Phlorotannin supplement mitigates anxiety- and depression-like symptoms in mice exposed to chronic unpredictable mild stress

Anxiety and depression are major mental health disorders often triggered by chronic stress. Although phlorotannins from Ecklonia cava have shown various pharmacological effects, their efficacy in mood disorders remains unclear. This study investigated the antidepressant and anxiolytic effects of phlorotannin supplement (PS) in a chronic unpredictable mild stress mouse model. Mice were administered PS (100 or 500 mg/kg/day) or fluoxetine (20 mg/kg/day) for 8 weeks. PS treatment significantly improved behavioral outcomes in the tail suspension, forced swim, open field, and elevated plus maze tests. Biochemically, PS reduced serum corticosterone, corticotropin-releasing hormone, and adrenocorticotropic hormone levels, suppressed hippocampal phosphorylated glucocorticoid receptor expression, and elevated monoamine neurotransmitters while decreasing monoamine oxidase levels. PS also downregulated pro-inflammatory cytokines and enzymes, activated ERK-CREB-BDNF signaling, and enhanced hippocampal neurogenesis. These findings suggest PS as a promising natural therapeutic candidate for stress-related anxiety and depression. • Phlorotannin supplement (PS) alleviates anxiety- and depression-like behaviors in CUMS exposed mice. • PS normalizes HPA axis activity and hippocampal GR phosphorylation under stress. • PS enhances brain monoamine levels and monoamine oxidase expression. • PS improves neurogenesis and ERK-CREB-BDNF signaling pathways in the hippocampus.