Abstract
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.
Highlights
Depression is expanding to become a global health problem and its exact cause has not been identified, much has been reported on its etiology [1,2]
Several drugs have been used for the treatment of depression, such as monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine-dopamine reuptake inhibitors (NDRIs), and N-methyl-D-aspartate receptor (NMDAR) antagonists [3,4]
Inhibitory activities of the extract against MAO-A, MAO-B, AChE, and BChE, relating to neurologic pathways, were evaluated along with a flavone C-glycoside spinosin, which is a major constituent of Semen Ziziphi Spinosae (SZS)
Summary
Depression is expanding to become a global health problem and its exact cause has not been identified, much has been reported on its etiology [1,2]. Several drugs have been used for the treatment of depression, such as monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), norepinephrine-dopamine reuptake inhibitors (NDRIs), and N-methyl-D-aspartate receptor (NMDAR) antagonists [3,4]. These inhibitors increase monoamine neurotransmitters such as norepinephrine (NE), 5-hydroxytryptamine (5-HT, serotonin), and dopamine (DA). Semen Ziziphi Spinosae (SZS), the dried seeds of Ziziphus jujuba Mill var. MAO-A, MAO-B, acetylcholinesterase (AChE), and butyrylcholinesterase (BChE) activities in the brain were assayed, levels of the monoamine neurotransmitters were analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS), and the level of BDNF was analyzed by Western blotting
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