Puerarin attenuates pressure overload-induced cardiac hypertrophy

• Published in: Journal of cardiology Vol. 63; no. 1; pp. 73 - 81
• Main Authors: Yuan, Yuan, PhD, Zong, Jing, PhD, Zhou, Heng, PhD, Bian, Zhou-Yan, PhD, Deng, Wei, PhD, Dai, Jia, PhD, Gan, Hua-Wen, MD, Yang, Zheng, PhD, Li, Hongliang, PhD, Tang, Qi-Zhu, PhD
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.01.2014
• Subjects: Administration, Oral; Animals; Aortic coarctation; Apoptosis - drug effects; Apoptosis - genetics; bcl-2-Associated X Protein; Cardiomegaly - drug therapy; Cardiomegaly - etiology; Cardiomegaly - genetics; Cardiomegaly - prevention & control; Cardiotonic Agents - administration & dosage; Cardiotonic Agents - pharmacology; Cardiovascular; Cells, Cultured; Disease Progression; Fibrosis; Gene Expression - drug effects; Heart Failure - drug therapy; Heart Failure - etiology; Heart Failure - prevention & control; Hypertrophy; Isoflavones - administration & dosage; Isoflavones - pharmacology; Male; MAP Kinase Signaling System - drug effects; Mice; Mice, Inbred C57BL; Myocardium - pathology; Myocytes, Cardiac - pathology; Pharmacology; Phosphatidylinositol 3-Kinases - antagonists & inhibitors; Phytotherapy; Pressure - adverse effects; Vasodilator Agents - administration & dosage; Vasodilator Agents - pharmacology; Aortic coarctation; Pharmacology; Hypertrophy
• ISSN: 0914-5087; 1876-4738
• DOI: 10.1016/j.jjcc.2013.06.008

Abstract Background Puerarin is the most abundant isoflavonoid in kudzu root. It has been used to treat angina pectoris and myocardial infarction clinically. However, little is known about the effect of puerarin on cardiac hypertrophy. Methods Aortic banding (AB) was performed to induce cardiac hypertrophy in mice. Puerarin premixed in diets was administered to mice after one week of AB. Echocardiography and catheter-based measurements of hemodynamic parameters were performed at 7 weeks after starting puerarin treatment (8 weeks post-surgery). The extent of cardiac hypertrophy was also evaluated by pathological and molecular analyses of heart samples. Cardiomyocyte apoptosis was assessed by measuring Bax and Bcl-2 protein expression and terminal deoxynucleotidyl transferase dUTP nick end labeling staining. In addition, the inhibitory effect of puerarin (1 μM, 5 μM, 10 μM, 20 μM, 40 μM) on mRNA expression of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in Ang II (1 μM)-stimulated H9c2 cells was investigated using quantitative real-time reverse transcription-polymerase chain reaction. Results Echocardiography and catheter-based measurements of hemodynamic parameters at 7 weeks revealed the amelioration of systolic and diastolic abnormalities. Puerarin also decreased cardiac fibrosis in AB mice. Moreover, the beneficial effect of puerarin was associated with the normalization in gene expression of hypertrophic and fibrotic markers. Further studies showed that pressure overload significantly induced the activation of phosphoinositide 3-kinase (PI3K)/Akt signaling and c-Jun N-terminal kinase (JNK) signaling, which was blocked by puerarin treatment. Cardiomyocyte apoptosis and induction of Bax in response to AB were suppressed by puerarin. Furthermore, the increased mRNA expression of ANP and BNP induced by Ang II (1 μM) was restrained to a different extent by different concentrations of puerarin. Conclusion Puerarin may have an ability to retard the progression of cardiac hypertrophy and apoptosis which is probably mediated by the blockade of PI3K/Akt and JNK signaling pathways.