3,6-dichlorobenzo[b]thiophene-2-carboxylic acid alleviates ulcerative colitis by suppressing mammalian target of rapamycin complex 1 activation and regulating intestinal microbiota

作     者：Qiong-Zi He Peng Wei Jun-Zhi Zhang Tong-Tong Liu Kun-Qun Shi Huan-Huan Liu Jing-Wei Zhang Shi-Jia Liu 

作者机构：Affiliated Hospital of Nanjing University of Chinese MedicineJiangsu Province Hospital of Chinese MedicineNanjing 210029Jiangsu ProvinceChina College of The First Clinical MedicineNanjing University of Chinese MedicineNanjing 210023Jiangsu ProvinceChina School of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 211198Jiangsu ProvinceChina 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2022年第28卷第46期

页      面：6522-6536页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by National Natural Science Foundation of China No. 82074241 Project of Jiangsu Province Hospital of Traditional Chinese Medicine Peak Talent No. y2021rc36 

主　　题：3,6-dichlorobenzo[b]thiophene-2-carboxylic acid Ulcerative colitis Mechanistic target of rapamycin complex 1 Intestinal flora Dextran sodium sulfate Cyclooxygenase-2 

摘      要：BACKGROUND 3,6-dichlorobenzo[b]thiophene-2-carboxylic acid(BT2)is a benzothiophene carboxylate derivative that can suppress the catabolism of branched-chain amino acid(BCAA)-associated mammalian target of rapamycin complex 1(mTORC1)*** studies have demonstrated the therapeutic effects of BT2 on arthritis,liver cancer,and kidney ***,the effects of BT2 on ulcerative colitis(UC)are *** To investigate the anti-UC effects of BT2 and the underlying *** Mouse UC models were created through the administration of 3.5%dextran sodium sulfate(DSS)for 7 *** mice in the treated groups were administered salazosulfapyridine(300 mg/kg)or BT2(20 mg/kg)orally from day 1 to day *** the end of the study,all of the mice were sacrificed,and colon tissues were removed for hematoxylin and eosin staining,immunoblot analyses,and immunohistochemical *** levels were measured by flow *** contents of BCAAs including valine,leucine,and isoleucine,in mouse serum were detected by liquid chromatography-tandem mass spectrometry,and the abundance of intestinal flora was analyzed by 16S ribosomal DNA *** Our results revealed that BT2 significantly ameliorated the inflammatory symptoms and pathological damage induced by DSS in ***2 also reduced the production of the proinflammatory cytokines interleukin 6(IL-6),IL-9,and IL-2 and increased the anti-inflammatory cytokine IL-10 *** addition,BT2 notably improved BCAA catabolism and suppressed mTORC1 activation and cyclooxygenase-2 expression in the colon tissues of UC ***,highthroughput sequencing revealed that BT2 restored the gut microbial abundance and diversity in mice with *** with the DSS group,BT2 treatment increased the ratio of Firmicutes to Bacteroidetes and decreased the abundance of Enterobacteriaceae and *** Our results indicated that BT2 significantly ameliorated DSS-induced UC and that the late