Antidepressant functions of Jie Yu Chu Fan capsule in promoting hippocampal nerve cell neurogenesis in a mouse model of chronic unpredictable mild stress

BACKGROUND: Depression is a major public health challenge that imposes a great societal burden. Depression has been attributed to the decreased level of neurotransmitters and brain-derived neurotrophic factor (BDNF) levels. Chinese herbal medicine Jie Yu Chu Fan (JYCF) capsule has been shown to be effective in the management of depression. However, the mechanism has yet to be determined. This study aimed to explore the activity of JYCF against depression by establishing a mouse model of chronic unpredictable mild stress (CUMS) with fluoxetine as the positive control drug. METHODS: The open field test, sucrose preference test, forced swim test, and tail suspension test were carried out to observe the behavioral changes of animals. The levels of norepinephrine (NE), dopamine (DA), and 5-hydroxytryptamine, as well as their respective metabolic products 5-hydroxyindoleacetic acid, homovanillic acid (HVA), and 3,4-dihydroxyphenylacetic acid in the mouse hippocampi were quantified by high-performance liquid chromatography (HPLC). Cell proliferation and apoptosis, and early and mature nerve cells in the hippocampi were observed by immunofluorescence. Reverse transcription polymerase chain reaction was used to identify BDNF expression in the hippocampi. RESULTS: After 5 weeks of unpredictable stimulation, a CUMS mouse model was successfully obtained, as indicated by sharply decreased sucrose preference and locomotor activity, as well as an increased immobility time in the forced swim test. Our results demonstrated that treatment with JYCF (1 and 5 g/kg) and fluoxetine (20 mg/kg) dramatically reversed the behavioral abnormalities in CUMS mice. At 1 g/kg, JYCF significantly increased NE, DA, and HVA levels in the hippocampi of CUMS mice. JYCF up-regulated the mRNA expression of BDNF and promoted cell proliferation in hippocampi of CUMS mice. CONCLUSIONS: Our study demonstrated that JYCF exhibits antidepressant activity comparable to that of fluoxetine in CUMS mice. Moreover, the antidepressant-like activity of JYCF was shown to be mediated by enhancing hippocampal nerve cell neurogenesis through increasing the levels of monoamine neurotransmitters and BDNF expression.