Fumigaclavine C, an fungal metabolite, improves experimental colitis in mice via downregulating Th1 cytokine production and matrix metalloproteinase activity.
In the present paper, the effect of Fumigaclavine C, a fungal metabolite, on experimental colitis was examined. Fumigaclavine C, when administered intraperitoneally once a day, significantly reduced the weight loss and mortality rate of mice with experimental colitis induced by intrarectally injection of 2, 4, 6-trinitrobenzene sulfonic acid (TNBS). This compound also markedly alleviated the macroscopic and microscopic appearances of colitis. Furthermore, Fumigaclavine C, given both in vivo and in vitro, showed a marked inhibition on the expression of several inflammatory cytokines, including IL-1beta, IL-2, IL-12alpha, IFN-gamma, TNF-alpha as well as MMP-9 in sacral lymph node cells, colonic patch lymphocytes and colitis tissues from the TNBS colitis mice. Meanwhile, the compound caused a dose-dependent reduction in IL-2 and IFN-gamma from the lymphocytes at the protein level and MMP-9 activity. These results suggest that Fumigaclavine C may alleviate experimental colitis mainly via down-regulating the production of Th1 cytokines and the activity of matrix metalloproteinase.
Wu
Xue-Feng
XF
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Han Kou Road, Nanjing 210093, China.
Fei
Ming-Jian
MJ
Shu
Ren-Geng
RG
Tan
Ren-Xiang
RX
Xu
Qiang
Q
D000164:Acremonium / Q000378:metabolism; D000818:Animals; D003092:Colitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D003106:Colon / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D004876:Ergot Alkaloids; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D026121:Indole Alkaloids / Q000627:therapeutic use*; D007249:Inflammation; D008198:Lymph Nodes / Q000187:drug effects / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D018417:Th1 Cells / Q000276:immunology*; D014302:Trinitrobenzenesulfonic Acid
D016207:Cytokines; D004876:Ergot Alkaloids; D026121:Indole Alkaloids; C492995:fumigaclavine C; D014302:Trinitrobenzenesulfonic Acid; D020782:Matrix Metalloproteinases