Anxiolytic Effect of Chanmu Anshen Granule and Its Bioactive Mechanism

Xiao-wei HU; Guang-bin LUO; Qiong-yin FAN; Yu-cong BI; Meng-ting WU; Bao-sheng ZHAO; Yan-tong XU; Ting WANG

doi:10.13422/j.cnki.syfjx.20191326

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Anxiolytic Effect of Chanmu Anshen Granule and Its Bioactive Mechanism

Pharmacology | 更新时间：2021-02-09

- Anxiolytic Effect of Chanmu Anshen Granule and Its Bioactive Mechanism
- Chinese Journal of Experimental Traditional Medical Formulae Vol. 25, Issue 13, Pages: 41-48(2019)
- 作者机构：
  
  北京中医药大学　北京中医药研究院，北京　 100029
- 作者简介：
- 基金信息：
- DOI：10.13422/j.cnki.syfjx.20191326
  CLC： R22; R242; R2-031; R285.5
- Received：30 January 2019，
  
  Published Online：20 March 2019，
  
  Published：05 July 2019
- 稿件说明：
移动端阅览
Xiao-wei HU, Guang-bin LUO, Qiong-yin FAN, et al. Anxiolytic Effect of Chanmu Anshen Granule and Its Bioactive Mechanism[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(13): 41-48.
DOI：

Xiao-wei HU, Guang-bin LUO, Qiong-yin FAN, et al. Anxiolytic Effect of Chanmu Anshen Granule and Its Bioactive Mechanism[J]. Chinese journal of experimental traditional medical formulae, 2019, 25(13): 41-48. DOI： 10.13422/j.cnki.syfjx.20191326.

摘要

目的：

观察柴牡安神颗粒的抗焦虑作用，并探讨其作用机制。

方法：

ICR小鼠按体质量随机分为正常组、地西泮(0.002 g·kg

－1

)组和解郁安神颗粒(1.4 g·kg

－1

)组，柴牡安神颗粒高、中、低剂量(1.98，0.99，0.495 g·kg

－1

)组，每组20只。为了考察药物抗焦虑作用，小鼠每天上午灌胃给药4周后，测试明暗箱、开场活动实验，然后动物取血，其中每组6只小鼠通过心脏灌注10%甲醛后取脑组织固定，其余小鼠取血后去取脑海马组织置于液氮保存。采用酶联免疫吸附方法检测小鼠海马组织和外周血中

-氨基丁酸(GABA)及谷氨酸(Glu)含量，计算GABA/Glu；采用免疫组化法测定海马组织

-氨基丁酸受体

蛋白的表达。为了考察药物催眠作用，小鼠灌胃给药7 d后，进行阈下剂量戊巴比妥钠协同催眠实验。

结果：

与正常组比较，明暗箱实验证实柴牡安神颗粒低、中剂量组显著延长了小鼠明箱停留持续时间(

0.05)，中剂量组增加了明箱进入次数(

0.05)；开场实验证实柴牡安神颗粒高剂量显著增加了小鼠在中心的区域距离(

0.01)和中心区域停留时间(

0.05)。进一步实验证实，在海马组织中，与正常组比较，柴牡安神颗粒高剂量组提高了GABA含量(

0.05)，显著降低了Glu含量(

0.01)，提高了GABA/Glu(

0.05)；在外周血，与正常组比较柴牡安神颗粒高剂量组显著降低了Glu含量(

0.01)，同时显著增加了GABA含量(

0.01)，从而显著提高了GABA/Glu(

0.01)。海马组织GABA

受体蛋白免疫组化结果显示柴牡安神颗粒中剂量组明显提高了GABA

蛋白表达。阈下剂量戊巴比妥钠协同催眠实验证实柴牡安神颗粒中剂量组明显提高了小鼠的入睡率(

0.05)。

结论：

柴牡安神颗粒具有显著抗焦虑作用，作用机制与提高海马GABA含量，降低Glu的含量，且提高了海马GABA

蛋白表达密切相关。外周血GABA，Glu含量变化与海马组织变化呈正相关，对临床诊断具有参考意义。柴牡安神颗粒同时具有改善睡眠的作用。

Abstract

Objective:

To assess the anxiolytic effect of Chaimu Anshen granules (CMASG) and investigate its bioactive mechanism.

Method:

ICR mice were randomly divided into normal group

diazepam group(0.002 g·kg

-1

)

Jieyu Anshen granules group(1.4 g·kg

-1

)

high

medium

and low-dose (1.98

0.99

0.495 g·kg

-1

)Chaimu Anshen granule groups

with 20 mice in each group. To detect the anxiolytic effect of CMASG

mice were intragastrically administered for 4 weeks in the morning

and light-dark box transition test and open field test were performed once the other day. After the behavior tests

blood samples were collected. Six mice of each group were perfused with formalin through heart

and then the brains were fixed for immunohistochemistry test. Hippocampus of the other mice in each group were collected and stored in liquid nitrogen. The content of

-aminobutyric acid(GABA)and glutamic acid(Glu)in hippocampus and blood samples were detected by enzyme-linked immunosorbent assay (ELISA)

and the ratio of GABA/Glu was calculated. The expression of GABA

receptor was evaluated by the immunohistochemistry method. To test the hypnosis effect of CMASG

mice were administered intragastrically for 7 days. The sub-threshold dose of pentobarbital sodium in the sleep experiment was tested.

Result:

Compared with normal group

the light-dark box transitions test demonstrated that low-dose and medium-dose CMASG groups significantly prolonged the duration in light box(

0.05)

and the middle-dose group significantly increased the frequency of entrance to light box(

0.05). The open field test confirmed that the high-dose CMASG significantly increased the travel distance (

0.01)and duration(

0.05) in central region. Further experiments demonstrated that in hippocampus

compared with the normal group

the high-dose CMASG significantly increased the content of GABA (

0.05)

but significantly reduced the Glu content(

0.01). The high-dose group significantly increased the GABA/Glu ratio(

0.01). In the blood samples

high-dose CMASG significantly reduced the Glu content(

0.01)

and the high-dose group significantly increased the GABA content(

0.01)and the GABA/Glu ratio(

0.01). The immunohistochemical results of GABA

receptor protein in hippocampus showed that the medium-dose CMASG significantly increased the expression of GABA

protein. The sub-threshold dose of pentobarbital sodium on sleep experiments confirmed that the medium-dose CMASG significantly increased the rate of sleep in mice.

Conclusion:

CMASG showed an anxiolytic effect

and its bioactive mechanism was related with the increase of GABA content

and the decrease of Glu content in hippocampus. Furthermore

it increased the expression of GABA

protein in hippocampus. The changes in content of GABA and Glu in peripheral blood were positively correlated with the changes in hippocampal tissues

which provided reference for clinical diagnosis. CMASG also exhibited an effect in improvement of sleep.

关键词

Keywords

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