Effects of six diterpenes on macrophage eicosanoid biosynthesis.
Six diterpenes (three clerodanes, two abietanes and one rosane) were tested for interactions with the cyclooxygenase and 5-lipoxygenase pathways of arachidonate metabolism and for effects of nitric oxide production. Two abietane diterpenes, aethiopinone and 11,12-dihydroxy-6-oxo-8,11,13-abietatriene and the rosane lagascatriol showed a remarkable effect on COX-1 pathway of PGE2 release in calcium ionophore A23187-stimulated peritoneal macrophages. Only the two latter diterpenes showed inhibition on COX-2 pathway of PGE2 release in E. coli LPS-stimulated peritoneal macrophages. In addition, all compounds assayed were inhibitors of LTC4 release with IC50 < or = 10 microM. Clerodane diterpenes were inactive in COX assay. None of the diterpenes assayed, except 11,12-dihydroxy-6-oxo-8,11,13-abietatriene, affected NO production. The results obtained suggest that the cellular mechanisms of action of some of these substances may involve inhibition of cyclooxygenase/lipoxygenase pathways and nitric oxide production.
de las Heras
B
B
Departamento de Farmacología, Facultad de Farmacia, Universidad Complutense de Madrid, Spain.
Abad
M J
MJ
Silván
A M
AM
Pascual
R
R
Bermejo
P
P
Rodríguez
B
B
Villar
A M
AM
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D004224:Diterpenes / Q000494:pharmacology*; D015777:Eicosanoids / Q000096:biosynthesis*; D007527:Isoenzymes / Q000378:metabolism; D017997:Leukotriene C4 / Q000096:biosynthesis; D017737:Macrophages, Peritoneal / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004224:Diterpenes; D015777:Eicosanoids; D007527:Isoenzymes; D017997:Leukotriene C4; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D015232:Dinoprostone