Antidepressant activity of a Dioscorea nipponica–prickly pear mixed extract via serotonin modulation

Depression is a major mental health problem with a steadily increasing prevalence in modern society, largely due to rising stress levels, creating a growing need for effective and safe alternative therapeutic options. In this study, the antidepressant effects of Dioscorea nipponica–prickly pear mixed (DPM) extract was evaluated, both of which are known for their beneficial anti-inflammatory, antioxidant, and metabolic activities. DPM extract treatment dose-dependently increased central serotonin–related tryptophan hydroxylase 2 (TPH-2) expression, while reducing peripheral serotonin–associated tryptophan hydroxylase 1 (TPH-1) and serotonin transporter (SERT) levels, accompanied by significant inhibition of serotonin uptake. In a restraint stress–induced depression model, DPM extract elevated serum serotonin levels and reduced immobility time in the forced swim test. Collectively, these findings demonstrated that DPM extract exerts antidepressant effects by modulating serotonin synthesis and reuptake, supporting its potential use as a functional food ingredient foralleviating stress-related depressive symptoms.