scholarly journals Design, Synthesis, and Neuroprotective Effects of a Series of Pyrazolines against 6-Hydroxydopamine-Induced Oxidative Stress

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2151 ◽  
Author(s):  
Ahmet Özdemir ◽  
Belgin Sever ◽  
Mehlika Altıntop ◽  
Elif Kaya Tilki ◽  
Miriş Dikmen
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
Neurodegenerative Disorder ◽  
Pharmacokinetic Parameters ◽  
Therapeutic Drug ◽  
Control Group ◽  
Neuroprotective Effects ◽  
In Silico Studies ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is a chronic, progressive, and age-related neurodegenerative disorder characterized by the loss of midbrain dopaminergic neurons caused by the accumulation of free radicals and oxidative stress. Based on the neuroprotective properties of 2-pyrazoline derivatives, in the current work, 1-(phenyl/4-substituted phenyl)-3-(2-furanyl/thienyl)-5-aryl-2-pyrazolines (3a–i, 4a–i) were synthesized via the cyclization of the chalcones (1, 2) with suitable phenylhydrazine hydrochloride derivatives. All these compounds were investigated for their neuroprotective effects using an in vitro 6-hydroxydopamine (6-OHDA)-induced neurotoxicity model of PD in the rat pheochromocytoma (PC-12) Adh cell line. In addition, some different pharmacokinetic parameters of all compounds were in silico predicted by the QikProp module of Schrödinger’s Maestro molecular modeling package. 4-Methylsulfonylphenyl substituted compounds 3h (20%) and 4h (23%) were determined as the most promising neuroprotective agents related to their inductive roles in cell viability when compared with the 6-OHDA-positive control group (43% and 42%, respectively). Moreover, in silico pharmacokinetic results indicated that all compounds were within the acceptable range intended for human use. According to both in vitro and in silico studies, compounds 3h and 4h draw attention as potential orally bioavailable therapeutic drug candidates against neurodegeneration in PD.

10-gingerol induces oxidative stress through HTR1A in cumulus cells: in-vitro and in-silico studies

2020 ◽  
Vol 0 (0) ◽  
Author(s):  
Kiptiyah Kiptiyah ◽  
Widodo Widodo ◽  
Gatot Ciptadi ◽  
Aulanni’am Aulanni’Am ◽  
Mohammad A. Widodo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Cell Culture ◽  
Superoxide Dismutase ◽  
In Silico ◽  
Cumulus Cell ◽  
Cumulus Cells ◽  
Sod Activity ◽  
In Silico Studies ◽  
Incubation Periods

AbstractBackgroundWe investigated whether 10-gingerol is able to induce oxidative stress in cumulus cells.MethodsFor the in-vitro research, we used a cumulus cell culture in M199, containing 10-gingerol in various concentrations (0, 12, 16, and 20 µM), and detected oxidative stress through superoxide dismutase (SOD) activity and malondialdehyde (MDA) concentrations, with incubation periods of 24, 48, 72, and 96 h. The obtained results were confirmed by in-silico studies.ResultsThe in-vitro data revealed that SOD activity and MDA concentration increased with increasing incubation periods: SOD activity at 0 µM (1.39 ± 0.24i), 12 µM (16.42 ± 0.35ab), 16 µM (17.28 ± 0.55ab), 20 µM (17.81 ± 0.12a), with a contribution of 71.1%. MDA concentration at 0 µM (17.82 ± 1.39 l), 12 µM (72.99 ± 0.31c), 16 µM (79.77 ± 4.19b), 20 µM (85.07 ± 2.57a), with a contribution of 73.1%. Based on this, the in-silico data uncovered that 10˗gingerol induces oxidative stress in cumulus cells by inhibiting HTR1A functions and inactivating GSK3B and AKT˗1.Conclusions10-gingerol induces oxidative stress in cumulus cells through enhancing SOD activity and MDA concentration by inhibiting HTR1A functions and inactivating GSK3B and AKT˗1.

