Exploring the potential mechanism of Rubus corchorifolius L. fruit polyphenol-rich extract in mitigating non-alcoholic fatty liver disease by integration of metabolomics and transcriptomics profiling†

Nonalcoholic fatty liver disease (NAFLD), as the commonest chronic liver disease, is accompanied by liver oxidative stress and inflammatory responses. Herein, the extract obtained from Rubus corchorifolius fruits was purified and characterized for its polyphenol composition. The liver protective effect of the purified R. corchorifolius fruit extract (RCE) on mice with high-fat-diet (HFD)-induced NAFLD were investigated, and the potential mechanisms were explored through the integration of transcriptomics and metabolomics. Results showed that the polyphenolic compounds in RCE mainly included (−)-epigallocatechin, procyanidin B₂, keracyanin, vanillin, dihydromyricetin, and ellagic acid. In addition, RCE intervention ameliorated liver and mitochondrial damage, which was evidenced by decreased indices of oxidative stress, liver function markers, and lipid profile levels. The liver metabonomics research revealed that RCE intervention affected the metabolic pathways of metabolites, including linoleic acid metabolism, galactose metabolism, alanine, aspartate and glutamate metabolism, retinol metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, aminoacyl-tRNA biosynthesis, riboflavin metabolism, starch and sucrose metabolism, and arachidonic acid metabolism. Additionally, liver transcriptomics research indicated that pathways like fatty acid degradation, circadian rhythm, valine, leucine and isoleucine degradation, primary bile acid biosynthesis, cytokine–cytokine receptor interaction, adipocytokine signaling pathway, glutathione metabolism, lipid and atherosclerosis were significantly enriched. The transcriptomics and metabolomics analysis demonstrated that RCE intervention had significant modulatory effects on the metabolic pathways associated with glycolipid metabolism. Moreover, RT-PCR results verified that RCE intervention regulated liver mRNA levels associated with the inflammatory response. Therefore, our findings suggest that the intake of RCE might be an effective strategy to alleviate liver damage.