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 cyclo-oxygenase pathway, inhibiting release of the cyclo-oxygenase metabolites prostaglandin E2 (IC50 values 45.6 microM, 72.1 microM and 35.5 microM, respectively) and to a lesser extent reducing thromboxane B2 levels (IC50 values 168 microM, 154 microM and 29.3 microM, 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 microM for prostaglandin E2 and 619 microM for thromboxane B2) and 5-lipoxygenase metabolites, but the effects are greater against leukotriene C4 (IC50 value 63.6 microM). 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.
Díaz Lanza
A M
AM
Department of Pharmacology, Faculty of Pharmacy, University Alcala, Alcala de Henares, Madrid, Spain.
Abad Martínez
M J
MJ
Fernández Matellano
L
L
Recuero Carretero
C
C
Villaescusa Castillo
L
L
Silván Sen
A M
AM
Bermejo Benito
P
P
D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D002934:Cinnamates / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004347:Drug Interactions; D015777:Eicosanoids / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005260:Female; D005960:Glucosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D006027:Glycosides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007476:Ionophores / Q000494:pharmacology; D017997:Leukotriene C4 / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000378:metabolism; D019684:Magnoliopsida / Q000737:chemistry; D008297:Male; D051379:Mice; D010636:Phenols; D010666:Phenylpropionates; D010946:Plants, Medicinal; D013929:Thromboxane B2 / Q000037:antagonists & inhibitors / Q000378:metabolism
D000890:Anti-Infective Agents; D000893:Anti-Inflammatory Agents; D002934:Cinnamates; D015777:Eicosanoids; D005960:Glucosides; D006027:Glycosides; D007476:Ionophores; D010636:Phenols; D010666:Phenylpropionates; D017997:Leukotriene C4; D013929:Thromboxane B2; C028305:syringin; D015232:Dinoprostone; C016316:coniferin; C009172:rhodioloside; C075528:phillyrin