Márquez Nieves, Sancho Rocío, Ballero Mauro, Bremner Paul, Appendino Giovanni, Fiebich Bernd L, Heinrich Michael, Muñoz Eduardo
Departamento de Biología Celular, Fisiología e Inmunología, Universidad de Córdoba, Facultad de Medicina, Córdoba, Spain.
Planta Med. 2004 Nov;70(11):1016-21. doi: 10.1055/s-2004-832640.
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-kappaB, 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-kappaB 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.
