Abstract:This study investigated the intervention mechanism of grafted Cyclocarya paliurus extract on highfat diet-induced non-alcoholic fatty liver disease （NAFLD） in mice through network pharmacology and animal experiments. Network pharmacological analysis identified 21 active components （e.g.， quercetin and kaempferol） that target farnesoid X receptor （FXR）， proliferator-activated receptor alpha （PPARα）， and nuclear factor kappa-B （NF-κB） to regulate lipid metabolism and inflammatory pathways. NAFLD mouse models were established using a high-fat diet and divided into normal， model， low-dose （50 mg/kg）， and high-dose（200 mg/kg） groups. The results showed that the extract significantly reduced serum and hepatic total cholesterol （TC） and low-density lipoprotein cholesterol （LDL-C） levels， elevated high-density lipoprotein cholesterol （HDL-C） levels， enhanced antioxidant enzyme activities， and suppressed malondialdehyde （MDA） production， thereby effectively alleviating hepatic steatosis and inflammatory infiltration. Mechanistically， the extract synergistically modulated nuclear receptors， including FXR， PPARα， and peroxisome proliferator-activated receptor gamma （PPARγ）， activated the AMP-activated protein kinase （AMPK）/PPARα/carnitine palmitoyltransferase 1A （CPT1A） fatty acid oxidation axis， and inhibited the FXR/sterol regulatory element binding protein-1c （SREBP-1c） lipid synthesis pathway， forming a multidimensional "lipid metabolism-antioxidantanti-inflammatory" regulatory network. In conclusion， Cyclocarya paliurus extract may exert protective effects against liver injury in mice with high-fat diet-induced NAFLD through multitarget synergistic regulation of lipid metabolism， oxidative stress， and inflammatory responses.