Spirocyclopiperazinium salt compound DXL-A-24 improves visceral sensation and gut microbiota in a rat model of irritable bowel syndrome
Irritable bowel syndrome (IBS) is characterized by visceral pain, impaired intestinal barrier and a disorder of the microbiota. DXL-A-24 has analgesic and anti-inflammatory effects by inhibiting neuropeptides and inflammatory factors. In this study, we used chronic unpredictable mild stress (CUMS) i...
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Elsevier
2023-06-01
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Online Access: | http://www.sciencedirect.com/science/article/pii/S2405844023037519 |
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author | Yan Xu Ru Yao Wenxue Zhao Jianguo Zhu Jingchun Yao Guimin Zhang Dongguang Liu |
author_facet | Yan Xu Ru Yao Wenxue Zhao Jianguo Zhu Jingchun Yao Guimin Zhang Dongguang Liu |
author_sort | Yan Xu |
collection | DOAJ |
description | Irritable bowel syndrome (IBS) is characterized by visceral pain, impaired intestinal barrier and a disorder of the microbiota. DXL-A-24 has analgesic and anti-inflammatory effects by inhibiting neuropeptides and inflammatory factors. In this study, we used chronic unpredictable mild stress (CUMS) induced IBS model, to assess the action of DXL-A-24 on visceral hypersensitivity, barrier function and microbiota. Visceral sensation was assessed by colorectal distension in a model of IBS. The expressions of substance P (SP) and calcitonin gene-related peptide (CGRP) were detected by immunohistochemistry and western blot, the contents of diamine oxidase (DAO) and D-lactic acid were detected by ELISA, and 16S rRNA to detect the diversity of gut microbiota. CUMS reduced visceral pain threshold and increased colonic permeability of rats. DXL-A-24 for 28 days inhibited these changes. DXL-A-24 also decreased the expression of SP, CGRP in colon and D-LA, DAO in serum. Besides, DXL-A-24 increased the richness and diversity of intestinal microbiota. In conclusions, DXL-A-24 reduced visceral sensitivity, improved intestinal barrier and regulated gut microbiota in rats with IBS. |
first_indexed | 2024-03-13T07:43:16Z |
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issn | 2405-8440 |
language | English |
last_indexed | 2024-03-13T07:43:16Z |
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publisher | Elsevier |
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spelling | doaj.art-e1a24f016e07445ebd6a3e8e75b83b432023-06-03T04:22:22ZengElsevierHeliyon2405-84402023-06-0196e16544Spirocyclopiperazinium salt compound DXL-A-24 improves visceral sensation and gut microbiota in a rat model of irritable bowel syndromeYan Xu0Ru Yao1Wenxue Zhao2Jianguo Zhu3Jingchun Yao4Guimin Zhang5Dongguang Liu6From the Center for New Drug Pharmacology, Lunan Pharmaceutical Group Corporation, Linyi, ChinaFrom the Center for New Drug Pharmacology, Lunan Pharmaceutical Group Corporation, Linyi, ChinaFrom the Center for New Drug Pharmacology, Lunan Pharmaceutical Group Corporation, Linyi, ChinaFrom the Center for New Drug Pharmacology, Lunan Pharmaceutical Group Corporation, Linyi, ChinaFrom the Center for New Drug Pharmacology, Lunan Pharmaceutical Group Corporation, Linyi, ChinaFrom the Center for New Drug Pharmacology, Lunan Pharmaceutical Group Corporation, Linyi, ChinaCorresponding author. Lunan Pharmaceutical Group Corporation, Linyi, 276000, Shandong, China.; From the Center for New Drug Pharmacology, Lunan Pharmaceutical Group Corporation, Linyi, ChinaIrritable bowel syndrome (IBS) is characterized by visceral pain, impaired intestinal barrier and a disorder of the microbiota. DXL-A-24 has analgesic and anti-inflammatory effects by inhibiting neuropeptides and inflammatory factors. In this study, we used chronic unpredictable mild stress (CUMS) induced IBS model, to assess the action of DXL-A-24 on visceral hypersensitivity, barrier function and microbiota. Visceral sensation was assessed by colorectal distension in a model of IBS. The expressions of substance P (SP) and calcitonin gene-related peptide (CGRP) were detected by immunohistochemistry and western blot, the contents of diamine oxidase (DAO) and D-lactic acid were detected by ELISA, and 16S rRNA to detect the diversity of gut microbiota. CUMS reduced visceral pain threshold and increased colonic permeability of rats. DXL-A-24 for 28 days inhibited these changes. DXL-A-24 also decreased the expression of SP, CGRP in colon and D-LA, DAO in serum. Besides, DXL-A-24 increased the richness and diversity of intestinal microbiota. In conclusions, DXL-A-24 reduced visceral sensitivity, improved intestinal barrier and regulated gut microbiota in rats with IBS.http://www.sciencedirect.com/science/article/pii/S2405844023037519Irritable bowel syndromeMicrobiotaVisceral hypersensitivityGut barrier |
spellingShingle | Yan Xu Ru Yao Wenxue Zhao Jianguo Zhu Jingchun Yao Guimin Zhang Dongguang Liu Spirocyclopiperazinium salt compound DXL-A-24 improves visceral sensation and gut microbiota in a rat model of irritable bowel syndrome Heliyon Irritable bowel syndrome Microbiota Visceral hypersensitivity Gut barrier |
title | Spirocyclopiperazinium salt compound DXL-A-24 improves visceral sensation and gut microbiota in a rat model of irritable bowel syndrome |
title_full | Spirocyclopiperazinium salt compound DXL-A-24 improves visceral sensation and gut microbiota in a rat model of irritable bowel syndrome |
title_fullStr | Spirocyclopiperazinium salt compound DXL-A-24 improves visceral sensation and gut microbiota in a rat model of irritable bowel syndrome |
title_full_unstemmed | Spirocyclopiperazinium salt compound DXL-A-24 improves visceral sensation and gut microbiota in a rat model of irritable bowel syndrome |
title_short | Spirocyclopiperazinium salt compound DXL-A-24 improves visceral sensation and gut microbiota in a rat model of irritable bowel syndrome |
title_sort | spirocyclopiperazinium salt compound dxl a 24 improves visceral sensation and gut microbiota in a rat model of irritable bowel syndrome |
topic | Irritable bowel syndrome Microbiota Visceral hypersensitivity Gut barrier |
url | http://www.sciencedirect.com/science/article/pii/S2405844023037519 |
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