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Objective: The Flower of Lobed Kudzuvine[Pueraria lobata (Willd.)Ohwi;Gehua in Chinese;GH]and Japanese Raisin Tree Seed (Hovenia dulcis Thunnb.;Zhijuzi in Chinese;ZJZ) are herbs that have been used in China for the treatment of alcohol intoxication and liver diseases.We aimed to evaluate the hepatoprotective potential of a combination of these in mice with acute alcohol-induced liver injury,and to elucidate the mechanisms involved.Methods: Male ICR mice were randomly allocated to six groups: a control group,an alcohol-administered group,and groups that were administered alcohol and one of silibinin,the GH,the ZJZ or a GH-ZJZ combination (at a ratio of 2∶1).Animals were orally administered 56％ alcohol (Er Guo-tou white spirit,0.12 mL/10 g/d) for 10 days and at the end of this period,hepatic biochemical indicators,antioxidant parameters,alcohol metabolic enzymes,and histopathologic changes were evaluated.Moreover,the expression of the signaling molecules KEAP1,NRF2,and AQP9 were measured by qRT-PCR and west blotting.Results: Compared with the model group,GH-ZJZ (2∶1) had lower serum ALT (12.15 ± 0.39,P =.003),AST (104.07 ± 1.03,P =.001),and ALP (148.09 ± 2.55,P =.010) activities,and lower TC (1.97 ± 0.05,P =.001) and TG (1.54 ± 0.07,P =.002) concentrations.GH-ZJZ (2∶1) also significantly increased the hepatic activities of SOD and GSH (4.24 ± 0.25 and 1.57 ± 0.06,respectively;both P ＜.01),reduced the ROS and MDA concentrations (97.50 ± 3.00 and 2.39 ± 0.19,respectively;both P ＜.01),and upregulated Nrf2 expression (P ＜.01).GH-ZJZ (2∶1) significantly reduced the expression of KEAP1 and AQP9 in the liver,compared with alcohol-administered mice (P ＜.01).Importantly,the GH-ZJZ combination caused a more marked improvement in acute liver injury than GH or ZJZ alone.Conclusion: We have demonstrated protective effects of GH-ZJZ (2∶1) against acute alcohol-induced hepatic injury,and shown that these effects may be associated with improvements in lipid and alcohol metabolism,antioxidant capacity,and lipid peroxidation.