Díaz A M, Abad M J, Fernández L, Recuero C, Villaescusa L, Silván A M, Bermejo P
Department of Pharmacology, Faculty of Pharmacy, University Alcala, Alcala de Henares, 28871 Madrid, Spain.
Biol Pharm Bull. 2000 Nov;23(11):1307-13. doi: 10.1248/bpb.23.1307.
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.
从木犀科植物狭叶木犀（Phillyrea latifolia L.）的叶子中分离出了两种环烯醚萜类化合物，橄榄苦苷和女贞苷，以及两种三萜类化合物，齐墩果酸和熊果酸。在钙离子载体刺激的小鼠腹腔巨噬细胞和人血小板中，测试了这些化合物与花生四烯酸代谢的环氧合酶（COX）和5-脂氧合酶（5-LOX）途径的相互作用，以及它们对细胞活力的影响。讨论了体外筛选结果所获得的构效关系。这些化合物能够对花生四烯酸级联反应的酶发挥抑制作用。所有测定的化合物对前列腺素E2（PGE2）的释放均有显著影响，抑制百分比与参考药物吲哚美辛相似（IC50 = 0.95 microM）。活性化合物的IC50值分别为：橄榄苦苷47 microM、女贞苷48.53 microM、齐墩果酸23.51 microM和熊果酸60.91 microM。在白三烯C4（LTC4）测定中，只有齐墩果酸显示出显著作用（IC50 = 16.79 microM）。我们还研究了这些化合物对钙离子载体诱导的人血小板血栓素B2（TXB2）释放的作用。在所有测试的化合物中，只有女贞苷（IC50 = 122.63 microM）和熊果酸（IC50 = 50.21 microM）显示出显著作用，尽管效力低于参考药物布洛芬（IC50 = 1.27 microM）。因此，我们的化合物具有一系列潜在有益的抗炎特性，这可能与其他成分一起，有助于其来源植物所宣称的治疗特性。
