scholarly journals Homo-Tris-Nitrones Derived from α-Phenyl-N-tert-butylnitrone: Synthesis, Neuroprotection and Antioxidant Properties

2020 ◽  
Vol 21 (21) ◽  
pp. 7949 ◽  
Author(s):  
Daniel Diez-Iriepa ◽  
Beatriz Chamorro ◽  
Marta Talaván ◽  
Mourad Chioua ◽  
Isabel Iriepa ◽  
...  
Keyword(s):  
Antioxidant Properties ◽  
Glucose Deprivation ◽  
Maximal Activity ◽  
Oxygen Glucose Deprivation ◽  
Neuroprotective Agents ◽  
Neuroprotective Agent ◽  
Oligomycin A ◽  
Deprivation Model

Herein we report the synthesis, antioxidant and neuroprotective power of homo-tris-nitrones (HTN) 1-3, designed on the hypothesis that the incorporation of a third nitrone motif into our previously identified homo-bis-nitrone 6 (HBN6) would result in an improved and stronger neuroprotection. The neuroprotection of HTNs 1-3, measured against oligomycin A/rotenone, showed that HTN2 was the best neuroprotective agent at a lower dose (EC50 = 51.63 ± 4.32 μM), being similar in EC50 and maximal activity to α-phenyl-N-tert-butylnitrone (PBN) and less potent than any of HBNs 4-6. The results of neuroprotection in an in vitro oxygen glucose deprivation model showed that HTN2 was the most powerful (EC50 = 87.57 ± 3.87 μM), at lower dose, but 50-fold higher than its analogous HBN5, and ≈1.7-fold less potent than PBN. HTN3 had a very good antinecrotic (IC50 = 3.47 ± 0.57 μM), antiapoptotic, and antioxidant (EC50 = 6.77 ± 1.35 μM) profile, very similar to that of its analogous HBN6. In spite of these results, and still being attractive neuroprotective agents, HTNs 2 and 3 do not have better neuroprotective properties than HBN6, but clearly exceed that of PBN.

scholarly journals Synthesis, Neuroprotection, and Antioxidant Activity of 1,1′-Biphenylnitrones as α-Phenyl-N-tert-butylnitrone Analogues in In Vitro Ischemia Models

Molecules ◽  
2021 ◽  
Vol 26 (4) ◽  
pp. 1127 ◽  
Author(s):  
Beatriz Chamorro ◽  
David García-Vieira ◽  
Daniel Diez-Iriepa ◽  
Estíbaliz Garagarza ◽  
Mourad Chioua ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Antioxidant Activities ◽  
Antioxidant Properties ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Human Neuroblastoma ◽  
In Vitro Ischemia ◽  
Lipoxygenase Inhibition ◽  
Antioxidant Agent

Herein, we report the neuroprotective and antioxidant activity of 1,1′-biphenyl nitrones (BPNs) 1–5 as α-phenyl-N-tert-butylnitrone analogues prepared from commercially available [1,1′-biphenyl]-4-carbaldehyde and [1,1′-biphenyl]-4,4′-dicarbaldehyde. The neuroprotection of BPNs1-5 has been measured against oligomycin A/rotenone and in an oxygen–glucose deprivation in vitro ischemia model in human neuroblastoma SH-SY5Y cells. Our results indicate that BPNs 1–5 have better neuroprotective and antioxidant properties than α-phenyl-N-tert-butylnitrone (PBN), and they are quite similar to N-acetyl-L-cysteine (NAC), which is a well-known antioxidant agent. Among the nitrones studied, homo-bis-nitrone BPHBN5, bearing two N-tert-Bu radicals at the nitrone motif, has the best neuroprotective capacity (EC50 = 13.16 ± 1.65 and 25.5 ± 3.93 μM, against the reduction in metabolic activity induced by respiratory chain blockers and oxygen–glucose deprivation in an in vitro ischemia model, respectively) as well as anti-necrotic, anti-apoptotic, and antioxidant activities (EC50 = 11.2 ± 3.94 μM), which were measured by its capacity to reduce superoxide production in human neuroblastoma SH-SY5Y cell cultures, followed by mononitrone BPMN3, with one N-Bn radical, and BPMN2, with only one N-tert-Bu substituent. The antioxidant activity of BPNs1-5 has also been analyzed for their capacity to scavenge hydroxyl free radicals (82% at 100 μM), lipoxygenase inhibition, and the inhibition of lipid peroxidation (68% at 100 μM). Results showed that although the number of nitrone groups improves the neuroprotection profile of these BPNs, the final effect is also dependent on the substitutent that is being incorporated. Thus, BPNs bearing N-tert-Bu and N-Bn groups show better neuroprotective and antioxidant properties than those substituted with Me. All these results led us to propose homo-bis-nitrone BPHBN5 as the most balanced and interesting nitrone based on its neuroprotective capacity in different neuronal models of oxidative stress and in vitro ischemia as well as its antioxidant activity.

scholarly journals A New Brominated Norsesquiterpene Glycoside From the Rhizomes of Acorus tatarinowii Schott

