Protective effects of imperatorin against cerebral ischemia/reperfusion-induced oxidative stress through Nrf2 signaling pathway in rats / 中国药理学与毒理学杂志

ABSTRACT

OBJECTIVE To investigates the effects of imperatorin on the oxidative stress in the cerebral cortex and hippocampus after focal cerebral ischemia/reperfusion injury. METHODS Transient 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. RESULTS As 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. CONCLUSION Our findings indicate that imperatorin can protect the brain against the excessive oxidative stress induced by cerebral ischemia/reperfusion through activation of Nrf2 signaling pathway.