Astragalus Improved Cardiac Function of Adriamycin-Injured Rat Hearts by Upregulation of SERCA2a Expression.
The traditional Chinese medical herb Astragalus, the dried root of Astragalus membranaceus (Fisch.) Bge., has been widely applied to treat patients with cardiovascular disease in China and has profound cardioprotective effects. This study investigated the effect of Astragalus on hemodynamic changes in adriamycin (ADR)-injured rat hearts and its underlying molecular mechanism. Sprague-Dawley rats were divided into four groups: control, ADR only, ADR + low dose of Astragalus and ADR + high dose of Astragalus. Rats were injected intraperitoneally with 6 equal doses of ADR (cumulative dose, 12 mg/kg) over a period of 2 weeks. Treatment of Astragalus began 1 day before the onset of ADR injection and was given orally once a day for 50 days (3.3 or 10 g/kg/day). Five weeks after the final injection of ADR, rats treated with ADR only showed a significant inhibition of cardiac diastolic function accompanied by the presence of ascites, a remarkable reduction in body weight and heart weight as well as survival rate compared to the controls. Moreover, SERCA2a mRNA and protein expressions in hearts were obviously downregulated by ADR. However, this impaired cardiac function was significantly improved in both doses of Astragalus feeding groups. The amount of ascites was also reduced in a similar extent in these 2 groups. Only the high dose treatment of Astragalus significantly attenuated the changes of SERCA2a expression in injured hearts and improved survival. These results indicated that Astragalus could improve cardiac function of ADR-injured rat hearts, which was partly mediated by upregulation of SERCA2a expression.
Su
Dan
D
Department of Pharmacology, School of Medicine, Tongji University, Shanghai 200092, China. sudandan@163.com
Li
Han-Yi
HY
Yan
Hao-Ran
HR
Liu
Peng-Fei
PF
Zhang
Liu
L
Cheng
Jian-Hua
JH
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000633:toxicity; D027885:Astragalus propinquus; D001835:Body Weight; D002316:Cardiotonic Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000633:toxicity; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D006331:Heart Diseases / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D006334:Heart Function Tests / Q000187:drug effects; D008297:Male; D009929:Organ Size; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism*; D015996:Survival Rate; D015854:Up-Regulation / Q000187:drug effects
D000903:Antibiotics, Antineoplastic; D002316:Cardiotonic Agents; D004365:Drugs, Chinese Herbal; D012333:RNA, Messenger; D004317:Doxorubicin; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases