Isoliquiritigenin induced endoplasmic reticulum stress in zebrafish embryos

Abstract Isoliquiritigenin (ISL), a natural flavonoid compound from the root of licorice, has antioxidant, anticancer, anti-inflammatory, and anti-allergic effects, and is commonly detected in both environmental and human samples. Our previous studies have demonstrated that exposure to ISL can result in developmental deformities and abnormal immune responses. However, the molecular mechanism underlying the toxicity of ISL towards zebrafish embryos remains incompletely understood. Therefore, this study aimed to investigate the effects of ISL exposure on endoplasmic reticulum (ER) stress in zebrafish embryos by examining the expression levels of ER stress markers HSPA5 and CHOP as well as related apoptosis factor under different concentrations of ISL, using Tm as a positive control group. Additionally, we performed targeted analysis of ER stress-related pathways via RNA transcriptome sequencing. The results showed that exposure to ISL induced high expression levels of HSPA5 and CHOP while activating ER stress pPERK-PEIF2a-ATF4 and ATF6 pathways in zebrafish embryos. These findings suggest that activation of endoplasmic reticulum stress signaling pathway may contribute to the developmental deformities observed following exposure to ISL in zebrafish embryos, highlighting potential ecological risks associated with its use.