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 PGE(2) release in calcium ionophore A23187-stimulated peritoneal macrophages. Only the two latter diterpenes showed inhibition on COX-2 pathway of PGE(2) release in E. coli LPS-stimulated peritoneal macrophages. In addition, all compounds assayed were inhibitors of LTC4 release with IC(50)less than or equal to 10 muM. 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. (C) 2001 Elsevier Science Inc. All rights reserved.