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Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress

Background: Chaihu-Shugan-San is a classical prescription to treat depression. According to the traditional Chinese medicine (TCM) principle, the 2 decomposed recipes in Chaihu-Shugan-San exert synergistic effects, including Shu Gan (stagnated Gan-Qi dispersion) and Rou Gan (Gan nourishment to allev...

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Autores principales: Zhu, Xiaofei, Li, Teng, Hu, En, Duan, Lihua, Zhang, Chunhu, Wang, Yang, Tang, Tao, Yang, Zhaoyu, Fan, Rong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802092/
https://www.ncbi.nlm.nih.gov/pubmed/35111057
http://dx.doi.org/10.3389/fphar.2021.791097
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author Zhu, Xiaofei
Li, Teng
Hu, En
Duan, Lihua
Zhang, Chunhu
Wang, Yang
Tang, Tao
Yang, Zhaoyu
Fan, Rong
author_facet Zhu, Xiaofei
Li, Teng
Hu, En
Duan, Lihua
Zhang, Chunhu
Wang, Yang
Tang, Tao
Yang, Zhaoyu
Fan, Rong
author_sort Zhu, Xiaofei
collection PubMed
description Background: Chaihu-Shugan-San is a classical prescription to treat depression. According to the traditional Chinese medicine (TCM) principle, the 2 decomposed recipes in Chaihu-Shugan-San exert synergistic effects, including Shu Gan (stagnated Gan-Qi dispersion) and Rou Gan (Gan nourishment to alleviate pain). However, the specific mechanism of Chaihu-Shugan-San on depression and its compatibility rule remain to be explored. Objective: We aimed to explore the anti-depression mechanisms and analyze the advantage of TCM compatibility of Chaihu-Shugan-San. Methods: The chronic unpredictable mild stress (CUMS) rat model was established. Antidepressant effects were evaluated by sucrose preference test (SPT), and forced swimming test (FST). Tandem Mass Tag (TMT)-based quantitative proteomics of the hippocampus was used to obtain differentially expressed proteins (DEPs). Bioinformatics analysis including Gene Ontology (GO), pathway enrichment, and protein-protein interaction (PPI) networks was utilized to study the DEPs connections. At last, the achieved key targets were verified by western blotting. Results: Chaihu-Shugan-San increased weight gain and food intake, as well as exhibited better therapeutic effects including enhanced sucrose preference and extended immobility time when compared with its decomposed recipes. Proteomics showed Chaihu-Shugan-San, Shu Gan, and Rou Gan regulated 110, 12, and 407 DEPs, respectively. Compared with Shu Gan or Rou Gan alone, the expression of 22 proteins was additionally changed by Chaihu-Shugan-San treatment, whereas the expression of 323 proteins whose expression was changed by Shu Gan or Rou Gan alone were not changed by Chaihu-Shugan-San treatment. Bioinformatics analysis demonstrated that Chaihu-Shugan-San affected neurotransmitter’s release and transmission cycle (e.g., γ-aminobutyric acid (GABA), glutamate, serotonin, norepinephrine, dopamine, and acetylcholine). GABA release pathway is also targeted by the 22 DEPs. Unexpectedly, only 2 pathways were enriched by the 323 DEPs: Metabolism and Cellular responses to external stimuli. Lastly, the expression of Gad2, Vamp2, and Pde2a was verified by western blotting. Conclusions: Chaihu-Shugan-San treats depression via multiple targets and pathways, which may include regulations of 110 DEPs and some neurotransmitter’s transmission cycle. Compared with Shu Gan and Rou Gan, the 22 Chaihu-Shugan-San advanced proteins and the affected GABA pathway may be the advantages of Chaihu-Shugan-San compatibility. This research offers data and theory support for the clinical application of Chaihu-Shugan-San.
