Basic Study
Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2020; 26(33): 4945-4959
Published online Sep 7, 2020. doi: 10.3748/wjg.v26.i33.4945
Resveratrol alleviates intestinal mucosal barrier dysfunction in dextran sulfate sodium-induced colitis mice by enhancing autophagy
Hang-Hai Pan, Xin-Xin Zhou, Ying-Yu Ma, Wen-Sheng Pan, Fei Zhao, Mo-Sang Yu, Jing-Quan Liu
Hang-Hai Pan, Wen-Sheng Pan, Fei Zhao, Department of Gastroenterology, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Xin-Xin Zhou, Mo-Sang Yu, Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, Zhejiang Province, China
Ying-Yu Ma, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Jing-Quan Liu, Critical Care Unit, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou 310014, Zhejiang Province, China
Author contributions: Pan HH designed the experiments; Ma YY, Yu MS and Zhao F performed the experiments and analyzed the data; Pan HH and Zhou XX drafted the manuscript; Ma YY critically revised the manuscript; Liu JQ and Pan WS offered help during the experiments; all authors have read and approved the final manuscript.
Supported by the National Natural Science Foundation of China, No. 81600414; Medical Health Science and Technology Project of Zhejiang Provincial Health Commission, No. 2018255969; Zhejiang TCM Science and Technology Project, No. 2016ZA123 and No. 2018ZA013.
Institutional review board statement: This study was reviewed and approved by the Institutional Review Board of Zhejiang Chinese Medical University.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Ethics Committee of Zhejiang Chinese Medical University.
Conflict-of-interest statement: No potential conflicts of interest exist.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (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/
Corresponding author: Ying-Yu Ma, MD, Research Assistant, Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, No. 158 Shangtang Road, Hangzhou 310014, Zhejiang Province, China. myy011525@163.com
Received: May 17, 2020
Peer-review started: May 17, 2020
First decision: June 18, 2020
Revised: June 27, 2020
Accepted: August 12, 2020
Article in press: August 12, 2020
Published online: September 7, 2020
Processing time: 109 Days and 22 Hours
ARTICLE HIGHLIGHTS
Research background

Intestinal mucosal barrier disorder plays a very important role in the pathogenesis of ulcerative colitis (UC). Recent studies have revealed that impaired autophagy is associated with intestinal mucosal dysfunction in the mucosa of colitis mice.

Research motivation

Resveratrol can regulate autophagy in the treatment of a few inflammatory diseases. Recently, few studies have indicated that resveratrol can alleviate clinical colitis activity in patients with active UC, while the mechanism for its anti-inflammatory effect remains elusive.

Research objectives

The aim of the study was to explore the effect and mechanism of resveratrol on protecting the integrity of the intestinal mucosal barrier and anti-inflammation in dextran sulfate sodium (DSS)-induced ulcerative colitis.

Research methods

DSS-induced ulcerative colitis was induced by DSS, then the disease activity index was used to assess the severity of colitis. Inflammatory cytokines were detected by enzyme-linked immunosorbent assay. Tissue sections were stained with haematoxylin and eosin, and mucosal damage was evaluated by mean histological score. The expression of occludin and ZO-1 was detected by immunohistochemical analysis. Reverse transcription-polymerase chain reaction and Western-blot were used to analyze autophagy-related gene expression, and morphology of autophagy was observed by transmission electron microscopy.

Research results

The resveratrol treatment group showed a 1.72-fold decrease in disease activity index scores and 1.42-, 3.81-, and 1.65-fold decrease in the production of the inflammatory cytokines tumor necrosis factor-α, interleukin-6 and interleukin-1β, respectively, in DSS-induced colitis mice compared with DSS group (P < 0.05). The expression of the tight junction proteins occludin and ZO-1 in DSS model group was reduced, while in resveratrol-treated colitis group was increased. Resveratrol also increased the levels of LC3B (1.39-fold compared with DSS group) and Beclin-1 (1.49-fold compared with DSS group) (P < 0.05), as well as the number of autophagosomes, which implies that the resveratrol may alleviate intestinal mucosal barrier dysfunction in DSS-induced UC mice by enhancing autophagy.

Research conclusions

Resveratrol treatment reduces the expression of inflammatory factors, increases the expression of tight junction proteins and alleviates UC intestinal mucosal barrier dysfunction; this effect is achieved via the regulation of autophagy in intestinal epithelial cells.

Research perspectives

This work suggests that resveratrol may be useful as a new approach to treat UC by enhancing autophagy. Further study of the functionary mechanism will help us to understand the role of resveratrol in colitis and provide a theoretical basis for future clinical application.