Peperomins as anti-inflammatory agents that inhibit the NF-kappaB signaling pathway.

ABSTRACT

The transcription factor nuclear factor kappaB (NF-kappaB) induces the expression of various inflammatory genes. In the common NF-kappaB signaling pathway, peperomin E and 2,6-didehydropeperomin B inhibited IkappaB degradation upon stimulation with TNF-alpha or interleukin-1. Consistent with these results, peperomin E and 2,6-didehydropeperomin B blocked the TNF-alpha-induced activation of IkappaB kinase, while they had no direct effect on the IkappaB kinase activity. Our present results clearly demonstrate that peperomins inhibit the NF-kappaB signaling pathway by blocking IkappaB kinase activation.