Acute inhibitory effect of alpha-mangostin on sarcoplasmic reticulum calcium-ATPase and myocardial relaxation

Abstract

The benefits of α-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 α-mangostin on cardiac function. Using a cardiac sarcoplasmic reticulum (SR) membrane preparation, α-mangostin inhibited SR Ca2+-ATPase activity in a dose-dependent manner (IC50 of 6.47 ± 0.7 μM). Its suppressive effect was specific to SR Ca2+-ATPase but not to myofibrillar Ca2+-ATPase. Using isolated cardiomyocytes, 50 μM of α-mangostin significantly increased the duration of cell relengthening and increased the duration of Ca2+ transient decay, suggesting altered myocyte relaxation. The relaxation effect of α-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 α-mangostin exerts specific inhibitory action on SR Ca2+-ATPase activity, leading to myocardial relaxation dysfunction. © 2017 Wiley Periodicals, Inc.