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spelling pubmed-88020922022-02-01 Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress Zhu, Xiaofei Li, Teng Hu, En Duan, Lihua Zhang, Chunhu Wang, Yang Tang, Tao Yang, Zhaoyu Fan, Rong Front Pharmacol Pharmacology Background: Chaihu-Shugan-San is a classical prescription to treat depression. According to the traditional Chinese medicine (TCM) principle, the 2 decomposed recipes in Chaihu-Shugan-San exert synergistic effects, including Shu Gan (stagnated Gan-Qi dispersion) and Rou Gan (Gan nourishment to alleviate pain). However, the specific mechanism of Chaihu-Shugan-San on depression and its compatibility rule remain to be explored. Objective: We aimed to explore the anti-depression mechanisms and analyze the advantage of TCM compatibility of Chaihu-Shugan-San. Methods: The chronic unpredictable mild stress (CUMS) rat model was established. Antidepressant effects were evaluated by sucrose preference test (SPT), and forced swimming test (FST). Tandem Mass Tag (TMT)-based quantitative proteomics of the hippocampus was used to obtain differentially expressed proteins (DEPs). Bioinformatics analysis including Gene Ontology (GO), pathway enrichment, and protein-protein interaction (PPI) networks was utilized to study the DEPs connections. At last, the achieved key targets were verified by western blotting. Results: Chaihu-Shugan-San increased weight gain and food intake, as well as exhibited better therapeutic effects including enhanced sucrose preference and extended immobility time when compared with its decomposed recipes. Proteomics showed Chaihu-Shugan-San, Shu Gan, and Rou Gan regulated 110, 12, and 407 DEPs, respectively. Compared with Shu Gan or Rou Gan alone, the expression of 22 proteins was additionally changed by Chaihu-Shugan-San treatment, whereas the expression of 323 proteins whose expression was changed by Shu Gan or Rou Gan alone were not changed by Chaihu-Shugan-San treatment. Bioinformatics analysis demonstrated that Chaihu-Shugan-San affected neurotransmitter’s release and transmission cycle (e.g., γ-aminobutyric acid (GABA), glutamate, serotonin, norepinephrine, dopamine, and acetylcholine). GABA release pathway is also targeted by the 22 DEPs. Unexpectedly, only 2 pathways were enriched by the 323 DEPs: Metabolism and Cellular responses to external stimuli. Lastly, the expression of Gad2, Vamp2, and Pde2a was verified by western blotting. Conclusions: Chaihu-Shugan-San treats depression via multiple targets and pathways, which may include regulations of 110 DEPs and some neurotransmitter’s transmission cycle. Compared with Shu Gan and Rou Gan, the 22 Chaihu-Shugan-San advanced proteins and the affected GABA pathway may be the advantages of Chaihu-Shugan-San compatibility. This research offers data and theory support for the clinical application of Chaihu-Shugan-San. Frontiers Media S.A. 2022-01-17 /pmc/articles/PMC8802092/ /pubmed/35111057 http://dx.doi.org/10.3389/fphar.2021.791097 Text en Copyright © 2022 Zhu, Li, Hu, Duan, Zhang, Wang, Tang, Yang and Fan. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Zhu, Xiaofei
Li, Teng
Hu, En
Duan, Lihua
Zhang, Chunhu
Wang, Yang
Tang, Tao
Yang, Zhaoyu
Fan, Rong
Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress
title Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress
title_full Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress
title_fullStr Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress
title_full_unstemmed Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress
title_short Proteomics Study Reveals the Anti-Depressive Mechanisms and the Compatibility Advantage of Chaihu-Shugan-San in a Rat Model of Chronic Unpredictable Mild Stress
title_sort proteomics study reveals the anti-depressive mechanisms and the compatibility advantage of chaihu-shugan-san in a rat model of chronic unpredictable mild stress
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8802092/
https://www.ncbi.nlm.nih.gov/pubmed/35111057
http://dx.doi.org/10.3389/fphar.2021.791097
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