Cargando…
Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments
Naringin has been shown to exert protective effects in an animal model of ulcerative colitis, but detailed mechanisms remain unclear. This study aimed to investigate function and signaling mechanisms underlying naringin-induced therapeutic effects on colitis. Two mouse models were established to mim...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421552/ https://www.ncbi.nlm.nih.gov/pubmed/34504431 http://dx.doi.org/10.3389/fphar.2021.729414 |
_version_ | 1783749105527291904 |
---|---|
author | Dong, Jianyi Chen, Yuanyuan Yang, Fang Zhang, Weidong Wei, Kun Xiong, Yongjian Wang, Liang Zhou, Zijuan Li, Changyi Wang, Jingyu Chen, Dapeng |
author_facet | Dong, Jianyi Chen, Yuanyuan Yang, Fang Zhang, Weidong Wei, Kun Xiong, Yongjian Wang, Liang Zhou, Zijuan Li, Changyi Wang, Jingyu Chen, Dapeng |
author_sort | Dong, Jianyi |
collection | PubMed |
description | Naringin has been shown to exert protective effects in an animal model of ulcerative colitis, but detailed mechanisms remain unclear. This study aimed to investigate function and signaling mechanisms underlying naringin-induced therapeutic effects on colitis. Two mouse models were established to mimic human Inflammatory bowel disease (IBD) by treating drinking water with dextran sodium sulphate or intra-colonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Transcriptomics combined with functional experiments were used to investigate underlying mechanisms. Colitis symptoms, including weight loss and high disease activity index were significantly reversed by naringin. The inflammatory response, oxidative reactions, and epithelial cell apoptosis that occur with colitis were also alleviated by naringin. After naringin treatment, transcriptomics results identified 753 differentially expressed mRNAs that were enriched in signaling pathways, including the neuroactive ligand-receptor interaction, calcium signaling, and peroxisome proliferator-activated receptor (PPAR) signaling. The naringin-induced alleviation of colitis was significantly inhibited by the PPAR-γ inhibitor BADGE. In IEC-6 and RAW264.7 cells incubated with lipopolysaccharide (LPS), NF-κB-p65, a downstream protein of PPAR-γ, was significantly increased. Naringin suppressed LPS-induced high expression of NF-κB-p65, which was inhibited by small interfering RNA targeting PPAR-γ. Our study clarifies detailed mechanisms underlying naringin-induced therapeutic effects on mice colitis, and PPAR-γ was found to be the main target of naringin by functional experiments both in vivo and in vitro. Our study supplies new scientific information for the use of naringin in colitis treatment. |
format | Online Article Text |
id | pubmed-8421552 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-84215522021-09-08 Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments Dong, Jianyi Chen, Yuanyuan Yang, Fang Zhang, Weidong Wei, Kun Xiong, Yongjian Wang, Liang Zhou, Zijuan Li, Changyi Wang, Jingyu Chen, Dapeng Front Pharmacol Pharmacology Naringin has been shown to exert protective effects in an animal model of ulcerative colitis, but detailed mechanisms remain unclear. This study aimed to investigate function and signaling mechanisms underlying naringin-induced therapeutic effects on colitis. Two mouse models were established to mimic human Inflammatory bowel disease (IBD) by treating drinking water with dextran sodium sulphate or intra-colonic administration of 2, 4, 6-trinitrobenzene sulfonic acid. Transcriptomics combined with functional experiments were used to investigate underlying mechanisms. Colitis symptoms, including weight loss and high disease activity index were significantly reversed by naringin. The inflammatory response, oxidative reactions, and epithelial cell apoptosis that occur with colitis were also alleviated by naringin. After naringin treatment, transcriptomics results identified 753 differentially expressed mRNAs that were enriched in signaling pathways, including the neuroactive ligand-receptor interaction, calcium signaling, and peroxisome proliferator-activated receptor (PPAR) signaling. The naringin-induced alleviation of colitis was significantly inhibited by the PPAR-γ inhibitor BADGE. In IEC-6 and RAW264.7 cells incubated with lipopolysaccharide (LPS), NF-κB-p65, a downstream protein of PPAR-γ, was significantly increased. Naringin suppressed LPS-induced high expression of NF-κB-p65, which was inhibited by small interfering RNA targeting PPAR-γ. Our study clarifies detailed mechanisms underlying naringin-induced therapeutic effects on mice colitis, and PPAR-γ was found to be the main target of naringin by functional experiments both in vivo and in vitro. Our study supplies new scientific information for the use of naringin in colitis treatment. Frontiers Media S.A. 2021-08-24 /pmc/articles/PMC8421552/ /pubmed/34504431 http://dx.doi.org/10.3389/fphar.2021.729414 Text en Copyright © 2021 Dong, Chen, Yang, Zhang, Wei, Xiong, Wang, Zhou, Li, Wang and Chen. 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 Dong, Jianyi Chen, Yuanyuan Yang, Fang Zhang, Weidong Wei, Kun Xiong, Yongjian Wang, Liang Zhou, Zijuan Li, Changyi Wang, Jingyu Chen, Dapeng Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments |
title | Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments |
title_full | Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments |
title_fullStr | Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments |
title_full_unstemmed | Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments |
title_short | Naringin Exerts Therapeutic Effects on Mice Colitis: A Study Based on Transcriptomics Combined With Functional Experiments |
title_sort | naringin exerts therapeutic effects on mice colitis: a study based on transcriptomics combined with functional experiments |
topic | Pharmacology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8421552/ https://www.ncbi.nlm.nih.gov/pubmed/34504431 http://dx.doi.org/10.3389/fphar.2021.729414 |
work_keys_str_mv | AT dongjianyi naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments AT chenyuanyuan naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments AT yangfang naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments AT zhangweidong naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments AT weikun naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments AT xiongyongjian naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments AT wangliang naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments AT zhouzijuan naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments AT lichangyi naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments AT wangjingyu naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments AT chendapeng naringinexertstherapeuticeffectsonmicecolitisastudybasedontranscriptomicscombinedwithfunctionalexperiments |