Quercetin alleviates metabolic-associated fatty liver disease by tuning hepatic lipid metabolism, oxidative stress and inflammation

The natural flavonoid quercetin, which exhibits a range of biological activities, has been implicated in liver disease resistance in recent research. <i>In vivo</i> study attesting to quercetin's protective effect against metabolic-associated fatty liver disease (MAFLD) is inadequate, however. Here, our investigation explored the potential benefits of quercetin in preventing MAFLD in C57BL/6 mice fed a high-fat diet (HFD). The results revealed that quercetin ameliorated the aberrant enhancement of body and liver weight. The hepatic histological anomalie induced by MAFLD were also mitigated by quercetin. HFD-induced imbalance in serum LDL, HDL, AST, ALT, TG, and LDH was mitigated by quercetin. Mechanically, we found that quercetin improved lipid metabolism by reducing lipogenesis proteins including ACC, FASN, and SREBP-1c and enhancing β-oxidation proteins including PPARα and CPT1A. <i>In vitro</i> study demonstrated that quercetin regulated hepatic lipid metabolism by targeting SREBP-1c and PPARα. Additionally, quercetin enhanced the antioxidant capacity in HFD-treated mice by downregulating Nrf2 and HO-1 expressions and upregulating SOD and GPX1 expressions. The hyper-activation of inflammation was also restored by quercetin via eliminating the phosphorylation of IκBα and NF-κB p65. Collectively, our observations highlight that quercetin exerts hepatoprotective properties in MAFLD mice by regulating hepatic lipid metabolism, oxidative stress and inflammatory response.