School of Traditional Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Brain Res Bull. 2018 May;139:197-202. doi: 10.1016/j.brainresbull.2017.12.001. Epub 2017 Dec 16.
Xiao Yao San (XYS) is a traditional Chinese medicine used to treat depression; however, the mechanism underlying its antidepressant properties remains unclear. The objective of the present study was to investigate the effects and action mechanisms of XYS on interferon-α-induced depression in mice.
Mice were divided into six groups: control; model; low-, medium-, and high-dose XYS; and escitalopram-treated group. Except for the control mice, all groups of mice were injected with interferon (IFN)-α to establish the depression model. XYS and escitalopram were then administered to the respective mice daily for 21 days. Sucrose preference test (SPT), forced swim test (FST), and tail suspension test (TST) were used to measure behavioral indices. High-performance liquid chromatography (HPLC) was used to measure serotonin (5-HT) concentrations, while western blots were used to examine indoleamine-2,3-dioxygenase 1 (IDO1) expression in the dorsal raphe nucleus (DRN). The number of microglia in the DRN was observed using immunofluorescence.
Compared with that of the control group, the model group showed a significant decrease in sucrose consumption (P < 0.05) and significant increase in the duration of immobility in the FST and TST (P < 0.05). These parameters improved significantly after XYS or escitalopram treatment. There was also a significantly higher and lower expression of IDO1 protein and 5-HT in the mouse DRN, respectively, which were reversed by administering XYS and escitalopram (P < 0.05). Moreover, the number of microglia in the mouse DRN increased significantly and was reduced by XYS and escitalopram (P < 0.05).
XYS reduced the number of microglia and expression of IDO1, which increased the levels of 5-HT in the mouse DRN and, thereby, improved the depressive behavior of mice. This may explain, at least in part, the antidepressant properties of XYS in patients.
逍遥散是一种用于治疗抑郁症的中药,但它抗抑郁的作用机制尚不清楚。本研究旨在探讨逍遥散对干扰素-α诱导的抑郁小鼠的作用及作用机制。
将小鼠分为六组:对照组;模型组;低、中、高剂量逍遥散组;依西酞普兰组。除对照组外,其余各组小鼠均注射干扰素(IFN)-α建立抑郁模型。然后分别给予逍遥散和依西酞普兰,连续给药 21 天。采用蔗糖偏好试验(SPT)、强迫游泳试验(FST)和悬尾试验(TST)检测行为学指标。采用高效液相色谱法(HPLC)测定 5-羟色胺(5-HT)浓度,采用 Western blot 检测中缝背核(DRN)吲哚胺 2,3-双加氧酶 1(IDO1)的表达。采用免疫荧光法观察 DRN 中微胶质细胞的数量。
与对照组相比,模型组小鼠蔗糖消耗明显减少(P<0.05),FST 和 TST 不动时间明显延长(P<0.05)。经逍遥散或依西酞普兰治疗后,上述参数明显改善。DRN 中 IDO1 蛋白和 5-HT 的表达也明显升高和降低,经逍遥散和依西酞普兰治疗后得到逆转(P<0.05)。此外,DRN 中小胶质细胞数量明显增加,经逍遥散和依西酞普兰治疗后减少(P<0.05)。
逍遥散减少了微胶质细胞的数量和 IDO1 的表达,增加了 DRN 中 5-HT 的水平,从而改善了抑郁小鼠的抑郁行为。这至少可以部分解释逍遥散在患者中的抗抑郁作用。