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

Abstract

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.

• Authors: Wenjie Guo, Shasha Hu, Ahmed Elgehama, Fenli Shao, Ren Ren, Wen Liu, Wenjing Zhang, Xinlei Wang, Renxiang Tan, Qiang Xu, Yang Sun, Ruihua Jiao
• Journal: Journal of pharmacological sciences (J Pharmacol Sci) Vol. 129 Issue 2 Pg. 101-6 (Oct 2015) ISSN: 1347-8648 [Electronic] Japan
• PMID: 26320672 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Chemical References

• Carrier Proteins
• Ergot Alkaloids
• Indole Alkaloids
• Inflammasomes
• Interleukin-17
• Interleukin-1beta
• NLR Family, Pyrin Domain-Containing 3 Protein
• Nlrp3 protein, mouse
• Tumor Necrosis Factor-alpha
• fumigaclavine C
• Dextran Sulfate
• Caspase 1

Topics

• Administration, Oral
• Animals
• Carrier Proteins (antagonists & inhibitors)
• Caspase 1 (metabolism)
• Cells, Cultured
• Colitis, Ulcerative (chemically induced, drug therapy)
• Colon (drug effects)
• Dextran Sulfate
• Dose-Response Relationship, Drug
• Ergot Alkaloids (administration & dosage, pharmacology, therapeutic use)
• Female
• Humans
• Indole Alkaloids (administration & dosage, pharmacology, therapeutic use)
• Inflammasomes (antagonists & inhibitors)
• Interleukin-17 (metabolism)
• Interleukin-1beta (metabolism)
• Macrophages, Peritoneal (metabolism)
• Mice, Inbred C57BL
• NLR Family, Pyrin Domain-Containing 3 Protein
• Tumor Necrosis Factor-alpha (metabolism)
• Weight Loss (drug effects)