title: 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: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Wenjie
authors: W
authors: Guo
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Shasha
authors: S
authors: Hu
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Ahmed
authors: A
authors: Elgehama
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Fenli
authors: F
authors: Shao
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Ren
authors: R
authors: Ren
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Wen
authors: W
authors: Liu
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Wenjing
authors: W
authors: Zhang
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Xinlei
authors: X
authors: Wang
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Renxiang
authors: R
authors: Tan
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
authors: Qiang
authors: Q
authors: Xu
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: sunyangnju@163.com.
authors: Yang
authors: Y
authors: Sun
authors: Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, School of Life Science, Nanjing University, Nanjing 210093, People's Republic of China. Electronic address: jiaoruihua@126.com.
authors: Ruihua
authors: R
authors: Jiao
mesh_terms: D000284:Administration, Oral; D000818:Animals; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D020170:Caspase 1 / Q000378:metabolism; D002478:Cells, Cultured; D003093:Colitis, Ulcerative / Q000139:chemically induced* / Q000188:drug therapy*; D003106:Colon / Q000187:drug effects; D016264:Dextran Sulfate; D004305:Dose-Response Relationship, Drug; D004876:Ergot Alkaloids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D026121:Indole Alkaloids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use*; D058847:Inflammasomes / Q000037:antagonists & inhibitors*; D020381:Interleukin-17 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism*; D017737:Macrophages, Peritoneal / Q000378:metabolism; D008810:Mice, Inbred C57BL; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015431:Weight Loss / Q000187:drug effects
chemical_list: D002352:Carrier Proteins; D004876:Ergot Alkaloids; D026121:Indole Alkaloids; D058847:Inflammasomes; D020381:Interleukin-17; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D014409:Tumor Necrosis Factor-alpha; C492995:fumigaclavine C; D016264:Dextran Sulfate; D020170:Caspase 1
keywords: Caspase-1; Colitis; Fumigaclavine C; IL-1β; NLRP3 inflammasome