Effect of astragalosides on intracellular calcium overload in cultured cardiac myocytes of neonatal rats.
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 Ca2+ load) in cultured cardiac myocytes from neonatal rats. Astragalosides (100 microg/ml) were incubated in the presence of isoproterenol (ISO) (10(-5) M) for 72 hours in cardiomyocytes. Metoprorol (10(-6) M), a beta1-selective antagonist, was cultured in the same condition as Astragalosides. The result showed that intracellular calcium concentration ([Ca2+]i) and SR Ca2+ load increased in ISO-treated cardiac myocytes as compared to control (P < 0.01). Astragalosides prevented ISO-induced increase in [Ca2+]i and SR Ca2+ load. Metoprolol also inhibited those increase. The mRNA expression and activity of sarcoplasmic reticulum Ca2+ 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 [Ca2+]i and SR Ca2+ load, enhancing free radical removal and decreasing lipid peroxidation in ISO-treated cardiomyocytes, which might account for their protective effect on myocardial injury.
Meng
Dan
D
Research Institute of Cardiovascular Disease, First Affiliated Hospital and Human Functional Genetics Lab of Jiangsu Province of Nanjing Medical University, Nanjing 210029, China.
Chen
Xiang-Jian
XJ
Bian
Yun-Yun
YY
Li
Ping
P
Yang
Di
D
Zhang
Ji-Nan
JN
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D000252:Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology; D002478:Cells, Cultured; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007545:Isoproterenol / Q000494:pharmacology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012503:Saponins / Q000737:chemistry / Q000494:pharmacology*; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D013482:Superoxide Dismutase / Q000378:metabolism; D014315:Triterpenes / Q000737:chemistry / Q000494:pharmacology*
D000447:Aldehydes; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D012503:Saponins; D014315:Triterpenes; C015977:malealdehyde; C052064:astragaloside A; D013482:Superoxide Dismutase; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000252:Calcium-Transporting ATPases; D007545:Isoproterenol; D002118:Calcium