18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels

Du, Yumin; Xia, Chengkun; Zhao, Ning; Lei, Ming; Xia, Jiahong

doi:10.1038/aps.2012.22

Cited by 20 publications

(12 citation statements)

References 38 publications

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“…Taking this into consideration, the drugs currently available in clinics are not satisfactory. Previous studies have revealed that GA can block peak and late I Na [19, 20]. In our task group, the results suggested that GA not only blocks I Kr (HERG) and I Ks but also inhibits I Ca-L .…”

Section: Discussionsupporting

confidence: 66%

“…These findings might help to elucidate the traditional use of licorice in therapy for cardiovascular disorders [19]. It has also been reported that 18 β -GA has significant potential for development as a novel antiarrhythmic agent and for treating myocardial ischemia by preferentially blocking the I Na,L [20]. However, the effects of GA on the potassium channel, especially the rapid and slow components of the delayed rectifier potassium current, are not clearly defined.…”

Section: Introductionmentioning

confidence: 99%

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Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

Jiang

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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Background. Licorice has long been used to treat many ailments including cardiovascular disorders in China. Recent studies have shown that the cardiac actions of licorice can be attributed to its active component, glycyrrhetinic acid (GA). However, the mechanism of action remains poorly understood. Aim. The effects of GA on the delayed rectifier potassium current (I K), the rapidly activating (I Kr) and slowly activating (I Ks) components of I K, and the HERG K+ channel expressed in HEK-293 cells were investigated. Materials and Methods. Single ventricular myocytes were isolated from guinea pig myocardium using enzymolysis. The wild type HERG gene was stably expressed in HEK293 cells. Whole-cell patch clamping was used to record I K (I Kr, I Ks) and the HERG K+ current. Results. GA (1, 5, and 10 μM) inhibited I K (I Kr, I Ks) and the HERG K+ current in a concentration-dependent manner. Conclusion. GA significantly inhibited the potassium currents in a dose- and voltage-dependent manner, suggesting that it exerts its antiarrhythmic action through the prolongation of APD and ERP owing to the inhibition of I K (I Kr, I Ks) and HERG K+ channel.

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Section: Discussionsupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

Jiang

et al. 2013

Evidence-Based Complementary and Alternative Medicine

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“…Our previous study demonstrated that GA reduced peak I Na and late I Na in Xenopus oocytes [20]. It has also been reported that GA exerts antiarrhythmic effects in the setting of myocardial ischemia via the blockage of Ina and Ica-L [21]. Additionally, GA inhibited potassium currents in both ventricular myocytes and HEK293 cells [22].…”

Section: Introductionmentioning

confidence: 77%

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

Yang

Jin

et al. 2015

Cell Physiol Biochem

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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.

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“…Furthermore, barbaloin also significantly inhibited ATX II-induced I Na.L enhancement. These findings indicated that barbaloin eliminates ATX II-induced EADs by inhibiting I Na.L enhancement; hence, these currents may be a promising target for the treatment of arrhythmias [29] .…”

Section: Discussionmentioning

confidence: 99%

Barbaloin inhibits ventricular arrhythmias in rabbits by modulating voltage-gated ion channels

et al. 2017

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Barbaloin (10-β-D-glucopyranosyl-1,8-dihydroxy-3-(hydroxymethyl)-9(10H)-anthracenone) is extracted from the aloe plant and has been reported to have anti-inflammatory, antitumor, antibacterial, and other biological activities. Here, we investigated the effects of barbaloin on cardiac electrophysiology, which has not been reported thus far. Cardiac action potentials (APs) and ionic currents were recorded in isolated rabbit ventricular myocytes using whole-cell patch-clamp technique. Additionally, the antiarrhythmic effect of barbaloin was examined in Langendorff-perfused rabbit hearts. In current-clamp recording, application of barbaloin (100 and 200 μmol/L) dose-dependently reduced the action potential duration (APD) and the maximum depolarization velocity (Vmax), and attenuated APD reverse-rate dependence (RRD) in ventricular myocytes. Furthermore, barbaloin (100 and 200 μmol/L) effectively eliminated ATX II-induced early afterdepolarizations (EADs) and Ca-induced delayed afterdepolarizations (DADs) in ventricular myocytes. In voltage-clamp recording, barbaloin (10-200 μmol/L) dose-dependently inhibited L-type calcium current (I) and peak sodium current (I) with IC values of 137.06 and 559.80 μmol/L, respectively. Application of barbaloin (100, 200 μmol/L) decreased ATX II-enhanced late sodium current (I) by 36.6%±3.3% and 71.8%±6.5%, respectively. However, barbaloin up to 800 μmol/L did not affect the inward rectifier potassium current (I) or the rapidly activated delayed rectifier potassium current (I) in ventricular myocytes. In Langendorff-perfused rabbit hearts, barbaloin (200 μmol/L) significantly inhibited aconitine-induced ventricular arrhythmias. These results demonstrate that barbaloin has potential as an antiarrhythmic drug.

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18β-Glycyrrhetinic acid preferentially blocks late Na current generated by ΔKPQ Nav1.5 channels

Cited by 20 publications

References 38 publications

Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

Inhibitory Effects of Glycyrrhetinic Acid on the Delayed Rectifier Potassium Current in Guinea Pig Ventricular Myocytes and HERG Channel

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

Barbaloin inhibits ventricular arrhythmias in rabbits by modulating voltage-gated ion channels

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