scholarly journals Jaceidin Flavonoid Isolated from Chiliadenus montanus Attenuates Tumor Progression in Mice via VEGF Inhibition: In Vivo and In Silico Studies

Plants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1031 ◽  
Author(s):  
Sameh S. Elhady ◽  
Enas E. Eltamany ◽  
Amera E. Shaaban ◽  
Alaa A. Bagalagel ◽  
Yosra A. Muhammad ◽  
...  
Keyword(s):  
Cell Line ◽  
Cancer Cell ◽  
In Silico ◽  
Cancer Cell Line ◽  
Control Group ◽  
Phytochemical Study ◽  
Aerial Parts ◽  
In Silico Studies

Phytochemical study of Chiliadenus montanus aerial parts afforded six compounds; Intermedeol (1), 5α-hydroperoxy-β-eudesmol (2), 5,7-dihydroxy-3,3’,4’-trimethoxyflavone (3), 5,7,4’-trihydroxy-3,6,3’-trimethoxyflavone (jaceidin) (4), eudesm-11,13-ene-1β,4β,7α-triol (5) and 1β,4β,7β,11-tetrahydroxyeudesmane (6). These compounds were identified based on their NMR spectral data. The isolated compounds were tested for their cytotoxicity against liver cancer cell line (HepG2) and breast cancer cell line (MCF-7). Jaceidin flavonoid (4) exhibited the highest cytotoxic effect in vitro. Therefore, both of jaceidin and C. montanus extract were evaluated for their in vivo anti-tumor activity against Ehrlich’s ascites carcinoma (EAC). Compared to control group, jaceidin and C. montanus extract decreased the tumor weight, improved the histological picture of tumor cells, lowered the levels of VEGF and ameliorate the oxidative stress. Molecular docking and in silico studies suggested that jaceidin was a selective inhibitor of VEGF-mediated angiogenesis with excellent membrane permeability and oral bioavailability.

scholarly journals β-Carotene: A Natural Compound Improves Cognitive Impairment and Oxidative Stress in a Mouse Model of Streptozotocin-Induced Alzheimer’s Disease

Biomolecules ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. 441 ◽  
Author(s):  
Sundas Hira ◽  
Uzma Saleem ◽  
Fareeha Anwar ◽  
Muhammad Farhan Sohail ◽  
Zohaib Raza ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
In Silico ◽  
Control Group ◽  
Enhancement Effect ◽  
Amyloid Β Protein ◽  
Group I ◽  
In Silico Studies ◽  
Β Carotene

Alzheimer’s disease (AD) is a neurodegenerative disease characterized by a cascade of changes in cognitive, behavioral, and social activities. Several areas of the brain are involved in the regulation of memory. Of most importance are the amygdala and hippocampus. Antioxidant therapy is used for the palliative treatment of different degenerative diseases like diabetes, cirrhosis, and Parkinson’s, etc. The objective of this study was to assess the effectiveness of exogenous antioxidants, in particular, β carotene (1.02 and 2.05 mg/kg) against intracerebroventricular injected streptozotocin-induced memory impairment in mice. Streptozotocin (3 mg/kg, i.c.v) was administered in two separate doses (on 1st and 3rd days of treatment) for neurodegeneration. Fifty Albino mice (male) were selected in the protocol, and they were classified into five groups (Group I—control, Group II—disease, Group III—standard, Group IV–V—β-carotene-treated) to investigate the cognitive enhancement effect of selected antioxidants. The cognitive performance was observed following the elevated plus-maze, passive avoidance, and open field paradigms. Acetylcholine esterase, β-amyloid protein, and biochemical markers of oxidative stress such as glutathione peroxidase, superoxide dismutase, and catalase were analyzed in brain homogenates. In silico activity against acetylcholinesterase (AChE) was determined by the molecular modeling of β-carotene. β-carotene at a dose of 2.05 mg/kg was found to attenuate the deleterious effects of streptozotocin-induced behavioral and biochemical impairments, including the inhibition of acetylcholinesterase activity. The in silico studies confirmed the binding capacity of β-carotene with the acetylcholinesterase enzyme. The administration of β-carotene attenuated streptozotocin-induced cognitive deficit via its anti-oxidative effects, inhibition of acetylcholinesterase, and the reduction of amyloid β-protein fragments. These results suggest that β-carotene could be useful for the treatment of neurodegenerative diseases such as Alzheimer’s disease.

