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

• Published in: Journal of pharmacological sciences 2015-10, Vol.129 (2), p.101-106
• Main Authors: Guo, Wenjie, Hu, Shasha, Elgehama, Ahmed, Shao, Fenli, Ren, Ren, Liu, Wen, Zhang, Wenjing, Wang, Xinlei, Tan, Renxiang, Xu, Qiang, Sun, Yang, Jiao, Ruihua
• Format: Article
• Language: English
• Subjects: Administration, Oral; Animals; Carrier Proteins - antagonists & inhibitors; Caspase 1 - metabolism; Caspase-1; Cells, Cultured; Colitis; Colitis, Ulcerative - chemically induced; Colitis, Ulcerative - drug therapy; Colon - drug effects; Dextran Sulfate; Dose-Response Relationship, Drug; Ergot Alkaloids - administration & dosage; Ergot Alkaloids - pharmacology; Ergot Alkaloids - therapeutic use; Female; Fumigaclavine C; Humans; IL-1β; Indole Alkaloids - administration & dosage; Indole Alkaloids - pharmacology; Indole Alkaloids - therapeutic use; Inflammasomes - antagonists & inhibitors; Interleukin-17 - metabolism; Interleukin-1beta - metabolism; Macrophages, Peritoneal - metabolism; Mice, Inbred C57BL; NLR Family, Pyrin Domain-Containing 3 Protein; NLRP3 inflammasome; Tumor Necrosis Factor-alpha - metabolism; Weight Loss - drug effects
• ISSN: 1347-8613; 1347-8648
• DOI: 10.1016/j.jphs.2015.05.003

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-α, IL-1β 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-1β 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.