Jiang Ning, Fan Lin-Xi, Yang Yu-Jie, Liu Xin-Min, Lin Hai-Ying, Gao Li, Wang Qiong
Preclinical Medicine Research Center/School of Pharmacy, Southwest Medical University, Luzhou 646000, China.
Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100193, China.
Sheng Li Xue Bao. 2017 Apr 25;69(2):159-166.
To investigate whether the extract of Dendrobium nobile Lindl (DNL) has an antidepressant effect on chronic unpredictable mild stress (CUMS)-induced depressive mice, 72 BALB/c male mice were randomly divided into the control group, the CUMS model group, the extract of DNL groups (50, 100 and 200 mg/kg DNL, i.g.) and the paroxetine group (10 mg/kg, i.g.). The different doses of DNL or the paroxetine was administered orally once daily to CUMS mice for 8 weeks (containing two-week preventive medication before the modeling). The same volume of distilled water was given to the control group and the CUMS group. Except for the control group, the other mice were exposed to chronic stress for 35 days. Behavioral tests were performed by using the sucrose preference test (SPT), the novelty-suppressed feeding (NSF) test, the tail suspension test (TST), and the forced swim test (FST). The levels of dopamine (DA) and 5-hydroxytryptamine (5-HT) were measured by the liquid chromatography-mass spectrometer (LC-MS)/MS. Compared with the control group, obvious behavioral changes were observed in the CUMS group after 5-week CUMS, including a decrease in the sucrose consumption, an increase in the latency to feeding in the NSF test and a prolongation of the immobility time in the TST. Compared with the CUMS group, the application of DNL resulted in a dose-dependent increase in sucrose consumption (P < 0.01) as paroxetine (10 mg/kg) did and a significant dose-dependent decrease in the latency to feeding in the NSF test (P < 0.05). In the TST, the application of paroxetine (10 mg/kg) and the high-dose DNL (200 mg/kg) obviously decreased the immobility time when compared with the CUMS group (P < 0.05). In the FST, compared with the CUMS group, all the groups had no significant differences in the immobility time (P > 0.05). In addition, in the hippocampus and cortex, the levels of 5-HT and DA were significantly decreased in the CUMS group compared with the control group (P < 0.05). In comparison with the CUMS group, paroxetine obviously increased the DA levels in the hippocampus and the cortex and the 5-HT level in the hippocampus (P < 0.05). DNL (50 and 200 mg/kg) significantly increased the DA level in cerebral cortex of the brain, and DNL (100 and 200 mg/kg) increased the DA level in the hippocampus. The 5-HT level in the 200 mg/kg DNL group was notably increased in both two brain regions (P < 0.05), but the 5-HT level in the 100 mg/kg DNL group was significantly increased only in the hippocampus (P < 0.01). These findings indicate that the extract of DNL has an antidepressant-like effect on CUMS-induced depressive mice and its mechanism may be related to the changes in DA and 5-HT in the hippocampus and cortex.
为研究金钗石斛提取物（DNL）对慢性不可预测性温和应激（CUMS）诱导的抑郁小鼠是否具有抗抑郁作用，将72只BALB/c雄性小鼠随机分为对照组、CUMS模型组、DNL提取物组（50、100和200 mg/kg DNL，灌胃）和帕罗西汀组（10 mg/kg，灌胃）。将不同剂量的DNL或帕罗西汀每日一次口服给予CUMS小鼠，持续8周（建模前含两周预防性用药）。对照组和CUMS组给予相同体积的蒸馏水。除对照组外，其他小鼠接受35天的慢性应激。通过蔗糖偏好试验（SPT）、新奇抑制摄食试验（NSF）、悬尾试验（TST）和强迫游泳试验（FST）进行行为测试。采用液相色谱-质谱联用仪（LC-MS）/MS测定多巴胺（DA）和5-羟色胺（5-HT）水平。与对照组相比，CUMS组在5周CUMS后出现明显行为变化，包括蔗糖消耗减少、NSF试验中摄食潜伏期延长以及TST中不动时间延长。与CUMS组相比，DNL的应用导致蔗糖消耗呈剂量依赖性增加（P < 0.01），与帕罗西汀（10 mg/kg）相同，且在NSF试验中摄食潜伏期呈显著剂量依赖性降低（P < 0.05）。在TST中，与CUMS组相比，帕罗西汀（10 mg/kg）和高剂量DNL（200 mg/kg）明显缩短了不动时间（P < 0.05）。在FST中，与CUMS组相比，所有组在不动时间上均无显著差异（P > 0.05）。此外，与对照组相比，CUMS组海马和皮质中5-HT和DA水平显著降低（P < 0.05）。与CUMS组相比，帕罗西汀明显增加了海马和皮质中的DA水平以及海马中的5-HT水平（P < 0.05）。DNL（50和200 mg/kg）显著增加了大脑皮质中的DA水平，DNL（100和200 mg/kg）增加了海马中的DA水平。200 mg/kg DNL组两个脑区的5-HT水平均显著升高（P < 0.05），但100 mg/kg DNL组的5-HT水平仅在海马中显著升高（P < 0.01）。这些结果表明，DNL提取物对CUMS诱导的抑郁小鼠具有抗抑郁样作用，其机制可能与海马和皮质中DA和5-HT的变化有关。
