Original Article

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

Authors: Yu Li, Ping Song, Qing Zhu, Qiu-y Yin, Jia-wen Ji, Wei Li, Hui-min Bian
DOI: 10.1038/aps.2014.75

Abstract

Yu LI1, 2, #, Ping SONG2, #, Qing ZHU1, Qiu-yi YIN1, Jia-wen JI2, Wei LI1, *, Hui-min BIAN1, *
1Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China; 2Department of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China

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-κB 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: Liguzinediol 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-κB expression.


Keywords: heart failure; cardiomyocyte; liguzinediol; apoptosis; caspases; Bcl-2; NF-κB; doxorubicin; Ligusticum wallichii

This study is supported by the National Natural Science Foundation of China (No 81072542), the Natural Science Foundation of Jiangsu Province (No BK2011077), and the Research Fund for the Doctoral Program of Higher Education (No 20123237110010), as well as the College Student’s Innovative Training Program, located in Jiangsu Province.
# These authors contributed equally to this manuscript.
* To whom correspondence should be addressed.
E-mail hmbian@sina.com (Hui-min BIAN); liwaii@126.com (Wei LI)
Received 2014-03-05 Accepted 2014-07-06
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