Published online Jan 14, 2015. doi: 10.3748/wjg.v21.i2.465
Peer-review started: April 15, 2014
First decision: May 13, 2014
Revised: June 8, 2014
Accepted: July 11, 2014
Article in press: July 11, 2014
Published online: January 14, 2015
AIM: To evaluate the effects of butein on inflammatory cytokines, matrix metalloproteinase-9 (MMP-9), and colitis in interleukin (IL)-10-/- mice.
METHODS: To synchronize colitis, 8- to 10-wk-old IL-10-/- mice were fed pellet-chow containing piroxicam for 2 wk. Subsequently, phosphate-buffered saline or butein (1 mg/kg per day, ip) was injected for 4 wk. Histologic scores, inflammatory cytokines, MMP-9 and phosphorylated signal transducer and activator of transcription 3 (pSTAT3) expressions were analyzed in IL-10-/- mice and in Colo 205 cells.
RESULTS: Butein reduced the colonic inflammatory score by > 50%. Expression levels of IL-6, IL-1β, interferon (IFN)-γ and MMP-9 were decreased in the colons of mice exposed to butein, whereas other inflammatory cytokines (IL-17A, IL-21 and IL-22) were unchanged. Immunohistochemical staining for pSTAT3 and MMP-9 was significantly decreased in the butein-treated groups compared with the controls. Butein inhibited IL-6-induced activation of STAT3 in Colo 205 cells.
CONCLUSION: Butein ameliorated colitis in IL-10-/- mice by regulating IL-6/STAT3 and MMP-9 activation.
Core tip: This study examined if butein, a naturally derived substance, has therapeutic effects in an animal model of inflammatory bowel disease, interleukin (IL)-10-/- mice. The results show that butein suppressed bowel inflammation and interfered with the IL-6/signal transducer and activator of transcription 3 and matrix metalloproteinase-9 pathways, suggesting that butein should be used to treat bowel inflammation-induced colon cancer. Although there have been several in vitro studies on tumor cells, there have been no in vivo studies examining the effect of butein on colitis in mice.