Physcion(PHY)is an anthraquinone compound derived from traditional Chinese medicine such as Rhei Radix et Rhizoma.The aim of this study is to investigate the improvement of PHY on non-alcoholic fatty liver disease(NAFLD)and its underlying mechanism.NAFLD was induced in mice by feeding with the methionine-and choline-deficient diet(MCD)for 6 weeks.This experiment was approved by the Experimental Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine(approval number:PZSHUTCM190705019).The results displayed that PHY(5 and 20 mg·kg-1)reversed liver damage,reduced hepatic lipid accumulation and decreased the elevated NAFLD activity score(NAS)in MCD-fed NAFLD mice.Results from Western blot and enzyme activity demonstrated that PHY could enhance the protein expression and enzyme activity of carnitine palmitoyltransferase 1A(CPT1A)in the liver and L-02 cells,but it did not affect Cpt1α mRNA expression.Immunofluorescence results indicated that PHY(10 and 25 μmol·L-1)could reduce the mitochondrial injury induced by non-esterified fatty acids(NEFA)in L-02 cells.Results from seahorse assay showed that PHY could enhance mitochondrial basic respiration,maximal respiration,ATP synthesis and reserve respiration in L-02 cells treated with NEFA,but had no effect on mitochondrial proton leakage.In summary,PHY reversed mitochondrial damage and enhanced fatty acid β-oxidation,thereby reducing hepatic steatosis and improving NAFLD.