Protective effect of edaravone on blood-brain barrier by affecting NRF-2/HO-1 signaling pathway

Liu, Jing; Jiang, Yan; Zhang, Guangping; Lin, Zaihong; Du, Shu

doi:10.3892/etm.2019.7859

Cited by 22 publications

(18 citation statements)

References 18 publications

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“…Several studies show that edaravone’s protective effect results from the activation of the Nrf2/HO-1 pathway, reducing cognitive damage through the activation of the Nrf2 pathway as well as acting as a defense mechanism against cell apoptosis. [ 34 , 36 ] Studies demonstrate that activation the NRF-2/hemeoxygenase-1 (HO-1) signaling pathway by edaravone enhances the integrity and stability of the BBB and can serve as a main target for the therapeutic treatment in in cerebral infarction [ 36 ].…”

Section: Edaravone and Its Mechanism Of Actionmentioning

confidence: 99%

Role of Edaravone as a Treatment Option for Patients with Amyotrophic Lateral Sclerosis

Cho

Shukla

2020

Pharmaceuticals

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Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive and fatal neurodegenerative disease that leads to a loss of muscle control due to nerve cells being affected in the brain and spinal cord. Some of the common clinical presentations of ALS include weakness of muscles, changes in behavior, dysfunction in speech, and cognitive difficulties. The cause of ALS is uncertain, but through several studies, it is known that mutations in SOD1 or C9orf72 genes could play a role as a factor of ALS. In addition, studies indicate that an excessive amount of free radicals, the reactive oxygen species (ROS), leads to neuronal damage by the peroxidation of unsaturated fatty acids in the neuronal cells. Edaravone, the newly approved antioxidant drug for ALS, halts the progression of ALS in the early stages through its cytoprotective effect and protects the nerves by reducing ROS. In this review, different aspects of ALS will be discussed, including its pathology, genetic aspect, and diagnosis. This review also focuses on edaravone as a treatment option for ALS, its mechanism of action, and its pharmacological properties. Clinical trials and adverse effects of edaravone and care for ALS patient are also discussed.

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Section: Edaravone and Its Mechanism Of Actionmentioning

confidence: 99%

Role of Edaravone as a Treatment Option for Patients with Amyotrophic Lateral Sclerosis

Cho

Shukla

2020

Pharmaceuticals

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“…EDA has also been reported to have a therapeutic effect on retinal injury through regulating nuclear factor κB (NF-κB) signaling pathways in diabetic rats ( Wan et al, 2019 ). Interestingly, EDA also could cross the blood–brain barrier (BBB) ( Fang et al, 2014 ) and maintain integrity of BBB by activating the NFE2-related factor 2 signaling pathway ( Liu et al, 2019 ). However, there is currently no such evidence for the role of EDA between microglia and dopaminergic neurons in inflammation.…”

Section: Introductionmentioning

confidence: 99%

Edaravone Plays Protective Effects on LPS-Induced Microglia by Switching M1/M2 Phenotypes and Regulating NLRP3 Inflammasome Activation

Dai

Zhou

et al. 2021

Front. Pharmacol.

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Parkinson’s disease is a neurodegenerative disorder in which activated microglia may appear prior to motor symptoms, but the specific therapeutic mechanisms remain unclear. This study investigated the potential effects of Edaravone (EDA) on M1/M2 polarization of microglia in rats with dopaminergic neurons damage induced by lipopolysaccharide (LPS) and its mechanism. Rats were randomly grouped as the following (n = 10): Control, EDA alone (10 mg/kg), LPS-model (LPS 5 μg), LPS + EDA (5 mg/kg) and LPS + EDA (10 mg/kg). After intragastric administration of EDA once a day for seven consecutive days, LPS was injected into SN pars unilaterally. Rotarod test, pole test, and traction test were used to analyze the intervention effect of EDA on neurobehavioral function in rats. Protein expression levels of TH, TNF-α, Arg-1, Iba-1, NLRP3 and caspase-1 were measured by immunofluorescence staining and western blot. In vitro, BV-2 cells were treated with LPS (100 ng/ml) before adding different doses of EDA. Levels of inflammatory cytokines in culture medium were detected by ELISA. Western blot and immunofluorescence were used to evaluate microglial activation and polarization. First, rotarod test, pole test, and traction test all showed that EDA mitigated motor dysfunction of PD rats. Second, pathological analysis suggested that EDA inhibited LPS-induced microglial activation and remitted declines of dopaminergic neurons. In addition, EDA shifted M1 pro-inflammatory phenotype of microglia to M2 anti-inflammatory state, while decreased expression of M1 markers (TNF-α and IL-1β) and facilitated expression of M2 markers (Arg-1 and IL-10). EDA suppressed inflammatory responses through inhibiting the expression of pro-inflammatory factors (IL-1β, IL-18 and NO), but the neuroprotective effects were invalid while siRNA NLRP3 existed. In conclusion, these results indicated that EDA could improve neurobehavioral functions and play anti-neuroinflammatory roles in PD rats, possibly by inhibiting NLPR3 inflammasome activation and regulating microglia M1/M2 polarization.

