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

Area of Science:

• Hepatology and Nutritional Science
• Molecular Biology and Biochemistry

Background:

• Metabolic-associated fatty liver disease (MAFLD) is a growing health concern.
• High-fat diets (HFD) are a primary driver of MAFLD, causing liver injury, inflammation, and insulin resistance.
• Exploring natural compounds for MAFLD treatment is crucial.

Purpose of the Study:

• To investigate the efficacy of raspberry (Rubus idaeus L. fruit) aqueous extract (RE) in an HFD-induced MAFLD mouse model.
• To elucidate the underlying molecular mechanisms of RE's therapeutic effects.
• To identify key active compounds within RE responsible for alleviating MAFLD.

Main Methods:

• Establishment of a MAFLD mouse model using a high-fat diet.
• Administration of raspberry aqueous extract (RE) to the mouse model.
• Comprehensive analysis using liver transcriptome and metabolomics.
• Validation of mechanisms using AMPK antagonist (Compound C) and TUNEL staining.

Main Results:

• RE supplementation significantly ameliorated HFD-induced liver injury, hepatosteatosis, inflammation, and insulin resistance.
• Transcriptome analysis revealed RE modulates key signaling pathways, including AMPK and PPAR, involved in fatty acid metabolism and inflammation.
• Metabolomics identified umbelliferone (UMB) enrichment in RE-treated livers, suggesting its role in mitigating lipid accumulation and hepatocyte injury via AMPK activation.
• AMPK inhibition reversed RE's protective effects, confirming the pathway's importance.

Conclusions:

• Raspberry extract (RE) demonstrates significant therapeutic potential for MAFLD.
• Umbelliferone (UMB) is likely the primary active component in RE for treating MAFLD.
• RE modulates MAFLD through apoptosis and the AMPK/PPARα signaling pathways, offering a promising natural therapeutic strategy.