scholarly journals The Study of the Neuroprotective Effect of the Extract from Chelidonium Majus L. in Vitro

2019 ◽  
Vol 4 (2) ◽  
pp. 106-113
Author(s):  
A. Zhalsrai ◽  
L. Ts. Sanzhieva
Keyword(s):  
Cortical Neurons ◽  
Neuroprotective Effect ◽  
Chain Complex ◽  
Luciferase Reporter ◽  
Chelidonium Majus ◽  
Total Alkaloids ◽  
Cultured Cortical Neurons ◽  
Important Challenge ◽  
Lipid Radicals

The protection of neurons from damage and death is an important challenge in the development of treatment of brain ischemia and neurodegenerative diseases. This study aims to investigate protective effect of the extract prepared from Chelidonium majus, which contains total alkaloids. In the present study, we examined antioxidant activity of total alkaloids from Chelidonium majus in vitro. Hydroxyl radical and lipid radicals were detected using spin trapping agents with ESR spectrometer. Chelidonium majus extract exhibited dose-dependent scavenging effects on lipid radicals. Halfmaximal inhibitory concentration (IC50) of the extract was 2.96 mg/ml, whereas for hydroxyl radicals it was 55.13 mg/ ml. These results showed that extract of Chelidonium majus is partly inhibited free radicals. Antioxidant effects of this extract were further demonstrated by protecting enzyme activity of the mitochondrial respiratory electron transport chain (complex I) in isolated brain mitochondrial dysfunction induced by MDA. However, it did not change the decreased level of complex II, and malate dehydrogenase (MDH) in a concentration of 12 and 25 mg/ml. Here, we examined the neuroprotective effect of the extract from Chelidonium majus against oxidative stress in cultured cortical neurons, using MTT. We found that pretreatment with the extract of Chelidonium majus (0.05 and 0.5 mg/ml) significantly inhibited H2O2-induced cell death in cortical neurons.Furthermore, the use of a luciferase reporter (ARE-luc) assay showed that extract from Chelidonium majus activates protective signaling pathway in primary cortical neurons through ARE/Nrf2 pathway.Together, this suggests that total alkaloids from Chelidonium majus may be neuroprotective by increasing anti-oxidant gene expression.

scholarly journals Neuroprotective effect of selumetinib on acrolein-induced neurotoxicity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hui-Ju Huang ◽  
Hsiang-Tsui Wang ◽  
Ting-Yu Yeh ◽  
Bo-Wei Lin ◽  
Young-Ji Shiao ◽  
...  
Keyword(s):  
Cell Death ◽  
Neurodegenerative Diseases ◽  
Neurite Outgrowth ◽  
Cortical Neurons ◽  
Neuroprotective Effect ◽  
Heme Oxygenase 1 ◽  
Interacting Protein ◽  
Erk Phosphorylation ◽  
Cultured Cortical Neurons

AbstractAbnormal accumulation of acrolein, an α, β unsaturated aldehyde has been reported as one pathological cause of the CNS neurodegenerative diseases. In the present study, the neuroprotective effect of selumetinib (a MEK–ERK inhibitor) on acrolein-induced neurotoxicity was investigated in vitro using primary cultured cortical neurons. Incubation of acrolein consistently increased phosphorylated ERK levels. Co-treatment of selumetinib blocked acrolein-induced ERK phosphorylation. Furthermore, selumetinib reduced acrolein-induced increases in heme oxygenase-1 (a redox-regulated chaperone protein) and its transcriptional factor, Nrf-2 as well as FDP-lysine (acrolein-lysine adducts) and α-synuclein aggregation (a pathological biomarker of neurodegeneration). Morphologically, selumetinib attenuated acrolein-induced damage in neurite outgrowth, including neuritic beading and neurite discontinuation. Moreover, selumetinib prevented acrolein-induced programmed cell death via decreasing active caspase 3 (a hallmark of apoptosis) as well as RIP (receptor-interacting protein) 1 and RIP3 (biomarkers for necroptosis). In conclusion, our study showed that selumetinib inhibited acrolein-activated Nrf-2-HO-1 pathway, acrolein-induced protein conjugation and aggregation as well as damage in neurite outgrowth and cell death, suggesting that selumetinib, a MEK–ERK inhibitor, may be a potential neuroprotective agent against acrolein-induced neurotoxicity in the CNS neurodegenerative diseases.

