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Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury
Recent evidence demonstrates that a double dose of Jasminoidin (2·JA) is more effective than Jasminoidin (JA) in cerebral ischemia therapy, but its dosage-effect mechanisms are unclear. In this study, the software GeneGo MetaCore was used to perform pathway analysis of the differentially expressed g...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976973/ https://www.ncbi.nlm.nih.gov/pubmed/29862259 http://dx.doi.org/10.1155/2018/2785636 |
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author | Li, Haixia Wang, Jingtao Wang, Pengqian Zhang, Yingying Liu, Jun Yu, Yanan Li, Bing Wang, Zhong |
author_facet | Li, Haixia Wang, Jingtao Wang, Pengqian Zhang, Yingying Liu, Jun Yu, Yanan Li, Bing Wang, Zhong |
author_sort | Li, Haixia |
collection | PubMed |
description | Recent evidence demonstrates that a double dose of Jasminoidin (2·JA) is more effective than Jasminoidin (JA) in cerebral ischemia therapy, but its dosage-effect mechanisms are unclear. In this study, the software GeneGo MetaCore was used to perform pathway analysis of the differentially expressed genes obtained in microarrays of mice belonging to four groups (Sham, Vehicle, JA, and 2·JA), aiming to elucidate differences in JA and 2·JA's dose-dependent pharmacological mechanism from a system's perspective. The top 10 enriched pathways in the 2·JA condition were mainly involved in neuroprotection (70% of the pathways), apoptosis and survival (40%), and anti-inflammation (20%), while JA induced pathways were mainly involved in apoptosis and survival (60%), anti-inflammation (20%), and lipid metabolism (20%). Regarding shared pathways and processes, 3, 1, and 3 pathways overlapped between the Vehicle and JA, Vehicle and 2·JA, and JA and 2·JA conditions, respectively; for the top ten overlapped processes these numbers were 3, 0, and 4, respectively. The common pathways and processes in the 2·JA condition included differentially expressed genes significantly different from those in JA. Seven representative pathways were only activated by 2·JA, such as Gamma-Secretase regulation of neuronal cell development. Process network comparison indicated that significant nodes, such as alpha-MSH, ACTH, PKR1, and WNT, were involved in the pharmacological mechanism of 2·JA. Function distribution was different between JA and 2·JA groups, indicating a dosage additive mechanism in cerebral ischemia treatment. Such systemic approach based on whole-genome multiple pathways and networks may provide an effective and alternative approach to identify alterations underlining dosage-dependent therapeutic benefits of pharmacological compounds on complex disease processes. |
format | Online Article Text |
id | pubmed-5976973 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-59769732018-06-03 Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury Li, Haixia Wang, Jingtao Wang, Pengqian Zhang, Yingying Liu, Jun Yu, Yanan Li, Bing Wang, Zhong Biomed Res Int Research Article Recent evidence demonstrates that a double dose of Jasminoidin (2·JA) is more effective than Jasminoidin (JA) in cerebral ischemia therapy, but its dosage-effect mechanisms are unclear. In this study, the software GeneGo MetaCore was used to perform pathway analysis of the differentially expressed genes obtained in microarrays of mice belonging to four groups (Sham, Vehicle, JA, and 2·JA), aiming to elucidate differences in JA and 2·JA's dose-dependent pharmacological mechanism from a system's perspective. The top 10 enriched pathways in the 2·JA condition were mainly involved in neuroprotection (70% of the pathways), apoptosis and survival (40%), and anti-inflammation (20%), while JA induced pathways were mainly involved in apoptosis and survival (60%), anti-inflammation (20%), and lipid metabolism (20%). Regarding shared pathways and processes, 3, 1, and 3 pathways overlapped between the Vehicle and JA, Vehicle and 2·JA, and JA and 2·JA conditions, respectively; for the top ten overlapped processes these numbers were 3, 0, and 4, respectively. The common pathways and processes in the 2·JA condition included differentially expressed genes significantly different from those in JA. Seven representative pathways were only activated by 2·JA, such as Gamma-Secretase regulation of neuronal cell development. Process network comparison indicated that significant nodes, such as alpha-MSH, ACTH, PKR1, and WNT, were involved in the pharmacological mechanism of 2·JA. Function distribution was different between JA and 2·JA groups, indicating a dosage additive mechanism in cerebral ischemia treatment. Such systemic approach based on whole-genome multiple pathways and networks may provide an effective and alternative approach to identify alterations underlining dosage-dependent therapeutic benefits of pharmacological compounds on complex disease processes. Hindawi 2018-05-16 /pmc/articles/PMC5976973/ /pubmed/29862259 http://dx.doi.org/10.1155/2018/2785636 Text en Copyright © 2018 Haixia Li et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article Li, Haixia Wang, Jingtao Wang, Pengqian Zhang, Yingying Liu, Jun Yu, Yanan Li, Bing Wang, Zhong Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury |
title | Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury |
title_full | Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury |
title_fullStr | Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury |
title_full_unstemmed | Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury |
title_short | Gene Expression Profiling Confirms the Dosage-Dependent Additive Neuroprotective Effects of Jasminoidin in a Mouse Model of Ischemia-Reperfusion Injury |
title_sort | gene expression profiling confirms the dosage-dependent additive neuroprotective effects of jasminoidin in a mouse model of ischemia-reperfusion injury |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5976973/ https://www.ncbi.nlm.nih.gov/pubmed/29862259 http://dx.doi.org/10.1155/2018/2785636 |
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