AbstractIn this study, based on the effect of compounds on the activation of NF-κB and NO release, compound51was discovered as the best one with NO release inhibition IC50value was 3.1 ± 1.1 μM and NF-κB activity inhibition IC50value was 172.2 ± 11.4 nM. Compound51could inhibit the activation of NF-κB through suppressing phosphorylation and nuclear translocation of NF-κB, and suppress LPS-induced inflammatory response in RAW264.7 cells, such as the over-expression of TNF-α and IL-6, which were target genes of NF-κB. This compound also showed preferable anti-inflammatory activity invivo, including alleviating significantly gastric distention and splenomegaly caused by LPS stimulation, reducing the level of oxidative stress induced by LPS, and inhibiting the expression of IL-6 and TNF-α in serum. Thus, it’s reasonable to consider that this compound is a promising small molecule with anti-inflammatory effect for inhibiting the NF-κB signalling pathway.