Biol. Pharm. Bull. 27(6) 926—928 (2004)

pressed in most immune system cells and regulate the transcription of cytokine genes critical for the immune response. The activity of NFAT proteins is tightly regulated by the Ca /calmodulin-dependent protein phosphatase 2B/calcineurin (CaN). Dephosphorylation of NFAT by CaN is required for NFAT nuclear localization, and then in the nucleus NFAT activates the transcription of target genes, such as interleukin-2, -3, -4, -5, -8, -13, tumor necrosis factor-a , granulocyte-macrophage colony-stimulating factor, and g-IFN. Normally activation of NFAT plays a key role in regulating a large number of inducible genes during the immune response. However, excessive activation provokes immunopathologic reactions including autoimmunity, transplant rejection, and inflammation. Current immunosuppressive drugs such as cyclosporin A (CsA) and FK506 block CaN activity, thus inhibiting nuclear translocation of NFAT and consequent cytokine gene transcription. Both CsA and FK506 have been effective in preventing organ graft rejection in the clinic. However, side effects observed with the clinical use of both of these compounds and gastrointestinal toxicity have markedly reduced their impact. In a searching for inhibitors of NFAT activity from natural products, the MeOH extract of the fruits of Evodia rutaecarpa showed significant inhibitory activity of NFAT as assessed by a reporter gene assay. Here we describe the isolation and effects of three known quinolone alkaloids (1—3) together with other quinolone alkaloids (4—9) from the Evodia fruits on the activities of NFAT and nuclear factor (NF)kB.