scholarly journals Hesperetin protects SH-SY5Y cells against 6- hydroxydopamine-induced neurotoxicity via activation of NRF2/ARE signaling pathways

2020 ◽  
Vol 19 (6) ◽  
pp. 1197-1201 ◽  
Author(s):  
Jing Li ◽  
Yue Liu ◽  
Li Wang ◽  
Zhaowei Gu ◽  
Zhigang Huan ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cell Viability ◽  
Heme Oxygenase 1 ◽  
Protective Effects ◽  
Neuroprotective Effects ◽  
Ldh Release ◽  
6 Hydroxydopamine

Purpose: To investigation the protective effects of hesperetin against 6-hydroxydopamine (6-OHDA)- induced neurotoxicity. Methods: SH-SY5Y cells were incubated with 6-OHDA to create an in vitro model of neurotoxicity. This model was used to test the neuroprotective effects of hesperetin. Cell viability was assessed by MTT and lactate dehydrogenase (LDH) release assays. Flow cytometry and western blot were used to quantify apoptosis. Oxidative stress was evaluated by determining intracellular glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), and reactive oxygen species (ROS). Results: In SH-SY5Y cells, treatment with 6-OHDA decreased cell viability and promoted LDH release. However, exogenous hesperetin protected against 6-OHDA-mediated toxicity. Similarly, although incubation with 6-OHDA induced apoptosis and increased cleaved caspase-3 and -9 levels, treatment with hesperetin protected against these effects. Treatment with 6-OHDA also led to significant oxidative stress, as indicated by reduced GSH and SOD levels and increased MDA and ROS levels in SH-SY5Y cells. However, these changes were reversed by pre-treatment with hesperetin. Of interest, hesperetin led to changes in 6-OHDA-induced expression of NRF2, heme oxygenase-1 (HO-1), glutamate-cysteine ligase (GCL) catalytic subunit (GCLC), and GCL modulatory (GCLM). Conclusion: Hesperetin protects against cell toxicity, apoptosis, and oxidative stress via activation of NRF2 pathway in a 6-OHDA-induced model of neurotoxicity. Future studies should investigate the use of hesperetin as a potential therapeutic approach for prevention or management of Parkinson’s disease. Keywords: Hesperetin, 6-OHDA, Neurotoxicity, NRF2, Parkinson’s disease

scholarly journals Quercetin and Coumarin Inhibit Dipeptidyl Peptidase-IV and Exhibits Antioxidant Properties: In Silico, In Vitro, Ex Vivo

Biomolecules ◽  
2020 ◽  
Vol 10 (2) ◽  
pp. 207 ◽  
Author(s):  
Anand-Krishna Singh ◽  
Pankaj Kumar Patel ◽  
Komal Choudhary ◽  
Jaya Joshi ◽  
Dhananjay Yadav ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
Ex Vivo ◽  
Antioxidant Properties ◽  
Dipeptidyl Peptidase ◽  
Dipeptidyl Peptidase Iv ◽  
Food Ingredients ◽  
Dpp Iv ◽  
In Silico Studies