scholarly journals Neurotherapeutic Effect of Inula britannica var. Chinensis against H2O2-Induced Oxidative Stress and Mitochondrial Dysfunction in Cortical Neurons

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 375
Author(s):  
Jin Young Hong ◽  
Hyunseong Kim ◽  
Junseon Lee ◽  
Wan-Jin Jeon ◽  
Seung Ho Baek ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitochondrial Dysfunction ◽  
Cortical Neurons ◽  
Inflammatory Diseases ◽  
Neuroprotective Effect ◽  
Neuroprotective Effects ◽  
Neuronal Viability ◽  
Inula Britannica ◽  
Oxidative Effects

Inula britannica var. chinensis (IBC) has been used as a traditional medicinal herb to treat inflammatory diseases. Although its anti-inflammatory and anti-oxidative effects have been reported, whether IBC exerts neuroprotective effects and the related mechanisms in cortical neurons remain unknown. In this study, we investigated the effects of different concentrations of IBC extract (5, 10, and 20 µg/mL) on cortical neurons using a hydrogen peroxide (H2O2)-induced injury model. Our results demonstrate that IBC can effectively enhance neuronal viability under in vitro-modeled reaction oxygen species (ROS)-generating conditions by inhibiting mitochondrial ROS production and increasing adenosine triphosphate level in H2O2-treated neurons. Additionally, we confirmed that neuronal death was attenuated by improving the mitochondrial membrane potential status and regulating the expression of cytochrome c, a protein related to cell death. Furthermore, IBC increased the expression of brain-derived neurotrophic factor and nerve growth factor. Furthermore, IBC inhibited the loss and induced the production of synaptophysin, a major synaptic vesicle protein. This study is the first to demonstrate that IBC exerts its neuroprotective effect by reducing mitochondria-associated oxidative stress and improving mitochondrial dysfunction.

scholarly journals Mumijo Traditional Medicine: Fossil Deposits from Antarctica (Chemical Composition and Beneficial Bioactivity)

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Anna Aiello ◽  
Ernesto Fattorusso ◽  
Marialuisa Menna ◽  
Rocco Vitalone ◽  
Heinz C. Schröder ◽  
...  
Keyword(s):  
Chemical Composition ◽  
Traditional Medicine ◽  
Cortical Neurons ◽  
Neuroprotective Effect ◽  
Amyloid Peptide ◽  
Neuroprotective Activity ◽  
Antiallergic Activity ◽  
Neuronal Pc12 Cells ◽  
Biomedical Potential

Mumijo is a widely used traditional medicine, especially in Russia, Altai Mountains, Mongolia, Iran Kasachstan and in Kirgistan. Mumijo preparations have been successfully used for the prevention and treatment of infectious diseases; they display immune-stimulating and antiallergic activity as well. In the present study, we investigate the chemical composition and the biomedical potential of a Mumijo(-related) product collected from the Antarctica. The yellow material originates from the snow petrels,Pagodroma nivea. Extensive purification and chemical analysis revealed that the fossil samples are a mixture of glycerol derivatives.In vitroexperiments showed that the Mumijo extract caused in cortical neurons a strong neuroprotective effect against the apoptosis-inducing amyloid peptide fragmentβ-fragment 25–35 (Aβ25–35). In addition, the fraction rich in glycerol ethers/wax esters displayed a significant growth-promoting activity in permanent neuronal PC12 cells. It is concluded that this new Mumijo preparation has distinct and marked neuroprotective activity, very likely due to the content of glycerol ether derivatives.

scholarly journals Glucose Deprivation Neuronal Injury in vitro is Modified by Withdrawal of Extracellular Glutamine

1990 ◽  
Vol 10 (3) ◽  
pp. 337-342 ◽  
Author(s):  
Hannelore Monyer ◽  
Dennis W. Choi
Keyword(s):  
Cortical Neurons ◽  
Excitatory Amino Acids ◽  
Neuronal Loss ◽  
Nmda Antagonist ◽  
Neuronal Injury ◽  
Glucose Deprivation ◽  
Glutamine Concentration ◽  
Energy Substrate ◽  
Cultured Cortical Neurons

