Neuroprotective Effects of Pycnogenol Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Primary Rat Astrocytes via NF-κB and ERK1/2 MAPK Pathways

Xia, Ruixue; Ji, Chunxue; Zhang, Leguo

doi:10.1159/000478681

Cited by 22 publications

(17 citation statements)

References 32 publications

(42 reference statements)

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“…OGD can induce oxidative stress, inflammatory cytokine accumulation, and MMP dissipation via NF-κB and ERK1/2 pathways in primary rat astrocytes. HG can result in the over-production of ROS and a loss of MMP [41][42][43]. Indeed, the results of this study showed that gp91phox is the common denominator in both processes.…”

Section: Cellular Physiology and Biochemistrymentioning

confidence: 56%

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Zeng¹,

Ren²,

Zhu³

et al. 2018

Cell Physiol Biochem

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Background/Aims: Peri-operative cerebral ischemia reperfusion injury is one of the most serious peri-operative complications that can be aggravated in patients with diabetes. A previous study showed that microglia NOX₂ (a NADPH oxidase enzyme) may play an important role in this process. Here, we investigated whether increased microglial derived gp91^phox, also known as NOX2, reduced oxygen glucose deprivation (OGD) after induction of hyperglycemia (HG). Methods: A rat neuronal-microglial in vitro co-culture model was used to determine the effects of gp91^phox knockdown on OGD after HG using six treatment groups: A rat microglia and neuron co-culture model was established and divided into the following six groups: high glucose + scrambled siRNA transfection (HG, n = 5); HG + gp91^phoxsiRNA transfection (HG-gp91siRNA, n = 5); oxygen glucose deprivation + scrambled siRNA transfection (OGD, n = 5); OGD + gp91^phoxsiRNA transfection (OGD-gp91siRNA, n = 5); HG + OGD + scrambled siRNA transfection (HG-OGD, n = 5); and HG + OGD + gp91^phoxsiRNA transfection (HG-OGD-gp91siRNA, n = 5). The neuronal survival rate was measured by the MTT assay, while western blotting was used to determine gp91^phox expression. Microglial derived ROS and neuronal apoptosis rates were analyzed by flow cytometry. Finally, the secretion of cytokines, including IL-6, IL-8, TNF-α, and 8-iso-PGF2α was determined using an ELISA kit. Results: Neuronal survival rates were significantly decreased by HG and OGD, while knockdown of gp91^phox reversed these rates. ROS production and cytokine secretion were also significantly increased by HG and OGD but were significantly inhibited by knockdown of gp91^phoxsiRNA. Conclusion: Knockdown of gp91^phoxsiRNA significantly reduced oxidative stress and the inflammatory response, and alleviated neuronal damage after HG and OGD treatment in a rat neuronal-microglial co-culture model.

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Section: Cellular Physiology and Biochemistrymentioning

confidence: 56%

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Zeng¹,

Ren²,

Zhu³

et al. 2018

Cell Physiol Biochem

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“…Cocultures were established using a 6-well Transwell cell culture system with a 0.4-μm membrane that cells cannot get through. For the SCI-AST+PDTC group, 5×10 4 astrocytes were seeded on the upper chamber and supplemented with 10 mM PDTC [27][28][29]. For the SCI-AST+MSC and SCI-AST+MSC+TNFα groups, 5×10 4 astrocytes were seeded on the upper chamber in the absence and presence of TNF-α (50 ng/mL; R&D Systems), respectively [30][31][32][33][34], with 5×10 4 MSCs seeded on the lower chamber.…”

Section: Astrocyte Coculture With Mscs or Msc-exomentioning

confidence: 99%

Mesenchymal Stem Cell-Derived Exosomes Reduce A1 Astrocytes via Downregulation of Phosphorylated NFκB P65 Subunit in Spinal Cord Injury

