| Summary: | This study aimed to investigate the protective effects of three propolis-abundant flavonoids, pinocembrin (PI), galangin (GA), and chrysin (CH) against ethanol-induced injuries in HepG2 cells. Results showed that the pre-treatment of flavonoids could significantly reverse cellular injuries caused by ethanol, which was evidenced by the decreased production of reactive oxygen species and malondialdehyde, less DNA damages, and the increased antioxidant status. Results from RNA-Seq revealed that differentially expressed genes in response to the pre-treatment of PI, GA, and CH were significantly enriched in different biological processes. Three flavonoids could significantly suppress ERK1/2 phosphorylation, AHR nuclear translocation, and CYP1A1 expression. In summary, three flavonoids had significant protective effects on ethanol-induced injuries through the inhibition of the ERK1/2-AHR-CYP1A1 signaling pathway. Our results provided theoretical bases for the promising use of PI, GA and CH in the prevention and treatment of ethanol-induced fatty liver diseases.
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