Fumigaclavine C ameliorates dextran sulfate sodium-induced murine experimental colitis via NLRP3 inflammasome inhibition

被引：32

作者：

Guo, Wenjie ^{[1
]}

Hu, Shasha ^{[1
]}

Elgehama, Ahmed ^{[1
]}

Shao, Fenli ^{[1
]}

Ren, Ren ^{[1
]}

Liu, Wen ^{[1
]}

Zhang, Wenjing ^{[1
]}

Wang, Xinlei ^{[1
]}

Tan, Renxiang ^{[1
]}

Xu, Qiang ^{[1
]}

Sun, Yang ^{[1
]}

Jiao, Ruihua ^{[1
]}

机构：

[1] Nanjing Univ, Sch Life Sci, State Key Lab Pharmaceut Biotechnol, Inst Funct Biomol, Nanjing 210093, Jiangsu, Peoples R China

来源：

JOURNAL OF PHARMACOLOGICAL SCIENCES | 2015年 / 129卷 / 02期

关键词：

Fumigaclavine C; Colitis; NLRP3; inflammasome; IL-1; beta; Caspase-1; TNF-ALPHA PRODUCTION; BOWEL-DISEASE; ULCERATIVE-COLITIS; MICE; INTERLEUKIN-1; PATHOGENESIS; INNATE; DSS;

D O I：

10.1016/j.jphs.2015.05.003

中图分类号：

R9 [药学];

学科分类号：

100702 [药剂学];

摘要：

In the present study, the effect of Fumigaclavine C, a fungal metabolite, on murine experimental colitis induced by dextran sulfate sodium (DSS) and its possible mechanism were examined in vivo and vitro. Oral administration of Fumigaclavine C dose-dependently attenuated the loss of body weight and shortening of colon length induced by DSS. The disease activity index, histopathologic scores of musco was also significantly reduced by Fumigaclavine C treatment. Protein and mRNA levels of DSS-induced pro-inflammatory cytokines in colon, including TNF-alpha, IL-1 beta and IL-17A, were markedly suppressed by Fumigaclavine C. At the same time, decreased activation of caspase-1 in peritoneal macrophages was detected in Fumigaclavine C -treated mice which suggested that the NLRP3 inflammasome activation was suppressed. Furthermore, in the LPS plus ATP cell model, we found that Fumigaclavine C dose-dependent inhibited IL-1 beta release and caspase-1 activation. Taken together, our results demonstrate the ability of Fumigaclavine C to inhibit NLRP3 inflammasome activation and give some evidence for its potential use in the treatment of inflammatory bowel diseases. (C) 2015 The Authors. Production and hosting by Elsevier B.V. on behalf of Japanese Pharmacological Society.

引用

页码：101 / 106

页数：6

共 28 条

[1]

The ICE inhibitor pralnacasan prevents DSS-induced colitis in C57BL/6 mice and suppresses IP-10 mRNA but not TNF-α mRNA expression [J].