Basic Study
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jan 14, 2015; 21(2): 465-474
Published online Jan 14, 2015. doi: 10.3748/wjg.v21.i2.465
Butein effects in colitis and interleukin-6/signal transducer and activator of transcription 3 expression
Sehe Dong Lee, Jung Wan Choe, Beom Jae Lee, Myoung Hee Kang, Moon Kyung Joo, Ji Hoon Kim, Jong Eun Yeon, Jong-Jae Park, Jae Seon Kim, Young-Tae Bak
Sehe Dong Lee, Jung Wan Choe, Beom Jae Lee, Myoung Hee Kang, Moon Kyung Joo, Ji Hoon Kim, Jong Eun Yeon, Jong-Jae Park, Jae Seon Kim, Young-Tae Bak, Division of Gastroenterology, Department of Internal Medicine, Korea University Medical Center, Seoul 152-703, South Korea
Author contributions: Lee SD and Choe JW contributed equally to this work; Lee BJ designed the study and performed the majority of the experiments; Lee SD, Choe JW, Kang MH, Joo MK, Kim JH, Yeon JE, Park JJ, Kim JS and Bak YT were involved in editing the manuscript; Lee SD and Choe JW wrote the paper.
Supported by Grants from the National Research Foundation of Korea, No. R1102452; Korea University, No. K1220161; and by experimental techniques from the Core Laboratory for Convergent Translational Research of College of Medicine.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Beom Jae Lee, MD, PhD, Division of Gastroenterology, Department of Internal Medicine, Korea University Medical Center, 97 Gurodong-gil, Guro-gu, Seoul 152-703, South Korea. l85210@medimail.co.kr
Telephone: +82-2-26263004 Fax: +82-2-8531943
Received: April 14, 2014
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
Abstract

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.

Keywords: Butein, Colitis, Inflammatory bowel disease, Interleukin-6/signal transducer and activator of transcription 3, Matrix metalloproteinase-9

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.