Pectin Polysaccharides from Cascara Prevent Metabolic Dysfunction-Associated Fatty Liver Disease Development by Regulating Gut Microbiota and Liver Metabolism.

Pectin polysaccharides from cascara are rich in rhamnogalacturonan I, which has good potential for regulating lipid metabolism. Improvement of lipid metabolism disorders is crucial for the treatment of metabolic dysfunction-associated fatty liver disease (MAFLD). This study revealed the physicochemical properties of cascara pectin polysaccharides (CPP), further evaluated their effects on MAFLD, and explored the underlying mechanisms. In this study, CPP significantly alleviated liver damage induced by a high-fat diet. Mechanistically, CPP increased the level of fumarate through decreasing the levels of fumarate hydrase and proteobacteria. Molecular docking analysis revealed that there was a direct interaction between fumarate and AMP-activated protein kinase α. Moreover, CPP promoted cholesterol clearance through the AMPK-FOXO3a-PCSK9-LDLR signaling pathway. Collectively, CPP may mitigate HFD-induced hepatic steatosis through the gut microbiota-metabolite-lipid pathway. As a sustainable prebiotic agent, CPP may provide a scientific foundation for dietary interventions in MAFLD management.