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Antioxidant and pro-angiogenic effects of corilagin in rat cerebral ischemia via Nrf2 activation.

ABSTRACT: The nuclear factor erythroid-2-related factor 2 (Nrf2) pathway has been considered as a potential target for neuroprotection in stroke. The aim of present study was to determine whether corilagin, a novel Nrf2 activator, can protect against ischemia-reperfusion injury and explore the underlying mechanism involved. In vivo, rats exposed to middle cerebral artery occlusion were applied to establish an ischemic stroke model. Posttreatment of corilagin significantly reduced infarct volumes and apoptotic cells as well as improved neurologic score after reperfusion, together with increased vascular density in the ischemic penumbra. Meanwhile, posttreatment with corilagin in MCAO rats significantly decreased malondialdehyde levels, restored the superoxide dismutase and glutathione activity, elevating the Nrf2, heme oxygenase-1, the vascular endothelial growth factor (VEGF) and VEGF receptor 2 (VEGFR2) expression. However, consecutive intrathecal injection of short interference RNAs targeting Nrf2 at 24-h intervals 72 h before ischemia reduced the beneficial effects of corilagin. In primary cultured neurons, corilagin dose-dependently protected against oxygen and glucose deprivation-induced insult, but the protective effect of corilagin was attenuated by knockdown of Nrf2. In conclusion, these findings indicate that corilagin exerts protective effects against cerebral ischemic injury by attenuating oxidative stress and enhancing angiogenesis via activation of Nrf2 signaling pathway.

SUBMITTER: Ding Y

PROVIDER: S-EPMC5777734 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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Antioxidant and pro-angiogenic effects of corilagin in rat cerebral ischemia via Nrf2 activation.

Ding Yi Y Ren Danjun D Xu Hang H Liu Wenxing W Liu Tianlong T Li Liang L Li Jianguang J Li Yuwen Y Wen AiDong A

Oncotarget 20171024 70

The nuclear factor erythroid-2-related factor 2 (Nrf2) pathway has been considered as a potential target for neuroprotection in stroke. The aim of present study was to determine whether corilagin, a novel Nrf2 activator, can protect against ischemia-reperfusion injury and explore the underlying mechanism involved. <i>In vivo</i>, rats exposed to middle cerebral artery occlusion were applied to establish an ischemic stroke model. Posttreatment of corilagin significantly reduced infarct volumes an ...[more]

PMID: 29383122

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Project description:The purpose of the present experiment was to investigate whether hexahydrocurcumin (HHC) attenuates brain damage and improves functional outcome via the activation of antioxidative activities, anti-inflammation, and anti-apoptosis following cerebral ischemia/reperfusion (I/R). In this study, rats with cerebral I/R injury were induced by a transient middle cerebral artery occlusion (MCAO) for 2 h, followed by reperfusion. The male Wistar rats were randomly divided into five groups, including the sham-operated, vehicle-treated, 10 mg/kg HHC-treated, 20 mg/kg HHC-treated, and 40 mg/kg HHC-treated I/R groups. The animals were immediately injected with HHC by an intraperitoneal administration at the onset of cerebral reperfusion. After 24 h of reperfusion, the rats were tested for neurological deficits, and the pathology of the brain was studied by 2,3,5-triphenyltetrazolium chloride (TTC) staining, hematoxylin and eosin (H&E) staining, and terminal deoxynucleotidyltransferase UTP nick end labeling (TUNEL) staining. In addition, the brain tissues were prepared for protein extraction for Western blot analysis, a malondialdehyde (MDA) assay, a nitric oxide (NO) assay, a superoxide dismutase (SOD) assay, a glutathione (GSH) assay, and a glutathione peroxidase (GSH-Px) assay. The data revealed that the neurological deficit scores and the infarct volume were significantly reduced in the HHC-treated rats at all doses compared to the vehicle group. Treatment with HHC significantly attenuated oxidative stress and inflammation, with a decreased level of MDA and NO and a decreased expression of NF-κB (p65) and cyclooxygenase-2 (COX-2) in the I/R rats. HHC also evidently increased Nrf2 (nucleus) protein expression, heme oxygenase-1 (HO-1) protein expression, the antioxidative enzymes, and the superoxide dismutase (SOD) activity. Moreover, the HHC treatment also significantly decreased apoptosis, with a decrease in Bax and cleaved caspase-3 and an increase in Bcl-XL, which was in accordance with a decrease in the apoptotic neuronal cells. Therefore, the HHC treatment protects the brain from cerebral I/R injury by diminishing oxidative stress, inflammation, and apoptosis. The antioxidant properties of HHC may play an important role in improving functional outcomes and may offer significant neuroprotection against I/R damage.

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Antioxidant and pro-angiogenic effects of corilagin in rat cerebral ischemia via Nrf2 activation.

Publications

Antioxidant and pro-angiogenic effects of corilagin in rat cerebral ischemia via Nrf2 activation.

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