Wang

Pei

Liang

et al. 2018

Cell Physiol Biochem

154

119

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Background/Aims: Neurotoxic A1 astrocytes are induced by inflammation after spinal cord injury (SCI), and the inflammation-related Nuclear Factor Kappa B (NFκB) pathway may be related to A1-astrocyte activation. Mesenchymal stem cell (MSC) transplantation is a promising therapy for SCI, where transplanted MSCs exhibit anti-inflammatory effects by downregulating proinflammatory factors, such as Tumor Necrosis Factor (TNF)-α and NFκB. MSC-exosomes (MSC-exo) reportedly mimic the beneficial effects of MSCs. Therefore, in this study, we investigated whether MSCs and MSC-exo exert inhibitory effects on A1 astrocytes and are beneficial for recovery after SCI. Methods: The effects of MSC and MSC-exo on SCIinduced A1 astrocytes, and the potential mechanisms were investigated in vitro and in vivo using immunofluorescence and western blot. In addition, we assessed the histopathology, levels of proinflammatory cytokines and locomotor function to verify the effects of MSC and MSC-exo on SCI rats. Results: MSC or MSC-exo co-culture reduced the proportion of SCIinduced A1 astrocytes. Intravenously-injected MSC or MSC-exo after SCI significantly reduced the proportion of A1 astrocytes, the percentage of p65 positive nuclei in astrocytes, and the percentage of TUNEL-positive cells in the ventral horn. Additionally, we observed decreased lesion area and expression of TNFα, Interleukin (IL)-1α and IL-1β, elevated expression of Myelin Basic Protein (MBP), Synaptophysin (Syn) and Neuronal Nuclei (NeuN), and improved Basso, Beattie & Bresnahan (BBB) scores and inclined-plane-test angle. In vitro assay showed that MSC and MSC-exo reduced SCI-induced A1 astrocytes, probably via inhibiting the nuclear translocation of the NFκB p65. Conclusion: MSC and MSC-exo reduce SCI-induced A1 astrocytes, probably via inhibiting nuclear translocation of NFκB p65, and exert antiinflammatory and neuroprotective effects following SCI, with the therapeutic effect of MSCexo comparable with that of MSCs when applied intravenously.

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“…; Xia et al . ). As shown here, the immunoreactivity of GFAP protein was increased in brain after MCAO and in astrocytes after OGD, and it was markedly inhibited after Z‐GS treatment (Fig.…”

Section: Discussionmentioning

confidence: 97%

“…Sustained activation of pro-inflammatory cytokines as well as enhanced expression of GFAP, are known to aggravate brain damage (Hennessy et al 2015), while the inhibition of these cytokines and activated astrocytes is beneficial to the therapy of ischemic stroke (Ashafaq et al 2016;Pan et al 2017). It was also reported that OGD induced the secretion of pro-inflammatory cytokines and the activation of astrocytes in vitro (Li et al 2015b;Xia et al 2017). As shown here, the immunoreactivity of GFAP protein was increased in brain after MCAO and in astrocytes after OGD, and it was markedly inhibited after Z-GS treatment (Fig.…”

Section: Discussionmentioning

confidence: 99%

Z‐Guggulsterone attenuates astrocytes‐mediated neuroinflammation after ischemia by inhibiting toll‐like receptor 4 pathway

Liu

Zhang

et al. 2018

Journal of Neurochemistry

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Inflammatory damage plays a pivotal role in ischemic stroke pathogenesis and may represent one of the therapeutic targets. Z-Guggulsterone (Z-GS), an active component derived from myrrh, has been used to treat various diseases. The traditional uses suggest that myrrh is a good candidate for anti-inflammatory damage. This study was to investigate the anti-inflammatory and neuroprotective effects of Z-GS following cerebral ischemic injury, as well as the exact mechanisms behind them. Rat middle cerebral artery occlusion (MCAO) model and in vitro astrocytes oxygen-glucose deprivation (OGD) model were adopted to simulate ischemic stroke. Z-GS (30 or 60 mg/kg) was administered intraperitoneally immediately after reperfusion, while astrocytes were maintained in 30 or 60 μM Z-GS before OGD treatment. The results indicated that Z-GS significantly alleviated neurological deficits, infarct volume and histopathological damage in vivo, and increased the astrocytes viability in vitro. Moreover, the treatment of Z-GS inhibited the astrocytes activation and down-regulated the mRNA levels of pro-inflammatory cytokines. Furthermore, the activated TLR4-NF-κB signaling pathways induced by MCAO or OGD were significantly suppressed by Z-GS treatment, which was achieved via inhibiting the phosphorylation of JNK. Our results demonstrated that Z-GS exerted neuroprotective and anti-inflammatory properties through preventing activation of TLR4-mediated pathway in the activated astrocytes after ischemia injury. Therefore, Z-GS could be considered as a promising candidate for the treatment of ischemic stroke.

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Neuroprotective Effects of Pycnogenol Against Oxygen-Glucose Deprivation/Reoxygenation-Induced Injury in Primary Rat Astrocytes via NF-κB and ERK1/2 MAPK Pathways

Cited by 22 publications

References 32 publications

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Gp91phox (NOX2) in Activated Microglia Exacerbates Neuronal Damage Induced by Oxygen Glucose Deprivation and Hyperglycemia in an in Vitro Model

Mesenchymal Stem Cell-Derived Exosomes Reduce A1 Astrocytes via Downregulation of Phosphorylated NFκB P65 Subunit in Spinal Cord Injury

Z‐Guggulsterone attenuates astrocytes‐mediated neuroinflammation after ischemia by inhibiting toll‐like receptor 4 pathway

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