Protective effects of imperatorin against cerebral ischemia/reperfusion-induced oxidative stress through Nrf2 signaling pathway in rats

Wei HE,Wei-wei CHEN,Xian-hua HUANG,Yu-mei ZHOU,Fang LIAO

(Department of Pharmacology,Gannan Medical University,Key Laboratory of Cerebrovascular Pharmacology of Jiangxi Province,Ganzhou 341000,China）

T2-5

Protective effects of imperatorin against cerebral ischemia/reperfusion-induced oxidative stress through Nrf2 signaling pathway in rats

Wei HE,Wei-wei CHEN,Xian-hua HUANG,Yu-mei ZHOU,Fang LIAO

(Department of Pharmacology,Gannan Medical University,Key Laboratory of Cerebrovascular Pharmacology of Jiangxi Province,Ganzhou 341000,China）

OBJECTIVETo investigates the effects of imperatorin on the oxidative stress in the cerebral cortex and hippocampus after focal cerebral ischemia/reperfusion injury.METHODSTransient focal cerebral ischemia/reperfusion model in male Sprague-Dawley rats was induced by 2 h middle cerebral artery occlusion followed by 24 h reperfusion.Imperatorin(1.25 and 2.5 mg·kg-1)or vehicle were administered intraperitoneally at 1,5 and 9 h after the onset of ischemia.At 24 h after reperfusion,the biomarkers of oxidative stress such as the levels of reactive oxygen species(ROS),lipid peroxidation products malondialdehyde(MDA),nitric oxide(NO)and total antioxidant capacity(T-AOC),the activities of inducible nitric oxide synthase(iNOS),superoxide dismutase(SOD)and catalase(CAT)in the cerebral cortex and hippocampus were observed.We also assessed the nuclear factor erythroid 2-related factor 2(Nrf2),heme oxygenase-1(HO-1),and the NAD(P)H-quinone oxidoreductase 1(NQO-1)protein expression by Western blot.RESULTSAs compared to vehicle-treated animals,imperatorin treatment significantly reduced the ROS,MDA,NO levels and iNOS activity,increased T-AOC and the activities of SOD and CAT.Furthermore,imperatorin treatment also significantly induced the nuclear translocation of Nrf2,enhanced the protein expression of HO-1 and NQO-1 in the cerebral cortex and hippocampus.CONCLUSIONOur findings indicate that imperatorin can protect the brain against the excessive oxidative stress induced by cerebral ischemia/reperfusion through activation of Nrf2 signaling pathway.

imperatorin;cerebral ischemia/reperfusion;reactive oxygen species;nuclear factor erythroid 2-related factor 2

The project supported by National Natural Science Foundation of China(81060269 and 81360492);and Natural Science Foundation of Jiangxi Province of China(20122BAB205036)

Wei HE,Tel:(0797)8169773;(0797)8169818.E-mail：hewei86087@163.com