生薬甘草の心臓への電気薬理学的作用： in vitroとin vivoモデルを用いた統合的解析

• Published in: 日本薬理学会年会要旨集 p. 1-O-D3-4
• Main Authors: 長澤（萩原）, 美帆子, 杉山, 篤, 千葉, 浩輝, 神林, 隆一, 川合, 眞一, 布井, 啓雄, 後藤, 愛, 中瀬古（泉）, 寛子, 武井, 義則, 松本, 明郎
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: arrhythmia; cardiac myocyte; sodium channel
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_1-O-D3-4

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 1st dosing and on the 3rd 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.