Liguzinediol improved the heart function and inhibited myocardial cell apoptosis in rats with heart failure

Aim： Liguzinediol is a novel derivative of ligustrazine isolated from the traditional Chinese medicine Chuanxiong （Ligusticum wallichii Franch）, and produces significant positive inotropic effect in isolated rat hearts. In this study we investigated the effects of liguzinediol on a rat model of hear...

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Published in:Acta pharmacologica Sinica 2014-10, Vol.35 (10), p.1257-1264
Main Authors: Li, Yu, Song, Ping, Zhu, Qing, Yin, Qiu-yi, Ji, Jia-wen, Li, Wei, Bian, Hui-min
Format: Article
Language:English
Subjects:
Animals
Apoptosis - drug effects
Bax蛋白
Bcl-2
bcl-2-Associated X Protein - metabolism
Caspase 3 - metabolism
caspase-3
Doxorubicin - pharmacology
Gene Expression - drug effects
Heart - drug effects
Heart Failure - drug therapy
Heart Failure - metabolism
Male
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
NF-kappa B - metabolism
NF-κB
Original
Proto-Oncogene Proteins c-bcl-2 - metabolism
Pyrazines - pharmacology
Rats
Rats, Sprague-Dawley
大鼠模型
心肌细胞凋亡
心脏功能
衰竭
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Summary:Aim： Liguzinediol is a novel derivative of ligustrazine isolated from the traditional Chinese medicine Chuanxiong （Ligusticum wallichii Franch）, and produces significant positive inotropic effect in isolated rat hearts. In this study we investigated the effects of liguzinediol on a rat model of heart failure. Methods： To induce heart failure, male SD rats were injected with doxorubicin （DOX, 2 mg=,/kg, ip） once a week for 4 weeks. Then the rats were administered with liguzinediol （5, 10, and 20 mg.kg-1.d-1, po） for 2 weeks. Hemodynamic examination was conducted to evaluate heart function. Myocardial cell apoptosis was examined morphologically. The expression of related genes and proteins were analyzed using immunohistochemical staining and Western blot assays, respectively. Results： Oral administration of liguzinediol dose-dependently improved the heart function in DOX-treated rats. Electron microscopy revealed that liguzinediol （10 mg.kg-1.d-1） markedly attenuated DOX-induced injury of cardiomyocytes, and decreased the number of apoptotic bodies in cardiomyocytes. Furthermore, liguzinediol significantly decreased Bax protein level, and increased Bcl-2 protein level in cardiomyocytes of DOX-treated rats, led to an increase in the ratio of Bcl-2/Bax. Moreover, liguzinediol significantly decreased the expression of both cleaved caspase-3 and NF-KB in cardiomyocytes of DOX-treated rats. Administration of digitalis （0.0225 mg.kg-1.d-1） also markedly improved the heart function and the morphology of cardiomyocytes in DOX-treated rats. Conclusion： Liguzinediot improves the heart function and inhibits myocardial cell apoptosis in the rat model of heart failure, which is associated with regulating Bcl-2, Bax, caspase-3, and NF-KB expression.
ISSN:1671-4083
1745-7254
DOI:10.1038/aps.2014.75