RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: The fight against chronic respiratory diseases needs the exploration of new active compounds with properties that contribute to diminish the symptoms or resolve the disease alongside current therapy. MATERIALS AND METHODS: Eight extracts obtained from the bark and leaves of a Mayan medicinal plant used to treat asthma, Cordia dodecandra A. DC., were investigated for their relaxant effect on rat isolated tracheal rings pre-contracted with carbachol [1⯵M]. The underlying functional mode of action of the most effective extract was assessed and the chromatographic fingerprints of more active extracts were analyzed. RESULTS: The dichloromethane bark extract (DECd-b) was the most effective and potent (Emax= 87.57⯱â¯1.32 %; EC50 = 392.7⯱â¯5.18⯵g/mL). DECd-b relaxant effect was maximized in presence of isoproterenol (ß-adrenergic agonist, [10⯵M]) and theophylline (phosphodiesterase unspecific inhibitor, [10⯵M]). DECd-b also showed efficient relaxation of KCl [80â¯mM]-induced contraction and inhibition of CaCl2-induced contraction. Pre-incubation with propranolol (non-selective ß-adrenergic antagonist, [10⯵M]), SQ22536 (adenylyl cyclase inhibitor; [100 µM]), ODQ (guanylyl cyclase inhibitor; [10⯵M]), l-NAME (nitric oxide synthase inhibitor; [10⯵M]), indomethacin (a cyclooxygenase unspecific inhibitor; [10⯵M]), glibenclamide (ATP-sensitive potassium channel blocker; [10⯵M]) and 2-aminopyridine (voltage-gated potassium channel blocker [100⯵M]) did not modify the DECd-b relaxant-effect curve. The chromatographic analysis of DECd-b suggests the cordiaquinones presence with double conjugated bounds such as menaquinone. CONCLUSIONS: Results suggest that DECd-b induces relaxation mainly by cAMP increase and Ca2+ channel blockade. The chromatographic profiles and UV spectrum of DECd-b and HECd-l suggest the presence of molecules with structure of meroterpenoid naphthoquinones. This work report scientific evidence of C. dodecandra medicinal specie, which contributes to the pharmacological and phytochemical background of C. dodecandra providing an added value to the traditional use of this specie.
Asunto(s)
Bloqueadores de los Canales de Calcio/farmacología , Cordia , AMP Cíclico/metabolismo , Parasimpatolíticos/farmacología , Extractos Vegetales/farmacología , Tráquea/efectos de los fármacos , Animales , Técnicas In Vitro , Masculino , Relajación Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , Corteza de la Planta , Hojas de la Planta , Ratas Wistar , Tráquea/fisiologíaRESUMEN
The aim of current study was to determinate ex vivo and chromatographic fingerprint by HPLC of four extracts of Euphorbia furcillata K. Ethyl acetate extract of Euphorbia furcillata (EaEEf) was the most effective and potent extract (Emax=98.69±1.24%) and its effect was partially endothelium-dependent. Functional vasorelaxant mechanism of action of EaEEf was determinate, EaEEf showed efficient relaxation of KCl [80 mM]-induced contraction and norepinephrine and CaCl2 contraction curves showed diminution of maximal contraction in the presence of EAEEf and EaEEf-relaxation curve was shifted to the right in the presence of L-NAME (nitric oxide synthase inhibitor) and ODQ (guanylate cyclase inhibitor). Chromatographic fingerprints analysis suggests presence of diterpenoid such as abietane, tigliane, and ingenane skeletons. Our experiments suggest the EaEEf vasorelaxant activity could be attributed to diterpenoid molecules whose mechanism involves nitric oxide production and calcium channel blockade.
Se determinoÌ el efecto vasorrelajante ex vivo y los perfiles cromatograÌficos mediante HPLC de cuatro extractos de Euphorbia furcillata K.. El extracto de acetato de etilo de E. furcillata (EaEEf) fue el maÌs eficaz y potente en la contraccioÌn inducida por norepinefrina (Emax=98.69±1.24%) y el efecto fue parcialmente dependiente del endotelio vascular. Se determinoÌ el mecanismo de accioÌn vasorrelajante para EaEEf, este mostroÌ ser eficaz sobre la contraccioÌn inducida por KCl [80 mM] y la curva de contraccioÌn en respuesta a norepinefrina y CaCl2 en presencia de EaEEf mostroÌ disminucioÌn en la contraccioÌn maÌxima, mientras que la curva de relajacioÌn de EaEEf en presencia de L-NAME (inhibidor de oÌxido niÌtrico sintasa) y ODQ (inhibidor de guanilato ciclasa) se desplazoÌ hacia la derecha. El anaÌlisis cromatograÌfico de EaEEf sugiere la presencia de moleÌculas diterpenoides como abietano, tigliano y esqueletos de ingenano. Nuestros resultados sugieren que el efecto vasorrelajante de EaEEf podriÌa atribuirse a moleÌculas diterpenoides, cuyo mecanismo de accioÌn involucra la produccioÌn de oÌxido niÌtrico y bloqueo de canales de calcio.