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Evodiamine Inhibits Angiotensin II-Induced Rat Cardiomyocyte Hypertrophy

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Abstract

Objective

To investigate the effects of evodiamine (Evo), a component of Evodiaminedia rutaecarpa (Juss.) Benth, on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) and further explore the potential mechanisms.

Methods

Cardiomyocytes from neonatal Sprague Dawley rats were isolated and characterized, and then the cadiomyocyte cultures were randomly divided into control, model (Ang II 0.1 μmol/L), and Evo (0.03, 0.3, 3 μmol/L) groups. The cardiomyocyte surface area, protein level, intracellular free calcium ([Ca2+]i) concentration, activity of nitric oxide synthase (NOS) and content of nitric oxide (NO) were measured, respectively. The mRNA expressions of atrial natriuretic factor (ANF), calcineurin (CaN), extracellular signal-regulated kinase-2 (ERK-2), and endothelial nitric oxide synthase (eNOS) of cardiomyocytes were analyzed by real-time reverse transcriptionpolymerase chain reaction. The protein expressions of calcineurin catalytic subunit (CnA) and mitogen-activated protein kinase phosphatase-1 (MKP-1) were detected by Western blot analysis.

Results

Compared with the control group, Ang II induced cardiomyocytes hypertrophy, as evidenced by increased cardiomyocyte surface area, protein content, and ANF mRNA expression; increased intracellular free calcium ([Ca2+]i) concentration and expressions of CaN mRNA, CnA protein, and ERK-2 mRNA, but decreased MKP-1 protein expression (P<0.05 or P<0.01). Compared with Ang II, Evo (0.3, 3 μmol/L) significantly attenuated Ang II-induced cardiomyocyte hypertrophy, decreased the [Ca2+]i concentration and expressions of CaN mRNA, CnA protein, and ERK-2 mRNA, but increased MKP-1 protein expression (P<0.05 or P<0.01). Most interestingly, Evo increased the NOS activity and NO production, and upregulated the eNOS mRNA expression (P<0.05).

Conclusion

Evo signifificantly attenuated Ang II-induced cardiomyocyte hypertrophy, and this effect was partly due to promotion of NO production, reduction of [Ca2+]i concentration, and inhibition of CaN and ERK-2 signal transduction pathways.

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Authors and Affiliations

  1. Key Laboratory of Basic Pharmacology of Guizhou, Department of Pharmacology, Zunyi Medical College, Zunyi, Guizhou Province, 563099, China

    Na He, Qi-hai Gong, Feng Zhang, Jing-yi Zhang, Shu-xian Lin, Hua-hua Hou, Qin Wu & An-sheng Sun

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  1. Na He
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  2. Qi-hai Gong
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  3. Feng Zhang
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Correspondence to An-sheng Sun.

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Supported by the National Natural Science Foundation of China (No. 81160528) and Foundation of Administration of Traditional Chinese Medicine of Guizhou Province (No. 2009-79)

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He, N., Gong, Qh., Zhang, F. et al. Evodiamine Inhibits Angiotensin II-Induced Rat Cardiomyocyte Hypertrophy. Chin. J. Integr. Med. 24, 359–365 (2018). https://doi.org/10.1007/s11655-017-2818-9

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  • DOI: https://doi.org/10.1007/s11655-017-2818-9

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