Abstract:Raisins are rich in polyphenols， which exhibit antioxidant activities. In this study， polyphenols were extracted from raisins using 70% ethanol， which was followed by separation and enrichment with AB-8 macroporous resin. The protective effects of raisin polyphenols on oxidatively damaged HepG2 cells were investigated in the H2O2-induced oxidatively damaged HepG2 cell model and analyzed by transcriptomics and metabolomics. The results showed that raisin polyphenols significantly reduced malondialdehyde （MDA） levels in oxidatively damaged HepG2 cells， and there were 6 243 differential genes， including genes located on chromosome 19 （FOSB）， activity-regulated cytoskeletal proteins （ARC）， Ras-related dexamethasone-induced 1（RASD1）， etc.， which were mainly enriched to 109 signaling pathways in oxidatively damaged HepG2 cells after raisin polyphenol intervention. There were 142 differential metabolites in oxidatively damaged HepG2 cells， mainly including phenylacetylglycine， nicotinamide， and p-coumarin， which were enriched into 83 metabolic pathways. Co-analysis revealed that the differential genes and differential metabolites in oxidatively damaged HepG2 cells were co-enriched in 11 pathways， and the differential metabolites， such as cis-4-hydroxy-D-proline and triethylamine， had a strong correlation with the differential genes， such as mitochondria-encoded cytochrome C oxidase 2 （MTCO2） and mitochondria-encoded cytochrome C oxidase 3 （MTCO3）. The results suggested that raisin polyphenols could mitigate the oxidative damage suffered by HepG2 cells， as well as modulate cellular genes and metabolite production.