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

• Main Authors: Zhao Z, Liu M, Zhang Y, Liang Y, Ma D, Wang H, Ma Z, Guan S, Wu Z, Chu X, Lin Y, Chu L
• Format: Article
• Language: English
• Published: Dove Medical Press 2020-01-01
• Series: Drug Design, Development and Therapy
• Subjects: cardiopretection; reactive oxygen species; calcium influx; isoproterenol; calcium concentration
• Online Access: https://www.dovepress.com/cardioprotective-effect-of-monoammonium-glycyrrhizinate-injection-agai-peer-reviewed-article-DDDT

Zhifeng Zhao, 1,* Miaomiao Liu, 1,* Yuanyuan Zhang, 1 Yingran Liang, 1 Donglai Ma, 1 Hongfang Wang, 1 Zhihong Ma, 2 Shengjiang Guan, 2 Zhonglin Wu, 3 Xi Chu, 3 Yue Lin, 2 Li Chu 1, 4 1School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, People’s Republic of China; 2School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, People’s Republic of China; 3The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, People’s Republic of China; 4Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang 050200, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li ChuSchool of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, People’s Republic of ChinaEmail [e-mail] LinSchool of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang 050200, Hebei, People’s Republic of ChinaTel/Fax [phone]Email [e-mail]: 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 ICa-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 Ca 2+ concentration. Exposure of the rats’ ventricular myocytes to MAG resulted in a concentration-dependent reduction in L-type calcium currents (ICa-L). MAG reduced ICa-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 ICa-L upwards and moved the activation and inactivation curves of ICa-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 Ca 2+ homeostasis by ICa-L.Keywords: cardiopretection, reactive oxygen species, calcium influx, isoproterenol, calcium concentration