Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages

doi:10.1038/aps.2017.185

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	Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages
	Yan, Yu-xi 2,3; Shao, Mei-juan 1; Qi, Qing 2; Xu, Yan-sheng 1; Yang, Xiao-qian 2; Zhu, Feng-hua 2; He, Shi-jun2 ; He, Pei-lan 2; Feng, Chun-lan 2; Wu, Yan-wei 2
刊名	ACTA PHARMACOLOGICA SINICA
	2018-10
卷号	39 期号:10 页码:1633-1644
关键词	SM934 artemisinin analogue ulcerative colitis inflammatory bowel disease (IBD) neutrophils macrophage NF-kappa B RAW 2647 cells THP-1-derived macrophages
ISSN号	1671-4083
DOI	10.1038/aps.2017.185
文献子类	Article
英文摘要	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-1 beta, IL-6 and TNF-alpha), 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 mu mol/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-kappa B 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-kappa B signaling, suggests that SM934 might be a potential effective drug for ulcerative colitis.
资助项目	"Personalized Medicines Molecular Signature-based Drug Discovery and Development", Strategic Priority Research Program of the Chinese Academy of Sciences[XDA12020107] ; National Science & Technology Major Project "New Drug Creation and Manufacturing Program", China[2017ZX09101002-002-010] ; National Natural Science Foundation of China (NSFC)[81673445]
WOS关键词	INFLAMMATORY-BOWEL-DISEASE ; NF-KAPPA-B ; SODIUM-INDUCED COLITIS ; NLRP3 INFLAMMASOME ; MURINE COLITIS ; MICE ; ACTIVATION ; MONOCYTES ; CYTOKINES ; MUCOSA
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000448391500009
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/279556]
专题	药理学第一研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Tang, Wei; Zuo, Jian-ping
作者单位	1.Shanghai Univ Tradit Chinese Med, Lab Immunol & Virol, Shanghai 201203, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, Lab Immunopharmacol, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China;
推荐引用方式 GB/T 7714	Yan, Yu-xi,Shao, Mei-juan,Qi, Qing,et al. Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages[J]. ACTA PHARMACOLOGICA SINICA,2018,39(10):1633-1644.
APA	Yan, Yu-xi.,Shao, Mei-juan.,Qi, Qing.,Xu, Yan-sheng.,Yang, Xiao-qian.,...&Zuo, Jian-ping.(2018).Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages.ACTA PHARMACOLOGICA SINICA,39(10),1633-1644.
MLA	Yan, Yu-xi,et al."Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages".ACTA PHARMACOLOGICA SINICA 39.10(2018):1633-1644.