Isorhamnetin in Quinoa Whole-Grain Flavonoids Intervenes in Non-Alcoholic Fatty Liver Disease by Modulating Bile Acid Metabolism through Regulation of FXR Expression

Non-alcoholic fatty liver disease (NAFLD) is a severe hepatic health threat with no effective treatment. Based on the results that Chenopodium quinoa Willd. flavonoids eluted with 30% ethanol (CQWF30) can effectively alleviate NAFLD, this study employed ultrahigh-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UPLC-ESI-MS/MS) to analyze the components of CQWF30., and screened for flavonoids with potential NAFLD-mitigating effects through network pharmacology. In vitro models using HepG2 and BEL-7402 cell lines induced with free fatty acid (FFA) showed that isorhamnetin administration reduced intracellular lipid deposition and reversed elevated triglyceride (TG) and total cholesterol (T-CHO) levels. In vivo experiments in high-fat diet (HFD) mice demonstrated that isorhamnetin significantly lowered serum and liver fat content, mitigated liver damage, and modulated bile acid metabolism by upregulating FXR and BSEP and downregulating SLCO1B3. Consequently, isorhamnetin shows promise as a treatment for NAFLD due to its lipid-lowering and hepatoprotective activities.