Xiaoyaosan alleviates CUMS rat by promoting hippocampal neurogenesis via modulating the JNK/GluR1 signaling pathway.

Abstract

OBJECTIVE: Depression is a syndrome of stress and emotional disorder, involving damage to synaptic plasticity in the central nervous system, particularly in the hippocampus. Xiaoyaosan (XYS) is a classic Traditional Chinese Medicine (TCM) prescription that has shown significant antidepressant effects in both clinical and experimental settings. This study aims to using the CUMS rat model of depression to explore the possible role of hippocampal synaptic plasticity in the pathogenesis of depression and to observe the effects of Xiaoyaosan on hippocampal synaptic plasticity mediated by the JNK/GluR1 pathway. METHODS: Forty-eight male SD rats were randomly divided into four groups based on body weight using the Excel randomization method: control, model, Xiaoyaosan, and fluoxetine groups. The chronic unpredictable mild stress (CUMS) method was used to establish a depression model in the three groups (excluding the control group) over a period of six weeks. From day 22, all groups except the control group were given double-distilled water, Xiaoyaosan decoction, or fluoxetine solution once daily by gavage for three consecutive weeks. Behavioral observations and relevant indicators were then assessed. Depression-like behaviors were evaluated using the sucrose preference test (SPT) and the open field test (OFT). The levels of neurotransmitters 5-HT and NE in the hippocampal tissue were measured using ELISA. RT-qPCR was employed to detect the mRNA levels of JNK, GluR1, GluR2, and PSD-95 in the hippocampus. The relative protein levels of JNK, GluR1, GluR2, and PSD-95 in the hippocampus were analyzed using Western blot. RESULTS: After six weeks of CUMS modeling, compared to the control group, the model group rats exhibited a decline in gross representation scores, body weight, food intake, and behavioral scores. In the hippocampal, JNK levels were elevated, while the expression levels of 5-HT, NE, GluR1, GluR2, and PSD-95 were reduced. Following intervention with Xiaoyaosan or fluoxetine, these indicators were corrected, and the depression-like state in the rats was improved.