In vitro protective effects of Withania somnifera (L.) dunal root extract against hydrogen peroxide and β-amyloid(1-42)-induced cytotoxicity in differentiated PC12 cells

The neurotoxicity of amyloid-β(Aβ) has been implicated as a critical cause of Alzheimer’s disease. Isorhynchophylline (IRN), an oxindole alkaloid isolated fromUncaria rhynchophylla,exerts neuroprotective effect againstAβ25–35-induced neurotoxicityin vitro. However, the exact mechanism for its neuroprotective effect is not well understood. The present study aimed to investigate the molecular mechanisms underlying the protective action of IRN againstAβ25–35-induced neurotoxicity in cultured rat pheochromocytoma (PC12) cells. Pretreatment with IRN significantly increased the cell viability, inhibited the release of lactate dehydrogenase and the extent of DNA fragmentation inAβ25–35-treated cells. IRN treatment was able to enhance the protein levels of phosphorylated Akt (p-Akt) and glycogen synthase kinase-3β(p-GSK-3β). Lithium chloride blockedAβ25–35-induced cellular apoptosis in a similar manner as IRN, suggesting that GSK-3βinhibition was involved in neuroprotective action of IRN. Pretreatment with LY294002 completely abolished the protective effects of IRN. Furthermore, IRN reversedAβ25–35-induced attenuation in the level of phosphorylated cyclic AMP response element binding protein (p-CREB) and the effect of IRN could be blocked by the PI3K inhibitor. These experimental findings unambiguously suggested that the protective effect of IRN againstAβ25–35-induced apoptosis in PC12 cells was associated with the enhancement of p-CREB expression via PI3K/Akt/GSK-3βsignaling pathway.

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Protective effect of nigella sativa extract and thymoquinone on serum/glucose deprivation-induced PC12 cells death

European Psychiatry ◽

10.1016/s0924-9338(11)72613-x ◽

2011 ◽

Vol 26 (S2) ◽

pp. 908-908

Author(s):

H.R. Sadeghnia ◽

S.H. Mousavi ◽

Z. Tayarani-Najaran ◽

M. Asghari

Keyword(s):

Cell Viability ◽

Pc12 Cells ◽

Neurodegenerative Disorders ◽

Nigella Sativa ◽

Glucose Deprivation ◽

Serum Glucose ◽

Ros Production ◽

Protective Effects ◽

Intracellular Ros

The serum/glucose deprivation (SGD)-induced cell death in cultured PC12 cells represents a useful in vitro model for the study of brain ischemia and neurodegenerative disorders.Nigella sativa L. and its active component, thymoquinone (TQ) have been known as a source of antioxidants. In the present study, the protective effects of N. sativa and TQ on cell viability and reactive oxygen species (ROS) production in cultured PC12 cells were investigated under SGD conditions. PC12 Cells were pretreated with different concentrations of N. sativa extract (15.62–250 μg/ml) and TQ (1.17–150 μM) for 2 h and then subjected to SGD for 6 or 18 h. Cell viability was quantitated by MTT assay. Intracellular ROS production was measured by flow cytometry using 2’,7’-dichlorofluorescin diacetate (DCF-DA) as a probe. SGD induced significant cells toxicity after 6, 18, or 24 h (p < 0.001). Pretreatment with N. sativa (15.62–250 μg/ml) and TQ (1.17–37.5 μM) reduced SGD-induced cytotoxicity in PC12 cells after 6 and 18 h. A significant increase in intracellular ROS production was seen following SGD (p < 0.001). N. sativa (250 μg/ml, p < 0.01) and TQ (2.34, 4.68, 9.37 μM, p < 0.01) pretreatment reversed the increased ROS production following ischemic insult. The experimental results suggest that N. sativa extract and TQ protects the PC12 cells against SGD-induced cytotoxicity via antioxidant mechanisms. Our findings might raise the possibility of potential therapeutic application of N. sativa extract and TQ for managing cerebral ischemic and neurodegenerative disorders.

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Undercarboxylated Osteocalcin Increases the Dopaminergic Activity of Neuronal Differentiated PC12 Cells In Vitro

10.1055/s-0041-1739641 ◽

2021 ◽

Author(s):

Michel Schultz ◽

Beatrice Hanusch ◽

Veronika Matschke ◽

Carsten Theiss ◽

Thomas Lücke ◽

...

Keyword(s):

Pc12 Cells ◽

Undercarboxylated Osteocalcin ◽

Dopaminergic Activity ◽

Differentiated Pc12 Cells

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Design and Synthesis of New Benzo[d]oxazole-Based Derivatives and Their Neuroprotective Effects on β-Amyloid-Induced PC12 Cells

Molecules ◽

10.3390/molecules25225391 ◽

2020 ◽

Vol 25 (22) ◽

pp. 5391

Author(s):

Zheng Liu ◽

Ming Bian ◽

Qian-Qian Ma ◽

Zhuo Zhang ◽

Huan-Huan Du ◽

...

