Document Detail


Breviscapine protects against cardiac hypertrophy through blocking PKC-alpha-dependent signaling.
MedLine Citation:
PMID:  20127712     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Breviscapine is a mixture of flavonoid glycosides extracted from the Chinese herbs. Previous studies have shown that breviscapine possesses comprehensive pharmacological functions. However, very little is known about whether breviscapine have protective role on cardiac hypertrophy. The aim of the present study was to determine whether breviscapine attenuates cardiac hypertrophy induced by angiotensin II (Ang II) in cultured neonatal rat cardiac myocytes in vitro and pressure-overload-induced cardiac hypertrophy in mice in vivo. Our data demonstrated that breviscapine (2.5-15 microM) dose-dependently blocked cardiac hypertrophy induced by Ang II (1 microM) in vitro. The results further revealed that breviscapine (50 mg/kg/day) prevented cardiac hypertrophy induced by aortic banding as assessed by heart weight/body weight and lung weight/body weight ratios, echocardiographic parameters, and gene expression of hypertrophic markers. The inhibitory effect of breviscapine on cardiac hypertrophy is mediated by disrupting PKC-alpha-dependent ERK1/2 and PI3K/AKT signaling. Further studies showed that breviscapine inhibited inflammation by blocking NF-kappaB signaling, and attenuated fibrosis and collagen synthesis through abrogating Smad2/3 signaling. Therefore, these findings indicate that breviscapine, which is a potentially safe and inexpensive therapy for clinical use, has protective potential in targeting cardiac hypertrophy and fibrosis through suppression of PKC-alpha-dependent signaling.
Authors:
Ling Yan; He Huang; Qi-Zhu Tang; Li-Hua Zhu; Lang Wang; Chen Liu; Zhou-Yan Bian; Hongliang Li
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of cellular biochemistry     Volume:  109     ISSN:  1097-4644     ISO Abbreviation:  J. Cell. Biochem.     Publication Date:  2010 Apr 
Date Detail:
Created Date:  2010-04-07     Completed Date:  2010-06-29     Revised Date:  2011-11-02    
Medline Journal Info:
Nlm Unique ID:  8205768     Medline TA:  J Cell Biochem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1158-71     Citation Subset:  IM    
Affiliation:
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
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MeSH Terms
Descriptor/Qualifier:
Animals
Blood Pressure / drug effects
Blotting, Western
Cardiomegaly / metabolism*,  prevention & control*
Cells, Cultured
Echocardiography
Electrophoretic Mobility Shift Assay
Flavonoids / therapeutic use*
Glycogen Synthase Kinase 3 / metabolism
Male
Mice
Mice, Inbred C57BL
Mitogen-Activated Protein Kinase 1 / metabolism
Mitogen-Activated Protein Kinase 3 / metabolism
Myocytes, Cardiac / drug effects,  metabolism
Phosphorylation / drug effects
Protein Kinase C-alpha / metabolism*
Rats
Rats, Sprague-Dawley
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction / drug effects*
Smad2 Protein / metabolism
Smad3 Protein / metabolism
Chemical
Reg. No./Substance:
0/Flavonoids; 0/Smad2 Protein; 0/Smad3 Protein; 116122-36-2/breviscapine; EC 2.7.11.1/glycogen synthase kinase 3 beta; EC 2.7.11.13/Protein Kinase C-alpha; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 2.7.11.24/Mitogen-Activated Protein Kinase 3; EC 2.7.11.26/Glycogen Synthase Kinase 3

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