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Drug Dev Res ; 80(7): 981-991, 2019 11.
Artículo en Inglés | MEDLINE | ID: mdl-31343767

RESUMEN

Salvia tiliifolia is used in folk medicine as a relaxant agent and for the treatment of diarrhea and neurodegenerative diseases. Tilifodiolide (TFD) is a diterpene obtained from this plant. The purpose of this work was to evaluate the antidiarrheal, vasorelaxant, and neuropharmacological actions of TFD. These effects were selected based on the folk medicinal use of S. tiliifolia. The antidiarrheal activity of 1-50 mg/kg p.o. TFD was assessed with the castor oil related tests. The vasorelaxant effect of TFD (0.9-298 µM) was performed with smooth muscle tissues from rats, and its mechanism of action was evaluated using different inhibitors. The sedative, anxiolytic, and antidepressant effects of 1-100 mg/kg TFD were assessed. The possible mechanisms of action of the anxiolytic and antidepressant effects of TFD were evaluated using inhibitors. TFD exhibited antidiarrheal (ED50 = 10.62 mg/kg) and vasorelaxant (EC50 = 48 ± 3.51 µM) effects. The coadministration of TFD with N(ω)-nitro-L-arginine methyl ester (L-NAME) or 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), reverted the vasorelaxant action showed by TFD alone. TFD exerted anxiolytic actions (ED50 = 20 mg/kg) in the cylinder exploratory test, whereas TFD (50 mg/kg) showed antidepressant actions in the tail suspension test by 44%. The pretreatment with 2 mg/kg flumazenil partially reverted the anxiolytic actions of TFD, whereas the pretreatment with 1 mg/kg yohimbine abolished the antidepressant effects of TFD. In summary, TFD exerted antidiarrheal activity by decreasing the intestinal fluid accumulation and vasorelaxant effects mediated by nitric oxide and cyclic guanosine monophosphate. TFD showed anxiolytic and antidepressant effects by the partial involvement of gamma-Aminobutyric acid (GABA) receptors and the possible participation of α2-adrenoreceptors, respectively.


Asunto(s)
Antidiarreicos/farmacología , Conducta Animal/efectos de los fármacos , Diterpenos/farmacología , Músculo Liso/efectos de los fármacos , Vasodilatadores/farmacología , Animales , Ansiolíticos/farmacología , Antidepresivos/farmacología , Diterpenos/antagonistas & inhibidores , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Flumazenil/farmacología , Hipnóticos y Sedantes/farmacología , Masculino , Ratones , NG-Nitroarginina Metil Éster/farmacología , Oxadiazoles/farmacología , Quinoxalinas/farmacología , Vasodilatadores/antagonistas & inhibidores , Yohimbina/farmacología
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