Discovery of an effective anti-inflammatory agent for inhibiting the activation of NF-B

In this study, based on the effect of compounds on the activation of NF-kappa B and NO release, compound 51 was discovered as the best one with NO release inhibition IC50 value was 3.1 +/- 1.1 lM and NF-kappa B activity inhibition IC50 value was 172.2 +/- 11.4 nM. Compound 51 could inhibit the activation of NF-kappa B through suppressing phosphorylation and nuclear translocation of NF-kappa B, and suppress LPS-induced inflammatory response in RAW264.7 cells, such as the over-expression of TNF-alpha and IL-6, which were target genes of NF-kappa B. This compound also showed preferable anti-inflammatory activity in vivo, 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-alpha in serum. Thus, it's reasonable to consider that this compound is a promising small molecule with anti-inflammatory effect for inhibiting the NF-kappa B signalling pathway.