of RA, GA, and 3-HT in adult zebrafish (Danio rerio). Compounds were administered by immersion (3 µg/L, once daily for 8 days). Anxiety-related behaviors were evaluated using the novel tank diving test (NTT). At the same time, cognitive performance was assessed using the Y-maze and novel object recognition (NOR) tests to examine spatial and recognition memory, respectively. RA significantly increased the top/bottom time ratio (p < 0.0001), indicating reduced anxiety‑like behavior; however, this effect was accompanied by reductions in locomotor activity (distance traveled, p < 0.05; swimming velocity, p < 0.01), suggesting a possible sedative component that warrants further differentiation. In contrast, GA and 3-HT elicited anxiety-like behavioral responses in the NTT without significantly affecting locomotion. Despite their anxiogenic profile, GA and 3-HT significantly enhanced spatial memory in the Y-maze test (p < 0.001), whereas RA and 3-HT increased exploration of the novel arm (p < 0.001). Moreover, 3-HT significantly improved recognition memory in the NOR test (p < 0.01). Together, these findings reveal distinct neurobehavioral profiles for each phenolic compound: RA exhibited pronounced anxiolytic activity, while GA and 3-HT primarily enhanced cognitive performance, with 3-HT exerting broad-spectrum memory-facilitating effects. Overall, these results underscore the value of zebrafish as a translational model for behavioral pharmacology and support the ethnopharmacological relevance of RA, GA, and 3-HT as potential candidates for further investigation in the context of anxiety and cognitive disorders.