Lignan and phenylpropanoid glycosides from Phillyrea latifolia and their in vitro anti-inflammatory activity

Three phenylpropanoid glycosides (salidroside, syringin and coniferin) and one lignan (phillyrin) isolated from the leaves of Phillyrea latifolia L. (Oleaceae) were tested for interactions with the cyclo-oxygenase and 5-lipoxygenase pathways of arachidonate metabolism in calcium-stimulated mouse peritoneal macrophages and human platelets, and for their effects on cell viability. These compounds are capable of exerting inhibitory actions on enzymes of the arachidonate cascade. Phillyrin, salidroside and syringin exert a preferential effect on the cyclooxygenase pathway, inhibiting release of the cyclo-oxygenase metabolites prostaglandin E-2 (IC50 values 45.6 muM, 72.1 muM and 35.5 muM, respectively) and to a lesser extent reducing thromboxane B-2 levels (IC50 values 168 muM. 154 muM and 29.3 muM. respectively), In contrast, coniferin can be classified as a dual inhibitor, since it produces reduction in generation of both cyclo-oxygenase (IC50 values 75.2 muM for prostaglandin E-2 and 619 muM for thromboxane B-2) and 5-lipoxygenase metabolites, but the effects are greater against leukotriene C-4 (IC50 Value 63.6 muM). Structure-activity relationships of the three phenylpropanoid glycosides are discussed. Thus, like some other compounds found in medicinal herbs, our molecules possess an array of potentially beneficial anti-eicosanoid properties which may, alongside other constituents, contribute to the claimed therapeutic properties of the plant from which they are derived.