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Ellagic Acid Activated PPAR Signaling Pathway to Protect Ileums Against Castor Oil-Induced Diarrhea in Mice: Application of Transcriptome Analysis in Drug Screening
BACKGROUND: Acute diarrhea is still a common and serious disease. The causes of acute diarrhea are very complicated. Therefore, we need to find a medicine to control diarrhea symptoms, save time for diagnosis of pathogens, and prevent drug abuse. Ellagic acid (EA), a natural polyphenol drug, has ant...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2020
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005255/ https://www.ncbi.nlm.nih.gov/pubmed/32082169 http://dx.doi.org/10.3389/fphar.2019.01681 |
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author | Chen, Jianqing Yang, Hongliang Sheng, Zunlai |
author_facet | Chen, Jianqing Yang, Hongliang Sheng, Zunlai |
author_sort | Chen, Jianqing |
collection | PubMed |
description | BACKGROUND: Acute diarrhea is still a common and serious disease. The causes of acute diarrhea are very complicated. Therefore, we need to find a medicine to control diarrhea symptoms, save time for diagnosis of pathogens, and prevent drug abuse. Ellagic acid (EA), a natural polyphenol drug, has anti-diarrhea effects. However, the action mechanisms of EA for non-specific diarrhea have not been characterized. MATERIALS AND METHODS: To study the mechanisms of EA, mice were divided into four groups. Group C were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml physiological saline, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group D were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group E were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml EA (10 mg/ml). Group V were intraperitoneally injected with 0.1ml GW9662 (1m g/ml) and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml EA (10 mg/ml). Transcriptome were performed on ileum tissues of mice in group D and E. Histological examination and qRT-PCR were performed on ileum tissues of mice in group C, D, E, and V. RESULTS: We found that a total of 273 differentially expressed genes (DEGs) were obtained, including 160 up-regulated DEGs and 113 down-regulated DEGs. The DEGs were enriched in 458 Gene Ontology (GO) terms and 15 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. The peroxisome proliferator activated receptor (PPAR) signaling pathway was the most significantly enriched in KEGG pathways. We used the PPAR-specific antagonist GW9662 to validate the anti-diarrhea and anti-inflammatory effect of EA in group V compared with group E. Conclusively, EA protected ileums against castor oil-induced inflammation and diarrhea by activating the PPAR signaling pathway and a method was used to study the mechanism of EA. |
format | Online Article Text |
id | pubmed-7005255 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-70052552020-02-20 Ellagic Acid Activated PPAR Signaling Pathway to Protect Ileums Against Castor Oil-Induced Diarrhea in Mice: Application of Transcriptome Analysis in Drug Screening Chen, Jianqing Yang, Hongliang Sheng, Zunlai Front Pharmacol Pharmacology BACKGROUND: Acute diarrhea is still a common and serious disease. The causes of acute diarrhea are very complicated. Therefore, we need to find a medicine to control diarrhea symptoms, save time for diagnosis of pathogens, and prevent drug abuse. Ellagic acid (EA), a natural polyphenol drug, has anti-diarrhea effects. However, the action mechanisms of EA for non-specific diarrhea have not been characterized. MATERIALS AND METHODS: To study the mechanisms of EA, mice were divided into four groups. Group C were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml physiological saline, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group D were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml physiological saline. Group E were intraperitoneally injected with 0.1 ml physiological saline and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml EA (10 mg/ml). Group V were intraperitoneally injected with 0.1ml GW9662 (1m g/ml) and orally given 0.2 ml castor oil, and then after experiment began 0.5 h, orally administered 0.3 ml EA (10 mg/ml). Transcriptome were performed on ileum tissues of mice in group D and E. Histological examination and qRT-PCR were performed on ileum tissues of mice in group C, D, E, and V. RESULTS: We found that a total of 273 differentially expressed genes (DEGs) were obtained, including 160 up-regulated DEGs and 113 down-regulated DEGs. The DEGs were enriched in 458 Gene Ontology (GO) terms and 15 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways, respectively. The peroxisome proliferator activated receptor (PPAR) signaling pathway was the most significantly enriched in KEGG pathways. We used the PPAR-specific antagonist GW9662 to validate the anti-diarrhea and anti-inflammatory effect of EA in group V compared with group E. Conclusively, EA protected ileums against castor oil-induced inflammation and diarrhea by activating the PPAR signaling pathway and a method was used to study the mechanism of EA. Frontiers Media S.A. 2020-01-31 /pmc/articles/PMC7005255/ /pubmed/32082169 http://dx.doi.org/10.3389/fphar.2019.01681 Text en Copyright © 2020 Chen, Yang and Sheng http://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 Chen, Jianqing Yang, Hongliang Sheng, Zunlai Ellagic Acid Activated PPAR Signaling Pathway to Protect Ileums Against Castor Oil-Induced Diarrhea in Mice: Application of Transcriptome Analysis in Drug Screening |
title | Ellagic Acid Activated PPAR Signaling Pathway to Protect Ileums Against Castor Oil-Induced Diarrhea in Mice: Application of Transcriptome Analysis in Drug Screening |
title_full | Ellagic Acid Activated PPAR Signaling Pathway to Protect Ileums Against Castor Oil-Induced Diarrhea in Mice: Application of Transcriptome Analysis in Drug Screening |
title_fullStr | Ellagic Acid Activated PPAR Signaling Pathway to Protect Ileums Against Castor Oil-Induced Diarrhea in Mice: Application of Transcriptome Analysis in Drug Screening |
title_full_unstemmed | Ellagic Acid Activated PPAR Signaling Pathway to Protect Ileums Against Castor Oil-Induced Diarrhea in Mice: Application of Transcriptome Analysis in Drug Screening |
title_short | Ellagic Acid Activated PPAR Signaling Pathway to Protect Ileums Against Castor Oil-Induced Diarrhea in Mice: Application of Transcriptome Analysis in Drug Screening |
title_sort | ellagic acid activated ppar signaling pathway to protect ileums against castor oil-induced diarrhea in mice: application of transcriptome analysis in drug screening |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7005255/ https://www.ncbi.nlm.nih.gov/pubmed/32082169 http://dx.doi.org/10.3389/fphar.2019.01681 |
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