Cultured cortical neurons deprived of glucose in a defined solution containing 2 m M glutamine became acutely swollen and went on to degenerate over the next day; this neuronal loss could be substantially attenuated by an N-methyl-D-aspartate (NMDA) antagonist. Removal of extracellular glutamine produced two effects: an increase in overall neuronal injury and a decrease in the protective effect of an NMDA antagonist. Both effects of glutamine removal were glutamine concentration dependent (EC50 for both ∼300 μ M) and not reversed by substitution of equimolar concentrations of alanine or arginine. These observations suggest that glucose deprivation neuronal injury may be tonically regulated by the presence of extracellular glutamine. We speculate that glutamine may reduce overall injury by serving as an energy substrate in the absence of glucose, but may increase NMDA receptor-mediated injury by serving as a precursor for transmitter excitatory amino acids.

scholarly journals MicroRNA-26b/PTEN Signaling Pathway Mediates Glycine-Induced Neuroprotection in SAH Injury

Neurosurgery ◽  
2019 ◽  
Vol 66 (Supplement_1) ◽  
Author(s):  
Xingping Qin
Keyword(s):  
Neuronal Death ◽  
Cortical Neurons ◽  
Detection System ◽  
Neuroprotective Effect ◽  
Signal Pathway ◽  
Neuroprotective Effects ◽  
Mortality And Morbidity ◽  
Microglial Polarization ◽  
Show Evidence ◽  
Cultured Cortical Neurons

Abstract INTRODUCTION Glycine is a nonessential amino acid with known neuroprotective effects. Subarachnoid hemorrhage (SAH) is a form of stroke associated with high mortality and morbidity. Despite extensive research, the treatment for SAH is limited. The present study was designed to investigate the role of glycine in neuroprotection following SAH. We have previously demonstrated that glycine is involved in neuroprotection in intracerebral hemorrhage via the PTEN/AKT signal pathway. However, whether it has a role in inducing neuroprotection following SAH is not known. METHODS We established the SAH model, evaluated the SAH grade, neurological scores, brain water content, glycine-mediated C (FJC) staining, cell viability and LDH release, and did cortical neuron and microglia culture. Treatment was conducted by intracerebroventricular injection. Cultured cortical neurons and cultured cortical microglia were treated with standard ECS for 60 min and then treated with glycine (100 μM) for 60 min. Cell replacement medium was used for subsequent experiments. vPCR was performed on the Opticon 2 real-time polymerase chain reaction (PCR) detection system using the corresponding primers and SYBR gene PCR master mix. RESULTS In this present study, we show evidence of glycine mediated amelioration of neuronal death and brain edema following SAH via a novel pathway. Following SAH there is evidence of downregulation of S473 phosphorylation of AKT (p-AKT), which is reversed with glycine treatment. We also found that glycine-regulated neuroprotection following SAH via AKT activation. Glycine was shown to down-regulate PTEN by up-regulating miRNA-26b, followed by activation of AKT, resulting in inhibition of neuronal death. Inhibition of AKT, PTEN depletion or suppression of miRNA-26b blocked the neuroprotective effect of glycine. Glycine treatment also suppresses SAH-induced M1 microglial polarization and promotes anti-inflammation, which indirectly inhibits neuronal death. CONCLUSION Glycine has neuroprotective effects in SAH injury and is mediated by the miRNA-26b/PTEN/AKT signal pathway, which may be a therapeutic target for treatment of SAH injury.

scholarly journals Notoginsenoside R2 reduces Aβ25-35-induced neuronal apoptosis and inflammation via miR-27a/SOX8/β-catenin axis

2021 ◽  
pp. 096032712110419
Author(s):  
Yueqiang Hu ◽  
Lin Wu ◽  
Lingfei Jiang ◽  
Ni Liang ◽  
Xiaomin Zhu ◽  
...  
Keyword(s):  
Cortical Neurons ◽  
Neuronal Apoptosis ◽  
Animal Experiments ◽  
Panax Notoginseng ◽  
Luciferase Reporter ◽  
Beta Peptide ◽  
Rat Cortical Neurons ◽  
Cellular Apoptosis ◽  
Apoptosis And Inflammation

