Resveratrol modulates the Akt/GSK-3β signaling pathway in a middle cerebral artery occlusion animal model

Park, Dong-Ju; Kang, Ju-Bin; Shah, Fawad Ali; Koh, Phil-Ok

doi:10.1186/s42826-019-0019-8

Cited by 21 publications

(16 citation statements)

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“…Among them, 86 records were excluded due to review, abstracts without full text, not having purified resveratrol, no in vivo experiment, not reporting the number of animals in groups, and or no adequate outcomes (infarction volume or functional outcome determined by neurobehavioral score measured on any scale/rotarod test). Therefore, 54 studies ( Huang et al, 2001 ; Sinha et al, 2002 ; Inoue, 2003 ; Gao et al, 2006 ; Tsai et al, 2007 ; Dong et al, 2008 ; Yousuf et al, 2009 ; Li et al, 2010 ; Sakata et al, 2010 ; Shin et al, 2010 ; Ren et al, 2011 ; Li et al, 2012 ; Shin et al, 2012 ; Hurtado et al, 2013 ; Lanzillotta et al, 2013 ; Lin et al, 2013 ; Orsu et al, 2013 ; Yan et al, 2013 ; Saleh et al, 2014 ; Wang et al, 2014 ; Fang et al, 2015 ; Hermann et al, 2015 ; Ishrat et al, 2015 ; Koronowski et al, 2015 ; Li et al, 2015 ; Narayanan et al, 2015 ; Pandey et al, 2015 ; Pang et al, 2015 ; Abdel-Aleem et al, 2016 ; Jeong et al, 2016 ; Li et al, 2016 ; Lopez et al, 2016 ; Su et al, 2016 ; Wan et al, 2016 ; Yang et al, 2016 ; Al Dera, 2017 ; He et al, 2017 ; Koronowski et al, 2017 ; Yu et al, 2017 ; Faggi et al, 2018 ; Hou et al, 2018 ; Liu et al, 2018 ; Dou et al, 2019 ; Grewal et al, 2019 ; Park et al, 2019 ; Yan et al, 2019 ; Alquisiras-Burgos et al, 2020 ; Lu et al, 2020 ; Mota et al, 2020 ; Pineda-Ramírez et al, 2020 ; Teertam et al, 2020 ; Yao et al, 2020 ; McDonald...…”

Section: Resultsmentioning

confidence: 99%

Resveratrol has an Overall Neuroprotective Role in Ischemic Stroke: A Meta-Analysis in Rodents

Liu¹,

He²,

Huang³

et al. 2021

Front. Pharmacol.

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Background: Resveratrol, a natural polyphenolic phytoalexin, is broadly presented in dietary sources. Previous research has suggested its potential neuroprotective effects on ischemic stroke animal models. However, these results have been disputable. Here, we conducted a meta-analysis to comprehensively evaluate the effect of resveratrol treatment in ischemic stroke rodent models.Objective: To comprehensively evaluate the effect of resveratrol treatment in ischemic stroke rodent models.Methods: A literature search of the databases Pubmed, Embase, and Web of science identified 564 studies that were subjected to pre-defined inclusion criteria. 54 studies were included and analyzed using a random-effects model to calculate the standardized mean difference (SMD) with corresponding confidence interval (CI).Results: As compared with controls, resveratrol significantly decreased infarct volume (SMD −4.34; 95% CI −4.98 to −3.69; p < 0.001) and the neurobehavioral score (SMD −2.26; 95% CI −2.86 to −1.67; p < 0.001) in rodents with ischemic stroke. Quality assessment was performed using a 10-item checklist. Studies quality scores ranged from 3 to 8, with a mean value of 5.94. In the stratified analysis, a significant decrease of infarct volume and the neurobehavioral score was achieved in resveratrol sub-groups with a dosage of 20–50 mg/kg. In the meta-regression analysis, the impact of the delivery route on an outcome is the possible source of high heterogeneity.Conclusion: Generally, resveratrol treatment presented neuroprotective effects in ischemic stroke models. Furthermore, this study can direct future preclinical and clinical trials, with important implications for human health.

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Section: Resultsmentioning

confidence: 99%

Resveratrol has an Overall Neuroprotective Role in Ischemic Stroke: A Meta-Analysis in Rodents

Liu¹,

He²,

Huang³

et al. 2021

Front. Pharmacol.

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“…At the same time, in normal brain tissue during ischemia/reoxygenation, there is a need to suppress the processes of necrosis and apoptosis. Our experiments showed that after incubation with SeNPs, not only complete inhibition of OGD/R-induced necrosis occurred but also an increase in the expression of PI3K and PKC, the role of which in suppressing apoptosis of brain cells is well known [ 44 , 45 , 46 , 47 , 48 ]. Our experiments have shown that incubation with SeNPs leads to suppression of IL-1β and Nf-κb expression after OGD/R exposure.…”

Section: Discussionmentioning

confidence: 99%

The Mechanisms Underlying the Protective Action of Selenium Nanoparticles against Ischemia/Reoxygenation Are Mediated by the Activation of the Ca2+ Signaling System of Astrocytes and Reactive Astrogliosis

