Study of three sesquiterpene lactones from Tithonia diversifolia on their anti-inflammatory 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 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 A2, or the transcription factor NF-kappa B. Here we show that these Sls 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 Sls were also studied for their antibacterial activity, but only Sl 1 was moderately active against Bacillus subtilis in the agar plate diffusion test.
Rüngeler
P
P
Institut für Pharmazeutische Biologie, Universität Freiburg, Germany.
Lyss
G
G
Castro
V
V
Mora
G
G
Pahl
H L
HL
Merfort
I
I
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D019659:Asteraceae / Q000737:chemistry*; D051545:Cyclooxygenase 1; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000187:drug effects; D019169:Jurkat Cells; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008565:Membrane Proteins; D015394:Molecular Structure; D016328:NF-kappa B / Q000378:metabolism*; D010741:Phospholipases A / Q000037:antagonists & inhibitors*; D054467:Phospholipases A2; D010946:Plants, Medicinal / Q000737:chemistry; D011451:Prostaglandin-Endoperoxide Synthases / Q000187:drug effects; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004791:Enzyme Inhibitors; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D016328:NF-kappa B; D012717:Sesquiterpenes; C115944:diversifolin; C115943:diversifolin methyl ether; C115942:tirotundin; D051545:Cyclooxygenase 1; C496511:PTGS1 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D010741:Phospholipases A; D054467:Phospholipases A2