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Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway
Ulcerative colitis (UC) is one of the most refractory digestive diseases in the world. Kui jie tong (KJT) is an effective traditional Chinese medicine used clinically to treat UC. This study observed the regulatory effects of KJT on NIMA-related kinase 7- (NEK7-) activated nod-like receptor protein-...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Hindawi
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273439/ https://www.ncbi.nlm.nih.gov/pubmed/35832643 http://dx.doi.org/10.1155/2022/2782112 |
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author | Xue, Shigui Xue, Yan Dou, Danbo Wu, Huan Zhang, Ping Gao, Yang Tang, Yini Xia, Zehua Yang, Sen Gu, Sizhen |
author_facet | Xue, Shigui Xue, Yan Dou, Danbo Wu, Huan Zhang, Ping Gao, Yang Tang, Yini Xia, Zehua Yang, Sen Gu, Sizhen |
author_sort | Xue, Shigui |
collection | PubMed |
description | Ulcerative colitis (UC) is one of the most refractory digestive diseases in the world. Kui jie tong (KJT) is an effective traditional Chinese medicine used clinically to treat UC. This study observed the regulatory effects of KJT on NIMA-related kinase 7- (NEK7-) activated nod-like receptor protein-3 (NLRP3)/caspase-1 classical pyroptosis pathway and intestinal flora in UC model rats. KJT components were analyzed using an ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). A UC Sprague Dawley (SD) rat model was established using sodium dextran sulfate (DSS). Rats were randomly divided into four groups: control group (CG), UC model group (UG), KJT group (KG), and sulfasalazine (SASP) group (SG). After seven days of intervention, each group's body weight, disease activity index (DAI) scores, and colon length were recorded. Intestinal mucosal injury to each group was observed using hematoxylin-eosin staining. Additionally, we investigated the expression levels of NEK7, NLRP3, ASC, caspase-1, and GSDMD in intestinal mucosa, as well as serum interleukin- (IL-) 1β, IL-18, and IL-33 proinflammatory factors. Intestinal microflora was analyzed using 16s rRNA sequencing. KJT controlled weight loss; decreased DAI scores; restored colon length; improved pathological injury in the colon; inhibited NEK7, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, and GSDMD-N expression; and decreased IL-1β, IL-18, and IL-33 contents in UG rats' serum and colon tissue (P <0.001 or P <0.05). KJT also increased Ruminococcaceae, unclassified_f_Ruminococcaceae, and unclassified_g_Ruminococcus_1 levels and decreased Erysipelotrichia, Erysipelotrichales, Erysipelotrichaceae, Turicibacter, and uncultured_bacterium_g_Turicibacter levels. KJT alleviated UC immune-inflammatory responses to NLRP3/caspase-1 by inhibiting the NEK-7-activated classic pyroptosis pathway and improving intestinal microflora. |
format | Online Article Text |
id | pubmed-9273439 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Hindawi |
record_format | MEDLINE/PubMed |
spelling | pubmed-92734392022-07-12 Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway Xue, Shigui Xue, Yan Dou, Danbo Wu, Huan Zhang, Ping Gao, Yang Tang, Yini Xia, Zehua Yang, Sen Gu, Sizhen Dis Markers Research Article Ulcerative colitis (UC) is one of the most refractory digestive diseases in the world. Kui jie tong (KJT) is an effective traditional Chinese medicine used clinically to treat UC. This study observed the regulatory effects of KJT on NIMA-related kinase 7- (NEK7-) activated nod-like receptor protein-3 (NLRP3)/caspase-1 classical pyroptosis pathway and intestinal flora in UC model rats. KJT components were analyzed using an ultraperformance liquid chromatography-tandem mass spectrometer (UPLC-MS/MS). A UC Sprague Dawley (SD) rat model was established using sodium dextran sulfate (DSS). Rats were randomly divided into four groups: control group (CG), UC model group (UG), KJT group (KG), and sulfasalazine (SASP) group (SG). After seven days of intervention, each group's body weight, disease activity index (DAI) scores, and colon length were recorded. Intestinal mucosal injury to each group was observed using hematoxylin-eosin staining. Additionally, we investigated the expression levels of NEK7, NLRP3, ASC, caspase-1, and GSDMD in intestinal mucosa, as well as serum interleukin- (IL-) 1β, IL-18, and IL-33 proinflammatory factors. Intestinal microflora was analyzed using 16s rRNA sequencing. KJT controlled weight loss; decreased DAI scores; restored colon length; improved pathological injury in the colon; inhibited NEK7, NLRP3, ASC, caspase-1, cleaved-caspase-1, GSDMD, and GSDMD-N expression; and decreased IL-1β, IL-18, and IL-33 contents in UG rats' serum and colon tissue (P <0.001 or P <0.05). KJT also increased Ruminococcaceae, unclassified_f_Ruminococcaceae, and unclassified_g_Ruminococcus_1 levels and decreased Erysipelotrichia, Erysipelotrichales, Erysipelotrichaceae, Turicibacter, and uncultured_bacterium_g_Turicibacter levels. KJT alleviated UC immune-inflammatory responses to NLRP3/caspase-1 by inhibiting the NEK-7-activated classic pyroptosis pathway and improving intestinal microflora. Hindawi 2022-07-04 /pmc/articles/PMC9273439/ /pubmed/35832643 http://dx.doi.org/10.1155/2022/2782112 Text en Copyright © 2022 Shigui Xue 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 Xue, Shigui Xue, Yan Dou, Danbo Wu, Huan Zhang, Ping Gao, Yang Tang, Yini Xia, Zehua Yang, Sen Gu, Sizhen Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway |
title | Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway |
title_full | Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway |
title_fullStr | Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway |
title_full_unstemmed | Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway |
title_short | Kui Jie Tong Ameliorates Ulcerative Colitis by Regulating Gut Microbiota and NLRP3/Caspase-1 Classical Pyroptosis Signaling Pathway |
title_sort | kui jie tong ameliorates ulcerative colitis by regulating gut microbiota and nlrp3/caspase-1 classical pyroptosis signaling pathway |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9273439/ https://www.ncbi.nlm.nih.gov/pubmed/35832643 http://dx.doi.org/10.1155/2022/2782112 |
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