In vitro anti-inflammatory activity of iridoids and triterpenoid compounds isolated from Phillyrea latifolia L.
Two iridoids, oleuropeoside and ligustroside, and two triterpenoid compounds, oleanolic acid and ursolic acid, have been isolated from the leaves of Phillyrea latifolia L. (Oleaceae). These compounds were tested for interactions with the cyclooxygenase (COX) and 5-lipoxygenase (5-LOX) pathways of arachidonate metabolism in calcium ionophore-stimulated mouse peritoneal macrophages and human platelets, and for their effect on cell viability. Structure-activity relationships obtained for in vitro screening results were discussed. These compounds are capable of exerting inhibitory actions on enzymes of the arachidonate cascade. All compounds assayed showed a significant effect on prostaglandin E2 (PGE2)-release, with inhibition percentages similar to the reference drug indomethacin (IC50 = 0.95 microM). The IC50 values of the active compounds are: oleuropeoside 47 microM, ligustroside 48.53 microM, oleanolic acid 23.51 microM and ursolic acid 60.91 microM. In the leukotriene C4 (LTC4)-assay, only oleanolic acid showed a significant effect (IC50 = 16.79 microM). We also investigated the action of compounds on thromboxane B2 (TXB2)-release induced by calcium ionophore in human platelets. Of all the tested compounds, only ligustroside (IC50 = 122.63 microM) and ursolic acid (IC50 = 50.21 microM) showed a significant effect, although with less potency than the reference drug ibuprofen (IC50 = 1.27 microM). Thus, our compounds possess an array of potentially beneficial anti-inflammatory properties which may, alongside other constituents, contribute to the claimed therapeutic properties of the plant from which they are derived.
Díaz
A M
AM
Department of Pharmacology, Faculty of Pharmacy, University Alcala, Alcala de Henares, 28871 Madrid, Spain.
Abad
M J
MJ
Fernández
L
L
Recuero
C
C
Villaescusa
L
L
Silván
A M
AM
Bermejo
P
P
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D015777:Eicosanoids / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D039823:Iridoids / Q000494:pharmacology*; D017997:Leukotriene C4 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D029592:Oleaceae / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D013268:Stimulation, Chemical; D013929:Thromboxane B2 / Q000378:metabolism; D014315:Triterpenes / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D015777:Eicosanoids; D007476:Ionophores; D039823:Iridoids; D014315:Triterpenes; D017997:Leukotriene C4; D000001:Calcimycin; D013929:Thromboxane B2; D015232:Dinoprostone