摘要Background:To explore the antioxidant capacity of α-asarone(ARE)in mice models of sodium valproate(SV)-induced liver injury,and to elucidate the underlying mechanism of ARE in liver injury treatment.Methods:Network pharmacology and molecular docking were used to predict ARE's potential pharmacological mechanisms in treating drug-induced liver injury.AML12 cell model was used to evaluate the antioxidant stress activation of ARE.In the evaluation of antioxidant activity,ARE was tested for its ability to scavenge hydroxyl radical(OH)radicals,2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid)(ABTS+),and 1,1-diphenyl-2-picrylhydrazyl(DPPH),with vitamin C serving as the positive control.And thirty-six male mice were divided into six groups.Group Ⅰ,the control,received saline.The other five groups received oral doses of 500 mg/kg/b.w.of SV daily for 14 days.Group Ⅱ received only SV.Group Ⅲ received the hepatic protectant bifendate at 100 mg/kg/b.w.,while groups Ⅳ,Ⅴ,and Ⅵ were treated with 20,40,and 80 mg/kg/b.w.of ARE,respectively,also for 14 days.After sacrifice,liver and blood samples were collected for biochemical or metabolomic analysis.Results:ARE significantly reduced the levels of reactive oxygen species and activated the Keap1/Nrf2 signaling pathway in liver injury AML12 cells.ARE demonstrated dose-dependent scavenging activity in DPPH,ABTS+,and OH assays.It lowered serum alanine aminotransferase and aspartate aminotransferase levels,increased glutathione peroxidase and superoxide dismutase activity in liver tissue,and reduced malondialdehyde content.Metabolomic analysis showed that ARE restored twenty liver metabolites to control levels and enriched three pathways(arginine biosynthesis,sucrose and starch metabolism,and biotin metabolism)with shared differential metabolites.Conclusion:These results shed light on ARE's mechanism in reducing oxidative stress,suggesting a potential strategy for preventing SV-induced liver disease by modulating metabolic products and enhancing antioxidant capacity.ARE could be a promising drug candidate for its antioxidant and liver-protective effects.