Artemisinin analogue SM934 ameliorates DSS-induced mouse ulcerative colitis via suppressing neutrophils and macrophages
| Autor: | Fenghua Zhu, Xiaoqian Yang, Shijun He, Heng Li, Qing Qi, Pei-Lan He, Yan-sheng Xu, Chunlan Feng, Jianping Zuo, Mei-juan Shao, Wei Tang, Yanwei Wu, Yu-xi Yan |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Colon Neutrophils Inflammation Pharmacology Inflammatory bowel disease Article Mice 03 medical and health sciences In vivo Oral administration Animals Medicine Mesenteric lymph nodes Pharmacology (medical) Colitis Mice Inbred BALB C biology business.industry Macrophages Anti-Inflammatory Agents Non-Steroidal Dextran Sulfate NF-kappa B General Medicine medicine.disease Ulcerative colitis Artemisinins RAW 264.7 Cells 030104 developmental biology medicine.anatomical_structure Myeloperoxidase biology.protein Cytokines Colitis Ulcerative Female medicine.symptom business Signal Transduction |
| Zdroj: | Acta Pharmacologica Sinica. 39:1633-1644 |
| ISSN: | 1745-7254 1671-4083 |
| DOI: | 10.1038/aps.2017.185 |
| Popis: | 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. We showed that 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 RAW264.7 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. |
| Databáze: | OpenAIRE |
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