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“…A large number of studies showed that the activation of Nrf2 pathway can lead to strong anti-oxidation and anti-apoptosis effects and BBB protection in the brain infarction [10][11][12][13][14][15][16]. In contrast, mass reports exhibited as well that the deletion or downregulation of Nrf2 exacerbated brain injuries in ischemia, in which the acceleratedly destroyed TJs in cerebral blood vessels and increased BBB breakdown and brain edema played a pivotal role [11,17].…”

Section: Introductionmentioning

confidence: 99%

Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia Via Nrf2 Antioxidation Pathway Dependent Cerebral Microvascular Protection

Fan

Yao

Yang

et al. 2021

Preprint

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Background: Stroke is one of the most devastating diseases worldwide. Chinese herbal preparation SaiLuoTong capsule (SLT) showed outstanding therapeutic effects over stroke and its sequelae. This study is to elucidate the mechanism. Methods: We duplicated cerebral ischemia model in rats by permanent MCAO, and simulated ischemia injury in cultured hCMEC/D3 cells with oxygen and glucose deprivation/reoxia (OGD/R); we treated them with SLT. Brain infarction volumes and micromorphology were examined with TTC and HE stainings, respectively; neurological function injuries were valued with deficits scoring; brain water contents were measured with the wet-dry method; and expressions of claudin-1, occludin, Nrf2 and HO-1 were examined with western blot assay and immunohistochemstry or immunocytofluorescnce stainings; activities of SOD and contents of GSH were measured by colorimetric method; cell viabilities were measured by CCK8 method; cell monolayer permeabilities were assessed by FITC-dextran diffusion method. Results: SLT (33 mg/kg) significantly decreased infarction volumes, relieved neuron degenerations and neuron loss, and ameliorated neurological functions; SLT also significantly inhibited elevations in brain water content and decreases of claudin-1 and occludin expressions; additionally SLT significantly increased the nucleus translocation of Nrf2, elevated expression of HO-1, and raised activity of SOD and content of GSH (p<0.05 or 0.01, compared with the model group, in quantitative data). These testified SLT’s anti-stroke effect, and hint the possible key role of cerebral blood vascular endothelial cells (CBVEC) protection and Nrf2 pathway in SLT’s therapy. In hCMEC/D3 cells, SLT significantly inhibited the drop in cell viabilities; SLT also significantly facilitated the nucleus translocation of Nrf2, and increased the expression of HO-1, the activity of SOD, and the content of GSH (in comparison to the model group, p<0.05 or 0.01). Lastly, the anti-OGD/R effects of SLT in hCMEC/D3 cells, including raising cell viabilities, inhibiting the elevation in cell monolayer permeabilities, and preserving the expressions of claudin-1 and occludin, were all abolished by Nrf2 siRNA interference. These undoubtedly confirmed SLT’s protective effect on CBVEC and the obligatory role of Nrf2 pathway in it. Conclusion: SLT’s therapeutic effect on brain ischemia is related to its protection on CBVEC, which is dependent on the activation of Nrf2 pathway.

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Protective effect of edaravone on blood-brain barrier by affecting NRF-2/HO-1 signaling pathway

Cited by 22 publications

References 18 publications

Role of Edaravone as a Treatment Option for Patients with Amyotrophic Lateral Sclerosis

Role of Edaravone as a Treatment Option for Patients with Amyotrophic Lateral Sclerosis

Edaravone Plays Protective Effects on LPS-Induced Microglia by Switching M1/M2 Phenotypes and Regulating NLRP3 Inflammasome Activation

Chinese Herbal Preparation SaiLuoTong Alleviates Brain Ischemia Via Nrf2 Antioxidation Pathway Dependent Cerebral Microvascular Protection

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