Amorfrutin A inhibits TNF-α-induced NF-κB activation and NF-κB-regulated target gene products

The nuclear factor-kappa B (NF-kappa B) transcription factors control many physiological processes including inflammation, immunity, apoptosis, and angiogenesis. In our search for NF-kappa B inhibitors from natural resources, we identified amorfrutin A as an inhibitor of NF-kappa B activation from the fruits of Amorpha fruticosa L. In present study, this compound significantly inhibited the TNF-alpha-induced expression of NF-kappa B reporter gene. Further analysis revealed that amorfrutin A was a potent inhibitor of NF-kappa B activation by the suppression of TNF-alpha-induced inhibitor of kappa B alpha (I kappa B alpha) degradation, p65 nuclear translocation, and DNA-binding activity of NF-kappa B. We also demonstrated that pretreatment of cells with this compound prevented the TNF-alpha-induced expression of NF-kappa B target genes, such as antiapoptosis (cIAP-1 and FLIP), proliferation (COX-2 and cyclinD1), invasion (MMP-9), angiogenesis (VEGF), and major inflammatory cytokines (TNF-alpha, IL-8, and MCP1). Furthermore, our results suggest that amorfrutin A potentiates TNF-alpha-induced apoptosis. Taken together, amorfrutin A could be a valuable candidate for the intervention of NF-kappa B-dependent pathological conditions such as inflammation. (C) 2014 Elsevier B.V. All rights reserved.