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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Main Authors: Yan Xu, Ru Yao, Wenxue Zhao, Jianguo Zhu, Jingchun Yao, Guimin Zhang, Dongguang Liu
Format: Article
Language:English
Published: Elsevier 2023-06-01
Series:Heliyon
Subjects:
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.
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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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