Breviscapine protects against cardiac hypertrophy through blocking PKC-alpha-dependent signaling.
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.
Yan
Ling
L
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, PR China.
Huang
He
H
Tang
Qi-Zhu
QZ
Zhu
Li-Hua
LH
Wang
Lang
L
Liu
Chen
C
Bian
Zhou-Yan
ZY
Li
Hongliang
H
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D006332:Cardiomegaly / Q000378:metabolism* / Q000517:prevention & control*; D002478:Cells, Cultured; D004452:Echocardiography; D024202:Electrophoretic Mobility Shift Assay; D005419:Flavonoids / Q000627:therapeutic use*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051571:Protein Kinase C-alpha / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects*; D051899:Smad2 Protein / Q000378:metabolism; D051900:Smad3 Protein / Q000378:metabolism
D005419:Flavonoids; D051899:Smad2 Protein; D051900:Smad3 Protein; C061097:breviscapine; D000071679:Glycogen Synthase Kinase 3 beta; D051571:Protein Kinase C-alpha; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D038362:Glycogen Synthase Kinase 3