Herba leonurine attenuates doxorubicin-induced apoptosis in H9c2 cardiac muscle cells.
Doxorubicin (DOX) is a highly effective antineoplastic drug. However, DOX-induced apoptosis in cardiomyocytes leads to irreversible degenerative cardiomyopathy and heart failure, which limits DOX clinical application. Leonurine is a special alkaloid for Herba leonuri, a traditional herb with cardioprotective effects. In current study, we investigated possible protective effects of Leonurine against DOX-induced cardiomyopathy in H9c2 cells. DOX-injured H9c2 cell model was made by application of 2 microM DOX. Leonurine was added to cells 2 h before DOX treatment. Pre-treated with Leonurine could attenuate DOX-induced apoptotic death of H9c2 cell, reduce MDA formation and intracellular Ca2+ overload. Leonurine also attenuated DOX-induced high expression of Bax, increased Bcl-2 expression in both protein and mRNA level. Myocardial mitochondrion is the target organelle of DOX-induced toxicity in cardiomyocytes. Leonurine moderated the dissipation of mitochondrial membrane potential (DeltaPsim) caused by DOX treatment. Our results indicated that Leonurine attenuated DOX-induced apoptosis in H9c2 cell by increasing anti-oxidant, anti-apoptotic ability and protecting mitochondrial function.
Department of Pharmacology, School of Pharmacy, Fudan University, Shanghai 200032, China.
Hong
H
Xin
Xin Hua
XH
Liu
Yi Zhun
YZ
Zhu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000378:metabolism; D006690:Bisbenzimidazole / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002232:Carbocyanines / Q000378:metabolism; D002316:Cardiotonic Agents / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D005456:Fluorescent Dyes / Q000378:metabolism; D005707:Gallic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D006352:Heart Ventricles / Q000166:cytology; D008315:Malondialdehyde / Q000032:analysis; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D032383:Myocytes, Cardiac / Q000187:drug effects*; D051381:Rats; D013778:Tetrazolium Salts / Q000378:metabolism; D013844:Thiazoles / Q000378:metabolism
D001562:Benzimidazoles; D002232:Carbocyanines; D002316:Cardiotonic Agents; D004396:Coloring Agents; D005456:Fluorescent Dyes; D013778:Tetrazolium Salts; D013844:Thiazoles; C013587:leonurine; C068624:5,5',6,6'-tetrachloro-1,1',3,3'-tetraethylbenzimidazolocarbocyanine; D008315:Malondialdehyde; D005707:Gallic Acid; D004317:Doxorubicin; C022616:thiazolyl blue; D006690:Bisbenzimidazole; D002118:Calcium