Abstract: |
The benefits of alpha-mangostin for various tissues have been reported, but its effect on the heart has not been clarified. This study aimed to evaluate the effects of alpha-mangostin on cardiac function. Using a cardiac sarcoplasmic reticulum (SR) membrane preparation, alpha-mangostin inhibited SR Ca2+ -ATPase activity in a dose-dependent manner (IC50 of 6.47 +/- 0.7 muM). Its suppressive effect was specific to SR Ca2+ -ATPase but not to myofibrillar Ca2+ -ATPase. Using isolated cardiomyocytes, 50 muM of alpha-mangostin significantly increased the duration of cell relengthening and increased the duration of Ca2+ transient decay, suggesting altered myocyte relaxation. The relaxation effect of alpha-mangostin was also supported in vivo after intravenous infusion. A significant suppression of both peak pressure and rate of ventricular relaxation (-dP/dt) relative to DMSO infusion was observed. The results from the present study demonstrated that alpha-mangostin exerts specific inhibitory action on SR Ca2+ -ATPase activity, leading to myocardial relaxation dysfunction. |