Effects of Some Iridoids from Plant Origin on Arachidonic Acid Metabolism in Cellular Systems

Abstract

Seven iridoid glycosides isolated from different extracts of Scrophularia scorodonia L., namely bartsioside, aucubin, harpagide, harpagoside, 8-acetylharpagide, scorodioside and scropolioside B, had been evaluated for their in vitro anti-inflammatory activity in cellular systems generating COX and LOX metabolites. Structure-activity relationships obtained from in vitro screening results were discussed. Most compounds assayed did not exhibit any significant effect on PGE₂- and LTC₄-release from calcium ionophore-stimulated mouse peritoneal macrophages. In the LTC₄-assay, only aucubin showed a significant effect, with an IC₅₀ value of 72 μM. Harpagoside and harpagide also inhibited release of LTC₄, but neither effect reached statistical significance. The release of PGE₂ by mouse peritoneal macrophages stimulated with calcium ionophore was inhibited by harpagoside and 8-acetylharpagide, but this effect is not statistically significant. However, most iridoids assayed showed a significant effect on TXB₂-release from calcium ionophore-stimulated human platelets, with inhibition percentages slightly lower than the reference drug ibuprofen. Only harpagide, scorodioside and scropolioside B had no significant effect on TXB₂-release. Our results indicate that selective inhibition of the TX-synthase enzyme may be the primary target of action of most of these iridoids, and one of the mechanisms through which they exert their anti-inflammatory effects.

Abbreviations

COX:cyclooxygenase5-LOX:5-lipoxygenaseAA:arachidonic acidPGs:prostaglandinsTXs:thromboxanesLTs:leukotrienesNSAIDs:non-steroidal anti-inflammatory drugsHETEs:hydroxy-eicosatetraenoic acidsNDGA:nordihydroguaiaretic acidDMSO:dimethyl sulfoxideEDTA:ethylenediaminotetraacetic acidMTT:3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromideELISA:enzyme-linked immunosorbent assayPBS:Dulbecco's phosphate-buffered salineDMEM:Dulbecco's modified Eagle's mediumFCS:fetal calf serumPMA:phorbol myristate acetatePKC:protein kinase C

Key words

Iridoids - Scrophularia scorodonia - Scrophulariaceae - anti-inflammatory activity - PGE₂ - LTC₄ - TXB₂

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