Phenolic constituents of Amorpha fruticosa that inhibit NF-kappaB activation and related gene expression

Abstract

NF-κB is known to play a crucial role in the regulation of genes controlling the immune system, apoptosis, tumor cell growth, and tissue differentiation. Bioassay-guided fractionation of the n-hexane-soluble fraction of a methanol extract of Amorpha fruticosa afforded four new compounds, 5, 7, 8, and 9, and eight known compounds. Their structures were elucidated by spectroscopic methods. All compounds inhibited NF-κB activity, and tephrosin (1), 11-hydroxytephrosin (2), and deguelin (3) were the most active, with IC50 values of 0.11, 0.19, and 0.22 μM, respectively, in TNF-α-stimulated HeLa cell-based reporter gene assays. Further investigations showed that compounds 1, 5, and 6 blocked NF-κB/DNA binding activity and suppressed the expression of NF-κB target genes.