Antidepressant-like Effects of Garcinia nigrolineata Resin Extract in a Chronic Mild Stress Mouse Model: Modulation of Monoaminergic and HPA-Axis Pathways.

The resin extract of Garcinia nigrolineata (GNR-E), a tropical plant used in Southeast Asian traditional medicine, was evaluated for its antidepressant-like effects in a chronic mild stress (CMS) mouse model, with imipramine as a reference drug. GNR-E dose-dependently alleviated CMS-induced anhedonia (sucrose preference test) and behavioral despair (forced swimming and tail suspension tests). Neurochemical analyses revealed that GNR-E increased serotonin (5-HT) and norepinephrine (NE) levels, reduced expression of their transporters (SERT, NET) and receptors (5-HT1A, 1B, 2A, 2C, 7; α2A, 2C) in the frontal cortex and hippocampus, and normalized HPA-axis hyperactivity by lowering serum corticosterone and modulating glucocorticoid receptor (GR) and SGK-1 mRNA expression. In vitro, GNR-E inhibited monoamine oxidase (MAO)-A and -B (Ki = 2.33 and 1.55 µg/mL, respectively). Phytochemical analysis identified xanthones, particularly cowanin, as key constituents. These findings highlight GNR-E's potential as a novel plant-based antidepressant, warranting further investigation into its active compounds and clinical applications.