Institute of Integrated Traditional Chinese Medicine and Western Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan, China; Department of Nuclear Medicine, the Third Xiangya Hospital of Central South University, Changsha, Hunan, China.
Institute of Integrated Traditional Chinese Medicine and Western Medicine, Xiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha 410008, Hunan, China.
J Ethnopharmacol. 2014 Mar 14;152(2):320-6. doi: 10.1016/j.jep.2014.01.004. Epub 2014 Jan 30.
Chaihu-Shugan-San (CSS) is a well-known, Chinese traditional medicine used to treat depression. Little is known about the antidepressant mechanism of CSS. The main aims of the this study were to evaluate the antidepressant-like effects of CSS and its components and further explore the CSS׳s effect upon signal transduction of extracellular signal-regulated kinase 5 (ERK5) expressions in the hippocampus of rats with depression induced by chronic unpredicted mild stress.
SD rats were randomly divided into six groups: Normal; Model; CSS; Component I; Component II; and Fluoxetine. Antidepressant-like effects of CSS and two of its constituents, Components I and II in aqueous extract, were assessed using rats exposed to chronic unpredictable mild stress (CUMS) by measuring weight change, observing the open-field test and measuring sucrose water consumption. Antidepressant mechanism were examined by measuring the effect of CSS, and two of its constituents, on extracellular signal-regulated kinase 5 (ERK5) expression, phosphorylation-ERK5 (p-ERK5), and ERK5 mRNA in the hippocampus by using western blotting and Real-time Polymerase Chain Reaction (PCR). Three preparations were prepared: (1) an aqueous extract of CSS (5.9 g/kg·d); (2) Component I (3.3 g/kg·d); and (3) Component II (2.6 g/kg·d). During the 28-day CUMS, the three preparations were intragastrically administered all three preparations. Simultaneously a parallel positive fluoxetine control group was given fluoxetine hydrochloride (1.8mg/kg·d). Normal and Model groups were intragastrically administered with a isovolumic distilled water (4.5 ml/kg·d).
Depressed rats had decreased weight gain; decreased locomotor activity as measured by the open field test; and reduced sucrose consumption. The rats׳ hippocampus ERK5 activation was significantly suppressed. CSS reduced the incidence of depressive-like behaviors and increased ERK5 activation in depressed rats at the same rate as fluoxetine. Component I, and II, each had only a partial effect on the depression indicators measured.
CSS aqueous extract has antidepressant-like effects on CUMS-induced depression model rats. The antidepressant effect of CSS is greater than that of either the two separate components measured. CSS׳s antidepressant mechanism may be mediated by reversing the stress-induced disruption of ERK5 activity.
柴胡疏肝散（CSS）是一种著名的中药，用于治疗抑郁症。对于 CSS 的抗抑郁机制知之甚少。本研究的主要目的是评估 CSS 及其成分的抗抑郁样作用，并进一步探讨 CSS 在慢性不可预测轻度应激诱导的抑郁大鼠海马细胞外信号调节激酶 5（ERK5）表达信号转导中的作用。
SD 大鼠随机分为六组：正常组；模型组；CSS 组；成分 I 组；成分 II 组；和氟西汀组。通过测量体重变化、观察旷场试验和测量蔗糖水消耗，评估 CSS 及其两种成分（水提取物中的成分 I 和成分 II）在慢性不可预测轻度应激（CUMS）暴露的大鼠中的抗抑郁样作用。通过 Western blot 和实时聚合酶链反应（PCR）测量 CSS 及其两种成分对细胞外信号调节激酶 5（ERK5）表达、磷酸化-ERK5（p-ERK5）和海马 ERK5 mRNA 的影响，研究 CSS 的抗抑郁机制。制备了三种制剂：（1）CSS 水提取物（5.9 g/kg·d）；（2）成分 I（3.3 g/kg·d）；和（3）成分 II（2.6 g/kg·d）。在 28 天的 CUMS 期间，三种制剂均通过灌胃给予。同时，平行给予阳性氟西汀对照组盐酸氟西汀（1.8mg/kg·d）。正常组和模型组给予等容量蒸馏水（4.5 ml/kg·d）。
抑郁大鼠体重增加减少；旷场试验测量的运动活动减少；和蔗糖消耗减少。大鼠海马 ERK5 激活明显受到抑制。CSS 降低了抑郁大鼠的抑郁样行为发生率，并以与氟西汀相同的速度增加了抑郁大鼠的 ERK5 激活。成分 I 和 II 对所测量的抑郁指标都只有部分作用。
CSS 水提取物对慢性不可预测轻度应激诱导的抑郁模型大鼠具有抗抑郁样作用。CSS 的抗抑郁作用大于所测两种成分的单独作用。CSS 的抗抑郁机制可能是通过逆转应激诱导的 ERK5 活性紊乱来介导的。
