Phenolic constituents of Amorpha fruticosa that inhibit NF-kappaB activation and related gene expression.
NF-kappaB 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-kappaB 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 microM, respectively, in TNF-alpha-stimulated HeLa cell-based reporter gene assays. Further investigations showed that compounds 1, 5, and 6 blocked NF-kappaB/DNA binding activity and suppressed the expression of NF-kappaB target genes.
Molecular Cancer Research Center, Korean Research Institute of Biosciences and Biotechnology, Daejeon, Korea.
Nguyen Tien
NT
Dat
Jeong-Hyung
JH
Lee
Kyeong
K
Lee
Young-Soo
YS
Hong
Young Ho
YH
Kim
Jung Joon
JJ
Lee
D000818:Animals; D004247:DNA / Q000187:drug effects; D007887:Fabaceae / Q000737:chemistry*; D006367:HeLa Cells / Q000378:metabolism; D006801:Humans; D007723:Korea; D008264:Macrophages / Q000187:drug effects; D051379:Mice; D015394:Molecular Structure; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D018515:Plant Leaves / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D010946:Plants, Medicinal / Q000737:chemistry*
D016328:NF-kappa B; D010636:Phenols; D004247:DNA