Background: Alzheimer’s disease (AD) has affected numerous elderly individuals worldwide. Panax notoginseng has been shown to ameliorate AD symptoms, and notoginsenoside R2 is a key saponin identified in this plant. Purpose: In the current study, we aimed to explore whether notoginsenoside R2 could improve the prognosis of AD. Methods: Herein, primary rat cortical neurons were isolated and they were treated with amyloid beta-peptide (A β) 25–35 oligomers. Cellular apoptosis was examined via flow cytometry and Western blotting. miR-27a and SOX8 mRNA expression levels were quantified by quantitative reverse transcription-polymerase chain reaction. Furthermore, the interaction between miR-27a and SOX8 was investigated by utilizing a dual-luciferase reporter assay. Finally, an AD mouse model was established to validate the in vitro findings. Results: Notoginsenoside R2 alleviated A β25-35-triggered neuronal apoptosis and inflammation. During this process, miR-27a expression was decreased by notoginsenoside R2, and miR-27a negatively modulated SOX8 expression. Furthermore, activation of SOX8 upregulated β-catenin expression, thus suppressing apoptosis and neuroinflammation. Conclusions: Our animal experiments revealed that notoginsenoside R2 enhanced the cognitive function of AD mice and inhibited neuronal apoptosis. Notoginsenoside R2 ameliorated AD symptoms by reducing neuronal apoptosis and inflammation, thus suggesting a novel direction for AD pharmacotherapy.

The AMPAR antagonist perampanel regulates neuronal necroptosis via Akt/GSK3β signaling after acute traumatic injury in cortical neurons

2020 ◽  
Vol 19 ◽  
Author(s):  
Tao Chen ◽  
Li-Kun Yang ◽  
Jie Zhu ◽  
Chun-Hua Hang ◽  
Yu-Hai Wang
Keyword(s):  
Traumatic Brain Injury ◽  
Protective Effect ◽  
Neuronal Death ◽  
Cortical Neurons ◽  
Therapeutic Potential ◽  
Traumatic Injury ◽  
Neuroprotective Effects ◽  
Stroke Models ◽  
Cultured Cortical Neurons

Background: Perampanel is a highly selective and non-competitive α-amino-3-hydroxy-5 -methyl-4-isoxazole propionate (AMPA) receptor (AMPAR) antagonist, which has been licensed as an orally administered antiepileptic drug in more than 55 countries. Recently, perampanel was found to exert neuroprotective effects in hemorrhagic and ischemic stroke models. Objective: In this study, the protective effect of perampanel was investigated. Method: The protective effect of perampanel was investigated in an in vitro traumatic neuronal injury (TNI) model in primary cultured cortical neurons. Conclusion: Our present data suggest that necroptosis plays a key role in the pathogenesis of neuronal death after TNI, and that perampanel might have therapeutic potential for patients with traumatic brain injury (TBI).

scholarly journals Nrg1 Intracellular Signaling Is Neuroprotective upon Stroke

2019 ◽  
Vol 2019 ◽  
pp. 1-15
Author(s):  
Carmen Navarro-González ◽  
Alba Huerga-Gómez ◽  
Pietro Fazzari
Keyword(s):  
Cortical Neurons ◽  
Intracellular Signaling ◽  
Neuronal Survival ◽  
Neuroprotective Effect ◽  
Inhibitory Synapses ◽  
Ischemic Lesion ◽  
Stroke Treatment

