Xanthohumol prevents dextran sulfate sodium-induced colitis via inhibition of IKK?/NF-?B signaling in mice.

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 I?B?, the nuclear translocation of NF-?B subunits and the transcriptional activity of NF-?B in vivo and in vitro. In contrast to XN, isoXN showed much less effects on the kinase activity of IKK? and I?B? 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 IKK?/NF-?B signaling pathway. Consistently, our docking analysis revealed that XN could bind to the active site, presumably at the Cys99 of IKK?. Taken together, these findings demonstrate a new function of XN to inhibit IKK?/NF-?B signaling, suggesting XN could be the potential therapeutic agent for the prevention of colitis.

SUBMITTER: Cho JM 

PROVIDER: S-EPMC5787519 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature