A Network Pharmacology-Based Study on Antidepressant Effect of <italic style="font-style: italic">Salicornia europaea</italic> L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice

Dan-chen SUN; Ran-ran WANG; Hao XU; Xue-hui ZHU; Yan SUN; Shi-qing QIAO; Wei QIAO

doi:10.1007/s11655-022-2879-2

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A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice

Original Article | Updated：2022-03-29

- A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice
- A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice
- Chinese Journal of Integrative Medicine 2022年28卷第4期页码：339-348
- Affiliations：
  
  Tianjin Key Laboratory on Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy,Tianjin Medical University, Tianjin (300070), China
- Author bio：
  
  QIAO Wei, E-mail: qiaowei@tmu.edu.cn
- Funds：
  
  the National Nature Science Foundation of China(81173530);Tianjin Research Program of Applied Basic and Cutting-edge Technologies(17JCZDJC33200;12JCZDJC25900)
- DOI：10.1007/s11655-022-2879-2
  中图分类号：
- 纸质出版日期：2022-04，
  
  网络出版日期：2022-01-19，
  
  录用日期：2021-06-10
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Dan-chen SUN, Ran-ran WANG, Hao XU, 等. A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice[J]. Chinese Journal of Integrative Medicine, 2022,28(4):339-348.

Dan-chen SUN, Ran-ran WANG, Hao XU, et al. A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice[J]. Chinese Journal of Integrative Medicine, 2022,28(4):339-348.
Dan-chen SUN, Ran-ran WANG, Hao XU, 等. A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice[J]. Chinese Journal of Integrative Medicine, 2022,28(4):339-348. DOI： 10.1007/s11655-022-2879-2.

Dan-chen SUN, Ran-ran WANG, Hao XU, et al. A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice[J]. Chinese Journal of Integrative Medicine, 2022,28(4):339-348. DOI： 10.1007/s11655-022-2879-2.

摘要

目的:

基于网络药理学方法研究海蓬子(SE)的药效物质基础、作用机制及靶向性疾病

并通过药理学试验验证海蓬子提取物的抗抑郁作用.

方法:

利用中药(CM)、PubMed、PharmMapper、MAS 3.0、Cytoscape等检索工具

搜索海蓬子的成分

预测其靶点及相关治疗疾病

构建海蓬子治疗中枢神经系统疾病的 "成分-靶点-通路" 网络. 进一步地

通过分析蛋白-蛋白交互网络及抗抑郁靶点的KEGG和GO功能注释来预测海蓬子的抗抑郁作用机制. 采用慢性不可预知温和应激 (CUMS) 方法建立具有抑郁症状的小鼠模型. 动物被随机分为6组

包括对照组 (无应激刺激且给予蒸馏水) 、模型组 (给予CUMS模型小鼠蒸馏水) 、文拉法辛组 (给予CUMS模型小鼠9.38 mg/kg文拉法辛) 、海蓬子高

中

低剂量组 (分别给予CUMS模型小鼠1.8

1.35

0.9 g/kg海蓬子) . 通过强迫游泳实验 (FST) 、悬尾实验 (TST) 和旷场实验 (OFT) 对相关指标进行了实验验证. 采用酶联免疫吸附法 (ELISA) 和免疫印迹法 (WB) 分别检测海马、大脑皮层中多巴胺(DA)的浓度

血液中白细胞介素-2 (IL-2) 和皮质醇 (CORT) 的水平

以及小鼠的核因子E2相关因子2 (Nrf2)

甲藻样环氧氯丙烷相关蛋白1 (Keap1)

NAD(P)H脱氢酶[醌]1 (NQO1)和血红素加氧酶-1 (HO-1)水平

探索可能的作用机制.

