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Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome

Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence in many countries. The purpose of this study is to explore the function of Schisandrin B and its underlying molecular mechanisms in colitis. In this study, mice with colitis were induced by giving 2.0%...

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Autores principales: Zhang, Weiwei, Wang, Wusan, Shen, Chaozhuang, Wang, Xiaohu, Pu, Zhichen, Yin, Qin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544312/
https://www.ncbi.nlm.nih.gov/pubmed/34628369
http://dx.doi.org/10.18632/aging.203611
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author Zhang, Weiwei
Wang, Wusan
Shen, Chaozhuang
Wang, Xiaohu
Pu, Zhichen
Yin, Qin
author_facet Zhang, Weiwei
Wang, Wusan
Shen, Chaozhuang
Wang, Xiaohu
Pu, Zhichen
Yin, Qin
author_sort Zhang, Weiwei
collection PubMed
description Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence in many countries. The purpose of this study is to explore the function of Schisandrin B and its underlying molecular mechanisms in colitis. In this study, mice with colitis were induced by giving 2.0% dextran sulfate sodium (DSS, MP) in the drinking water for seven days. Furthermore, TCMSP server and GEO DataSets were used to analyze the mechanism of Schisandrin B in colitis. It was found that Schisandrin B presented colitis in mice model. At the same time, Schisandrin B not only reduced inflammation in vivo and vitro model of colitis, but also suppressed the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome in vivo and vitro model of colitis. In addition, Schisandrin B induced AMP-activated protein kinase (AMPK) / Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in model of colitis, and regulated AMPK protein at 316 sites. The inhibition of AMPK reduced the anti-inflammation effects of Schisandrin B on NLRP3 inflammasome. Apart from that, Schisandrin B decreased reactive oxygen species (ROS)-induced mitochondrial damage and reduced epithelial cells damage of colitis through regulating pyroptosis. Collectively, our novel findings for first time showed that, Schisandrin B suppressed NLRP3 inflammasome activation-mediated interleukin-1beta (IL-1β) level and pyroptosis in intestinal epithelial cells of colitis model through the activation of AMPK/Nrf2 dependent signaling-ROS-induced mitochondrial damage, which may be a significant therapeutic approach in the treatment of acute colitis.
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spelling pubmed-85443122021-10-26 Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome Zhang, Weiwei Wang, Wusan Shen, Chaozhuang Wang, Xiaohu Pu, Zhichen Yin, Qin Aging (Albany NY) Research Paper Ulcerative colitis (UC) is a chronic inflammatory disease with increasing incidence and prevalence in many countries. The purpose of this study is to explore the function of Schisandrin B and its underlying molecular mechanisms in colitis. In this study, mice with colitis were induced by giving 2.0% dextran sulfate sodium (DSS, MP) in the drinking water for seven days. Furthermore, TCMSP server and GEO DataSets were used to analyze the mechanism of Schisandrin B in colitis. It was found that Schisandrin B presented colitis in mice model. At the same time, Schisandrin B not only reduced inflammation in vivo and vitro model of colitis, but also suppressed the nucleotide-binding oligomerization domain, leucine-rich repeat and pyrin domain-containing 3 (NLRP3) inflammasome in vivo and vitro model of colitis. In addition, Schisandrin B induced AMP-activated protein kinase (AMPK) / Nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in model of colitis, and regulated AMPK protein at 316 sites. The inhibition of AMPK reduced the anti-inflammation effects of Schisandrin B on NLRP3 inflammasome. Apart from that, Schisandrin B decreased reactive oxygen species (ROS)-induced mitochondrial damage and reduced epithelial cells damage of colitis through regulating pyroptosis. Collectively, our novel findings for first time showed that, Schisandrin B suppressed NLRP3 inflammasome activation-mediated interleukin-1beta (IL-1β) level and pyroptosis in intestinal epithelial cells of colitis model through the activation of AMPK/Nrf2 dependent signaling-ROS-induced mitochondrial damage, which may be a significant therapeutic approach in the treatment of acute colitis. Impact Journals 2021-10-09 /pmc/articles/PMC8544312/ /pubmed/34628369 http://dx.doi.org/10.18632/aging.203611 Text en Copyright: © 2021 Zhang et al. https://creativecommons.org/licenses/by/3.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/3.0/) (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhang, Weiwei
Wang, Wusan
Shen, Chaozhuang
Wang, Xiaohu
Pu, Zhichen
Yin, Qin
Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome
title Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome
title_full Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome
title_fullStr Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome
title_full_unstemmed Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome
title_short Network pharmacology for systematic understanding of Schisandrin B reduces the epithelial cells injury of colitis through regulating pyroptosis by AMPK/Nrf2/NLRP3 inflammasome
title_sort network pharmacology for systematic understanding of schisandrin b reduces the epithelial cells injury of colitis through regulating pyroptosis by ampk/nrf2/nlrp3 inflammasome
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8544312/
https://www.ncbi.nlm.nih.gov/pubmed/34628369
http://dx.doi.org/10.18632/aging.203611
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