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柴胡疏肝散水提取物对大鼠的抗抑郁样活性及其可能机制

Antidepressant-like activity of Chaihu-Shugan-San aqueous extract in rats and its possible mechanism.

作者信息

Wang Sue, Hu Suiyu, Zhang Chunhu, Qiu Juan, Li Yunhui

机构信息

Department of Integrative Medicine, Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha, Hunan, China ; Department of Integrative Medicine, Key Unit of State Administration of Traditional Chinese Medicine of the People's Republic of China, Changsha, Hunan, China.

Department of Nuclear Medicine, Xiangya 3rd Hospital, Central South University, Changsha, Hunan, China.

出版信息

Pharmacogn Mag. 2014 Jan;10(Suppl 1):S50-6. doi: 10.4103/0973-1296.127342.

Abstract

BACKGROUND

Chaihu-Shugan-San (CHSGS), a traditional Chinese medicinal formula, is commonly used for the treatment of depression in China. However, the molecular mechanism underlying its antidepressant action is unknown.

OBJECTIVE

The objective of this study is to evaluate the antidepressant-like effects of CHSGS and further explore the possible molecular mechanism implicated in its actions.

MATERIALS AND METHODS

THE RATS WERE RANDOMLY DIVIDED INTO FOUR GROUPS: The normal control group, the model control group, the CHSGS group and the fluoxetine control group. The antidepressant-like effects of CHSGS aqueous extract were assessed in rats exposed to chronic mild stress (CMS) using the open-field test and sucrose water consumption test, its underlying mechanism of anti-depression was explored by determining the effect of CHSGS on the extracellular signal-regulated kinase (ERK) and phospho-ERK (P-ERK) in the hippocampus using western blot. The aqueous extract of CHSGS at a dose of standard (5.9 g/kg·d) was administered intragastrically for 14 days during the CMS model while the fluoxetine control group was given at the same time using fluoxetine hydrochloride (1.8 mg/kg·d).

RESULTS

The stressed rats demonstrated decreased locomotor activity in open field test and reduction in sucrose consumption and decreased levels of P-ERK1/2 and the ratio of P-ERK1/2 to total ERK1/2 in the hippocampus. CHSGS alleviated the depressive-like behaviors and increased levels of P-ERK1/2 and the ratio of P-ERK1/2 to total ERK1/2 in stressed rats as well as fluoxetine.

CONCLUSION

In summary, these results suggest that CHSGS aqueous extract possesses an antidepressant-like activity in CMS induced depression model rats, which might be mediated, at least in part, by reversing the stress-induced disruption of ERK activity.

摘要

背景

柴胡疏肝散(CHSGS)是一种传统中药配方,在中国常用于治疗抑郁症。然而,其抗抑郁作用的分子机制尚不清楚。

目的

本研究旨在评估柴胡疏肝散的抗抑郁样作用,并进一步探讨其作用可能涉及的分子机制。

材料与方法

将大鼠随机分为四组:正常对照组、模型对照组、柴胡疏肝散组和氟西汀对照组。采用旷场试验和糖水消耗试验评估柴胡疏肝散水提取物对慢性轻度应激(CMS)大鼠的抗抑郁样作用,通过蛋白质免疫印迹法检测柴胡疏肝散对海马细胞外信号调节激酶(ERK)和磷酸化ERK(P-ERK)的影响,探讨其抗抑郁的潜在机制。在CMS模型期间,以标准剂量(5.9 g/kg·d)的柴胡疏肝散水提取物灌胃给药14天,同时氟西汀对照组给予盐酸氟西汀(1.8 mg/kg·d)。

结果

应激大鼠在旷场试验中表现出运动活性降低、糖水消耗减少,海马中P-ERK1/2水平及P-ERK1/2与总ERK1/2的比值降低。柴胡疏肝散和氟西汀均可减轻应激大鼠的抑郁样行为,提高海马中P-ERK1/2水平及P-ERK1/2与总ERK1/2的比值。

结论

总之,这些结果表明柴胡疏肝散水提取物在CMS诱导的抑郁模型大鼠中具有抗抑郁样活性,这可能至少部分是通过逆转应激诱导的ERK活性破坏来介导的。

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