The Aqueous Extract from Ceratonia siliqua Leaves Protects against 6-Hydroxydopamine in Zebrafish: Understanding the Underlying Mechanism

Abidar, Sara; Boiangiu, Răzvan Ştefan; Dumitru, Gabriela; Todirascu-Ciornea, Elena; Amakran, Amina; Cioancă, Oana; Hrițcu, Lucian; Nhiri, Mohamed

doi:10.3390/antiox9040304

Cited by 29 publications

(20 citation statements)

References 103 publications

(137 reference statements)

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“…To the best of our knowledge, this study is the first to assess the neuroprotective effect of MJe in 6-OHDA-stressed SH-SY5Y cells, a widely employed cell line to mimic the cellular PD’s environment [ 28 ]. Among the most recognized PD models, we chose the 6-OHDA, a neurotoxin inducing depletion of dopaminergic neurons in the substantia nigra pars compacta, given the scientific evidence, both in vitro [ 29 ] ad in vivo [ 30 , 31 ], supporting its use.…”

Section: Discussionmentioning

confidence: 99%

A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes

et al. 2021

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Parkinson’s disease (PD) is a degenerative disorder of the nervous system due to unceasing impairment of dopaminergic neurons situated in the substantia nigra. At present, anti-PD drugs acting on dopamine receptors are mainly symptomatic and have only very limited neuroprotective effects, whereas drugs slowing down neurodegeneration of dopaminergic neurons and deterioration of clinical symptoms are not yet available. Given that, the development of more valuable pharmacological strategies is highly demanded. Comprehensive research on innovative neuroprotective drugs has proven that anti-inflammatory and antioxidant molecules from food sources may prevent and/or counteract neurodegenerative diseases, such as PD. The present study was aimed at the evaluation the protective effect of mandarin juice extract (MJe) against 6-hydroxydopamine (6-OHDA)-induced SH-SY5Y human neuroblastoma cell death. Treatment of differentiated SH-SY5Y cells with 6-OHDA brought cell death, and specifically, apoptosis, which was significantly inhibited by the preincubation with MJe through caspase 3 blockage and the modulation of p53, Bax, and Bcl-2 genes. In addition, it showed antioxidant properties in abiotic models as well as in vitro, where it reduced both reactive oxygen and nitrogen species induced by 6-OHDA, along with restored mitochondrial membrane potential, and prevented the oxidative DNA damage evoked by 6-OHDA. Furthermore, MJe restored the impaired balance of SNCA, LRRK2, PINK1, parkin, and DJ-1 gene levels, PD-related factors, caused by 6-OHDA oxidative stress. Overall, these results indicate that MJe exerts neuroprotective effects against 6-OHDA-induced cell death in SH-SY5Y cells by mechanisms involving both the specific interaction with intracellular pathways and its antioxidant capability. Our study suggests a novel possible strategy to prevent and/or ameliorate neurodegenerative diseases, such as PD.

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Section: Discussionmentioning

confidence: 99%

A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes

et al. 2021

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“…In the 62 articles that utilized a 6-OHDA-treated experimental model, multiple different types of cognitive impairment in addition to motor symptoms were induced ( Table 3 ). Except for zebrafish, which were exposed to 6-OHDA by dissolving it into the culture medium, rodent and gray treefrog models received stereotactic injections of 6-OHDA into different anatomic regions ( Endepols et al, 2004 ; Ramos-Moreno et al, 2012 ; Choi et al, 2019 ; Abidar et al, 2020 ) such as the SN, the MFB, the striatum, PFC, VTA, hippocampus, and the third ventricle ( Gasbarri et al, 1996 ; Gu et al, 2012 ; Kadowaki Horita et al, 2013 ; Razavinasab et al, 2013 ; Zhou et al, 2017 ; Bayo-Olugbami et al, 2020 ; Schneider et al, 2021 ). Of these, the target proportions for unilateral stereotactic 6-OHDA injection were more common in the MFB and the SN, whereas the target proportions for bilateral injection were more common in the striatum.…”

Section: Neurotoxin-induced Experimental Models Of Cognitive Impairmentmentioning

confidence: 99%

Experimental Models of Cognitive Impairment for Use in Parkinson’s Disease Research: The Distance Between Reality and Ideal

Fan

Han

Zhao

et al. 2021

Front. Aging Neurosci.