The schizophrenia risk gene NRG1 controls the formation of excitatory and inhibitory synapses in cortical circuits. While the expression of different NRG1 isoforms occurs during development, adult neurons primarily express the CRD-NRG1 isoform characterized by a highly conserved intracellular domain (NRG1-ICD). We and others have demonstrated that Nrg1 intracellular signaling promotes dendrite elongation and excitatory connections during neuronal development. However, the role of Nrg1 intracellular signaling in adult neurons and pathological conditions remains largely unaddressed. Here, we investigated the role of Nrg1 intracellular signaling in neuroprotection and stroke. Our bioinformatic analysis revealed the evolutionary conservation of the NRG1-ICD and a decrease in NRG1 expression with age in the human frontal cortex. Hence, we first evaluated whether Nrg1 signaling may affect pathological hallmarks in an in vitro model of neuronal senescence; however, our data failed to reveal a role for Nrg1 in the activation of the stress-related pathway p38 MAPK and DNA damage. Previous studies demonstrated that the soluble EGF domain of Nrg1 alleviated brain ischemia, a pathological process involving the generation of free radicals, reactive oxygen species (ROS), and excitotoxicity. Hence, we tested the hypothesis that Nrg1 intracellular signaling could be neuroprotective in stroke. We discovered that Nrg1 expression significantly increased neuronal survival upon oxygen-glucose deprivation (OGD), an established in vitro model for stroke. Notably, the specific activation of Nrg1 intracellular signaling by expression of the Nrg1-ICD protected neurons from OGD. Additionally, time-lapse experiments confirmed that Nrg1 intracellular signaling increased the survival of neurons exposed to OGD. Finally, we investigated the relevance of Nrg1 intracellular signaling in stroke in vivo. Using viral vectors, we expressed the Nrg1-ICD in cortical neurons and subsequently challenged them by a focal hemorrhagic stroke; our data indicated that Nrg1 intracellular signaling improved neuronal survival in the infarcted area. Altogether, these data highlight Nrg1 intracellular signaling as neuroprotective upon ischemic lesion both in vitro and in vivo. Given the complexity of the neurotoxic effects of stroke and the involvement of various mechanisms, such as the generation of ROS, excitotoxicity, and inflammation, further studies are required to determine the molecular bases of the neuroprotective effect of Nrg1 intracellular signaling. In conclusion, our research highlights the stimulation of Nrg1 intracellular signaling as a promising target for cortical stroke treatment.

scholarly journals Overexpressed microRNA-539-5p inhibits inflammatory response of neurons to impede the progression of cerebral ischemic injury by histone deacetylase 1

2020 ◽  
Vol 319 (2) ◽  
pp. C381-C391
Author(s):  
Hang Xue ◽  
Jianpeng Liu ◽  
Lin Shi ◽  
Hongfa Yang
Keyword(s):  
Spatial Memory ◽  
Histone Deacetylase ◽  
Cortical Neurons ◽  
Ischemic Injury ◽  
Luciferase Reporter ◽  
Histone Deacetylase 1 ◽  
Gene Assay ◽  
Cerebral Ischemic Injury ◽  
Cerebral Ischemic

Several microRNAs (miRNAs or miRs) regulate cerebral ischemic injury outcomes; however, little is known about the role of miR-539-5p during cerebral ischemic injury or the postischemic state. Cerebral ischemic injury was modeled in vitro by exposing human cortical neurons to oxygen-glucose deprivation (OGD) and in vivo by occluding the middle cerebral artery (MCAO) in a rat model. The effects of miR-539-5p, histone deacetylase 1 (HDAC1), and early growth response 2 (EGR2) on cerebral ischemia were investigated using gain- and loss-of-function experiments. We identified changes in miR-539-5p, HDAC1, EGR2, and phosphorylated c-Jun NH2-terminal kinase (JNK). The interaction among miR-539-5p, HDAC1, and EGR2 was determined by dual luciferase reporter gene assay, chromatin immunoprecipitation, and coimmunoprecipitation. We also investigated the effects on cell viability and apoptosis and changes in inflammatory cytokine expression and spatial memory on MCAO rats. miR-539-5p and EGR2 were poorly expressed, while HDAC1 was highly expressed in OGD-treated HCN-2 cells. miR-539-5p targeted HDAC1, while HDAC1 prevented acetylation of EGR2 resulting in its downregulation and subsequent activation of the JNK pathway. Overexpression of miR-539-5p or EGR2 or silencing HDAC1 improved viability and reduced apoptosis of OGD-treated HCN-2 cells in vitro. Furthermore, overexpression of miR-539-5p improved spatial memory, while decreasing cell apoptosis and inflammation in MCAO rats. Collectively, these data suggest that miR-539-5p targets HDAC1 to upregulate EGR2, thus blocking the JNK signaling pathway, by which cerebral ischemic injury is alleviated.

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