Antidepressant-Like Effects of Ethanol Extract of Ziziphus jujuba Mill Seeds in Mice

The antidepressant-like activity of ethanol extract of Ziziphus jujuba Mill var. spinosa seeds (Semen Ziziphi Spinosae, SZS) was investigated by behavioral tests, such as a forced swimming test (FST), a tail-suspension test (TST), and an open field test (OFT), using mice exposed to chronic unpredictable mild stress (CUMS). In the TST, immobility times of the extract-treated groups E100 and E300 (CUMS + 100 and 300 mg/kg extract, respectively) were significantly decreased in a dose-dependent manner compared with the negative control (CUMS; p < 0.01, though those of E100 and E300 were higher than those of the positive control (CUMS + 15 mg/kg fluoxetine). In the FST, immobility times of E100 and E300 were decreased compared to the normal control. In the OFT, total and zone distances of E100 and E300 were significantly higher than those of negative controls (p < 0.01) with a dose dependency. In liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis after behavioral tests, norepinephrine (NE) and 5-hydroxytryptamine (5-HT) levels in the hippocampus tissues of E100 and E300 were significantly higher than those of negative controls. Brain-derived neurotrophic factor (BDNF) levels in the hippocampus tissues of E100 and E300 were higher than those of negative controls. From these results, the SZS ethanol extract exhibited significant antidepressant-like effects via immobility decrease, distance increase, hippocampal NE and 5-HT increase, and BDNF expression. These results suggest that the extract could be a potential antidepressant agent.