Zhao Hui, Liang Bingyu, Yu Linjie, Xu Yun
Department of Neurology, Affiliated Drum Tower Hospital, Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China.
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, Jiangsu 210008, P.R. China.
Exp Ther Med. 2017 Aug;14(2):1086-1094. doi: 10.3892/etm.2017.4601. Epub 2017 Jun 14.
Jieyu chufan (JYCF) is a well-known Chinese traditional medicine used for depression; however, the molecular mechanism underlying its anti-depressant action has remained elusive. In the present study, the anti-depressant effects of JYCF and the potential mechanisms were investigated in a mouse model. Five groups of 12 C57BL/6 mice each were used in the study, including a normal control group (NC group), a model control group (MC group) and three groups, which received different doses of JYCF (1.25, 2.5 and 5 g/kg) orally for 21 days (JYCF groups). The MC group and the three JYCF groups were subjected to 3 weeks of unpredictable chronic mild stress (UCMS) to induce depression-like behavior. All groups were subjected to a sucrose consumption test along with a forced swimming test to confirm depression-like behavior, an open-field test and an elevated plus maze test to confirm anxiety-like behavior, and a Morris water maze test to evaluate spatial learning and memory. In addition, synaptic density in the hippocampus was evaluated and western blot and immunostaining were used to analyze hippocampal expression of postsynaptic density protein-95 (PSD95), synaptophysin (Syn), cyclic adenosine monophosphate response element binding protein (CREB), brain-derived neurotrophic factor (BDNF), Akt and glycogen synthase kinase (GSK)-3β as well as their phosphorylated (p) versions. The results showed that JYCF (2.5 and 5 g/kg) alleviated depressive-like behaviors and increased synaptic density in UCMS mice. Moreover, JYCF upregulated the expression of PSD95, Syn and BDNF and increased phosphorylated Akt, CREB and GSK-3β in the hippocampus. These results suggested that JYCF exerts an anti-depressant-like activity in UCMS-induced mice, which is likely to be mediated by reversing the stress-induced disruption of BDNF and GSK-3β activity.
解郁除烦（JYCF）是一种治疗抑郁症的著名中药；然而，其抗抑郁作用的分子机制仍不清楚。在本研究中，在小鼠模型中研究了JYCF的抗抑郁作用及其潜在机制。研究使用了五组，每组12只C57BL/6小鼠，包括正常对照组（NC组）、模型对照组（MC组）和三组，这三组小鼠口服不同剂量的JYCF（1.25、2.5和5 g/kg），持续21天（JYCF组）。MC组和三个JYCF组接受3周的不可预测的慢性轻度应激（UCMS）以诱导抑郁样行为。所有组均进行蔗糖消耗试验以及强迫游泳试验以确认抑郁样行为，进行旷场试验和高架十字迷宫试验以确认焦虑样行为，并进行莫里斯水迷宫试验以评估空间学习和记忆。此外，评估海马体中的突触密度，并使用蛋白质免疫印迹和免疫染色分析海马体中突触后致密蛋白95（PSD95）、突触素（Syn）、环磷酸腺苷反应元件结合蛋白（CREB）、脑源性神经营养因子（BDNF）、Akt和糖原合酶激酶（GSK）-3β及其磷酸化（p）形式的表达。结果表明，JYCF（2.5和5 g/kg）减轻了UCMS小鼠的抑郁样行为并增加了突触密度。此外，JYCF上调了海马体中PSD95、Syn和BDNF的表达，并增加了磷酸化的Akt、CREB和GSK-3β。这些结果表明，JYCF在UCMS诱导的小鼠中发挥抗抑郁样活性，这可能是通过逆转应激诱导的BDNF和GSK-3β活性破坏来介导的。