2021 ◽  
Vol 16 (2) ◽  
pp. 1934578X2199226
Author(s):  
Zhi-You Hao ◽  
Gang Ni ◽  
Dong Liang ◽  
Yan-Fei Liu ◽  
Chun-Lei Zhang ◽  
...  
Keyword(s):  
Nuclear Magnetic Resonance ◽  
Magnetic Resonance ◽  
Pc12 Cells ◽  
Absolute Configuration ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
In Vitro Tests ◽  
Nuclear Magnetic Resonance Spectra ◽  
Acorus Tatarinowii

A new brominated norsesquiterpene glycoside, acoruside (1), has been isolated from the rhizomes of Acorus tatarinowii Schott, together with 8 known compounds (2-9). Their structures were elucidated mainly based on 1-dimensional (1D) and 2D nuclear magnetic resonance spectra. The absolute configuration of compound 1 was determined by comparing its experimental and calculated electronic circular dichroism spectra. The in vitro tests indicated that at 10 µM, compounds 2, 3, and 4 aggravated serum deprivation injuries of PC12 cells, compound 2 aggravated rotenone-induced injuries of PC12 cells, and compounds 3 and 4 aggravated the oxygen-glucose deprivation-induced injuries of PC12 cells.

Effect of Ischemia In vivo and Oxygen-Glucose Deprivation In vitro on NOS Pools in the Spinal Cord: Comparative Study

2006 ◽  
Vol 26 (7-8) ◽  
pp. 1279-1292 ◽  
Author(s):  
Mária Kolesárová ◽  
Jaroslav Pavel ◽  
Nadežda Lukáčová ◽  
Dalibor Kolesár ◽  
Jozef Maršala
Keyword(s):  
Spinal Cord ◽  
Comparative Study ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation

scholarly journals MicroRNA-429/Cxcl1 Axis Protective Against Oxygen Glucose Deprivation/Reoxygenation-Induced Injury in Brain Microvascular Endothelial Cells

Dose-Response ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 155932582091378
Author(s):  
Jun Leng ◽  
Wei Liu ◽  
Li Li ◽  
Fang Yue Wei ◽  
Meng Tian ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Luciferase Reporter ◽  
Microvascular Endothelial Cells ◽  
Oxygen Glucose Deprivation ◽  
Brain Microvascular Endothelial Cells ◽  
Public Data ◽  
Microvascular Endothelial

Objective: The objective of the present work was to study the role of Cxcl1 in cerebral ischemia–reperfusion (I/R) injury and to in-depth explore its pathogenesis. Methods: The expression of Cxcl1 based on the public data was analyzed. Then, we constructed an oxygen glucose deprivation/reoxygenation (OGD/R) model in vitro using mice brain microvascular endothelial cells (BMECs) to simulate cerebral I/R in vivo. Results: The results of quantitative real-time polymerase chain reaction assay uncovered that Cxcl1 showed higher expression while miR-429 showed lower expression in BMECs damaged by OGD/R, whereas overexpression of Cxcl1 or inhibition of miR-429 expression can strengthen this effect. Hereafter, through dual luciferase reporter assay, we verified that miR-429 directly targets Cxcl1 and negatively regulates Cxcl1 expression. Furthermore, the results also revealed that overexpression of Cxcl1 can reverse the miR-429-mediated effects. Conclusion: We concluded that miR-429 exerts protective effects against OGD/R-induce injury in vitro through modulation of Cxcl1 and nuclear factor kinase B pathway, hoping provide a new view on the pathogenesis of cerebral I/R injury and a feasible potential therapeutic target.

scholarly journals Comparative transcriptome of neurons after oxygen–glucose deprivation: Potential differences in neuroprotection versus reperfusion

2018 ◽  
Vol 38 (12) ◽  
pp. 2236-2250 ◽  
Author(s):  
Shuzhen Guo ◽  
Anna Tjärnlund-Wolf ◽  
Wenjun Deng ◽  
Emiri Tejima-Mandeville ◽  
Lauren J Lo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Glucose Deprivation ◽  
Oxygen Glucose Deprivation ◽  
Comparative Transcriptome ◽  
Gene Arrays ◽  
Mk 801 ◽  
Metabolic Inflammation ◽  
Cell Death Pathways ◽  
Rapid Restoration

In the context of ischemic stroke, rescuing neurons can be theoretically achieved with either reperfusion or neuroprotection. Reperfusion works via the rapid restoration of oxygen and glucose delivery. Neuroprotection comprises molecular strategies that seek to block excitotoxicity, oxidative stress or various cell death pathways. Here, we propose the hypothesis that neurons rescued with reperfusion are different from neurons rescued with molecular neuroprotection. Neurons were subjected to oxygen–glucose deprivation (OGD) and then treated with “in vitro reperfusion” (i.e. energetic rescue via restoration of oxygen and glucose) or Z-VADfmk (to block apoptosis) or MK-801 (to block excitotoxicity). Levels of injury were titrated so that equivalent levels of neuronal salvage were achieved with reperfusion or neuroprotection. Gene arrays showed that OGD significantly altered the transcriptomic profiles of surviving neurons. Pathway analysis confirmed that a large spectrum of metabolic, inflammation, and signaling genes were perturbed. In spite of the fact that equal levels of neuronal salvage were achieved, energetic rescue renormalized the transcriptomic profiles in surviving neurons to a larger degree compared to neuroprotection with either Z-VADfmk or MK-801. These findings suggest that upstream reperfusion may bring salvaged neurons back “closer to normal” compared to downstream molecular neuroprotection.

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