title: Tetrandrine blocks cardiac hypertrophy by disrupting reactive oxygen species-dependent ERK1/2 signalling.
abstract: OBJECTIVE
  Tetrandrine, a well-known naturally occurring calcium antagonist with anti-inflammatory, antioxidant and anti-fibrogenetic activities, has long been used clinically for treatment of cardiovascular diseases such as hypertension and arrhythmia. However, little is known about the effect of tetrandrine on cardiac hypertrophy. The aims of the present study were to determine whether tetrandrine could attenuate cardiac hypertrophy and to clarify the underlying molecular mechanisms.
  
  
  METHODS
  Tetrandrine (50 mg x kg(-1) x day(-1)) was administered by oral gavage three times a day for one week and then the mice were subjected to either chronic pressure overload generated by aortic banding (AB) or sham surgery (control group). Cardiac function was determined by echocardiography.
  
  
  RESULTS
  Tetrandrine attenuated the cardiac hypertrophy induced by AB, as assessed by heart weight/body weight and lung weight/body weight ratios, cardiac dilatation and the expression of genes of hypertrophic markers. Tetrandrine also inhibited fibrosis and attenuated the inflammatory response. The cardioprotective effects of tetrandrine were mediated by blocking the increased production of reactive oxygen species and the activation of ERK1/2-dependent nuclear factor-kappaB and nuclear factor of activated T cells that occur in response to hypertrophic stimuli.
  
  
  CONCLUSIONS
  Taken together, our results suggest that tetrandrine can improve cardiac function and prevent the development of cardiac hypertrophy by suppressing the reactive oxygen species-dependent ERK1/2 signalling pathway.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China.
authors.forename: Di-Fei
authors.initials: DF
authors.lastname: Shen
authors.forename: Qi-Zhu
authors.initials: QZ
authors.lastname: Tang
authors.forename: Ling
authors.initials: L
authors.lastname: Yan
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li-Hua
authors.initials: LH
authors.lastname: Zhu
authors.forename: Lang
authors.initials: L
authors.lastname: Wang
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Zhou-Yan
authors.initials: ZY
authors.lastname: Bian
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000831:Animals, Newborn; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis; D044182:Benzylisoquinolines / Q000008:administration & dosage / Q000494:pharmacology*; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000201:enzymology / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004789:Enzyme Activation; D005355:Fibrosis; D006333:Heart Failure / Q000150:complications / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology; D051379:Mice; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000235:genetics / Q000378:metabolism; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects*; D013997:Time Factors; D014162:Transfection; D014463:Ultrasonography; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D044182:Benzylisoquinolines; D002316:Cardiotonic Agents; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D017382:Reactive Oxygen Species; C009438:tetrandrine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3