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Berberine Attenuates Cardiac Hypertrophy Through Inhibition of mTOR Signaling Pathway

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Abstract

Purpose

Berberine was reported to exert beneficial effects on cardiac hypertrophy. However, its cellular and molecular mechanisms still remained unclear.

Methods

Cardiac hypertrophy was induced in male Sprague-Dawley (SD) rats by transverse aorta constriction (TAC), with or without 6-week treatment of berberine. Echocardiography was performed to evaluate cardiac function. Rats were then sacrificed for histological assay, with detection for proteins and mRNA. H9c2 cells were pretreated with berberine of different concentrations (0, 1 μM, and 10 μM), followed by treatment with 2 μM norepinephrine (NE). Cells of different groups were measured for cell surface area, with mRNA detected by qRT-PCR and proteins by western blot.

Results

Compared with the sham group, rats of the TAC group showed significantly increased cardiac hypertrophy and fibrosis, which could be ameliorated by treatment with berberine. Western blot showed that mammalian target of rapamycin (mTOR) signaling-related protein expressions, including phospho-mTOR, phospho-4EBP1, and phospho-p70 S6K (Thr389), but not phospho-p70 S6K (Ser371), were significantly increased in the TAC group, which were inhibited by berberine treatment. H9c2 cells were treated with NE to induce hypertrophy with increased cell surface area and mRNA expressions of anp and bnp. Berberine of 10 μM, but not 1 μM, significantly ameliorated NE-induced hypertrophy and inhibited protein expressions of mTOR signaling pathway similar to those in the rat model.

Conclusions

Berberine can exert cardioprotective effects on both pressure-overloaded cardiac hypertrophy and failure in vivo and NE-induced hypertrophy in vitro. Our results suggest berberine could be a potential treatment for patients with cardiac hypertrophy and failure.

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Acknowledgments

We thank Zhenkun Guan and Nurul Farhanah Binte Abdul Latif from Guangzhou Medical University for the English writing revision.

Funding

This study was funded by the Medical Research Foundation of Guangdong Province, China (grant number A2018307) and the Research Foundation for Doctors and Returned Overseas Scholars of Guangzhou Medical University, China (grant number 2016C19).

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Authors and Affiliations

  1. Department of Geriatrics, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China

    Xing Chen, Xingzuan Jiang, Shuyan Huang & Miqing Xu

  2. Guangzhou Institute of Cardiovascular Disease, the Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510260, China

    Xing Chen, Chuanfang Cheng, Jing Chen & Shiming Liu

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  1. Xing Chen
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Correspondence to Miqing Xu or Shiming Liu.

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The authors declare that they have no conflict of interest.

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All applicable international, national, and/or institutional guidelines for the care and use of animals were followed. All procedures for rats were in accordance with the Guide for the Care and Use of Laboratory Animals and approved by the Animal Ethics and the Use Committee of the Second Affiliated Hospital of Guangzhou Medical University.

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Chen, X., Jiang, X., Cheng, C. et al. Berberine Attenuates Cardiac Hypertrophy Through Inhibition of mTOR Signaling Pathway. Cardiovasc Drugs Ther 34, 463–473 (2020). https://doi.org/10.1007/s10557-020-06977-z

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