RESUMEN
The effects of sarco-endoplasmic reticulum Ca(2+)-ATPase (SERCA) activators, ellagic acid and gingerol, on the contraction and Ca(2+) transient were examined in isolated myocardia from streptozotocin-induced diabetic mice and compared with control mice. The time required for relaxation of the right ventricular free wall was significantly longer in streptozotocin-treated mice. The basal Ca(2+) concentration of isolated ventricular myocytes from streptozotocin-treated mice was significantly higher than those from control mice. The Ca(2+) transient decay rate was significantly lower in myocytes from streptozotocin-treated mice. Cyclopiazonic acid, a SERCA inhibitor, decreased the rate of relaxation and the rate of Ca(2+) transient decay; these effects were larger in control mice. Both ellagic acid and gingerol accelerated the rate of relaxation and the rate of Ca(2+) transient decay; these effects were larger in the streptozotocin-treated mice. The acceleration of relaxation by ellagic acid and gingerol was completely inhibited by cyclopiazonic acid. These results suggest that the diabetes mellitus-induced myocardial diastolic dysfunction is partly caused by reduction of SERCA function and can be ameliorated by SERCA activators.
Asunto(s)
Catecoles/farmacología , Diabetes Mellitus Experimental/fisiopatología , Ácido Elágico/farmacología , Alcoholes Grasos/farmacología , Miocitos Cardíacos/efectos de los fármacos , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/fisiología , Animales , Calcio/fisiología , Diabetes Mellitus Experimental/tratamiento farmacológico , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Técnicas In Vitro , Indoles/farmacología , Masculino , Ratones , Contracción Miocárdica/efectos de los fármacos , Miocardio , Miocitos Cardíacos/fisiología , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/antagonistas & inhibidoresRESUMEN
An efficient procedure for transesterification of methyl caffeate was developed to produce caffeic acid phenethyl ester analogues with Candida antarctica lipase B using an ionic liquid, 1-butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide, as a solvent. The system provided 48.8mM 2-cyclohexylethyl caffeate and 46.9 mM 3-cyclohexylpropyl caffeate with conversion yields of 97.6% and 93.8%, respectively. Reusability of the system was investigated, and the yield of 4-phenylbutyl caffeate was increased from 30.4 to 45.7 mM when the transesterification was carried out under reduced pressure to remove a by-product, methanol. Additionally, we showed that both 2-cyclohexylethyl caffeate and 3-cyclohexylpropyl caffeate exhibit strong antiproliferative activities, which are comparable to that of 5-fluorouracil by MTT assay.