Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jun 7, 2015; 21(21): 6572-6581
Published online Jun 7, 2015. doi: 10.3748/wjg.v21.i21.6572
Effect of resveratrol on Treg/Th17 signaling and ulcerative colitis treatment in mice
Jun Yao, Cheng Wei, Jian-Yao Wang, Ru Zhang, Ying-Xue Li, Li-Sheng Wang
Jun Yao, Cheng Wei, Ru Zhang, Ying-Xue Li, Li-sheng Wang, Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen Municipal People’s Hospital, Shenzhen 518020, Guangdong Province, China
Jian-Yao Wang, Department of General Surgery, Shenzhen Children’s Hospital, Shenzhen 518026, Guangdong Province, China
Author contributions: Yao J, Wei C and Wang JY contributed equally to this work; Yao J, Wei C and Wang JY performed the majority of experiments; Zhang R and Li YX provided vital reagents and analytical tools and were also involved in editing the manuscript; Yao J and Wang LS designed the study and wrote the manuscript.
Supported by Outstanding Doctoral Thesis Support Project of Guangdong Province, No. 85514045; the Technical Research and Development Project of Shenzhen, No. JCYJ20130402092657774; and the Medical Research Foundation of Guangdong Province, No.B2013347.
Ethics approval: All experimental procedures were conducted in conformity with institutional guidelines for the care and use of laboratory animals in Southern Medical University, Guangdong, China, and conformed to the National Institutes of Health Guide for Care and Use of Laboratory Animals (Publication No. 85-23, revised 1985).
Institutional animal care and use committee: All animal experiments were reviewed and approved by the Guangdong Animal Medical Ethics Committee, China.
Conflict-of-interest: The authors declared that they have no conflicts of interest to this work.
Data sharing: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Dr. Li-Sheng Wang, Department of Gastroenterology, Jinan University of Medical Sciences, Shenzhen Municipal People’s Hospital, 1017 East Gate Road, Shenzhen, 518020, Guangdong Province, China. wangls168@163.com
Telephone: +86-755-25533018 Fax: +86-755-25533497
Received: November 26, 2014
Peer-review started: November 27, 2014
First decision: December 11, 2014
Revised: January 23, 2015
Accepted: March 12, 2015
Article in press: March 12, 2015
Published online: June 7, 2015
Processing time: 197 Days and 0.1 Hours
Abstract

AIM: To determine the therapeutic efficacy of resveratrol on ulcerative colitis (UC) and its underlying mechanisms.

METHODS: The mouse UC model was developed using 5% dextran sulfate sodium. Mice were randomly divided into four groups: normal control, UC model group, resveratrol low-dose group (RLD; 50 mg/kg per day), and resveratrol high-dose group (RHD; 100 mg/kg per day).

RESULTS: The results showed that RLD regulates Treg/Th17 balance mainly through reducing the number of Th17 cells, whereas RHD regulates Treg/Th17 balance through both downregulating the number of Th17 cells and upregulating the number of Treg cells. Resveratrol can also regulate the level of plasma and intestinal mucosal cytokines including interleukin (IL)-10, transforming growth factor-β1, IL-6, and IL-17. The expressions of hypoxia inducible factor (HIF)-1α, mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 were significantly decreased in the intestinal tissues of mice treated with resveratrol.

CONCLUSION: The therapeutic efficacy of resveratrol in UC is dose dependent and closely associated with the regulation of Treg/Th17 balance and the HIF-1α/mTOR signaling pathway.

Keywords: Hypoxia inducible factor-α; Mammalian target of rapamycin; Resveratrol; Th17 cells; Treg cells; Ulcerative colitis

Core tip: Ulcerative colitis is an inflammatory bowel disease manifested by recurrent chronic diarrhea, bloody and mucous stools, and abdominal pain. The etiology and pathogenesis are not clear. Resveratrol is a natural and biologically active polyphenol with a variety of anti-inflammatory and antioxidant functions, which are beneficial to human health. This study aimed determine the therapeutic efficacy of resveratrol on ulcerative colitis and its underlying mechanisms. The results demonstrate that the therapeutic efficacy of resveratrol is dose dependent and closely associated with the regulation of Treg/Th17 balance and the hypoxia inducible factor-1α/mammalian target of rapamycin signaling pathway.