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©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
3,6-dichlorobenzo[b]thiophene-2-carboxylic acid alleviates ulcerative colitis by suppressing mammalian target of rapamycin complex 1 activation and regulating intestinal microbiota
Qiong-Zi He, Peng Wei, Jun-Zhi Zhang, Tong-Tong Liu, Kun-Qun Shi, Huan-Huan Liu, Jing-Wei Zhang, Shi-Jia Liu
Qiong-Zi He, Peng Wei, Jun-Zhi Zhang, Tong-Tong Liu, Kun-Qun Shi, Huan-Huan Liu, Shi-Jia Liu, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Qiong-Zi He, Peng Wei, Jun-Zhi Zhang, Tong-Tong Liu, Kun-Qun Shi, Huan-Huan Liu, College of The First Clinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
Jing-Wei Zhang, School of Life Science and Technology, China Pharmaceutical University, Nanjing 211198, Jiangsu Province, China
Author contributions: He QZ and Wei P contributed equally to this work; He QZ, Wei P, and Liu HH conceived and performed experiments; He QZ, Zhang JZ, Liu TT, and Shi KQ analyzed the data; He QZ and Wei P wrote the paper; Liu SJ revised the manuscript and obtained funding for the project; All authors read and approved the final manuscript.
Supported by National Natural Science Foundation of China, No. 82074241; and Project of Jiangsu Province Hospital of Traditional Chinese Medicine Peak Talent, No. y2021rc36.
Institutional animal care and use committee statement: All experimental procedures with mice were performed in accordance and in compliance with the regulations of the Pharmacological Laboratory and Animal Ethics Committee in Affiliated Hospital of Nanjing University of Traditional Chinese Medicine (SYXK2017-0069).
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors 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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Shi-Jia Liu, PhD, Research Fellow, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, Jiangsu Province, China. liushijia2011@163.com
Received: July 20, 2022
Peer-review started: July 20, 2022
First decision: October 22, 2022
Revised: November 4, 2022
Accepted: November 22, 2022
Article in press: November 22, 2022
Published online: December 14, 2022
ARTICLE HIGHLIGHTS
Research background
Ulcerative colitis (UC) is a chronic inflammatory disorder caused by multiple factors. As a novel inhibitor, 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid (BT2) was recently shown to play an important role in improving amino acid metabolism and anti-inflammation. However, no relevant studies have reported the protective effect of BT2 on UC.
Research motivation
To investigate the therapeutic effect of BT2 on UC and the potential pharmacological mechanism.
Research objectives
To clarify the role of BT2 in UC treatment and its underlying mechanism.
Research methods
The acute colitis model was induced by 3.5% dextran sodium sulfate (DSS). The protective effect of BT2 was evaluated via clinical manifestations and colonic pathological changes. Flow cytometry was used to detect the contents of cytokines. Western blot analysis, immunohistochemical assays and liquid chromatography-tandem mass spectrometry were employed to estimate the mechanistic target of rapamycin complex 1 (mTORC1) activity and branched-chain amino acid (BCAA) catabolism. Moreover, the abundance of intestinal microbiota in feces was measured by 16S ribosomal DNA sequencing.
Research results
BT2 markedly alleviated colonic damage and reduced the release of proinflammatory cytokines in the DSS colitis model. BT2 also obviously improved BCAA catabolism in UC mice, as evidenced by the detection of related kinases in colon tissues and the targeted quantification of amino acids in serum. mTORC1 activity was enhanced in UC mice but inhibited by BT2 treatment. Moreover, 16S rRNA sequencing revealed that BT2 could prevent the decrease in the Firmicutes/Bacteroidetes ratio and the increase in harmful bacteria induced by DSS.
Research conclusions
BT2 relieved colitis by inhibiting BCAA-related mTORC1 activation and restoring gut microbiota metabolism homeostasis.
Research perspectives
BT2 showed significant efficacy on colitis and could serve as a promising therapeutic agent for UC treatment.