Varlamova

Turovsky

Babenko

et al. 2021

IJMS

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In recent years, much attention has been paid to the study of the therapeutic effect of the microelement selenium, its compounds, especially selenium nanoparticles, with a large number of works devoted to their anticancer effects. Studies proving the neuroprotective properties of selenium nanoparticles in various neurodegenerative diseases began to appear only in the last 5 years. Nevertheless, the mechanisms of the neuroprotective action of selenium nanoparticles under conditions of ischemia and reoxygenation remain unexplored, especially for intracellular Ca2+ signaling and neuroglial interactions. This work is devoted to the study of the cytoprotective mechanisms of selenium nanoparticles in the neuroglial networks of the cerebral cortex under conditions of ischemia/reoxygenation. It was shown for the first time that selenium nanoparticles dose-dependently induce the generation of Ca2+ signals selectively in astrocytes obtained from different parts of the brain. The generation of these Ca2+ signals by astrocytes occurs through the release of Ca2+ ions from the endoplasmic reticulum through the IP3 receptor upon activation of the phosphoinositide signaling pathway. An increase in the concentration of cytosolic Ca2+ in astrocytes leads to the opening of connexin Cx43 hemichannels and the release of ATP and lactate into the extracellular medium, which trigger paracrine activation of the astrocytic network through purinergic receptors. Incubation of cerebral cortex cells with selenium nanoparticles suppresses ischemia-induced increase in cytosolic Ca2+ and necrotic cell death. Activation of A2 reactive astrocytes exclusively after ischemia/reoxygenation, a decrease in the expression level of a number of proapoptotic and proinflammatory genes, an increase in lactate release by astrocytes, and suppression of the hyperexcitation of neuronal networks formed the basis of the cytoprotective effect of selenium nanoparticles in our studies.

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“…Akt and mTOR overexpression improved the protective effects after cerebral ischemia-reperfusion injury in MCAO rats, suggesting that the activation of the PI3K/Akt/mTOR signaling pathway provides significant neuroprotective effects against cerebral ischemia-reperfusion injury. P-Akt and p-mTOR ( Li et al, 2016 ; Yang et al, 2017 ; Park et al, 2019 ; Sun et al, 2020 ) are commonly recognized as markers for activation of the PI3K/Akt/mTOR pathway. In the present study, the levels of p-AKT and p-mTOR were significantly decreased following I/R injury and were activated by TFCJ treatment.…”

Section: Discussionmentioning

confidence: 99%

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

et al. 2021

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Background: Pharmacological research results showed that total flavonoids of Chuju (TFCJ) could be used to treat acute myocardial ischemia and myocardial ischemia-reperfusion injury. In this study, we explored the protective effect of TFCJ on ischemic stroke (IS) in the IS rat model. We hypothesized that TFCJ might exert its neuroprotective effects by suppressing apoptosis and oxidative stress that are closely related to PI3K/Akt/mTOR signaling pathway.Method: TFCJ (10, 20, and 40 mg/kg) was administered for 7 days. Rats (260 ± 20 g) were subjected to middle cerebral artery occlusion (MCAO) for 2 h and reperfusion for 24 h. The neuroprotective effect of TFCJ was substantiated in terms of neurological deficits, oxidative stress (superoxide dismutase, glutathione peroxidase, catalase, and malondialdehyde), pathomorphological changes (HE staining and TUNEL staining), and neurobehavioral functions in the rats. Then, we employed network pharmacology to reveal the potential mechanism of TFCJ against IS. Western blot was used to determine the levels of PI3K/AKT/mTOR pathway proteins. The expression of BCL-2, BAX, and cleaved-Caspase-3 was also measured by Western blots and RT-PCR.Results: The histopathological assessment showed that TFCJ reduced MCAO-induced brain damage. Besides, TFCJ exerted a protective role in MCAO rats by alleviating cell apoptosis and oxidative stress. Network pharmacology showed that TFCJ might be used against IS through the PI3K/AKT signaling pathway. TFCJ reduced cell apoptosis and oxidative stress by increasing the level of p-AKT and p-mTOR in MCAO rats, while the effect of TFCJ was significantly reversed when applying LY294002 (PI3k inhibitor).Conclusion: These results indicated that TFCJ might decrease oxidative stress and apoptosis that are closely related to PI3K/Akt/mTOR pathway in IS. TFCJ is a promising authentic traditional Chinese medicine for the management of IS.

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Resveratrol modulates the Akt/GSK-3β signaling pathway in a middle cerebral artery occlusion animal model

Cited by 21 publications

References 58 publications

Resveratrol has an Overall Neuroprotective Role in Ischemic Stroke: A Meta-Analysis in Rodents

Resveratrol has an Overall Neuroprotective Role in Ischemic Stroke: A Meta-Analysis in Rodents

The Mechanisms Underlying the Protective Action of Selenium Nanoparticles against Ischemia/Reoxygenation Are Mediated by the Activation of the Ca2+ Signaling System of Astrocytes and Reactive Astrogliosis

Total Flavonoids of Chuju Decrease Oxidative Stress and Cell Apoptosis in Ischemic Stroke Rats: Network and Experimental Analyses

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