Astragalosides were the main active components from a native Chinese herb Astragalus membranaceus. Recent studies have shown that Astragalosides have a protective effect on myocardial injury in rats. The present study was designed to investigate the effect of Astragalosides on intracellular calcium overload and sarcoplasmic reticulum calcium load (SR Ca 2+ load) in cultured cardiac myocytes from neonatal rats. Astragalosides (100 μg/ml) were incubated in the presence of isoproterenol (ISO) (10-5 M) for 72 hours in cardiomyocytes. Metoprorol (10-6 M), a β1-selective antagonist, was cultured in the same condition as Astragalosides. The result showed that intracellular calcium concentration ([ Ca 2+] i ) and SR Ca 2+ load increased in ISO-treated cardiac myocytes as compared to control (P<0.01). Astragalosides prevented ISO-induced increase in [ Ca 2+] i and SR Ca 2+ load. Metoprolol also inhibited those increase. The mRNA expression and activity of sarcoplasmic reticulum Ca 2+ ATPase (SERCA) were enhanced following ISO treatment in cardiac myocytes, and these increases were inhibited by Astragalosides or metoprolol (P<0.05). The decrease of superoxide dismutase (SOD) activity and the elevation of intracellular maleic dialdehyde (MDA) were observed after ISO treatment in cardiac myocytes. Both Astragalosides and metoprolol restored the SOD activity and reduced the level of MDA. We conclude that Astragalosides have the effects on reducing [ Ca 2+] i and SR Ca 2+ load, enhancing free radical removal and decreasing lipid peroxidation in ISO-treated cardiomyocytes, which might account for their protective effect on myocardial injury.
Correlation between calmodulin-dependent increase in the rate of calcium transport and calmodulin-dependent phosphorylation of cardiac sarcoplasmic reticulum. Characterization of calmodulin-dependent phosphorylation