Allantopyrone A, an α-pyrone metabolite from an endophytic fungus, inhibits the tumor necrosis factor α-induced nuclear factor κB signaling pathway.

Tumor necrosis factor α (TNF-α) induces the activation of transcription factor nuclear factor κB (NF-κB), which upregulates a variety of genes, including the gene encoding intercellular adhesion molecule-1 (ICAM-1). Allantopyrone A, a recently identified α-pyrone metabolite from an endophytic fungus, was found to inhibit the TNF-α-induced expression of ICAM-1 in human lung carcinoma A549 cells. Allantopyrone A also inhibited the TNF-α-induced luciferase expression of an NF-κB-responsive reporter. In the NF-κB signaling pathway, allantopyrone A inhibited the nuclear translocation of NF-κB subunits as well as the phosphorylation and subsequent degradation of the inhibitor of NF-κB (IκB) α proteins. By contrast, allantopyrone A did not directly affect the catalytic activity of active IκB kinase β. These findings indicate that allantopyrone A inhibits the NF-κB signaling pathway at a step upstream of IκBα phosphorylation.