In conclusion, our study provides that XN has protective effects against DSS-induced colitis in mice and H2O2- or LPS-treated IEC-6 cells by inhibiting IKKβ/NF-κB signaling pathway, indicating the possible interaction between electrophilic carbon center of α, β-unsaturated carbonyl moiety in XN and Cys99 in IKKβ. The gene discussed is IKBKB; the disease is colitis.