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 ◽  
...  

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.

2019 ◽  
Vol 3 (1) ◽  
pp. 51-55 ◽  
Author(s):  
Nirmala Jamarkattel-Pandit ◽  
Hocheol Kim

Metaplexis japonica (Apocynaceae) is a perennial herb, extensively used in traditional medicinal system for various diseases. The purpose of the study was to evaluate the protective effect of M. japonica against in vitro ischemia. In the present study, 70% ethanol extract of M. japonica was fractionated with different polarity solvents. For in vitro ischemia, oxygen-glucose deprivation followed by reoxygenation (OGD-R) in cells was used to investigate the effects of M. japonica and its fractions. For oxidative stress model, Hydrogen peroxide (H2 O2 ) induced cell death was studied in HT22 cell line. M. japonica and its fractions significantly reduced the HT22 cell damage, which was induced by 4 hrs of OGD followed by 24 hrs of reoxygenation and 24 hrs of H2 O2, respectively. The effectiveness of ethyl acetate fraction was higher than other fractions/crude extract. Our results suggest that M. japonica could be a neuroprotective agent for the treatment of stroke. Key words: Metaplexis japonica, Stroke, Oxygen-glucose deprivation, Neuroprotection


2020 ◽  
Vol 2 (3) ◽  
pp. 653-662
Author(s):  
Rokiman Letsara ◽  
Rigobert Andrianantenaina ◽  
Gédéon Ngiala Bongo ◽  
Colette Masengo Ashande ◽  
Mahendra Ilmi S Matondang ◽  
...  

The World Health Organization reported that at least 80% of populations rely on traditional medicine and medicinal plants for their primary health care. Due to their phytochemical compounds, the plants of the Aloe genus are reported to have high potential antiCovid-19 (and antioxidant properties. The aim of this study is to evaluate the in vitro antioxidant activity of some Malagasy endangered species of Aloe genus. The ethanolic extract of few Aloe of Madagascar leaf extracts was fractionated by liquid-liquid partition using hexane. In total 18 different fractions from 9 species have been used to determine their antioxidant activity through in vitro model by using 2,2-Diphenyl-1-picrylhydrazyl (DPPH) assay. Both hexanic extract and aqueous extract displayed antioxidant activities in four species. The most evident antioxidant activity was expressed by A. helenae.


2020 ◽  
Vol 21 (21) ◽  
pp. 7949 ◽  
Author(s):  
Daniel Diez-Iriepa ◽  
Beatriz Chamorro ◽  
Marta Talaván ◽  
Mourad Chioua ◽  
Isabel Iriepa ◽  
...  

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.


Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 295 ◽  
Author(s):  
Kun Xie ◽  
Xi He ◽  
Keyu Chen ◽  
Jihua Chen ◽  
Kozue Sakao ◽  
...  

Ampelopsis grossedentata, also called vine tea, has been used as a traditional beverage in China for centuries. Vine tea contains rich polyphenols and shows benefit to human health, but the chemical and antioxidant properties of vine tea polyphenols from different locations remain unclear. This study aims to investigate the chemical and antioxidant properties of vine tea from three major production areas in China including Guizhou, Hunan, and Guangxi Provinces. The highest amount of polyphenol from vine tea was extracted by 70% ethanol at 70 °C for 40 min with ultrasonic treatment. The major compound in vine tea polyphenols (VTP) was determined as dihydromyricetin (DMY) by high-performance liquid chromatography (HPLC) and the content was estimated as 21.42%, 20.17%, and 16.47% of dry weight basis from Hunan, Guizhou, and Guangxi products, respectively. The antioxidant activities were investigated in vitro and in culture hepatic cells. VTP and DMY showed strong 1,1-Diphenyl-2-picrylhydrazyl free radical (DPPH) scavenging ability and high oxygen radical absorption capacity (ORAC) value in vitro. VTP and DMY also increased the level of nicotinamide adenine dinucleotide phosphate (NADPH):quinone oxidoreductase (NQO1) in HepG2 cells. Moreover, VTP and DMY enhanced the level of nuclear factor erythroid 2-related factor 2 (Nrf2) and reduced the level of Kelch-like ECH-associated protein 1 (Keap1). Taken together, our data demonstrated that the extraction of vine tea by 70% ethanol with ultrasonic treatment is a novel method to efficiently obtain components possessing stronger antioxidant activity. Furthermore, the results from the culture cells suggest that the bioactive component of vine tea might exert the antioxidant activity by activating the cellular Nrf2/Keap1 pathway.


