Senkyunolide I protects rat brain against focal cerebral ischemia-reperfusion injury by up-regulating p-Erk1/2, Nrf2/HO-1 and inhibiting caspase 3.

Abstract

Oxidative damage and apoptosis are critical factors contributing to neuronal death during a stroke. The aim of the present study was to evaluate the neuroprotective effects of senkyunolide I (SEI) on focal cerebral ischemia-reperfusion (I/R) injury in rats, and investigate the underlying mechanisms. Male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion (tMCAO) for 2h, followed by 24h reperfusion, and then randomly assigned into four groups: Sham (sham-operated), Vehicle (tMCAO +normal saline), SEI-L (tMCAO +SEI 36 mg/kg) and SEI-H (tMCAO +SEI 72 mg/kg) groups. SEI was administered intravenously, 15 min after occlusion. Neurological deficit, brain edema and infarct volume were detected after 24h of reperfusion. Histological structures of cortices and hippocampus were observed by hematoxylin and eosin staining. Biochemical indexes in the cortex were assayed by colorimetry. The impact of SEI on the Nrf2-ARE-interaction was assayed using a luciferase reporter gene. Western blotting was performed to analysis the expressions of proteins related to anti-oxidation and apoptosis. SEI administration significantly ameliorated the neurological deficit, reduced the infarct volume and brain edema, reversed the cerebral morphologic damage, decreased the levels of MDA and increased the activities of superoxide dismutase. Furthermore, the high dose SEI could significantly activate the Nrf2/ARE pathway by up-regulating the phosphorylation of Erk1/2 and inducing Nrf2 nuclear translocation with enhanced HO-1 and NQO1 expressions. Additionally, treatment with SEI remarkably promoted the ratio of Bcl-2/Bax and inhibited the expressions of cleaved caspase 3 and caspase 9. These results suggest that the neuroprotective mechanisms of SEI are associated with its anti-oxidation and anti-apoptosis properties.

• Authors: Yangye Hu, Muyin Duan, Shuang Liang, Yuan Wang, Yi Feng
• Journal: Brain research (Brain Res) Vol. 1605 Pg. 39-48 (Apr 24 2015) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 25698615 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Benzofurans
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Nfe2l2 protein, rat
• Protective Agents
• senkyunolide I
• Heme Oxygenase-1
• Caspase 3
• Caspase 9

Topics

• Animals
• Antioxidants (pharmacology)
• Apoptosis (drug effects)
• Benzofurans (pharmacology)
• Brain Ischemia (drug therapy, metabolism, pathology)
• Caspase 3 (metabolism)
• Caspase 9 (metabolism)
• HEK293 Cells
• Heme Oxygenase-1 (metabolism)
• Humans
• Infarction, Middle Cerebral Artery (pathology)
• MAP Kinase Signaling System (drug effects)
• Male
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects)
• Protective Agents (pharmacology)
• Random Allocation
• Rats
• Rats, Sprague-Dawley
• Reperfusion Injury (pathology, prevention & control)
• Up-Regulation (drug effects)