Therapeutic targets of oxidative/nitrosative stress and neuroinflammation in ischemic stroke: Applications for natural product efficacy with omics and systemic biology

Chen, Hansen; He, Yacong; Chen, Shuang; Qi, Suhua; Shen, Jiangang

doi:10.1016/j.phrs.2020.104877

Cited by 150 publications

(84 citation statements)

References 238 publications

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“…For example, antioxidants have been shown to protect against stroke-induced brain damage in a multiplicity of animal models (reviewed in Ref. [ 8 , 88 , 89 ]). However, they haven't proven effective in the treatment of stroke in humans [ 8 , [89] , [90] , [91] ].…”

Section: A Failure Of Antioxidants Does Not Negate the Importance Of mentioning

confidence: 99%

“…However, they haven't proven effective in the treatment of stroke in humans [ 8 , [89] , [90] , [91] ]. In an animal model, the antioxidants are usually given prior to vessel occlusion, sometimes at carefully chosen time points afterwards [ 8 , 88 , 89 ]. However, when my research group worked with neurologists to study levels of oxidative damage in stroke patients, using a range of plasma biomarkers, levels were already very high when the patients were first examined ( Fig.…”

Section: A Failure Of Antioxidants Does Not Negate the Importance Of mentioning

confidence: 99%

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Reflections of an aging free radical

Halliwell

2020

Free Radical Biology and Medicine

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In this mini-reflection, I explain how during my doctoral work in a Botany Department I first became interested in H 2 O 2 and later in my career in other reactive oxygen species, especially the role of “catalytic” iron and haem compounds (including leghaemoglobin) in promoting oxidative damage. The important roles that H 2 O 2 , other ROS and dietary plants play in respect to humans are discussed. I also review the roles of diet-derived antioxidants in relation to human disease, presenting reasons why clinical trials using high doses of natural antioxidants have generally given disappointing results. Iron chelators and ergothioneine are reviewed as potential cytoprotective agents with antioxidant properties that may be useful therapeutically. The discovery of ferroptosis may also lead to novel agents that can be used to treat certain diseases.

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Section: A Failure Of Antioxidants Does Not Negate the Importance Of mentioning

confidence: 99%

Section: A Failure Of Antioxidants Does Not Negate the Importance Of mentioning

confidence: 99%

Reflections of an aging free radical

Halliwell

2020

Free Radical Biology and Medicine

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“…Oxidative stress is the major cause of BBB damages in ischemia, which refers to a state in that the generation of reactive oxygen species (ROS) exceeds far behind the body's dispose ability, leading to serious impairments [7,8]. Redressing this imbalance between ROS and ROS scavenging in the brain blood vascular endothelial cells is necessary and urgent for the stroke treatment.…”

Section: Introductionmentioning

confidence: 99%

“…Redressing this imbalance between ROS and ROS scavenging in the brain blood vascular endothelial cells is necessary and urgent for the stroke treatment. In comparison to direct eliminating ROS, inspiring the innate antioxidation system is a better choice for it has a higher e ciency, longer effecting duration and larger safety [7,8].…”

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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“…In addition to ischemia-reperfusion injury, following ischemic stroke, post-stroke secondary neuroinflammation is responsible for critical pathological processes that promote further cell injury, resulting in ischemic brain cell death, disability, and poor outcomes [ 11 , 13 , 14 , 15 ]. The post-stroke immune response consists of the aberrant activation of glial cells, particularly microglial cells, infiltration of peripheral leukocytes, and release of damage-associated molecular pattern (DAMP) molecules from the damaged cells of ischemic brain [ 11 , 16 ].…”

Section: Introductionmentioning

confidence: 99%

Serum Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 Associated with the Severity and Outcome of Acute Ischemic Stroke

Huang

Chen

et al. 2020

JCM

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Stroke is a neurological emergency, where the mechanism of the blood supply to the brain is impaired, resulting in brain cell ischemia and death. Neuroinflammation is a key component in the ischemic cascade that results in cell damage and death after cerebral ischemia. The triggering receptor expressed on myeloid cells-1 (TREM-1) modulates neuroinflammation after acute ischemic stroke. In the present study, 60 patients with acute ischemic stroke, who had been subjected to neurological examinations and National Institutes of Health Stroke Scale (NIHSS) and brain magnetic resonance imaging studies, were enrolled in the emergency room of Kaohsiung Chang Gung Memorial Hospital. Twenty-four healthy volunteers were recruited as controls. The serum levels of soluble TREM-1 (sTREM-1), human S100 calcium-binding protein B (S100B), and proinflammatory cytokines and chemokines, including tumor necrosis α (TNF-α), interleukin 1β, interleukin 6 (IL-6), interleukin 8, and interferon-γ were measured immediately after acute ischemic stroke. The serum levels of sTREM-1, TNFα, IL-6, and S100B were correlated with the stroke volume and NIHSS, after acute ischemic stroke. Additionally, the serum levels of sTREM-1 were significantly positively correlated with S100B. The functional outcomes were evaluated 6 months after ischemic stroke by the Barthel index, which was correlated with the age and levels of sTREM-1 and S100B. We suggest that acute ischemic stroke induces neuroinflammation by the activation of the TREM-1 signaling pathway and the downstream inflammatory machinery that modulates the inflammatory response and ischemic neuronal cell death. From a translational perspective, our results may allow for the development of a new therapeutic strategy for acute ischemic stroke by targeting the TREM-1 signaling pathway.

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Therapeutic targets of oxidative/nitrosative stress and neuroinflammation in ischemic stroke: Applications for natural product efficacy with omics and systemic biology

Cited by 150 publications

References 238 publications

Reflections of an aging free radical

Reflections of an aging free radical

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

Serum Levels of Soluble Triggering Receptor Expressed on Myeloid Cells-1 Associated with the Severity and Outcome of Acute Ischemic Stroke

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