2019 ◽  
Vol 15 ◽  
Author(s):  
Aleksandra Kładna ◽  
Paweł Berczyński ◽  
Oya Bozdağ Dündar ◽  
Irena Kruk ◽  
Beyza Torun ◽  
...  

Background: Stilbene phytalexis (1,2-diphenyloethylen) and benzamide are beneficial for human health. To increase the stilbene ring activity, a new series of its derivatives containing benzamide structure was synthesized and evaluated for their in vitro antioxidant power. Methods: 1H nuclear magnetic resonance, mass spectroscopy, and chromatographic analyses were used to confirm the successful synthesis. The antioxidant properties were determined by the elimination of , HO , DPPH , ABTS+ radicals, total antioxidant status (TAS) and the ferric reducing antioxidant activities (TAC) measurements. Results: Stilbenebenzamide compounds showed a wide spectrum of antioxidant ability, however their total antioxidant power was weaker than those of butylated hydroxytoluene (BHT), ascorbic acid, and resveratrol. The highest antiradical activity towards and HO was shown by the compounds with structures containing amine group (SBEBA, SBA) ( : 37.7 – 38.0% and 40.8 – 43.5%, HO : 29.8%, 28.7% inhibition, respectively) at1.25 mM concentration. The antiradical power of SBEBA (0.29) in DPPH assay was lower than those of resveratrol (1.83), ascorbic acid (3.63) and BHT (4.09). The TAS values of the synthesized compounds ranged from 152.9±5.3 to 240.2±6.7µM trolox equivalent/gram (TE/g) and were much lower than those of BHT (1304±43.0), reservatrol (1360±29.0) and ascorbic acid (2782±39.7) µM TE/g. Similarly, the TAC values ranging from 29.7±0.9 to 41.5±1.6 µM TE were weaker than that of resveratrol (239.2 ±6.7 µM TE/g). Conclusion: The results suggest that the presence of hydroxyl group in stilbene ring should be considered in further design of stilbenebenzamide compounds to enhance their antioxidant activity.


2002 ◽  
Vol 22 (2) ◽  
pp. 206-214 ◽  
Author(s):  
Chen Wang ◽  
Henry N. Nguyen ◽  
Jamie L. Maguire ◽  
David C. Perry

To determine the role of calcium homeostasis in ischemic neuronal death, the authors used an in vitro model of oxygen–glucose deprivation in neuronal cell lines. Exposure of human neuroblastoma SH-SY5Y cells to 10- to 16-hour oxygen–glucose deprivation decreased viability to 50% or less, and longer exposure times killed almost all cells. The death following 10- to 16-hour oxygen–glucose deprivation was not manifested until 24 to 72 hours after exposure. Deprivation of both glucose and oxygen together was required for expression of toxicity at these exposure times. Dantrolene, which blocks the release of endoplasmic reticulum Ca2+ stores, partially protected SH-SY5Y cells from oxygen–glucose deprivation toxicity. The addition of dantrolene during the deprivation phase alone produced the maximal drug effect; no further protection was obtained by continued drug exposure during the recovery phase. Prevention of Ca2+ influx by chelation or channel blockade or the chelation of cytosolic Ca2+ did not inhibit oxygen-glucose deprivation toxicity. In contrast, increasing extracellular Ca2+ or stimulating Ca2+ influx did inhibit toxicity. Calcium measurements with fura-2 acetoxymethylester revealed that oxygen–glucose deprivation caused a significant reduction in thapsigargin-releasable endoplasmic reticular stores of Ca2+. These studies suggest that an important component of the neuronal toxicity in cerebral ischemia is due to disruption of calcium homeostasis, particularly to the depletion of intracellular Ca2+ stores.


