Ranolazine,a late sodium current inhibitor,has been demonstrated to be effective on heart failure.18β-glycyrrhetinic acid(18β-GA)has the similar inhibitory effect on late sodium currents.However,its effect on diastolic function is still unknown.This study aimed to determine whether 18β-GA can improve the diastolic function and to explore the underlying mechanisms.Eighty male Sprague Dawley(SD)rats of Langendorff model were randomly divided into the following groups:group A,normal cardiac perfusion group;group B,ischemia-reperfusion group;group C,ischemia-reperfusion with anemoniasulcata toxin Ⅱ(ATX-Ⅱ);group D,ranolazine group;and group E,18β-GA group with four different concentrations.Furthermore,a pressure-overloaded rat model induced by trans-aortic constriction(TAC)was established.Echocardiography and hemodynamics were used to evaluate diastolic function at 14th day after TAC.Changes of free intracellular calcium(Ca2+)concentration was indirectly detected by laser scanning confocal microscope to confirm the inhibition of late sodium currents.With the intervention of ATX-Ⅱ on ischemia reperfusion injury group,5 μmol/L ranolazine,and 5,10,20,40 μmol/L 18β-GA could improve ATX-Ⅱ-induced cardiac diastolic dysfunction.630 mg/kg glycyrrhizin tablets could improve cardiac diastolic function in the pressure-overloaded rats.18β-GA and ranolazine had similar effects on reducing the free calcium in cardiomyocytes.The study demonstrates that 18β-GA and glycyrrhizin could improve diastolic dysfunction induced by ischemia-reperfusion injury in Langendorff-perfused rat hearts and pressure-overloaded rats.The mechanism may be attributed to the inhibition of enhanced late sodium currents.