Protective effects of naringenin-7-O-glucoside on doxorubicin-induced apoptosis in H9C2 cells

被引:77
作者
Han, Xiuzhen [1 ]
Ren, Dongmei [1 ]
Fan, Peihong [1 ]
Shen, Tao [1 ]
Lou, Hongxiang [1 ]
机构
[1] Shandong Univ, Sch Pharmaceut Sci, Dept Nat Prod Chem, Jinan 250012, Peoples R China
关键词
naringenin-7-O-glucoside; heme oxygenase-1; Bcl-2; apoptosis; doxorubicin;
D O I
10.1016/j.ejphar.2007.11.048
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Doxorubicin, a widely used chemotherapeutic agent, can give rise to severe cardiotoxicity by inducing cardiomyocyte apoptosis. Dracocephalum rupestre Hance, a Chinese traditional herb, has therapeutic potential for cardiovascular diseases. Naringenin-7-O-glucoside is the main active constituent of D. rupestre and there is increasing interest in its therapeutic applications. The aim of this study was to evaluate the effects of naringenin-7-O-glucoside on cardiomyocyte apoptosis induced by doxorubicin. Cell viability was detected by MTT assay. Naringenin-7-O-glucoside (10, 20, and 40 mu M) significantly enhanced cardiomyocyte proliferation relative to that of doxorubicin. Furthermore, natingenin-7-O-glucoside increased the protein levels of heme oxygenase-1 (HO-1) and Bcl-2 in cardiomyocytes (as detected by Western blotting) and suppressed the mRNA expression of caspase-3 and caspase-9 (as detected by RT-PCR). These results suggest that naringenin-7-O-glucoside has protective effects against doxorubicin-induced apoptosis, effects which could underlie the use of naringenin-7-O-glucoside therapeutic agent for treating or preventing cardiomyopathy associated with doxorubicin. (C) 2007 Elsevier B.V. All rights reserved.
引用
收藏
页码:47 / 53
页数:7
相关论文
共 31 条
[1]   Molecular mechanisms of cardioprotection by a novel grape seed proanthocyanidin extract [J].
Bagchi, DB ;
Sen, CK ;
Ray, SD ;
Das, DK ;
Bagchi, M ;
Preuss, HG ;
Vinson, JA .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2003, 523 :87-97
[2]   Protectors against doxorubicin-induced cardiotoxicity:: Flavonoids [J].
Bast, A. ;
Kaiserova, H. ;
den Hartog, G. J. M. ;
Haenen, G. R. M. M. ;
van der Vijgh, W. J. F. .
CELL BIOLOGY AND TOXICOLOGY, 2007, 23 (01) :39-47
[3]   Carbon monoxide generated by heme oxygenase 1 suppresses endothelial cell apoptosis [J].
Brouard, S ;
Otterbein, LE ;
Anrather, J ;
Tobiasch, E ;
Bach, FH ;
Choi, AMK ;
Soares, MP .
JOURNAL OF EXPERIMENTAL MEDICINE, 2000, 192 (07) :1015-1025
[4]   Potent induction of cellular antioxidants and phase 2 enzymes by resveratrol in cardiomyocytes: protection against oxidative and electrophilic injury [J].
Cao, ZX ;
Li, YB .
EUROPEAN JOURNAL OF PHARMACOLOGY, 2004, 489 (1-2) :39-48
[5]   Doxorubicin in experimental and clinical heart failure [J].
Christiansen, Stefan ;
Autschbach, Ruediger .
EUROPEAN JOURNAL OF CARDIO-THORACIC SURGERY, 2006, 30 (04) :611-616
[6]   Grape seed polyphenols protect cardiac cells from apoptosis via induction of endogenous antioxidant enzymes [J].
Du, Yu ;
Guo, Huaifang ;
Lou, Hongxiang .
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, 2007, 55 (05) :1695-1701
[7]   A critical evaluation of the mechanisms of action proposed for the antitumor effects of the anthracycline antibiotics Adriamycin and daunorubicin [J].
Gewirtz, DA .
BIOCHEMICAL PHARMACOLOGY, 1999, 57 (07) :727-741
[8]   Esmolol is antiarrhythmic in doxorubicin-induced arrhythmia in cultured cardiomyocytes - determination by novel rapid cardiomyocyte assay [J].
Gorelik, J ;
Vodyanoy, I ;
Shevchuk, AI ;
Diakonov, IA ;
Lab, MJ ;
Korchev, YE .
FEBS LETTERS, 2003, 548 (1-3) :74-78
[9]   A RAPID AND SIMPLE METHOD FOR THE ISOLATION OF APOPTOTIC DNA FRAGMENTS [J].
HERRMANN, M ;
LORENZ, HM ;
VOLL, R ;
GRUNKE, M ;
WOITH, W ;
KALDEN, JR .
NUCLEIC ACIDS RESEARCH, 1994, 22 (24) :5506-5507
[10]   MODULATION OF THE IN-VITRO CARDIOTOXICITY OF DOXORUBICIN BY FLAVONOIDS [J].
HUSKEN, BCP ;
DEJONG, J ;
BEEKMAN, B ;
ONDERWATER, RCA ;
VANDERVIJGH, WJF ;
BAST, A .
CANCER CHEMOTHERAPY AND PHARMACOLOGY, 1995, 37 (1-2) :55-62