Wang Q-S, Tian J-S, Cui Y-L, Gao S
Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Institute of Medical Equipment, Academy of Military Medical Sciences, Tianjin 300161, PR China.
Tianjin State Key Laboratory of Modern Chinese Medicine, Research Center of Traditional Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, PR China; Modern Research Center for Traditional Chinese Medicine of Shanxi University, Taiyuan 030006, PR China.
Neuroscience. 2014 Sep 5;275:365-73. doi: 10.1016/j.neuroscience.2014.06.032. Epub 2014 Jun 24.
Genipin, an important bioactive component from Gardenia jasminoides Eills, was demonstrated to possess antidepressant-like effects in a previous study. However, the molecular mechanism of antidepressant-like effects on genipin was not clear. The present study aimed to investigate the possible mechanism of antidepressant-like effects on genipin with a chronic unpredictable mild stress (CUMS)-induced depression model in rats. In CUMS-induced depressive rats, bodyweight and 1% sucrose consumption decreased significantly compared with the normal control group. Furthermore, these changes could be significantly reversed by genipin application. The levels of 5-hydroxytryptamine (5-HT), norepinephrine (NE) in the hippocampus decreased and the level of 5-hydroxyindole acetic acid (5-HIAA) increased in the CUMS-induced depressive rats. However, pre-treatments with genipin significantly increased the levels of 5-HT, NE and decreased the level of 5-HIAA in the hippocampus. The concentration of cAMP in the hippocampus was increased by genipin compared to the CUMS-exposed model group. The mRNA expressions of 5-hydroxytryptamine 1A receptor (5-HT1AR), cAMP response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in rats were decreased exposed to CUMS, which were reversed by genipin-treated rats exposed to CUMS. Compared to the CUMS-exposed model group, the mRNA expression of 5-hydroxytryptamine 2A receptor (5-HT(2A)R) was decreased significantly by genipin-treated rats. The mRNA and protein expression of CREB, BDNF were increased in genipin-treated rats compared to the CUMS-exposed model group. Moreover, the levels of corticosterone in serum were decreased by genipin-treated compared to the CUMS-exposed model group. These results suggest that the possible mechanism of antidepressant-like effects on genipin, at least in one part, resulted from monoaminergic neurotransmitter system and the potential dysfunctional regulation of the post-receptor signaling pathway, which particularly affected the 5-HT(1A)R, 5-HT(2A)R and BDNF levels in the hippocampus.
京尼平是栀子中的一种重要生物活性成分，在先前的一项研究中已证明其具有抗抑郁样作用。然而，京尼平抗抑郁样作用的分子机制尚不清楚。本研究旨在通过慢性不可预测轻度应激（CUMS）诱导的大鼠抑郁模型，探讨京尼平抗抑郁样作用的可能机制。在CUMS诱导的抑郁大鼠中，与正常对照组相比，体重和1%蔗糖消耗量显著降低。此外，应用京尼平可显著逆转这些变化。CUMS诱导的抑郁大鼠海马中5-羟色胺（5-HT）、去甲肾上腺素（NE）水平降低，5-羟吲哚乙酸（5-HIAA）水平升高。然而，京尼平预处理可显著提高海马中5-HT、NE水平，并降低5-HIAA水平。与CUMS暴露模型组相比，京尼平可提高海马中cAMP的浓度。暴露于CUMS的大鼠中5-羟色胺1A受体（5-HT1AR）、环磷酸腺苷反应元件结合蛋白（CREB）和脑源性神经营养因子（BDNF）的mRNA表达降低，而经京尼平处理的暴露于CUMS的大鼠可使其逆转。与CUMS暴露模型组相比，经京尼平处理的大鼠5-羟色胺2A受体（5-HT(2A)R）的mRNA表达显著降低。与CUMS暴露模型组相比，经京尼平处理的大鼠CREB、BDNF的mRNA和蛋白表达增加。此外，与CUMS暴露模型组相比，经京尼平处理可降低血清中皮质酮水平。这些结果表明，京尼平抗抑郁样作用的可能机制至少部分是由单胺能神经递质系统和受体后信号通路的潜在功能失调调节所致，这尤其影响了海马中5-HT(1A)R、5-HT(2A)R和BDNF的水平。
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