结果:

网络药理学预测的 "靶点-疾病" 网络图显示海蓬子的潜在靶点涉及多种中枢神经系统 (CNS) 疾病

其中抑郁症为主要疾病. 实验结果显示

与模型组相比

给予海蓬子(1.8、1.35 g/kg) 3周后均显著缩短了FST和TST实验中小鼠的不动时间

而海蓬子对小鼠在OFT实验中的探索行为无显著影响. 与模型组相比

海蓬子低剂量(0.9 g/kg)组小鼠的海马和大脑皮层DA水平差异显著(

0.05). 此外

与模型组相比

海蓬子高剂量 (1.8 g/kg)可显著降低CORT活性(

0.05); 也可降低血清中IL-2水平

但无统计学差异. WB结果显示

与模型组相比

海篷子高剂量(1.8 g/kg)组小鼠的Nrf2、Keap1、NQO1和HO-1蛋白表达均显著上调(均

0.01).

结论:

海蓬子提取物可能通过调节Nrf2-ARE通路

提高海马和皮层DA和CORT水平发挥抗抑郁作用.

Abstract

Objective:

To investigate the pharmacodynamic material basis

mechanism of actions and targeted diseases of

Salicornia europaea

L. (SE) based on the network pharmacology method

and to verify the antidepressant-like effect of the SE extract by pharmacological experiments.

Methods:

Retrieval tools including Chinese medicine (CM)

PubMed

PharmMapper

MAS 3.0 and Cytoscape were used to search the components of SE

predict its targets and related therapeutic diseases

and construct the "Component-Target- Pathway" network of SE for central nervous system (CNS) diseases. Further

protein-protein interaction (PPI) network

Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) function annotation of depression-related targets were analyzed to predict the antidepressant mechanism of SE. Chronic unpredictable mild stress (CUMS) model was used to construct a mouse model with depression-like symptoms. And the animals were randomly divided into 6 groups (

=10) including the normal group (nonstressed mice administered with distilled water)

the CUMS group (CUMS mice administered with distilled water)

the venlafaxine group (CUMS mice administered with venlafaxine 9.38 mg/kg)

SE high-

medium-

and low-dose groups (CUMS mice administered with SE 1.8

1.35 and 0.9 g/kg

respectively). Then some relevant indicators were determined for experimental verification by the forced swim test (FST)

the tail suspension test (TST) and open-field test (OFT). Dopamine (DA) concentration in hippocampus and cerebral cortex

IL-2 and corticosterone (CORT) levels in blood

and nuclear factor E2 related factor 2 (Nrf2)

kelch-like epichlorohydrin related protein 1 (Keap1)

NAD(P) H dehydrogenase [quinone] 1 (NQO1) and heme oxygenase-1 (HO-1) levels in mice were measured by enzyme linked immunosorbent assay (ELISA) and Western blot respectively to explore the possible mechanisms.

Results:

The "target-disease" network diagram predicted by network pharmacology

showed that the potential target of SE involves a variety of CNS diseases

among which depression accounts for the majority. The experimental results showed that SE (1.8

1.35 g/kg) significantly decreased the immobility period

compared with the CUMS group in FST and TST in mice after 3-week treatment

while SE exhibited no significant effect on exploratory behavior in OFT in mice. Compared with CUMS group

the SE group (0.9 g/kg) showed significant differences (

0.05) in DA levels in the hippocampus and cerebral cortex. In addition

compared with CUMS control group

SE (1.8 g/kg) group showed a significant effect on decreasing the activities of CORT (

0.05)

and serum IL-2 level with no statistical significance. Finally

Western blot results showed that compared with the model group

Nrf2

Keap1

NQO1 and HO-1 protein expressions in SE group (1.8 g/kg) were up-regulated (all

0.01).

Conclusion:

The SE extract may have an antidepressant effect

which appeared to regulate Nrf2-ARE pathway and increased levels of DA and CORT in the hippocampus and cortex.

关键词

Keywords

Salicornia europaea L.network pharmacologytail suspension testforced swim testdepression

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A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice

A Network Pharmacology-Based Study on Antidepressant Effect of Salicornia europaea L. Extract with Experimental Support in Chronic Unpredictable Mild Stress Model Mice

DOI：10.1007/s11655-022-2879-2

摘要

Abstract

关键词

Keywords

references