Keyword(s):

Pc12 Cells ◽

Glycogen Synthase ◽

B Cell Lymphoma ◽

Nuclear Factor Κb ◽

In Vivo Studies ◽

Neuroprotective Effects ◽

Β Amyloid ◽

Gsk 3Β

A series of novel synthetic substituted benzo[d]oxazole-based derivatives (5a–5v) exerted neuroprotective effects on β-amyloid (Aβ)-induced PC12 cells as a potential approach for the treatment of Alzheimer’s disease (AD). In vitro studies show that most of the synthesized compounds were potent in reducing the neurotoxicity of Aβ25-35-induced PC12 cells at 5 μg/mL. We found that compound 5c was non-neurotoxic at 30 μg/mL and significantly increased the viability of Aβ25-35-induced PC12 cells at 1.25, 2.5 and 5 μg/mL. Western blot analysis showed that compound 5c promoted the phosphorylation of Akt and glycogen synthase kinase (GSK-3β) and decreased the expression of nuclear factor-κB (NF-κB) in Aβ25-35-induced PC12 cells. In addition, our findings demonstrated that compound 5c protected PC12 cells from Aβ25-35-induced apoptosis and reduced the hyperphosphorylation of tau protein, and decreased the expression of receptor for AGE (RAGE), β-site amyloid precursor protein (APP)-cleaving enzyme 1 (BACE1), inducible nitric oxide synthase (iNOS) and Bcl-2-associated X protein/B-cell lymphoma 2 (Bax/Bcl-2) via Akt/GSK-3β/NF-κB signaling pathway. In vivo studies suggest that compound 5c shows less toxicity than donepezil in the heart and nervous system of zebrafish.

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Hydrogen Gas Attenuates Hypoxic-Ischemic Brain Injury via Regulation of the MAPK/HO-1/PGC-1a Pathway in Neonatal Rats

Oxidative Medicine and Cellular Longevity ◽

10.1155/2020/6978784 ◽

2020 ◽

Vol 2020 ◽

pp. 1-16 ◽

Cited By ~ 1

Author(s):

Peipei Wang ◽

Mingyi Zhao ◽

Zhiheng Chen ◽

Guojiao Wu ◽

Masayuki Fujino ◽

...

Keyword(s):

Brain Injury ◽

Protein Kinase ◽

Pc12 Cells ◽

Heme Oxygenase 1 ◽

Ischemic Brain Injury ◽

Protective Effects ◽

Neonatal Rats ◽

Ischemic Brain ◽

Differentiated Pc12 Cells ◽

Hypoxic Ischemic Brain Injury

Neonatal hypoxic-ischemic encephalopathy (HIE) is a leading cause of death in neonates with no effective treatments. Recent advancements in hydrogen (H2) gas offer a promising therapeutic approach for ischemia reperfusion injury; however, the impact of this approach for HIE remains a subject of debate. We assessed the therapeutic effects of H2 gas on HIE and the underlying molecular mechanisms in a rat model of neonatal hypoxic-ischemic brain injury (HIBI). H2 inhalation significantly attenuated neuronal injury and effectively improved early neurological outcomes in neonatal HIBI rats as well as learning and memory in adults. This protective effect was associated with initiation time and duration of sustained H2 inhalation. Furthermore, H2 inhalation reduced the expression of Bcl-2-associated X protein (BAX) and caspase-3 while promoting the expression of Bcl-2, nuclear factor erythroid-2-related factor 2, and heme oxygenase-1 (HO-1). H2 activated extracellular signal-regulated kinase and c-Jun N-terminal protein kinase and dephosphorylated p38 mitogen-activated protein kinase (MAPK) in oxygen-glucose deprivation/reperfusion (OGD/R) nerve growth factor-differentiated PC12 cells. Inhibitors of MAPKs blocked H2-induced HO-1 expression. HO-1 small interfering RNA decreased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and sirtuin 1 (SIRT1) and reversed the protectivity of H2 against OGD/R-induced cell death. These findings suggest that H2 augments cellular antioxidant defense capacity through activation of MAPK signaling pathways, leading to HO-1 expression and subsequent upregulation of PGC-1α and SIRT-1 expression. Thus, upregulation protects NGF-differentiated PC12 cells from OGD/R-induced oxidative cytotoxicity. In conclusion, H2 inhalation exerted protective effects on neonatal rats with HIBI. Early initiation and prolonged H2 inhalation had better protective effects on HIBI. These effects of H2 may be related to antioxidant, antiapoptotic, and anti-inflammatory responses. HO-1 plays an important role in H2-mediated protection through the MAPK/HO-1/PGC-1α pathway. Our results support further assessment of H2 as a potential therapeutic for neurological conditions in which oxidative stress and apoptosis are implicated.

