Combined Protective Effects of Raffinose and Isoflavones Against High-Fructose-Induced Liver Damage via Improved Bioavailability and Metabolic Regulation

This study investigated the combined administration of raffinose (RAF) and isoflavones (ISO) to enhance ISO bioavailability and alleviate high-fructose (HF)-induced liver damage. Mice were administered 20% HF water with RAF, ISO, or their combination (RAF + ISO) for 10 weeks. UPLC-qTOP/MS analysis showed that RAF + ISO significantly increased total ISO levels in serum, urine, and feces by 18.5%, 37.4%, and 13.6%, respectively, compared to ISO alone (p < 0.05). The combined treatment more effectively reduced HF-induced weight gain, visceral fat accumulation, and dyslipidemia, partly through suppression of FAS and ACC gene expression (p < 0.05). Furthermore, RAF + ISO more efficiently attenuated hepatic oxidative stress, inflammation, and insulin resistance than either agent alone. Liver enzyme activities (AST, ALT, ALP) were significantly reduced by RAF + ISO treatment, consistent with histopathological improvements in liver tissue. These findings demonstrate that RAF enhances the systemic availability of ISO and potentiates its protective effects against HF-induced metabolic and hepatic alterations.