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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Paulina Bermejo Benito
Department of Pharmacology Faculty of Pharmacy University Complutense
28040 Madrid
Spain
eMail: naber@eucmax.sim.ucm.es
Telefon: +34-1-3941764