Imperatorin inhibits T-cell proliferation by targeting the transcription factor NFAT

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Márquez N, Sancho R, Ballero M, Bremner P, Appendino G, Fiebich BL, Heinrich M & Muñoz, E 2004, 'Imperatorin inhibits T-cell proliferation by targeting the transcription factor NFAT', Planta Medica, vol. 70, no. 11, pp. 1016-1021.

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In our ongoing research into anti-inflammatory compounds from medicinal plants in the Mediterranean area, we have isolated several furanocoumarins from the roots of Oppopanax chironium (L.), and have evaluated them for activity related to T-cell functionality. Heraclenin (1) and imperatorin (2) significantly inhibited T cell receptor-mediated proliferation in human primary T cells in a concentration-dependent manner. In transient transfection experiments with a plasmid containing the IL-2 promoter we found that imperatorin is a potent inhibitor of IL-2 gene transcription. To further characterize the inhibitory mechanisms of imperatorin at the transcriptional level, we examined the DNA-binding and transcriptional activities of NF-κB, NFAT, and AP-1 transcription factors in Jurkat T cells. We found that imperatorin inhibited both the NFAT binding to DNA and transcriptional activities, without affecting significantly the activation of the NF-κB and AP-1 transcription factors. These findings provide new insights into the molecular mechanisms involved in the immunomodulatory and anti-inflammatory activities of natural furanocoumarins.

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