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Parkinson’s disease (PD) is the second most common neurodegenerative disease. Cognitive impairment is one of the key non-motor symptoms of PD, affecting both mortality and quality of life. However, there are few experimental studies on the pathology and treatments of PD with mild cognitive impairment (PD-MCI) and PD dementia (PDD) due to the lack of representative models. To identify new strategies for developing representative models, we systematically summarized previous studies on PD-MCI and PDD and compared differences between existing models and diseases. Our initial search identified 5432 articles, of which 738 were duplicates. A total of 227 articles met our inclusion criteria and were included in the analysis. Models fell into three categories based on model design: neurotoxin-induced, transgenic, and combined. Although the neurotoxin-induced experimental model was the most common type that was used during every time period, transgenic and combined experimental models have gained significant recent attention. Unfortunately, there remains a big gap between ideal and actual experimental models. While each model has its own disadvantages, there have been tremendous advances in the development of PD models of cognitive impairment, and almost every model can verify a hypothesis about PD-MCI or PDD. Finally, our proposed strategies for developing novel models are as follows: a set of plans that integrate symptoms, biochemistry, neuroimaging, and other objective indicators to judge and identify that the novel model plays a key role in new strategies for developing representative models; novel models should simulate different clinical features of PD-MCI or PDD; inducible α-Syn overexpression and SH-SY5Y-A53T cellular models are good candidate models of PD-MCI or PDD.

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“…The pathogenesis of PD is complex, and oxidative stress is an important pathogenic factor [ 3 , 4 ]. Therefore, this study used PC12 cells, which have many similar characteristics to DA neurons, and applied dopamine analogs and the neurotoxin 6-OHDA, which can produce oxidative stress in vitro and in vivo, to simulate DA neuron damage caused by oxidative stress in vitro .…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, actively exploring the pathogenesis and therapeutic drugs of PD has important scientific significance and social value. With the deepening of people’s understanding of PD, an increasing number of studies have shown that abnormal signaling pathways caused by oxidative stress injury play a vital role in the occurrence and development of PD [ 3 , 4 ]. Pathological examination revealed that Akt phosphorylation in the substantia nigra pars compacta (SNc) of PD patients was significantly reduced, and there were a large number of apoptotic dopaminergic (DA) neurons [ 5 ].…”

Section: Introductionmentioning

confidence: 99%

Resveratrol against 6-OHDA-induced damage of PC12 cells via PI3K/Akt

Huang

Zhang

et al. 2021

Translational Neuroscience

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Objective Our previous in vivo study found that resveratrol (Res), which is a phytoalexin, attenuated 6-hydroxydopamine (6-OHDA)-induced motor dysfunction by activating the phosphatidylinositol 3-kinase/protein kinase B (PI3K/Akt) signaling pathway in rats. Therefore, we further explored the protective effect of Res on 6-OHDA-induced damage to PC12 cells in vitro with respect to the PI3K/Akt signaling pathway. Methods We incubated PC12 cells with 75 μM 6-OHDA for 24 h, and Res was then added at a final concentration of 25 μM; the protective effect was examined via MTT and lactate dehydrogenase (LDH) assays. In addition, the PI3K inhibitor LY294002 was used to investigate the potential mechanism. JC-1 staining was used to detect the mitochondrial membrane potential (MMP), and western blotting (WB) was used to detect the phosphorylation of Akt-Ser473. Results Compared with that in the control, the cell viability, total superoxide dismutase (SOD) activity, MMP, and p-Akt-Ser473 level of 6-OHDA-treated PC12 cells were significantly decreased, while the leakage rate of LDH was increased. And after treatment with 25 μM Res, the cell viability, total SOD activity, MMP, and p-Akt-Ser473 level of 6-OHDA-treated PC12 cells were significantly increased compared with those of the control cells, while the leakage rate of LDH was decreased. These effects of Res were antagonized by LY294002. Conclusions Res ameliorates 6-OHDA-induced damage to PC12 cells via activation of the PI3K/Akt signaling pathway.

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The Aqueous Extract from Ceratonia siliqua Leaves Protects against 6-Hydroxydopamine in Zebrafish: Understanding the Underlying Mechanism

Cited by 29 publications

References 103 publications

A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes

A Flavonoid-Rich Extract of Mandarin Juice Counteracts 6-OHDA-Induced Oxidative Stress in SH-SY5Y Cells and Modulates Parkinson-Related Genes

Experimental Models of Cognitive Impairment for Use in Parkinson’s Disease Research: The Distance Between Reality and Ideal

Resveratrol against 6-OHDA-induced damage of PC12 cells via PI3K/Akt

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