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s-Ethyl Cysteine ands-Propyl Cysteine Alleviate β-Amyloid Induced Cytotoxicity in Nerve Growth Factor Differentiated PC12 Cells

Journal of Agricultural and Food Chemistry ◽

10.1021/jf1009318 ◽

2010 ◽

Vol 58 (11) ◽

pp. 7104-7108 ◽

Cited By ~ 12

Author(s):

Shih-Jei Tsai ◽

Chia-Yu Lin ◽

Mei-Chin Mong ◽

Mao-Wang Ho ◽

Mei-Chin Yin

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Pc12 Cells ◽

Nerve Growth ◽

Differentiated Pc12 Cells ◽

Β Amyloid

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Effect of Chitosan Nanoparticle-Loaded Thymus serpyllum on Hydrogen Peroxide-Induced Bone Marrow Stromal Cell Damage

Stem Cells International ◽

10.1155/2019/5142518 ◽

2019 ◽

Vol 2019 ◽

pp. 1-12

Author(s):

Salma Baig ◽

Ainnul Hamidah Syahadah Azizan ◽

Hanumantha Rao Balaji Raghavendran ◽

Elango Natarajan ◽

Sangeetha Naveen ◽

...

Keyword(s):

Hydrogen Peroxide ◽

Cell Death ◽

Cell Damage ◽

Radical Scavenging Activity ◽

Radical Scavenging ◽

Potential Candidate ◽

Protective Effects ◽

Active Components ◽

Thymus Serpyllum

We have determined the protective effects of Thymus serpyllum (TS) extract and nanoparticle-loaded TS on hydrogen peroxide-induced cell death of mesenchymal stromal cells (MSCs) in vitro. Gas chromatography–mass spectroscopy confirmed the spectrum of active components in the extract. Out of the three different extracts, the hexane extract showed significant free radical scavenging activity. Treatment of MSCs with H2O2 (hydrogen peroxide) significantly increased intracellular cell death; however, pretreatment with TS extract and nanoparticle-loaded TS (200 μg/ml) suppressed H2O2-induced elevation of Cyt-c and MMP13 and increased the survival rates of MSCs. H2O2-induced (0.1 mM) changes in cytokines were attenuated in the extract and nanoparticles by pretreatment and cotreatment at two time points (p<0.05). H2O2 increased cell apoptosis. In contrast, treatment with nanoparticle-loaded TS suppressed the percentage of apoptosis considerably (p<0.05). Therefore, TS may be considered as a potential candidate for enhancing the effectiveness of MSC transplantation in cell therapy.

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Effect of alpha-ketoglutarate and N-acetyl cysteine on cyanide-induced oxidative stress mediated cell death in PC12 cells

Toxicology and Industrial Health ◽

10.1177/0748233710365695 ◽

2010 ◽

Vol 26 (5) ◽

pp. 297-308 ◽

Cited By ~ 13

Author(s):

RM Satpute ◽

J. Hariharakrishnan ◽

R. Bhattacharya

Keyword(s):

Oxidative Stress ◽

Cell Death ◽

Pc12 Cells ◽

Caspase 3 ◽

Critical Role ◽

Total Antioxidant Status ◽

Protective Effects ◽

Simultaneous Treatment ◽

Acetyl Cysteine

Cyanide is a mitochondrial poison, which is ubiquitously present in the environment. Cyanide-induced oxidative stress is known to play a key role in mediating the neurotoxicity and cell death in rat pheochromocytoma (PC12) cells. PC12 cells are widely used as a model for neurotoxicity assays in vitro. In the present study, we investigated the protective effects of alpha-ketoglutarate (A-KG), a potential cyanide antidote, and N-acetyl cysteine (NAC), an antioxidant against toxicity of cyanide in PC12 cells. Cells were treated with various concentrations (0.625—1.25 mM) of potassium cyanide (KCN) for 4 hours, in the presence or absence of simultaneous treatment of A-KG (0.5 mM) and NAC (0.25 mM). Cyanide caused marked decrease in the levels of cellular antioxidants like superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Lipid peroxidation indicated by elevated levels of malondialdehyde (MDA) was found to be accompanied by decreased levels of reduced glutathione (GSH) and total antioxidant status (TAS) of the cells. Cyanide-treated cells showed notable increase in caspase-3 activity and induction of apoptotic type of cell death after 24 hours. A-KG and NAC alone were very effective in restoring the levels of GSH and TAS, but together they significantly resolved the effects of cyanide on antioxidant enzymes, MDA levels, and caspase-3 activity. The present study reveals that combination of A-KG and NAC has critical role in abbrogating the oxidative stress-mediated toxicity of cyanide in PC12 cells. The results suggest potential role of A-KG and NAC in cyanide antagonism.

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