Artemisinin analogue SM934 ameliorates DSSinduced mouse ulcerative colitis via suppressing neutrophils and macrophages

Authors: Yu-xi YAN1,2, Mei-juan SHAO3, Qing QI1, Yan-sheng XU1, Xiao-qian YANG1, Feng-hua ZHU1, Shi-jun HE1, Pei-lan HE1, Chun-lan FENG1, Yan-wei WU1, Heng LI1,2, Wei TANG1,2, Jian-ping ZUO1,2,3
1 Laboratory of Immunopharmacology, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China
2 University of Chinese Academy of Sciences, Beijing 100049, China
3 Laboratory of Immunology and Virology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China
Corresponding to: Wei TANG:, Jian-ping ZUO:,
DOI: 10.1038/aps.2017.185
Received: 19 November 2017
Accepted: 21 December 2017
Advance online: 31 May 2018


Ulcerative colitis (UC) is a chronic, nonspecific inflammatory bowel disease (IBD) characterized by complicated and relapsing inflammation in the gastrointestinal tract. SM934 is a water-soluble artemisinin analogue that shows anti-inflammatory and immuno-regulatory effects. In this study, we investigated the effects of SM934 on UC both in vivo and in vitro. A mouse model of colitis was established in mice by oral administration of 5% dextran sulfate sodium (DSS). SM934 (3, 10 mg/kg per day, ig) was administered to the mice for 10 days. After the mice were sacrificed, colons, spleens and mesenteric lymph nodes (MLNs) were collected for analyses. SM934 administration restored DSS-induced body weight loss, colon shortening, injury and inflammation scores. Furthermore, SM934 administration significantly decreased the disease activity index (DAI), histopathological scores, and myeloperoxidase (MPO) activities in colonic tissues. Moreover, SM934 administration dose-dependently decreased the mRNA and protein levels of DSS-induced pro-inflammatory cytokines (IL-1β, IL-6 and TNF-α), and the percentage of macrophages and neutrophils in colon tissues. The effects of SM934 on LPS-stimulated RAW 264.7 cells and THP-1-derived macrophages were examined in vitro. Treatment with SM934 (0.8, 8, 80 μmol/L) dose-dependently decreased the production of pro-inflammatory mediators in LPS-stimulated RAW 264.7 cells and THP-1-derived macrophages via inhibiting activation of the NF-κB signaling. Our results reveal the protective effects of SM934 on DSS-induced colitis can be attributed to its suppressing effects on neutrophils and macrophages and its inhibitory role in the NF-κB signaling, suggests that SM934 might be a potential effective drug for ulcerative colitis.
Keywords: SM934; artemisinin analogue; ulcerative colitis; inflammatory bowel disease (IBD); neutrophils macrophage; NF-κB; RAW 264.7 cells; THP-1-derived macrophages

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