title: 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: OBJECTIVE
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Beijing Haidian Hospital, Haidian Section of Peking University Third Hospital, Beijing, China.
authors.forename: Hong-Jin
authors.initials: HJ
authors.lastname: Wu
authors.forename: Ji-Yuan
authors.initials: JY
authors.lastname: Yang
authors.forename: Min
authors.initials: M
authors.lastname: Jin
authors.forename: Sheng-Qi
authors.initials: SQ
authors.lastname: Wang
authors.forename: De-Lin
authors.initials: DL
authors.lastname: Wu
authors.forename: Yu-Na
authors.initials: YN
authors.lastname: Liu
authors.forename: Xu
authors.initials: X
authors.lastname: Yan
authors.forename: Cui
authors.initials: C
authors.lastname: Yang
authors.forename: Ge
authors.initials: G
authors.lastname: Zhang
authors.forename: Jing
authors.initials: J
authors.lastname: He
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000627:therapeutic use*; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D006034:Glycyrrhetinic Acid / Q000627:therapeutic use*; D015994:Incidence; D032342:Muscle Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000150:complications* / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D017207:Rats, Sprague-Dawley; D017180:Tachycardia, Ventricular / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D014693:Ventricular Fibrillation / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control
chemical_list: D000889:Anti-Arrhythmia Agents; D020746:Calcium Channels, L-Type; D006034:Glycyrrhetinic Acid; D002118:Calcium