Zhang Jin-Qiang, Wu Xiao-Hui, Feng Yi, Xie Xiao-Fang, Fan Yong-Hua, Yan Shuo, Zhao Qiu-Ying, Peng Cheng, You Zi-Li
School of Life Science and Technology, University of Electronic Science and Technology of China, Chengdu 610054, China.
State Key Laboratory Breeding Base of Systematic Research, Development and Utilization of Chinese Medicine Resources, College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, China.
Acta Pharmacol Sin. 2016 Sep;37(9):1141-53. doi: 10.1038/aps.2016.63. Epub 2016 Jul 18.
Major depressive disorder (MDD) is a debilitating mental disorder associated with dysfunction of the neurotransmitter-neuroendocrine system and neuroinflammatory responses. Salvianolic acid B (SalB) has shown a variety of pharmacological activities, including anti-inflammatory, antioxidant and neuroprotective effects. In this study, we examined whether SalB produced antidepressant-like actions in a chronic mild stress (CMS) mouse model, and explored the mechanisms underlying the antidepressant-like actions of SalB.
Mice were subjected to a CMS paradigm for 6 weeks. In the last 3 weeks the mice were daily administered SalB (20 mg·kg(-1)·d(-1), ip) or a positive control drug imipramine (20 mg·kg(-1)·d(-1), ip). The depressant-like behaviors were evaluated using the sucrose preference test, the forced swimming test (FST), and the tail suspension test (TST). The gene expression of cytokines in the hippocampus and cortex was analyzed with RT-PCR. Plasma corticosterone (CORT) and cerebral cytokines levels were assayed with an ELISA kit. Neural apoptosis and microglial activation in brain tissues were detected using immunofluorescence staining.
Administration of SalB or imipramine reversed the reduced sucrose preference ratio of CMS-treated mice, and significantly decreased their immobility time in the FST and TST. Administration of SalB significantly decreased the expression of pro-inflammatory cytokines IL-1β and TNF-α, and markedly increased the expression of anti-inflammatory cytokines IL-10 and TGF-β in the hippocampus and cortex of CMS-treated mice, and normalized their elevated plasma CORT levels, whereas administration of imipramine did not significantly affect the imbalance between pro- and anti-inflammatory cytokines in the hippocampus and cortex of CMS-treated mice. Finally, administration of SalB significantly decreased CMS-induced apoptosis and microglia activation in the hippocampus and cortex, whereas administration of imipramine had no significant effect on CMS-induced apoptosis and microglia activation in the hippocampus and cortex.
SalB exerts potent antidepressant-like effects in CMS-induced mouse model of depression, which is associated with the inhibiting microglia-related apoptosis in the hippocampus and the cortex.
重度抑郁症（MDD）是一种使人衰弱的精神障碍，与神经递质 - 神经内分泌系统功能障碍和神经炎症反应有关。丹酚酸B（SalB）已显示出多种药理活性，包括抗炎、抗氧化和神经保护作用。在本研究中，我们研究了SalB在慢性轻度应激（CMS）小鼠模型中是否产生抗抑郁样作用，并探讨了SalB抗抑郁样作用的潜在机制。
将小鼠进行6周的CMS范式。在最后3周，每天给小鼠腹腔注射SalB（20mg·kg⁻¹·d⁻¹）或阳性对照药物丙咪嗪（20mg·kg⁻¹·d⁻¹）。使用蔗糖偏好试验、强迫游泳试验（FST）和悬尾试验（TST）评估抑郁样行为。用RT-PCR分析海马和皮质中细胞因子的基因表达。用ELISA试剂盒检测血浆皮质酮（CORT）和脑组织中细胞因子水平。使用免疫荧光染色检测脑组织中的神经细胞凋亡和小胶质细胞活化。
给予SalB或丙咪嗪可逆转CMS处理小鼠降低的蔗糖偏好率，并显著减少它们在FST和TST中的不动时间。给予SalB可显著降低CMS处理小鼠海马和皮质中促炎细胞因子IL-1β和TNF-α的表达，并显著增加抗炎细胞因子IL-10和TGF-β的表达，并使它们升高的血浆CORT水平恢复正常，而给予丙咪嗪对CMS处理小鼠海马和皮质中促炎和抗炎细胞因子之间的失衡没有显著影响。最后，给予SalB可显著减少CMS诱导的海马和皮质中的细胞凋亡和小胶质细胞活化，而给予丙咪嗪对CMS诱导的海马和皮质中的细胞凋亡和小胶质细胞活化没有显著影响。
SalB在CMS诱导的小鼠抑郁模型中发挥强大的抗抑郁样作用，这与抑制海马和皮质中与小胶质细胞相关的细胞凋亡有关。
