Oncotarget

Research Papers:

Xanthohumol prevents dextran sulfate sodium-induced colitis via inhibition of IKKβ/NF-κB signaling in mice

Jae-Min Cho, Sun-Mi Yun, Young-Ho Choi, Jinyuk Heo, Nam-Jung Kim, Seok-Ho Kim and Eun-Hee Kim _

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Oncotarget. 2018; 9:866-880. https://doi.org/10.18632/oncotarget.23183

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Abstract

Jae-Min Cho1,*, Sun-Mi Yun1,*, Young-Ho Choi1, Jinyuk Heo2, Nam-Jung Kim2, Seok-Ho Kim1 and Eun-Hee Kim1

1College of Pharmacy and Institute of Pharmaceutical Sciences, CHA University, Seongnam 13488, Korea

2College of Pharmacy, Kyung Hee University, Seoul 02447, Korea

*These authors contributed equally to this work

Correspondence to:

Eun-Hee Kim, email: [email protected]

Seok-Ho Kim, email: [email protected]

Keywords: xanthohumol; DSS; colitis; NF-κB; IKKβ

Received: September 13, 2017     Accepted: November 15, 2017     Published: December 12, 2017

ABSTRACT

Xanthohumol (XN), a prenylated chalcone isolated from the hop plant, has been reported to exhibit multiple biological functions including anti-inflammation. However, the pharmacological function of XN on colitis remains unknown. In this study, we investigated the anti-inflammatory effect of synthesized XN and molecular mechanism on dextran sulfate sodium (DSS)-induced experimental colitis. XN attenuated the colitis symptoms along with the prevention of colonic lesions after DSS challenge. XN inhibited the production of pro-inflammatory cytokines, oxidative stress and cyclooxygenase-2 expression in DSS-treated mice. Moreover, XN inhibited the phosphorylation of IκBα, the nuclear translocation of NF-κB subunits and the transcriptional activity of NF-κB in vivo and in vitro. In contrast to XN, isoXN showed much less effects on the kinase activity of IKKβ and IκBα phosphorylation induced by XN in this study, suggesting that an electrophilic carbon center present in XN is critical for the anti-inflammation in colitis, especially inhibition of IKKβ/NF-κB signaling pathway. Consistently, our docking analysis revealed that XN could bind to the active site, presumably at the Cys99 of IKKβ. Taken together, these findings demonstrate a new function of XN to inhibit IKKβ/NF-κB signaling, suggesting XN could be the potential therapeutic agent for the prevention of colitis.


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