| Summary: | 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 western 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. Keywords: GH-ZJZ combination, Acute alcohol-induced liver injury, Oxidative stress, AQP9, KEAP1-NRF2-ARE
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