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

초록

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

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