A novel diterpenoid labdane from Sideritis javalambrensis inhibits eicosanoid generation from stimulated macrophages but enhances arachidonate release

Biochemical Pharmacology
L PangJ R Hoult

Abstract

The diterpenoid ent-8alpha-hydroxy-labda-13(16),14-dien ("labdane F2") was obtained from an anti-inflammatory extract of Sideritis javalambrensis. Labdane F2 inhibited prostaglandin E2 generation in cultured mouse peritoneal macrophages, treated with zymosan, ionophore A23187, or arachidonic acid itself, and in J774 macrophage-like cells activated by bacterial lipopolysaccharide (LPS). The mechanism was investigated by prelabelling the macrophages with radiolabelled arachidonic acid or oleic acid, followed by cell activation in the presence or absence of nontoxic concentrations of labdane F2. Surprisingly, under those conditions in which reduced PGE2 generation was observed, labdane F2 consistently enhanced the release of labelled fatty acid, in a manner similar to that displayed by thimerosal a known acyl-CoA: lysolecithin transferase inhibitor. Labdane E2 therefore appears to possess 2 mutually opposing actions on the eicosanoid system in macrophages: potentiation of delivery of substrate following cell activation, followed by inhibition of conversion of substrate to product. It was also found that nontoxic concentrations of labdane F2 reduced the expression of the inducible isoforms of cyclooxygenase and nitric oxide synthas...Continue Reading

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Citations

May 22, 2002·Journal of Ethnopharmacology·Margarita Hernández-Pérez, Rosa M Rabanal
Jul 25, 2000·Journal of Ethnopharmacology·C VillenaA M Villar
Oct 12, 1999·British Journal of Pharmacology·B de las HerasA Villar
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Aug 8, 2002·Phytotherapy Research : PTR·Margarita Hernández-Pérez, Rosa M Rabanal Gallego
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Apr 4, 2008·Phytotherapy Research : PTR·Maria-Thiresia CharamiChristos Souleles
May 14, 2008·Journal of Natural Products·Mohamed-Elamir F HegazyToshifumi Hirata

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