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18β-Glycyrrhetinic Acid Improves Cardiac Diastolic Function by Attenuating Intracellular Calcium Overload

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Summary

Ranolazine, a late sodium current inhibitor, has been demonstrated to be effective on heart failure. 18β-glycyrrhetinic acid (18β-GA) has the similar inhibitory effect on late sodium currents. However, its effect on diastolic function is still unknown. This study aimed to determine whether 18β-GA can improve the diastolic function and to explore the underlying mechanisms. Eighty male Sprague Dawley (SD) rats of Langendorff model were randomly divided into the following groups: group A, normal cardiac perfusion group; group B, ischemia-reperfusion group; group C, ischemia-reperfusion with anemoniasulcata toxin II (ATX-II); group D, ranolazine group; and group E, 18β-GA group with four different concentrations. Furthermore, a pressure-overloaded rat model induced by trans-aortic constriction (TAC) was established. Echocardiography and hemodynamics were used to evaluate diastolic function at 14th day after TAC. Changes of free intracellular calcium (Ca2+) concentration was indirectly detected by laser scanning confocal microscope to confirm the inhibition of late sodium currents. With the intervention of ATX-II on ischemia reperfusion injury group, 5 µmol/L ranolazine, and 5, 10, 20, 40 µmol/L 18β-GA could improve ATX-II-induced cardiac diastolic dysfunction. 630 mg/kg glycyrrhizin tablets could improve cardiac diastolic function in the pressure-overloaded rats. 18β-GA and ranolazine had similar effects on reducing the free calcium in cardiomyocytes. The study demonstrates that 18β-GA and glycyrrhizin could improve diastolic dysfunction induced by ischemia-reperfusion injury in Langendorff-perfused rat hearts and pressure-overloaded rats. The mechanism may be attributed to the inhibition of enhanced late sodium currents.

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Author notes

  1. The authors contributed equally to this study.

Authors and Affiliations

  1. Department of Cardiology, Wuhan Fourth Hospital Puai Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430033, China

    Jun Han

  2. Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Guan-hua Su, Yu-hui Wang, Yong-xin Lu, Hong-liang Zhao & Xin-xin Shuai

Authors
  1. Jun Han
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  2. Guan-hua Su
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  3. Yu-hui Wang
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  4. Yong-xin Lu
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  5. Hong-liang Zhao
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  6. Xin-xin Shuai
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Corresponding author

Correspondence to Xin-xin Shuai.

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The authors have declared that no conflicts of interest exists.

Additional information

This project was supported by the National Natural Science Foundation of China (No. 81600317 and No. 81700345) and the Open Foundation of Hubei Key Laboratory of Biological Targeted Therapy (No. 02.03.2014-10).

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Han, J., Su, Gh., Wang, Yh. et al. 18β-Glycyrrhetinic Acid Improves Cardiac Diastolic Function by Attenuating Intracellular Calcium Overload. CURR MED SCI 40, 654–661 (2020). https://doi.org/10.1007/s11596-020-2232-y

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  • DOI: https://doi.org/10.1007/s11596-020-2232-y

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