Cardioprotective Effect of Monoammonium Glycyrrhizinate Injection Against Myocardial Ischemic Injury in vivo and in vitro: Involvement of Inhibiting Oxidative Stress and Regulating Ca²⁺ Homeostasis by L-Type Calcium Channels

Abstract

Purpose

Monoammonium glycyrrhizinate (MAG) is an aglycone of glycyrrhizin that is found in licorice and is often used clinically as an injection to treat liver diseases. However, the effect of MAG injection on cardiac function and its possible cellular mechanisms remain unclear. We explored the protective effects of MAG against myocardial ischemic injury (MII) induced by isoproterenol (ISO), as well as the cellular mechanisms via molecular biology techniques and patch-clamp recording.

Methods

A rat model of myocardial ischemia injury was induced by administering ISO (85 mg/kg) subcutaneously for 2 consecutive days. ECG, cardiac functional parameters, CK and LDH levels, SOD and GSH activities, MDA concentration, histological myocardium inspection, mitochondria ultrastructure changes, intracellular calcium concentrations were observed. Influences of MAG on I_Ca-L and contraction in isolated rat myocytes were observed by the patch-clamp technique.

Results

MAG reduced damage, improved cardiac morphology, inhibited oxidative stress, decreased the generation of reactive oxygen species, and decreased intracellular Ca²⁺ concentration. Exposure of the rats’ ventricular myocytes to MAG resulted in a concentration-dependent reduction in L-type calcium currents (I_Ca-L). MAG reduced I_Ca-L in a consistent and time-dependent fashion with a semi-maximal prohibitive concentration of MAG of 14 μM. MAG also shifted the I-V curve of I_Ca-L upwards and moved the activation and inactivation curves of I_Ca-L to the left.

Conclusion

The findings indicate that MAG injection exerts a protective influence on ISO-induced MII by inhibiting oxidative stress and regulating Ca²⁺ homeostasis by I_Ca-L.

Keywords:

• cardiopretection
• reactive oxygen species
• calcium influx
• isoproterenol
• calcium concentration

Acknowledgments

This work was supported by Research Foundation of Hebei University of Chinese Medicine (No. KTZ 2019041). Zhifeng Zhao and Miaomiao Liu are co-first authors for this study.

Disclosure

The authors declare no conflicts of interest in this work.