AUTHOR=Xu Ying , Cui Su-Ying , Ma Quan , Shi Jing , Yu Ying , Li Jian-Xin , Zheng Liang , Zhang Yi , Si Jian-Min , Yu Ying-Cong 

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

JOURNAL=Frontiers in Pharmacology

VOLUME=9

YEAR=2018

URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2018.00631

DOI=10.3389/fphar.2018.00631

ISSN=1663-9812

ABSTRACT=<p><bold>Background:</bold> 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 <italic>trans</italic>-Resveratrol affects chronic-acute combined stress (CACS)-induced IBS-like symptoms including depression, anxiety and intestinal dysfunction.</p><p><bold>Methods:</bold> ICR male mice were exposed to the CACS for 3 weeks. <italic>trans</italic>-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 <italic>trans</italic>-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.</p><p><bold>Results:</bold> Administration with <italic>trans</italic>-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 <italic>trans</italic>-Resveratrol in treatment of IBS-like disorder. Furthermore, <italic>trans</italic>-Resveratrol improved hippocampal neuronal remodeling, protected ileal and colonic epithelial barrier structure against CACS insults. The further study suggested that <italic>trans</italic>-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 <italic>trans</italic>-Resveratrol.</p><p><bold>Conclusions:</bold> The dual effects of <italic>trans</italic>-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.</p>