Fanlian Huazhuo Formula alleviates high-fat diet-induced non-alcoholic fatty liver disease by modulating autophagy and lipid synthesis signaling pathway.

ABSTRACT

BACKGROUND: Fanlian Huazhuo Formula (FLHZF) has the functions of invigorating spleen and resolving phlegm, clearing heat and purging turbidity. It has been identified to have therapeutic effects on type 2 diabetes mellitus (T2DM) in clinical application. Non-alcoholic fatty liver disease (NAFLD) is frequently diagnosed in patients with T2DM. However, the therapeutic potential of FLHZF on NAFLD and the underlying mechanisms need further investigation. AIM: To elucidate the effects of FLHZF on NAFLD and explore the underlying hepatoprotective mechanisms in vivo and in vitro. METHODS: HepG2 cells were treated with free fatty acid for 24 hours to induce lipid accumulation cell model. Subsequently, experiments were conducted with the different concentrations of freeze-dried powder of FLHZF for 24 hours. C57BL/6 mice were fed a high-fat diet for 8-week to establish a mouse model of NAFLD, and then treated with the different concentrations of FLHZF for 10 weeks. RESULTS: FLHZF had therapeutic potential against lipid accumulation and abnormal changes in biochemical indicators in vivo and in vitro. Further experiments verified that FLHZF alleviated abnormal lipid metabolism might by reducing oxidative stress, regulating the AMPKα/SREBP-1C signaling pathway, activating autophagy, and inhibiting hepatocyte apoptosis. CONCLUSION: FLHZF alleviates abnormal lipid metabolism in NAFLD models by regulating reactive oxygen species, autophagy, apoptosis, and lipid synthesis signaling pathways, indicating its potential for clinical application in NAFLD.