Study of three sesquiterpene lactones from Tithonia diversifolia on their anti-inflammatory activity using the transcription factor NF-κB and enzymes of the arachidonic acid pathway as targets

In Central America leaf extracts from the Asteraceae Tithonia diversifolia are used externally for the treatment of haematomas and wounds. Therefore, the main sesquiterpene lactones (Sls) of this species growing 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, phospholipase A(2), or the transcription factor NF-kappa B. Here we show that these Sis do not influence the enzymes of the arachidonic acid pathway, but inhibit the activation of NF-kappa B. Thereby, the synthesis of inflammatory 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 Bacillus subtilis in the agar plate diffusion test.