Quercetin and coumarin, two naturally occurring phytochemicals of plant origin, are known to regulate hyperglycemia and oxidative stress. The present study was designed to evaluate the inhibitory activity of quercetin and coumarin on dipeptidyl peptidase-IV (DPP-IV) and their antioxidant potential. DPP-IV inhibition assays were performed, and evaluated IC50 values of diprotin A, quercetin, coumarin, and sitagliptin were found to be 0.653, 4.02, 54.83, and 5.49 nmol/mL, respectively. Furthermore, in silico studies such as the drug-likeliness and docking efficiency of quercetin and coumarin to the DPP-IV protein were performed; the ex vivo antiperoxidative potential of quercetin and coumarin were also evaluated. The results of the present study showed that the DPP-IV inhibitory potential of quercetin was slightly higher than that of sitagliptin. Virtual docking revealed the tight binding of quercetin with DPP-IV protein. Quercetin and coumarin reduced oxidative stress in vitro and ex vivo systems. We report for the first time that both compounds inhibited the DPP-IV along with antioxidant activity and thus may be use as function food ingredients in the prevention of diabetes.

scholarly journals Tetramethylpyrazine Analogue T-006 Exerts Neuroprotective Effects against 6-Hydroxydopamine-Induced Parkinson’s Disease In Vitro and In Vivo

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Hefeng Zhou ◽  
Min Shao ◽  
Xuanjun Yang ◽  
Chuwen Li ◽  
Guozhen Cui ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Motor Coordination ◽  
Neurodegenerative Disorder ◽  
Nerve Fibers ◽  
Substantia Nigra Pars Compacta ◽  
Neuroprotective Effects ◽  
6 Hydroxydopamine

Parkinson’s disease (PD) is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc), and there is no cure for it at present. We have previously reported that the tetramethylpyrazine (TMP) derivative T-006 exhibited beneficial effects in Alzheimer’s disease (AD) models. However, its effect on PD remains unclear. In the present study, we investigated the neuroprotective effects and underlying mechanisms of T-006 against 6-hydroxydopamine- (6-OHDA-) induced lesions in in vivo and in vitro PD models. Our results demonstrated that T-006 alleviated mitochondrial membrane potential loss and restored the energy metabolism and mitochondrial biogenesis that were induced by 6-OHDA in PC12 cells. In addition, animal experiments showed that administration of T-006 significantly attenuated the 6-OHDA-induced loss of tyrosine hydroxylase- (TH-) positive neurons in the SNpc, as well as dopaminergic nerve fibers in the striatum, and also increased the concentration of dopamine and its metabolites (DOPAC, HVA) in the striatum. Functional deficits were restored following T-006 treatment in 6-OHDA-lesioned mice, as demonstrated by improved motor coordination and rotational behavior. In addition, we found that the neuroprotective effects of T-006 were mediated, at least in part, by the activation of both the PKA/Akt/GSK-3β and CREB/PGC-1α/NRF-1/TFAM pathways. In summary, our findings demonstrate that T-006 could be developed as a novel neuroprotective agent for PD, and the two pathways might be promising therapeutic targets for PD.

scholarly journals Neuroprotective Activity of Mentha Species on Hydrogen Peroxide-Induced Apoptosis in SH-SY5Y Cells

2020 ◽  
Author(s):  
Doaa M. Hanafy ◽  
Paul D. Prenzler ◽  
Geoffrey E. Burrows ◽  
Saliya Gurusinghe ◽  
Bashar Thejer ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorder ◽  
Cell Model ◽  
Neuronal Cell ◽  
Neuroprotective Activity ◽  
Caspase Activity ◽  
Neuroprotective Effects ◽  
Jnk Pathway ◽  
Apoptotic Protein