Author(s):  
Parisa Sadighara ◽  
Ehsan Haghi ◽  
Tahereh Mohajerfar ◽  
Mahmoud Bahmani ◽  
Majid Asadi- Samani

Chitosan is a natural polysaccharide that has antioxidant properties. It can consider as an antioxidant agent in food supplements. In this study the effect of extraction methods on the antioxidant activity of chitosan was investigated. Three methods including enzymatic, acid and alkaline methods were applied for isolating the chitosan from shrimp waste. The content of extracted chitosan was measured and its antioxidant activity was investigated by employing various analyses such as assay of their power on the oxidative stability in sunflower oil and DPPH. Inhibition of lipid per-oxidation was evaluated by thiobarbituric acid reactive substances assay. The extracted chitosan by enzymatic method had best antioxidant activities. Furthermore, the results demonstrated that good yields can be obtained via enzymatic treatment. According to the results, the content of chitosan influences on antioxidant activity. The chitosan extracted by enzymatic method can be a source of antioxidant agents in manufacturing food and supplement.


2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Miia Juntunen ◽  
Sanna Hagman ◽  
Anaick Moisan ◽  
Susanna Narkilahti ◽  
Susanna Miettinen

Stroke is a devastating neurological disorder and one of the leading causes of mortality and disability. To understand the cellular and molecular mechanisms of stroke and to develop novel therapeutic approaches, two different in vitro human cell-based stroke models were established using oxygen-glucose deprivation (OGD) conditions. In addition, the effect of adipose stem cells (ASCs) on OGD-induced injury was studied. In the present study, SH-SY5Y human neuroblastoma cells and human induced pluripotent stem cells (hiPSCs) were differentiated into neurons, cultured under OGD conditions (1% O2) for 24 h, and subjected to a reperfusion period for 24 or 72 h. After OGD, ASCs were cocultured with neurons on inserts for 24 or 72 h to study the neuroprotective potential of ASCs. The effect of OGD and ASC coculture on the viability, apoptosis, and proliferation of and axonal damage to neuronal cells was studied. The results showed that OGD conditions induced cytotoxicity and apoptosis of SH-SY5Y- and hiPSC-derived neurons, although more severe damage was detected in SH-SY5Y-derived neurons than in hiPSC-derived neurons. Coculture with ASCs was protective for neurons, as the number of dead ASC-cocultured neurons was lower than that of control cells, and coculture increased the proliferation of both cell types. To conclude, we developed in vitro human cell-based stroke models in SH-SY5Y- and hiPSC-derived neurons. This was the first time hiPSCs were used to model stroke in vitro. Since OGD had different effects on the studied cell types, this study highlights the importance of using several cell types in in vitro studies to confirm the outcomes of the study. Here, ASCs exerted a neuroprotective effect by increasing the proliferation and decreasing the death of SH-SY5Y- and hiPSC-derived neurons after OGD.


2020 ◽  
Vol 49 (1) ◽  
pp. 91-96
Author(s):  
Omer Elkiran ◽  
Cumhur Avşar

The chemical composition, antimicrobial and antioxidant properties of the essential oil (EO), obtained from the leaves of Vaccinium myrtillus naturally grown in the northernmost of Turkey were determined by GC and GC-MS and chemical differences were discussed with the help of chemotaxonomy. The leaves of the plant samples were hydro-distilled to produce oil in the yields of 1%. Nineteen components were identified representing 96.4% of the oil. The main compounds in the EO of V. myrtillus were; 1,8-cineole (38.6%), α- pinene (21%), linalool (19.5%), α-terpineol (5.8%). The EO extract was screened for their antimicrobial activities against the 9 bacteria and 3 yeast species by using disc-diffusion and MIC procedure. The EO extract displayed more effective against all the tested bacteria (especially, S. aureus ATCC 6538 and MRSA) and yeast (only C. krusei). The MIC values of sample against tested microorganisms were found to be in the range of 320 to ≥1280 μg/ml. The most effective MIC values were observed against the S. aureus and MRSA (320 μg/ml). In vitro the antioxidant activity based on the 1,1-diphenly-2-picrylhydrazyl (DPPH) free radical was evaluated for the EO extract, and it was found that the extract had good antioxidant activity in the range of the IC50 = 583.4 ±11 μg ml. Antibacterial and antioxidant activities of the EO from the leaves of V. myrtillus has been reported for the first time.


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