Tetrandrine blocks cardiac hypertrophy by disrupting reactive oxygen species-dependent ERK1/2 signalling.

Abstract

BACKGROUND AND PURPOSE:

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.

EXPERIMENTAL APPROACH:

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.

KEY 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 AND IMPLICATIONS:

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: Di-Fei Shen, Qi-Zhu Tang, Ling Yan, Yan Zhang, Li-Hua Zhu, Lang Wang, Chen Liu, Zhou-Yan Bian, Hongliang Li
• Journal: British journal of pharmacology (Br J Pharmacol) Vol. 159 Issue 4 Pg. 970-81 (Feb 2010) ISSN: 1476-5381 [Electronic] England
• PMID: 20105174 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• Benzylisoquinolines
• Cardiotonic Agents
• NF-kappa B
• NFATC Transcription Factors
• Reactive Oxygen Species
• tetrandrine
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3

Topics

• Administration, Oral
• Animals
• Animals, Newborn
• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Apoptosis
• Benzylisoquinolines (administration & dosage, pharmacology)
• Cardiomegaly (diagnostic imaging, enzymology, etiology, physiopathology, prevention & control)
• Cardiotonic Agents (administration & dosage, pharmacology)
• Cells, Cultured
• Disease Models, Animal
• Enzyme Activation
• Fibrosis
• Heart Failure (complications, diagnostic imaging, drug therapy, enzymology, physiopathology)
• Mice
• Mitogen-Activated Protein Kinase 1 (metabolism)
• Mitogen-Activated Protein Kinase 3 (metabolism)
• Myocytes, Cardiac (drug effects, enzymology, pathology)
• NF-kappa B (genetics, metabolism)
• NFATC Transcription Factors (genetics, metabolism)
• Phosphorylation
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Recovery of Function
• Signal Transduction (drug effects)
• Time Factors
• Transfection
• Ultrasonography
• Ventricular Function, Left (drug effects)