Ellagic acid and gingerol, activators of the sarco-endoplasmic reticulum Ca²⁺-ATPase, ameliorate diabetes mellitus-induced diastolic dysfunction in isolated murine ventricular myocardia.

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.