Honey-fried licorice in the treatment of arrhythmia: Structure elucidation and the mechanism of antiarrhythmic activity

Phytomedicine. 2024 Nov 15:136:156259. doi: 10.1016/j.phymed.2024.156259. Online ahead of print.

Abstract

Aim of the study: To evaluate the therapeutic mechanism of Honey-fried licorice on arrhythmia, to explore the distribution of main components of Honey-fried licorice in vivo before and after processing, and to elucidate the active ingredient of Honey-fried licorice on arrhythmia.

Materials and methods: UPLC-Q-TOF/MS were used to analyze the common and different components of raw and honey-fried licorice before and after processing. Yin deficiency syndrome was established by continuous irritability and water platform sleep deprivation, and then ventricular arrhythmia model was established by injection of calcium chloride into the tail vein. Applying the electrocardiograph changes in heart rate in rats. Subsequently, ELISA and histopathological examinations were conducted to assess the therapeutic effects of honey-fried licorice on arrhythmia. Metabonomics analysis was employed to predict key regulatory pathways involved in the treatment response. Finally, RT-PCR and enzyme activity assays were utilized to verify the expression and function of key genes and proteins, providing insights into the underlying mechanisms.

Results: The heart rate of rats increased after injection of Cacl2 solution into the tail vein. Honey-fried licorice has a certain improvement effect on heart injury and tachycardia, and its mechanism may be through the obvious correction effect on SOD, MDA, LDH, Na+-K+-ATPase, CaM and CAMK2 in the arrhythmia model. Under pathological conditions, Metabonomics revealed that the heart was highly exposed to glycyrrhetic acid 3-O-glucuronide, isoformononetin, araboglycyrrhizin, 18β-glycyrrhetinic acid, liquiritigenin, licoflavonol and isoliquiritigenin are known to have anti-arrhythmic effects through immune regulation and oxidation. Notably, both PCR and ELISA analyses indicated that honey-fried licorice may effectively treat arrhythmia, potentially through the modulation of the arachidonic acid pathway.

Conclusion: These results suggested that honey-fried licorice could protect against arrhythmia and alleviate oxidative stress and tissue damage caused by arrhythmia. Through correlation analysis and metabolomics, it was found that glycyrrhetic acid 3-O-glucuronide, isoformononetin, araboglycyrrhizin, 18β-glycyrrhetinic acid, liquiritigenin, licoflavonol and isoliquiritigenin can be used as the active ingredient of honey-fried licorice in the treatment of arrhythmia. Moreover, our results suggested that the therapeutic effect of honey-fried licorice on arrhythmia may be linked to the regulation of the arachidonic acid pathway. This study elucidates the mechanisms by which honey-fried licorice treats arrhythmia from a metabolic perspective, highlighting its role in "tonifying the spleen and stomach, supplementing qi, and replenishing the pulse." These findings provide a foundation for the further application of honey-fried licorice and the development of related products.

Keywords: Honey-fried licorice; Mechanism of action; UPLC-Q-TOF-MS/MS; Untargeted metabolomics.