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 microM. 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 ionophorestimulated 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.

Estimation of the relative antiinflammatory efficacies of six commercial preparations of Harpagophytum procumbens (Devil's Claw)

“…However, some negative or non-signifi cant results have also been obtained in in vitro studies that tested varied extracts for their action on leukotrienes and prostaglandins in human or mouse blood. The results showed no significant effect on the synthesis of these eicosanoids hence on COX-2 and LOX pathways (Moussard et al, 1992;Benito et al, 2000). In addition to the varied formulation types and doses, discrepancies in the clinical results can also be related to the route of administration as well as to the type and location of infl ammation.…”

Devil’s Claw (Harpagophytum procumbens): An Anti-Inflammatory Herb with Therapeutic Potential

“…This study also demonstrated that the extract inhibits LPS-induced sysnthesis of IL-6, IL-1b and PGE 2 but at concentrations of more than 100 lg of extract/ml. Several iridoid glycosides that are characteristic of Devil's Claw extracts but isolated from Scrophularia scorodonia L., including harpagide, harpagoside, 8-acetylharpagide and aucubin were tested in vitro for effects on the cyclo-oxygenase (COX) and lipo-oxygenase (LOX) pathways in isolated mouse peritoneal macrophages and human blood platelets (Benito et al, 2000). Most of the compounds that were tested did not exhibit a significant effect on the stimulated release of prostaglandin E 2 (PGE 2 ) (product of COX pathway) and of the cysteinyl-leukotriene, LTC 4 , (the major secreted product of the LOX pathway) in calcium ionophore-stimulated mouse peritoneal macrophages.…”

Naturally Occurring Secoiridoids and Bioactivity of Naturally Occurring Iridoids and Secoiridoids. A Review, Part 2

“…Lonicera japonica (Caprifoliaceae). 12) 46.9 (C-9), 118.6 (C-10), 168.4 (C-11), 55.0 (OMe), 97.9 (C-1Ј), 73.0 (C-2Ј), 76.7 (C-3Ј), 70.0 (C-4Ј), 77.0 (C-5Ј), 61.1 (C-6Ј). Gentiana scabra (Gentianaceae).…”