trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis

Background: Irritable bowel syndrome (IBS) is a functional disorder characterized by abdominal pain and abnormalities in defecation associated with psychiatric disorders such as depression and anxiety due to the dysfunction of brain-gut axis. This study aims to determine whether trans-Resveratrol af...

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Main Authors: Ying Xu, Su-Ying Cui, Quan Ma, Jing Shi, Ying Yu, Jian-Xin Li, Liang Zheng, Yi Zhang, Jian-Min Si, Ying-Cong Yu
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-06-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphar.2018.00631/full
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author Ying Xu
Ying Xu
Su-Ying Cui
Su-Ying Cui
Quan Ma
Jing Shi
Ying Yu
Jian-Xin Li
Liang Zheng
Yi Zhang
Jian-Min Si
Ying-Cong Yu
Ying-Cong Yu
author_facet Ying Xu
Ying Xu
Su-Ying Cui
Su-Ying Cui
Quan Ma
Jing Shi
Ying Yu
Jian-Xin Li
Liang Zheng
Yi Zhang
Jian-Min Si
Ying-Cong Yu
Ying-Cong Yu
author_sort Ying Xu
collection DOAJ
description Background: Irritable bowel syndrome (IBS) is a functional disorder characterized by abdominal pain and abnormalities in defecation associated with psychiatric disorders such as depression and anxiety due to the dysfunction of brain-gut axis. This study aims to determine whether trans-Resveratrol affects chronic-acute combined stress (CACS)-induced IBS-like symptoms including depression, anxiety and intestinal dysfunction.Methods: ICR male mice were exposed to the CACS for 3 weeks. trans-Resveratrol were administrated daily (2.5, 5, and 10 mg/kg, i.g.) 30 min before CACS. Behavioral tests were performed to evaluate the treatment effects of trans-Resveratrol on IBS. Hippocampus tissues were collected and processed Golgi staining and immuno-blot analysis. Ileum and colon tissues were collected and processed Hematoxylin and Eosin staining and immuno-blot analysis.Results: Administration with trans-Resveratrol before CACS for 3 weeks significantly reversed CACS-induced depression- and anxiety-like behaviors and intestinal dysfunction in mice, which implied a crucial role of trans-Resveratrol in treatment of IBS-like disorder. Furthermore, trans-Resveratrol improved hippocampal neuronal remodeling, protected ileal and colonic epithelial barrier structure against CACS insults. The further study suggested that trans-Resveratrol normalized phosphodiesterases 4A (PDE4A) expression and CREB-BDNF signaling that were disturbed by CACS. The increased pCREB and BDNF expression in the hippocampus were found, while decreased pCREB and BDNF levels were observed after treatment with trans-Resveratrol.Conclusions: The dual effects of trans-Resveratrol on stress-induced psychiatric and intestinal dysfunction may be related to normalization of PDE4A expression and subsequent pCREB-BDNF signaling in the hippocampus, ileum and colon.
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spelling doaj.art-1e182345249743a0acdba59434e7db322022-12-22T03:50:11ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122018-06-01910.3389/fphar.2018.00631387278trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut AxisYing Xu0Ying Xu1Su-Ying Cui2Su-Ying Cui3Quan Ma4Jing Shi5Ying Yu6Jian-Xin Li7Liang Zheng8Yi Zhang9Jian-Min Si10Ying-Cong Yu11Ying-Cong Yu12Department of Gastroenterology, Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, ChinaDepartments of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, United StatesDepartments of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, United StatesDepartment of Pharmacology, Peking University, School of Basic Medical Science, Beijing, ChinaDepartments of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, United StatesSchool of Pharmacy, Hangzhou Medical College, Hangzhou, ChinaDepartment of Gastroenterology, Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, ChinaDepartment of Gastroenterology, Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, ChinaDepartment of Gastroenterology, Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, ChinaDepartments of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, State University of New York at Buffalo, Buffalo, NY, United StatesInstitute of Gastroenterology, Zhejiang University, Hangzhou, ChinaDepartment of Gastroenterology, Wenzhou No. 3 Clinical Institute Affiliated to Wenzhou Medical University, Wenzhou People's Hospital, Wenzhou, ChinaInstitute of Gastroenterology, Zhejiang University, Hangzhou, ChinaBackground: Irritable bowel syndrome (IBS) is a functional disorder characterized by abdominal pain and abnormalities in defecation associated with psychiatric disorders such as depression and anxiety due to the dysfunction of brain-gut axis. This study aims to determine whether trans-Resveratrol affects chronic-acute combined stress (CACS)-induced IBS-like symptoms including depression, anxiety and intestinal dysfunction.Methods: ICR male mice were exposed to the CACS for 3 weeks. trans-Resveratrol were administrated daily (2.5, 5, and 10 mg/kg, i.g.) 30 min before CACS. Behavioral tests were performed to evaluate the treatment effects of trans-Resveratrol on IBS. Hippocampus tissues were collected and processed Golgi staining and immuno-blot analysis. Ileum and colon tissues were collected and processed Hematoxylin and Eosin staining and immuno-blot analysis.Results: Administration with trans-Resveratrol before CACS for 3 weeks significantly reversed CACS-induced depression- and anxiety-like behaviors and intestinal dysfunction in mice, which implied a crucial role of trans-Resveratrol in treatment of IBS-like disorder. Furthermore, trans-Resveratrol improved hippocampal neuronal remodeling, protected ileal and colonic epithelial barrier structure against CACS insults. The further study suggested that trans-Resveratrol normalized phosphodiesterases 4A (PDE4A) expression and CREB-BDNF signaling that were disturbed by CACS. The increased pCREB and BDNF expression in the hippocampus were found, while decreased pCREB and BDNF levels were observed after treatment with trans-Resveratrol.Conclusions: The dual effects of trans-Resveratrol on stress-induced psychiatric and intestinal dysfunction may be related to normalization of PDE4A expression and subsequent pCREB-BDNF signaling in the hippocampus, ileum and colon.https://www.frontiersin.org/article/10.3389/fphar.2018.00631/fullirritable bowel syndromedepressionanxietytrans-Resveratrolphosphodiesterases 4A
spellingShingle Ying Xu
Ying Xu
Su-Ying Cui
Su-Ying Cui
Quan Ma
Jing Shi
Ying Yu
Jian-Xin Li
Liang Zheng
Yi Zhang
Jian-Min Si
Ying-Cong Yu
Ying-Cong Yu
trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis
Frontiers in Pharmacology
irritable bowel syndrome
depression
anxiety
trans-Resveratrol
phosphodiesterases 4A
title trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis
title_full trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis
title_fullStr trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis
title_full_unstemmed trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis
title_short trans-Resveratrol Ameliorates Stress-Induced Irritable Bowel Syndrome-Like Behaviors by Regulation of Brain-Gut Axis
title_sort trans resveratrol ameliorates stress induced irritable bowel syndrome like behaviors by regulation of brain gut axis
topic irritable bowel syndrome
depression
anxiety
trans-Resveratrol
phosphodiesterases 4A
url https://www.frontiersin.org/article/10.3389/fphar.2018.00631/full
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