STUDY OF 3 SESQUITERPENE LACTONES FROM TITHONIA-DIVERSIFOLIA ON THEIRANTIINFLAMMATORY ACTIVITY USING THE TRANSCRIPTION FACTOR NF-KAPPA-B AND ENZYMES OF THE ARACHIDONIC-ACID PATHWAY AS TARGETS

In Central America leaf extracts from the Asteraceae Tithonia diversif olia are used externally for the treatment of haematomas and wounds. T herefore, the main sesquiterpene lactones (Sls) of this species growin g in Costa Rica, diversifolin (1), diversifolin methyl ether (2), and tirotundin (3), were studied for their anti-inflammatory activity. We determined whether these compounds inhibit cyclooxygenase-I, phospholi pase A(2), or the transcription factor NF-kappa B. Here we show that t hese Sis do not influence the enzymes of the arachidonic acid pathway, but inhibit the activation of NF-kappa B. Thereby, the synthesis of i nflammatory mediators such as cytokines and chemokines is reduced. Our results indicate that the inhibitory activity of compounds 1 3 is due to alkylation of cysteine residues, which are probably located in the DNA binding domain of NF-kappa B. The Sis were also studied for their antibacterial activity, but only SI 1 was moderatly active against Ba cillus subtilis in the agar plate diffusion test.