Background: Some Kampo preparations, which are made from licorice containing glycyrrhizic acid (GZA) of ≥2%, have been used for treating patients with palpitation; however, it is not fully understood how licorice may control it.
Methods: Exp 1: Glycyrrhetinic acid (GRA), a major hydrolyzed metabolite of orally taken GZA, at 0.1, 1 and 10 μg/mL was cumulatively applied to human induced pluripotent stem cell-derived cardiomyocytes sheets (n=6).  Exp 2: Kanzoto, 6.0 g of which contains a decoction made of 8.0 g licorice, in a dose of 2 or 6 g/body/day was orally administered to conscious chronic atrioventricular block dogs for 3 consecutive days (n=4), and Holter electrocardiographic monitoring was performed before 1^st dosing and on the 3^rd day of dosing.
Results: Exp 1: GRA prolonged the effective refractory period in rate- and concentration-dependent manners and delayed the conduction within initial 300 μm from the pacing site in the sheets, indicating its Na⁺ channel blockade with rapid dissociation. Exp 2: The high dose suppressed sinoatrial and idioventricular automaticity without slowing intraventricular conduction, and caused cardiac arrest in 1 out of 4 dogs, which was not induced by the low dose.
Conclusion: Licorice may possess lidocaine-like Na⁺ channel blocking property, which will partly explain its clinical utility.