Asunto(s)
Humanos , Femenino , Carcinoma Ductal de Mama/complicaciones , Carcinoma Ductal de Mama/diagnóstico , Carcinoma Ductal de Mama/cirugía , Metástasis de la Neoplasia/patología , Recurrencia Local de Neoplasia/complicaciones , Recurrencia Local de Neoplasia/diagnóstico , Neoplasias de la Tiroides/complicaciones , Neoplasias de la Tiroides/diagnóstico , Carcinoma Ductal de Mama/patología , Carcinoma Ductal de Mama , Metástasis de la Neoplasia/terapia , Metástasis de la Neoplasia , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia , Glándula Tiroides/patología , Glándula Tiroides , Neoplasias de la Tiroides/patología , Neoplasias de la TiroidesRESUMEN
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.
Asunto(s)
Antiinflamatorios/farmacología , Eicosanoides/antagonistas & inhibidores , Glicósidos/farmacología , Fenoles , Fenilpropionatos , Animales , Antiinfecciosos/química , Antiinfecciosos/farmacología , Antiinflamatorios/química , Antiinflamatorios/aislamiento & purificación , Plaquetas/efectos de los fármacos , Plaquetas/metabolismo , Células Cultivadas , Cinamatos/química , Cinamatos/aislamiento & purificación , Cinamatos/farmacología , Dinoprostona/metabolismo , Interacciones Farmacológicas , Eicosanoides/biosíntesis , Femenino , Glucósidos/química , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Glicósidos/química , Glicósidos/aislamiento & purificación , Humanos , Ionóforos/farmacología , Leucotrieno C4/metabolismo , Macrófagos Peritoneales/metabolismo , Magnoliopsida/química , Masculino , Ratones , Plantas Medicinales , Tromboxano B2/antagonistas & inhibidores , Tromboxano B2/metabolismoRESUMEN
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.
Asunto(s)
Ácido Araquidónico/metabolismo , Glicósidos/farmacología , Plantas/química , Animales , Secuencia de Carbohidratos , Femenino , Humanos , Masculino , Ratones , Datos de Secuencia MolecularRESUMEN
Buddlejasaponin I and saikosaponin 1 and 2, biologically active compounds from Scrophularia scorodonia and Bupleurum rigidum respectively, exert potent in vivo antiinflammatory effects on mouse ear edema induced by phorbol myristate acetate (PMA). The effects of these compounds on swelling and other inflammatory parameters are described. In screening for in vitro effects of saikosaponins on cellular systems generating cyclooxygenase (COX) and lipoxygenase (LOX) metabolites, we observed that most saikosaponins showed a significant effect. The action is more marked on LOX metabolite LTC4. Our data support the inhibition of arachidonic acid metabolism as one of the biochemical mechanisms that might be the rationale for the putative antiphlogistic activity of these saikosaponins.