Abstract / Summary
Abstract For centuries, Armillaria mellea (A. mellea) has been used in East Asian traditional medicine, with its polysaccharides (AMP) known for anti-apoptotic and antioxidant properties, though their antidepressant effects remain unexplored. This study investigated AMP's effects in a chronic restraint stress (CRS)-induced mouse model of depression, assessing behavioral, cognitive, and molecular mechanisms. Male C57BL/6 mice (6–8 weeks old) were divided into control, CRS, CRS + low/high-dose AMP, and CRS+fluoxetine groups. Subsequent assessments included behavioral tests, Morris water maze (MWM) analysis, and Western blotting for inflammatory cytokines, apoptosis, and synaptic plasticity markers, alongside histopathological evaluation. Results showed AMP alleviated depression-like behaviors and improved cognitive function in CRS mice, while reducing neuroinflammation, hippocampal synaptic damage, and apoptosis, likely via JNK/p38 MAPK pathway modulation. These findings demonstrate AMP's antidepressant potential through anti-inflammatory, neuroprotective, and synaptic plasticity-enhancing mechanisms, bridging traditional use with modern pharmacological evidence.