To explore protective effect of isoquercitrin on Aβ_25-35-induced injury in PC12 cells.The interaction of isoquercitrin with AMPK was determined by molecular docking.Aβ_25-35 (20 μmol/L) -induced PC12 cells injury was accepted as an model of oxidative stress in vitro.Cell viability was detected using MTT assay,LDH release,ROS content,MDA content and antioxidant enzymes including SOD and GSH-Px activities were measured by corresponding kits.Expressions of p-AMPK,PGC-1α,Sirt3 and IDH2 proteins were determined using Western blot analysis.The results showed that the binding energy between isoquercitrin and AMPK was -9.48 kJ/mol.Pre-treatment with isoquercitrin (1,10,100 μmol/L) concentration-dependent suppressed PC12 cell death-induced by Aβ_25-35.Isoquercitrin not only decreased ROS and MDA contents,but also elevated SOD and GSH-Px activities. Furthermore,isoquercitrin also up-regulated p-AMPK,PGC-1α,Sirt3 and IDH2 protein expressions.These findings indicated that isoquercitrin protected against Aβ_25-35-induced oxidative injury in PC12 via AMPK/Sirt3 signaling pathway.