Anti-arrhythmia potential of honey-processed licorice in zebrafish model: Antioxidant, histopathological and tissue distribution

Honey-processed licorice (HPL) is the roasted product of licorice. It is recorded in the "Shang Han Lun" that licorice has better protection on heart after honey-processed. However, researches regarding its protective effect on the heart and the distribution of HPL in vivo are still limited.To evaluate the cardio-protection of HPL and explore the law of ten main components distribution in vivo under physiological and pathological conditions for an attempt to clarify the pharmacological substance basis of HPL in treating arrhythmia.The adult zebrafish arrhythmia model was established by doxorubicin (DOX). Electrocardiogram (ECG) was used to detect the heart rate changes of zebrafish. SOD and MDA assays were used to evaluate oxidative stress levels in the myocardium. HE staining was used to observe the morphological change of myocardial tissues after HPL treatment. The UPLC-MS/MS was adapted to detect the content of ten main components of HPL in heart, liver, intestine, and brain under normal and heart injury conditions.Heart rate of zebrafish was decreased, the SOD activity was attenuated and MDA content was increased in myocardium after administration of DOX. Moreover, tissue vacuolation and inflammatory infiltration were detected in zebrafish myocardium induced by DOX. HPL could ameliorate heart injury and bradycardia induced by DOX to a certain extent by increasing SOD activity and reducing MDA content. In addition, the study of tissue distribution revealed that the content of liquiritin, isoliquiritin, and isoliquiritigenin in the heart was higher in the presence of arrhythmias than those in the normal condition. Under pathological conditions, the heart highly exposed to these three components could elicit anti-arrhythmic effects by regulating immunity and oxidation.These findings indicate that the HPL is protective against heart injury induced by DOX, and its effect is associated with the alleviation of oxidative stress and tissue injury. And the cardioprotective effect of HPL under pathological conditions may be related to the high distribution of liquiritin, isoliquiritin, and isoliquiritigenin in heart tissue. This study provides an experimental basis for the cardioprotective effects and tissue distribution of HPL.