title: Liguzinediol improved the heart function and inhibited myocardial cell apoptosis in rats with heart failure.
abstract: OBJECTIVE
  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, 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: 1] Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China [2] Department of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Song
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Zhu
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Qiu-yi
authors.initials: QY
authors.lastname: Yin
authors.affiliation: Department of Preclinical Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Jia-wen
authors.initials: JW
authors.lastname: Ji
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Jiangsu Key Laboratory for Chinese Medicine Processing, Collage of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
authors.forename: Hui-min
authors.initials: HM
authors.lastname: Bian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D006321:Heart / Q000187:drug effects*; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011719:Pyrazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C572935:2,5-dihydroxymethyl-3,6-dimethylpyrazine; D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D011719:Pyrazines; D051028:bcl-2-Associated X Protein; D004317:Doxorubicin; D053148:Caspase 3