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Network Pharmacology Study on the Mechanism of Gastrodin Reversing Depressive Symptoms in Traumatically Stressed Rats
BACKGROUND: Depression is a typical outcome of the repair of posttraumatic stress disorder (PTSD). Based on network pharmacology and neuropharmacology experiments, this study aimed to explore how gastrodin (GAS) reverses depressive symptoms in traumatically stressed rats. METHODS: GAS-related target...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bentham Science Publishers
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245802/ https://www.ncbi.nlm.nih.gov/pubmed/36173042 http://dx.doi.org/10.2174/1386207325666220928143206 |
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author | Zhao, Ruodan Li, Xie Zhang, Haizhu Chen, Xubing Wang, Ying |
author_facet | Zhao, Ruodan Li, Xie Zhang, Haizhu Chen, Xubing Wang, Ying |
author_sort | Zhao, Ruodan |
collection | PubMed |
description | BACKGROUND: Depression is a typical outcome of the repair of posttraumatic stress disorder (PTSD). Based on network pharmacology and neuropharmacology experiments, this study aimed to explore how gastrodin (GAS) reverses depressive symptoms in traumatically stressed rats. METHODS: GAS-related targets were predicted by SwissTargetPrediction; depression-related targets were collected from GeneCards and therapeutic target database (TTD); protein-protein interaction (PPI) network was constructed with its action mechanism being predicted by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. The animal model of PTSD was replicated by single prolonged stress (SPS). The antidepressant effect of GAS was investigated by the forced swim test (FST) and tail suspension test (TST). The levels of tyrosine hydroxylase (TH) and corticotropin-releasing factor type I receptor (CRF1) in locus ceruleus (LC) and the expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus (PVN) and central amygdala (CeA) were measured by immunofluorescence. RESULTS: GAS significantly shortened the tail suspension and swimming immobility in SPS rats in TST and FST experiments (p < 0.05 or p < 0.01). The network analysis showed that the critical antidepressant targets of GAS were 86 targets such as GAPDH, CASP3 MMP9, HRAS, DPP4, and TH, which were significantly enriched in the pathways such as pathways neuroactive ligand-receptor interaction. High doses of GAS could significantly reduce the level of TH and CRF in CEA in the brain of rats with depressive symptoms (p < 0.01) and, at the same time, lower the expression of CRF in PVN (p < 0.05). CONCLUSION: The effect of GAS on depressive symptoms in SPS rats may be closely related to its reduction of CRF expression in PVN and CeA and inhibition of neuron (NE) synthesis in LC. |
format | Online Article Text |
id | pubmed-10245802 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-102458022023-06-08 Network Pharmacology Study on the Mechanism of Gastrodin Reversing Depressive Symptoms in Traumatically Stressed Rats Zhao, Ruodan Li, Xie Zhang, Haizhu Chen, Xubing Wang, Ying Comb Chem High Throughput Screen Chemistry, Combinatorial Chemistry and High Throughput Screening, BIOCHEMICAL RESEARCH METHODS, Chemistry, APPLIED CHEMISTRY, Pharmacology BACKGROUND: Depression is a typical outcome of the repair of posttraumatic stress disorder (PTSD). Based on network pharmacology and neuropharmacology experiments, this study aimed to explore how gastrodin (GAS) reverses depressive symptoms in traumatically stressed rats. METHODS: GAS-related targets were predicted by SwissTargetPrediction; depression-related targets were collected from GeneCards and therapeutic target database (TTD); protein-protein interaction (PPI) network was constructed with its action mechanism being predicted by gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. The animal model of PTSD was replicated by single prolonged stress (SPS). The antidepressant effect of GAS was investigated by the forced swim test (FST) and tail suspension test (TST). The levels of tyrosine hydroxylase (TH) and corticotropin-releasing factor type I receptor (CRF1) in locus ceruleus (LC) and the expression of corticotropin-releasing factor (CRF) in the paraventricular nucleus of the hypothalamus (PVN) and central amygdala (CeA) were measured by immunofluorescence. RESULTS: GAS significantly shortened the tail suspension and swimming immobility in SPS rats in TST and FST experiments (p < 0.05 or p < 0.01). The network analysis showed that the critical antidepressant targets of GAS were 86 targets such as GAPDH, CASP3 MMP9, HRAS, DPP4, and TH, which were significantly enriched in the pathways such as pathways neuroactive ligand-receptor interaction. High doses of GAS could significantly reduce the level of TH and CRF in CEA in the brain of rats with depressive symptoms (p < 0.01) and, at the same time, lower the expression of CRF in PVN (p < 0.05). CONCLUSION: The effect of GAS on depressive symptoms in SPS rats may be closely related to its reduction of CRF expression in PVN and CeA and inhibition of neuron (NE) synthesis in LC. Bentham Science Publishers 2023-04-27 2023-04-27 /pmc/articles/PMC10245802/ /pubmed/36173042 http://dx.doi.org/10.2174/1386207325666220928143206 Text en © 2023 Bentham Science Publishers https://creativecommons.org/licenses/by/4.0/This is an Open Access article published under CC BY 4.0 https://creativecommons.org/licenses/by/4.0/legalcode |
spellingShingle | Chemistry, Combinatorial Chemistry and High Throughput Screening, BIOCHEMICAL RESEARCH METHODS, Chemistry, APPLIED CHEMISTRY, Pharmacology Zhao, Ruodan Li, Xie Zhang, Haizhu Chen, Xubing Wang, Ying Network Pharmacology Study on the Mechanism of Gastrodin Reversing Depressive Symptoms in Traumatically Stressed Rats |
title | Network Pharmacology Study on the Mechanism of Gastrodin Reversing Depressive Symptoms in Traumatically Stressed Rats |
title_full | Network Pharmacology Study on the Mechanism of Gastrodin Reversing Depressive Symptoms in Traumatically Stressed Rats |
title_fullStr | Network Pharmacology Study on the Mechanism of Gastrodin Reversing Depressive Symptoms in Traumatically Stressed Rats |
title_full_unstemmed | Network Pharmacology Study on the Mechanism of Gastrodin Reversing Depressive Symptoms in Traumatically Stressed Rats |
title_short | Network Pharmacology Study on the Mechanism of Gastrodin Reversing Depressive Symptoms in Traumatically Stressed Rats |
title_sort | network pharmacology study on the mechanism of gastrodin reversing depressive symptoms in traumatically stressed rats |
topic | Chemistry, Combinatorial Chemistry and High Throughput Screening, BIOCHEMICAL RESEARCH METHODS, Chemistry, APPLIED CHEMISTRY, Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10245802/ https://www.ncbi.nlm.nih.gov/pubmed/36173042 http://dx.doi.org/10.2174/1386207325666220928143206 |
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