Therapeutic Potential of Raspberry Extract in High-Fat Diet-Induced Liver Injury via Apoptosis and AMPK/PPARα Pathways

This study aimed to explore the efficacy and mechanisms of raspberry (Rubus idaeus L. fruit) aqueous extract (RE) in alleviating high-fat diet (HFD)-induced metabolic-associated fatty liver disease (MAFLD). The MAFLD mouse model was established to examine the effects of RE through liver transcriptome and metabolomics analysis. In this study, RE supplementation significantly alleviated HFD-induced liver injury, hepatosteatosis, inflammation, and Insulin resistance. Liver transcriptome analysis demonstrated that RE supplementation favorably regulated signaling pathways involved in fatty acid metabolism and inflammation, including the AMPK signaling pathway, PPAR signaling pathway, Apoptosis, etc. Furthermore, the injection of compound C, an antagonist of AMPK, notably reversed the hepatoprotective effects of RE, evidenced by increased lipid profile levels, accelerated fatty acid-related gene disorder, and increased positive tunnel staining area. Furthermore, liver metabolomics analysis demonstrated that RE treatment led to substantial enrichment of the liver tissue metabolite umbelliferone (UMB), which has the potential to ameliorate lipid accumulation and hepatocyte injury through the AMPK signaling pathway. In summary, RE intervention mitigated HFD-induced liver dysfunction in mice, with UMB likely being the primary component responsible for its therapeutic efficacy in the liver. In addition, this study provided new insights, suggesting that RE could be used as a promising therapeutic approach for modulating MAFLD via Apoptosis and the AMPK/PPARα signaling pathway.

AMPK; PPARα; Rubus idaeus; apoptosis; metabolic-associated fatty liver disease; metabolites.