Study on component change regularity in honey-processed licorice processing and verifying its enhanced antiarrhythmic bioactivity

Honey-processing significantly influences the chemical composition and antiarrhythmic efficacy of liquorice. This study optimised processing parameters and investigated dynamic chemical transformations and pharmacological mechanisms. Stir-frying under controlled intensity and duration (700 W, 13.5 min; drug temperature 120 °C) was identified as optimal. During early heating, glycosides were hydrolysed into aglycones; intermediate stages involved dehydration-limited hydrolysis and partial dihydroflavonoid-chalcone conversion; prolonged heating induced glycoside degradation and Maillard reactions. The optimised honey-processed liquorice exhibited elevated liquiritin and glycyrrhizic acid levels and demonstrated superior cardioprotective effects compared with raw liquorice and other processed samples in a zebrafish arrhythmia model. High-dose honey-processed liquorice and medium-dose isoliquiritin significantly improved cardiac morphology and function, with isoliquiritin showing the strongest antiarrhythmic activity. Metabolomic analysis revealed that regulation of unsaturated fatty acid metabolism was a key pathway underlying therapeutic effects. These findings clarify processing-constituent-efficacy relationships and highlight isoliquiritin as a principal bioactive component.