Abstract
Glycyrrhizic acid (GA) is one of the main active components in licorice and has often been reported to have cardioprotective effects. However, the underlying cellular mechanisms remain unclear. The aim of this study is to verify the protective effects of GA against isoproterenol (ISO)-induced myocardial ischemia injury in rats. Another aim is to explore the cellular mechanisms based on the L-type Ca2+ channel, myocardial cell contraction, and intracellular Ca2+ ([Ca2+]i) transient. The results show that GA reduced the ST segment elevation, decreased the heart rate, prevented ISO-induced QT-interval shortening, improved heart morphology, and decreased the activity of CK and LDH. GA blocked ICa-L in a dose-dependent manner. The concentration for 50% of the maximal effect (EC50) of GA was 145.54 μg/mL, and the maximal inhibition was 47.43 ± 0.75% at 1000 μg/mL. However, GA did not affect the dynamical properties of the Ca2+ channel. GA reversibly reduced the amplitude of cell contraction in a dose-dependent manner and slowed down its deflection and recovery, as well as the [Ca2+]i transient. The data demonstrate that GA inhibits L-type Ca2+ channels, decreases the [Ca2+]i transient, and shows a negative cardiac inotropic effect in the ventricular myocardial cells of adult rats. It also protects the myocardia from ischemia injury induced by ISO.
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Author contribution statement
LC and SG conceived and designed the research. ML, YX, and ZW conducted the experiments. ML, ZW, and ZM analyzed the data. XH interpreted the data. ML wrote the manuscript. DM and SS searched the literature. SS collected funds. All authors read and approved the manuscript.
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This work was supported by the Department of Education of Hebei Province (Nos. ZD2018038 and ZD2016091) and the State Administration of Traditional Chinese Medicine of the People’s Republic of China (Nos. 2019075 and 2019135).
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All programs involving animals in this study were in accordance with the Guidelines of Animal Experiments of the Committee of Medical Ethics, the Declaration of Helsinki principles, and the Ministry of Health of China. All experimental animal handling procedures were approved by the Ethics Committee for Animal Experiments of Hebei University of Chinese Medicine (approval number: DWLL2018004; approval date: August 6, 2018).
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Li, M., Wen, Z., Xue, Y. et al. Cardioprotective effects of glycyrrhizic acid involve inhibition of calcium influx via L-type calcium channels and myocardial contraction in rats. Naunyn-Schmiedeberg's Arch Pharmacol 393, 979–989 (2020). https://doi.org/10.1007/s00210-019-01767-3
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DOI: https://doi.org/10.1007/s00210-019-01767-3