Background: Acute liver damage is mainly induced by virus,alcohol,drugs and immune etc.Agents with the ability to inhibit tyrosinase and protect against DNA damage caused by reactive oxygen species(ROS)may be therapeutically useful for the prevention or treatment of ROS related diseases.Methods: The experiment examined the hepatoprotective effects of phloretin and PIH on D-GalN-induced acute liver damage in Kunming mice as well as the possible mechanisms.The serum levels of alanine aminotransferase(ALT),aspartate aminotransferase(AST),γ-glutamyl transferase(γ-GT),alkaline phosphatase(ALP)and total bilirubin(TB),and histopathological changes in mouse liver sections were determined.The antioxidant effects of phloretin,quercetin and PIH on lipid peroxidation in rat liver mitochondria in vitro,DPPH or ABTS free radical scavenging activity in vitro,and supercoiled pBR322 plasmid DNA were determined.The experiment also examined the antityrosinase activity,the inhibition type and inhibition constant of phloretin and PIH.Results: Phloretin,quercetin or PIH significantly prevented the increase in serum ALT,AST,γ-GT,ALP and TB in acute liver damage induced by D-GalN and produced a marked amelioration in the histopathological hepatic lesions.Phloretin,quercetin or PIH also exhibited antioxidant effects on lipid peroxidation in rat liver mitochondria in vitro,DPPH or ABTS free radical scavenging activity in vitro,and supercoiled pBR322 plasmid DNA.Phloretin,quercetin or PIH also exhibited good antityrosinase activity.Conclusion: This was the first time to study the hepatoprotective effects of phloretin and PIH on D-GalN-induced acute liver damage in Kunming mice as well as the possible mechanisms.This was also the first time to study the lipid peroxidation inhibition activity of phloretin and PIH in liver mitochondria induced by Fe2+/Vc system in vitro,the protective effects on supercoiled pBR322 plasmid DNA,and the antityrosinase activity of phloretin and PIH.