Glycyrrhetinic Acid Protects the Heart from Ischemia/Reperfusion Injury by Attenuating the Susceptibility and Incidence of Fatal Ventricular Arrhythmia During the Reperfusion Period in the Rat Hearts

Abstract

Background/Aims: Licorice has been used to treat many diseases, including palpitations, in both Eastern and Western societies for thousands of years. It has been reported that glycyrrhetinic acid (GA), an aglycone saponin extracted from licorice root, exerts protective effects on the cardiovascular system, limits infarct sizes and protects against the development of arrhythmia. However, the mechanisms underlying the effects of glycyrrhetinic acid on the cardiovascular system remain poorly understood. This study aimed to determine the mechanisms underlying the protective effects of GA against lethal cardiac arrhythmias induced via ischemia-reperfusion in rat hearts, and to examine its electropharmacological properties. Materials and Methods: Anesthetized rats were divided into control (CTL), GA5, GA10, and GA20 groups. GA was administered intravenously 15 min before the occlusion of the left anterior descending coronary artery, at dosages of 5, 10 and 20 mg/kg, respectively. Single ventricular myocytes were isolated using enzymolysis. The whole-cell patch clamp technique was utilized to record Ica, L, Ito and action potentials (APs). Results: During reperfusion, the incidence of ventricular fibrillation (VF) was decreased in each of the groups compared with the CTL group (p<0.05). The ventricular tachycardia (VT)/VF score was significantly decreased in the GA20 group. Action potential durations (APDs) were prolonged by GA; both L-type calcium current (Ica-L) and transient outward potassium current (Ito) were blocked in a concentration-dependent manner by GA. Conclusion: These results suggest that GA attenuates both the susceptibility to and the incidence of fatal ventricular arrhythmia during reperfusion in rat hearts via the prolongation of the APD and the inhibition of both Ica-L and Ito. GA appears to be a promising antiarrhythmic agent in the setting of ischemia/reperfusion.

Protective mechanisms of hypaconitine and glycyrrhetinic acid compatibility in oxygen and glucose deprivation injury

“…2) have aglycone saponins. It has been proved that GA can ameliorate ventricular arrhythmia (Wu et al, 2015) and GL transforms to GA in the absorption process (Fan et al, 2016). HA is considered to be effective on CVD, and its heat stability in water is better than that of other alkaloids (Yue et al, 2008;Zhang et al, 2015).…”

The comparative pharmacokinetics of four bioactive ingredients after administration of Ramulus Cinnamomi–Radix Glycyrrhizae herb pair extract, Ramulus Cinnamomi extract and Radix Glycyrrhizae extract

“…RC is frequently used to treat common colds, abdominal pains owing to chills, neuralgia, neurasthenia and rheumatic pain (Huang et al, 1997). 1), which increase coronary circulation (Song et al, 2013) and protect against the development of arrhythmia (Yi et al, 2012;Weqener and Nawrath, 1997;Wu et al, 2015), are effective constituents of the RC-RG herb pair for the cardiovascular system. Cinnamic acid (in RC), liquiritin (in RG), isoliquiritigenin (in RG) and glycyrrhetinic acidin (in RG) (Fig.…”

“…Cinnamic acid (in RC), liquiritin (in RG), isoliquiritigenin (in RG) and glycyrrhetinic acidin (in RG) ( Fig. 1), which increase coronary circulation (Song et al, 2013) and protect against the development of arrhythmia (Yi et al, 2012;Weqener and Nawrath, 1997;Wu et al, 2015), are effective constituents of the RC-RG herb pair for the cardiovascular system. Therefore, in order to reveal pharmacokinetic variation, these four bioactive ingredients were selected to investigate potential relativity of the RC-RG herb pair [Guizhigancao Decoction (GGD) and Lingguizhugan Decoction (LGZGD)].…”

Phytochemical composition, health effects, and crop management of liquorice (Glycyrrhiza glabraL.): Α medicinal plant

“…(93) Furthermore, liquorice extracts and their individual bioactive compounds provide several other health benefits for kidney, cardiovascular, immunological, respiratory, endocrine and central nervous systems which need to be underlined, since so far many physiological effects of liquorice on human body systems have been confirmed. (66,85,(100)(101)(102)(103)(104)(105)(106)(107)(108)(109)(110)(111)(112)(113)(114) The health benefits of liquorice and its constituents have been suggested to be attributed to various physiological mechanisms, including modulation of vascular injury and atherogenesis, (111) inhibition of tyrosinase activity, (103) improvement of the brain energy supply, (110) increased glucose tolerance, (112) activation of the immune system, (101) protection against the oxidative stress of the liver, (95) memory enhancing effects (105) and improvement of the renal function. (114) Other physiological effects of liquorice on human body systems are presented in Table 2.…”