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that develops as a consequence of different factors such as oxidative stress and accumulation of the protein amyloid β (Aβ) in the brain, resulting in apoptosis of neuronal cells. The search for a treatment for this disorder is essential as current medications are limited to alleviating symptoms and palliative effects. The aim of this study is to investigate the effects of mint extracts on selected mechanisms implicated in the development of AD. To enable a thorough investigation of mechanisms, including effects on -secretase (the enzyme the leads to the formation of A), on Aβ aggregation, and on oxidative stress and apoptosis pathways, a neuronal cell model, SH-SY5Y cells was selected. Six Mentha taxa were investigated for their in vitro β-secretase (BACE) and Aβ-aggregation inhibition activities. Also, their neuroprotective effects on H2O2-induced oxidative stress and apoptosis in SH-SY5Y cells were evaluated through caspase activity. Real-time PCR and Western blot analysis were carried out for the two most promising extracts to determine their effects on signalling pathways in SH-SY5Y cells. All mint extracts had strong BACE inhibition activity. M. requienii extracts showed excellent inhibition of Aβ-aggregation, while other extracts showed moderate inhibition. M. diemenica and M. requienii extracts lowered caspase activity. Exposure of SH-SY5Y cells to M. diemenica extracts resulted in a decrease in the expression of pro-apoptotic protein, Bax, and an elevation in the anti-apoptotic protein, Bcl-xL, potentially mediated by down-regulation of ASK1-JNK pathway. These results indicate that mint extracts could prevent the formation of Aβ and also could prevent their aggregation if they had already formed. M. diemenica and M. requienii extracts have potential to suppress apoptosis at the cellular level. Hence, mint extracts could provide a source of efficacious compounds for a therapeutic approach for AD.

Neuroprotective effects of prenylated flavanones isolated from Dalea species, in vitro and in silico studies

2020 ◽  
Vol 206 ◽  
pp. 112718
Author(s):  
María D. Santi ◽  
Florencia Arredondo ◽  
Diego Carvalho ◽  
Carolina Echeverry ◽  
Giselle Prunell ◽  
...  
Keyword(s):  
In Silico ◽  
Neuroprotective Effects ◽  
In Silico Studies

Antioxidative and anti-proliferative potential of Curculigo orchioides Gaertn in oxidative stress induced cytotoxicity: In vitro, ex vivo and in silico studies

2018 ◽  
Vol 115 ◽  
pp. 244-259 ◽  
Author(s):  
Iram Iqbal Hejazi ◽  
Rashmin Khanam ◽  
Syed Hassan Mehdi ◽  
Abdul Roouf Bhat ◽  
M.Moshahid Alam Rizvi ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
In Silico ◽  
Ex Vivo ◽  
Proliferative Potential ◽  
Curculigo Orchioides ◽  
In Silico Studies

scholarly journals Neuroprotective effects of taurine on SH-SY5Y cells under hydrocortisone induced stress

2021 ◽  
Vol 10 (9) ◽  
pp. e55510918426
Author(s):  
Rafaella Carvalho Rossato ◽  
Alessandro Eustaquio Campos Granato ◽  
Carlos Dailton Guedes de Oliveira Moraes ◽  
Geisa Nogueira Salles ◽  
Cristina Pacheco Soares
Keyword(s):  
Oxidative Stress ◽  
Neurodegenerative Disorder ◽  
Memory Loss ◽  
Study Strategies ◽  
Neuroprotective Effects ◽  
Human Neuroblastoma ◽  
Induced Stress ◽  
Behavioral Abnormalities ◽  
First Time

Alzheimer's disease (AD) is the most common, progressive and irreversible neurodegenerative disorder, characterized by memory loss, cognitive impairment and behavioral abnormalities. Although there is no cure, several study strategies seek to elucidate mechanisms of the disease. Recent studies address the benefits of taurine. Thus, the present study aims to analyze neuroprotective effects of taurine in human neuroblastoma (SH-SY5Y), using an in vitro experimental model of oxidative stress induced by hydrocortisone. This work showed for the first time that taurine can promote neuroprotection in SH-SY5Y under oxidative stress caused by hydrocortisone. Cell viability was evaluated using crystal violet and the evaluation of cell morphology was performed by scanning electron microscopy (SEM). The viability of SH-SY5Y pre-treated with taurine and stressed with hydrocortisone was preserved, compared to the stressed only group, which was also morphologically observed. Therefore, taurine can represent a considerable therapeutic candidate in the prevention of neurodegenerative diseases, such as AD.

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