Journal of Enzyme Inhibition and Medicinal Chemistry (Dec 2023)

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

  • Yaoyao Yan,
  • Qi Lv,
  • Feilong Zhou,
  • Yujie Jian,
  • Liu Xinhua,
  • Xing Chen,
  • Yong Hu

DOI
https://doi.org/10.1080/14756366.2023.2225135
Journal volume & issue
Vol. 38, no. 1

Abstract

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In this study, based on the effect of compounds on the activation of NF-κB and NO release, compound 51 was discovered as the best one with NO release inhibition IC50 value was 3.1 ± 1.1 μM and NF-κB activity inhibition IC50 value was 172.2 ± 11.4 nM. Compound 51 could 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 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-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.

Keywords