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Isoliquiritigenin attenuates pathological cardiac hypertrophy via regulating AMPKα in vivo and in vitro

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Abstract

Isoliquiritigenin (ISL) is a type of flavonoid, derived from the root of the legume plant Glycyrrhiza, that has multiple pharmacological properties. However, its role in cardiac remodeling induced by pressure overload has yet to be fully elucidated. Aortic banding (AB) surgery was used to establish a cardiac hypertrophy model in male C57BL/6 mice. Mice were randomly divided into four groups (n = 20 per group) as follows: Sham + vehicle, sham + ISL, AB + vehicle and AB + ISL. ISL was administered to the mice intragastrically for 1 week after the operation. To evaluate the role of ISL in mice challenged with AB, echocardiography, histological analysis and molecular biochemistry examinations were performed. ISL treatment decreased cardiac hypertrophy and improved cardiac dysfunction induced by pressure overload. In addition, ISL decreased the cross-sectional area of cardiomyocytes. Furthermore, ISL reversed the AB-mediated increase in phosphorylated (p-)mTOR and p-ERK protein levels and further increased the protein expression of p-AMP-activated protein kinase (AMPK)α in response to AB, whereas knockout of AMPKα abolished the protective effects of ISL. The present study suggested that ISL could suppress pressure overload-induced cardiac hypertrophy through the activation of AMPKα. Therefore, ISL may serve as a therapeutic target for cardiac remodeling.

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The analyzed datasets generated in the present study are available from the corresponding author upon reasonable request.

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MLG, QC, SS, and TLD contributed to the conception of the study. MLG, HCS, HXW, MML, and SS contributed to the experimental research, data collection, and statistical analysis. MLG and TLD contributed significantly to analysis and manuscript preparation. MLG, HXW, MML, and TLD contributed to the writing, review, and revision of the manuscript. All authors were responsible for the final content and read and approved the final manuscript.

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Correspondence to Tieli Dong.

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The authors declare that they have no competing interests.

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The animal protocols used complied with the National Institutes of Health guide for the care and use of laboratory animals (Jiang et al. 2014) and the guidelines of the International Association for the Study of Pain (Du et al. 2016). The use of animals in the present study was reviewed and approved by the Ethics Committee of the Second Affiliated Hospital of Zhengzhou University (Zhengzhou, China).

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Gao, M., Cai, Q., Si, H. et al. Isoliquiritigenin attenuates pathological cardiac hypertrophy via regulating AMPKα in vivo and in vitro. J Mol Histol 53, 679–689 (2022). https://doi.org/10.1007/s10735-022-10090-w

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  • DOI: https://doi.org/10.1007/s10735-022-10090-w

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