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International Journal of Molecular Medicine
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Article

Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-β1-mediated hypertrophic signaling in vitro and in vivo

  • Authors:
    • Linjie Si
    • Jing Xu
    • Chenlong Yi
    • Xiaohan Xu
    • Fang Wang
    • Weijuan Gu
    • Yuqing Zhang
    • Xiaowei Wang
  • View Affiliations / Copyright

    Affiliations: Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China, Department of Cardiology, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, Jiangsu 211100, P.R. China
  • Pages: 499-506
    |
    Published online on: May 14, 2014
       https://doi.org/10.3892/ijmm.2014.1781
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Abstract

Cardiac hypertrophy is a major cause of morbidity and mortality worldwide. Transforming growth factor-β1 (TGF-β1) signaling has been considered as a trigger causally contributing to pathological cardiac hypertrophy. Asiatic acid (AA) is a triterpenoid compound extracted from Centella asiatica and exhibits a variety of pharmacological effects. In this study, we investigated the anti-hypertrophic effects and mechanisms of action of AA in a TGF-β1-stimulated hypertrophic response using cultured neonatal cardiomyocytes in vitro and in a mouse model of cardiac hypertrophy induced by pressure overload in vivo. Treatment with AA markedly attenuated the TGF-β1-induced hypertrophic responses of cardiomyocytes as reflected by reduction in the cardiomyocyte surface area and the inhibition of atrial natriuretic peptide (ANP) mRNA expression. The protective effects of AA on hypertrophic cardiomyocytes were associated with the blocking of p38 and extracellular signal‑regulated kinase (ERK)1/2 phosphorylation and the reduction of nuclear factor-κB (NF-κB) binding activity. In vivo experiments indicated that the administration of AA prevented cardiac hypertrophy and dysfunction induced by pressure overload. It was found that AA markedly reduced the excessive production of TGF-β1 in the hypertrophic myocardium, blocked the phosphorylation of p38 and ERK1/2 and inhibited the activation of NF-κB. Our data suggest that AA may be a novel therapeutic agent for cardiac hypertrophy. The inhibition of TGF-β1‑mediated hypertrophic signaling may be the mechanism through which AA prevents cardiac hypertrophy.
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Copy and paste a formatted citation
Spandidos Publications style
Si L, Xu J, Yi C, Xu X, Wang F, Gu W, Zhang Y and Wang X: Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-β1-mediated hypertrophic signaling in vitro and in vivo. Int J Mol Med 34: 499-506, 2014.
APA
Si, L., Xu, J., Yi, C., Xu, X., Wang, F., Gu, W. ... Wang, X. (2014). Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-β1-mediated hypertrophic signaling in vitro and in vivo. International Journal of Molecular Medicine, 34, 499-506. https://doi.org/10.3892/ijmm.2014.1781
MLA
Si, L., Xu, J., Yi, C., Xu, X., Wang, F., Gu, W., Zhang, Y., Wang, X."Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-β1-mediated hypertrophic signaling in vitro and in vivo". International Journal of Molecular Medicine 34.2 (2014): 499-506.
Chicago
Si, L., Xu, J., Yi, C., Xu, X., Wang, F., Gu, W., Zhang, Y., Wang, X."Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-β1-mediated hypertrophic signaling in vitro and in vivo". International Journal of Molecular Medicine 34, no. 2 (2014): 499-506. https://doi.org/10.3892/ijmm.2014.1781
Copy and paste a formatted citation
x
Spandidos Publications style
Si L, Xu J, Yi C, Xu X, Wang F, Gu W, Zhang Y and Wang X: Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-β1-mediated hypertrophic signaling in vitro and in vivo. Int J Mol Med 34: 499-506, 2014.
APA
Si, L., Xu, J., Yi, C., Xu, X., Wang, F., Gu, W. ... Wang, X. (2014). Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-β1-mediated hypertrophic signaling in vitro and in vivo. International Journal of Molecular Medicine, 34, 499-506. https://doi.org/10.3892/ijmm.2014.1781
MLA
Si, L., Xu, J., Yi, C., Xu, X., Wang, F., Gu, W., Zhang, Y., Wang, X."Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-β1-mediated hypertrophic signaling in vitro and in vivo". International Journal of Molecular Medicine 34.2 (2014): 499-506.
Chicago
Si, L., Xu, J., Yi, C., Xu, X., Wang, F., Gu, W., Zhang, Y., Wang, X."Asiatic acid attenuates cardiac hypertrophy by blocking transforming growth factor-β1-mediated hypertrophic signaling in vitro and in vivo". International Journal of Molecular Medicine 34, no. 2 (2014): 499-506. https://doi.org/10.3892/ijmm.2014.1781
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