Silent information regulator 1 ameliorates oxidative stress injury via PGC-1α/PPARγ-Nrf2 pathway after ischemic stroke in rat.

Previous studies have shown that metformin not only is a hypoglycemic agent but also has neuroprotective effects. However, the mechanism of action of metformin in ischemic stroke is unclear. Oxidative stress is an important factor in the pathogenesis of cerebral ischemia-reperfusion injury. It has been reported that metformin is associated with stroke risk in the clinical population. This study is aimed at investigating the effect and mechanism of metformin in an experimental model of oxidative stress induced by ischemia/reperfusion (I/R) in vivo and oxygen glucose deprivation/reperfusion (OGD/R) in vitro. Metformin (100, 200, and 300 mg/kg) was administered intraperitoneally immediately after induction of cerebral ischemia. The indicators of oxidative stress selected were antioxidant enzyme activities of catalase, malondialdehyde (MDA), nitric oxide (NO), superoxide dismutase (SOD), and glutathione peroxidation enzyme (GSHPx). First, we demonstrated that metformin can significantly alleviate acute and chronic cerebral I/R injury and it has a strong regulatory effect on stroke-induced oxidative stress. It can reduce the elevated activities of MDA and NO and increase the levels of GSHPx and SOD in the cerebrum of mice and N2a cells exposed to I/R. Furthermore, real-time PCR and western blot were used to detect the expression of long noncoding RNA H19 (lncRNA-H19), microRNA-148a-3p (miR-148a-3p), and Rho-associated protein kinase 2 (Rock2). The direct interaction of lncRNA-H19, miR-148a-3p, and Rock2 was tested using a dual luciferase reporter assay. lncRNA-H19 altered OGD/R-induced oxidative stress by modulating miR-148a-3p to increase Rock2 expression. The expression of lncRNA-H19 and Rock2 could be downregulated with metformin in vivo and in vitro. In conclusion, our study confirmed that metformin exerts neuroprotective effects by regulating ischemic stroke-induced oxidative stress injury via the lncRNA-H19/miR-148a-3p/Rock2 axis. These results provide new evidence that metformin may represent a potential treatment for stroke-related brain injury.

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Cottonseed Oil Alleviates Ischemic Stroke-Induced Oxidative Stress Injury Via Activating the Nrf2 Signaling Pathway

Molecular Neurobiology ◽

10.1007/s12035-020-02256-y ◽

2021 ◽

Author(s):

Min Liu ◽

Hao Li ◽

Lixia Zhang ◽

Zhipeng Xu ◽

Yuxiang Song ◽

...

Keyword(s):

Oxidative Stress ◽

Ischemic Stroke ◽

Signaling Pathway ◽

Cottonseed Oil ◽

Stress Injury ◽

Oxidative Stress Injury ◽

Nrf2 Signaling Pathway

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Rhizoma Paridis total saponins alleviate H2O2‑induced oxidative stress injury by upregulating the Nrf2 pathway

Molecular Medicine Reports ◽

10.3892/mmr.2019.10827 ◽

2019 ◽

Cited By ~ 2

Author(s):

Baocheng Zhao ◽

Zhenjun Wang ◽

Jiagang Han ◽

Guanghui Wei ◽

Bingqiang Yi ◽

...

Keyword(s):

Oxidative Stress ◽

Stress Injury ◽

Nrf2 Pathway ◽

Oxidative Stress Injury

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Scutellarin acts on the AR-NOX Axis to Remediate Oxidative Stress Injury in a Mouse Model of Cerebral Ischemia/Reperfusion Injury

10.21203/rs.3.rs-471790/v1 ◽

2021 ◽

Author(s):

Llin Peng ◽

Minzhen Deng ◽

Yan Huang ◽

Shuang Wu ◽

Yucheng Cao ◽

...

Keyword(s):

Oxidative Stress ◽

Ischemic Stroke ◽

Cerebral Ischemia ◽

Brain Damage ◽

Ischemia Reperfusion ◽

Ischemic Injury ◽

Neurological Function ◽

Enzyme Linked Immunosorbent Assay ◽

Stress Injury ◽

Oxidative Stress Injury

Abstract BackbroundOxidative stress plays an important role in the ischemic stroke induced brain damage. Our previous study showed that Scutellarin protects against ischemic injury in vitro and in vivo induced oxidative damage in rats, and we also reported that the involvement of Aldose reductase (AR) in oxidative stress and cerebral ischemic injury, in this study we furtherly explicit whether the antioxidant effect of Scutellarin on cerebral ischemia injury is related to AR gene regulation and its specific mechanism.MethodsC57BL/6N mice (Wild-type, WT) and AR knockout (AR-/-) mice were subjected to transient middle cerebral artery occlusion (tMCAO) model with 1h occlusion followed by 3d reperfusion, and Scutellarin was administered from 2h before surgery to 3 days after surgery. Subsequently, Neurological function were assessed by the modified Longa score method, the histopathological morphology observed with 2,3,5-triphenyltetrazolium chloride and hematoxylin-eosin staining. Enzyme-linked immunosorbent assay was used to detect the levels of ROS, 4-hydroxynonenal (4-HNE), 8-hydroxydeoxyguanosine (8-OHDG), Neurotrophin-3 (NT-3), poly ADP-ribose polymerase-1 (PARP1) and 3-nitrotyrosine (3-NT) in the ischemic penumbra regions. Quantitative proteomics profiling using quantitative nano-HPLC-MS/MS were performed to compare the protein expression difference between AR-/- and WT mice with or without tMCAO injury. The expression of AR, NOX1, NOX2 and NOX4 in the ipsilateral side of ischemic brain were detected by Real time-PCR, Western blot and immunofluorescence co-staining with NeuN.ResultsScutellarin treatment alleviated brain damage suffered from tMCAO injury such as improved neurological function deficit, brain infarct area and neuronal injury and reduced the expression of oxidation-related products, moreover, also down-regulated tMCAO induced AR mRNA and protein expression.ConclusionsScutellarin would be a potential drug for the treatment of ischemic stroke through regulating AR-NOX Axis modulate oxidative stress injury to play the protective role of cerebral ischemia injury.

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