Pinocembrin-7-Methylether Protects SH-SY5Y Cells Against 6-Hydroxydopamine-Induced Neurotoxicity via Modulating Nrf2 Induction Through AKT and ERK Pathways

Zou, Zhi-Cong; Fu, Jijun; Dang, Yanan; Zhang, Qian; Wang, Xiufen; Chen, Hanbin; Jia, Xuejing; Lee, Simon Ming‐Yuen; Li, Chuwen

doi:10.1007/s12640-021-00376-4

Cited by 18 publications

(9 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Evidence of OS existing in PD is further supported by PD animals modeled with toxins that can cause OS, which includes 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) ( Dong et al, 2021 ), rotenone ( Sharma et al, 2021 ), paraquat ( Ahmad et al, 2021 ), and 6-hydroxydopamine (6-OHDA) ( Zou et al, 2021 ). Moreover, in vivo observations revealed that several markers of OS are altered in the cerebrospinal fluid and blood samples of PD patients ( Vinish et al, 2011 ).…”

Section: The Role Of Oxidative Stress In Parkinson’s Diseasementioning

confidence: 99%

Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease

et al. 2021

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a complex neurodegenerative disorder featuring both motor and nonmotor symptoms associated with a progressive loss of dopaminergic neurons in the substantia nigra pars compacta. Oxidative stress (OS) has been implicated in the pathogenesis of PD. Genetic and environmental factors can produce OS, which has been implicated as a core contributor to the initiation and progression of PD through the degeneration of dopaminergic neurons. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) orchestrates activation of multiple protective genes, including heme oxygenase-1 (HO-1), which protects cells from OS. Nrf2 has also been shown to exert anti-inflammatory effects and modulate both mitochondrial function and biogenesis. Recently, a series of studies have reported that different bioactive compounds were shown to be able to activate Nrf2/antioxidant response element (ARE) and can ameliorate PD-associated neurotoxin, both in animal models and in tissue culture. In this review, we briefly overview the sources of OS and the association between OS and the pathogenesis of PD. Then, we provided a concise overview of Nrf2/ARE pathway and delineated the role played by activation of Nrf2/HO-1 in PD. At last, we expand our discussion to the neuroprotective effects of pharmacological modulation of Nrf2/HO-1 by bioactive compounds and the potential application of Nrf2 activators for the treatment of PD. This review suggests that pharmacological modulation of Nrf2/HO-1 signaling pathway by bioactive compounds is a therapeutic target of PD.

show abstract

Section: The Role Of Oxidative Stress In Parkinson’s Diseasementioning

confidence: 99%

Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Studies have indicated that 6-OHDA-induced apoptosis of SH-SY5Y cells is related to the activation of JNK and p38 signaling molecular [ 17 ], however, the up-regulation of ERK and Akt pathways can prevent this effect [ 33 ]. SH-SY5Y cells were pretreated with or without 1-μM NCS for 24 h, and then exposed to 6-OHDA for 3, 6, or 9 h, respectively.…”

Section: Resultsmentioning

confidence: 99%

Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway

Tsai

Liu

et al. 2022

Antioxidants

View full text Add to dashboard Cite

We assessed the antioxidant potential of narcissoside from Sambucus nigra flowers (elderflowers) in Parkinson’s disease models in vitro and in vivo. The results showed that narcissoside lessened the 6-hydroxydopamine (6-OHDA)-induced increase in reactive oxygen species (ROS) and apoptosis in SH-SY5Y cells. In the 6-OHDA-exposed Caenorhabditis elegans model, narcissoside reduced degeneration of dopaminergic neurons and ROS generation, and also improved dopamine-related food-sensitive behavior and shortened lifespan. Moreover, NCS increased total glutathione (GSH) by increasing the expression of the catalytic subunit and modifier subunit of γ-glutamylcysteine ligase in cells and nematodes. Treatment with a GSH inhibitor partially abolished the anti-apoptotic ability of narcissoside. Furthermore, narcissoside diminished the 6-OHDA-induced phosphorylation of JNK and p38, while rising activities of ERK and Akt in resisting apoptosis. The antioxidant response element (ARE)-luciferase reporter activity analysis and electromobility gel shift assay showed that narcissoside promotes the transcriptional activity mediated by Nrf2. Finally, we found that narcissoside augmented the expression of miR200a, a translational inhibitor of the Nrf2 repressor protein Keap1. Downregulation of Nrf2 and miR200a by RNAi and anti-miR200a, respectively, reversed the neuroprotective ability of narcissoside. In summary, narcissoside can enhance the miR200a/Nrf2/GSH antioxidant pathway, alleviate 6-OHDA-induced apoptosis, and has the neuroprotective potential.

show abstract

“…Nrf2 silencing (siRNA) abolished PME-mediated protection, highlighting its role in modulating the Nrf2/HO-1 pathway. Mechanistically, PME-induced positive regulation of Nrf2 was found to occur in part through phosphorylation of Akt and ERK [ 51 ]. To recreate a model of AD, Aβ 1-42 was injected into the brains of mice.…”

Section: Phenolic Compoundsmentioning

confidence: 99%

Natural Products as Modulators of Nrf2 Signaling Pathway in Neuroprotection

Moratilla-Rivera

Sánchez

Valdés-González

et al. 2023

IJMS

View full text Add to dashboard Cite

Neurodegenerative diseases (NDs) affect the West due to the increase in life expectancy. Nervous cells accumulate oxidative damage, which is one of the factors that triggers and accelerates neurodegeneration. However, cells have mechanisms that scavenge reactive oxygen species (ROS) and alleviate oxidative stress (OS). Many of these endogenous antioxidant systems are regulated at the gene expression level by the transcription factor Nrf2 (nuclear factor erythroid 2-related factor 2). In the presence of prooxidant conditions, Nrf2 translocates to the nucleus and induces the transcription of genes containing ARE (antioxidant response element). In recent years, there has been an increase in the study of the Nrf2 pathway and the natural products that positively regulate it to reduce oxidative damage to the nervous system, both in in vitro models with neurons and microglia subjected to stress factors and in vivo models using mainly murine models. Quercetin, curcumin, anthocyanins, tea polyphenols, and other less studied phenolic compounds such as kaempferol, hesperetin, and icariin can also modulate Nrf2 by regulating several Nrf2 upstream activators. Another group of phytochemical compounds that upregulate this pathway are terpenoids, including monoterpenes (aucubin, catapol), diterpenes (ginkgolides), triterpenes (ginsenosides), and carotenoids (astaxanthin, lycopene). This review aims to update the knowledge on the influence of secondary metabolites of health interest on the activation of the Nrf2 pathway and their potential as treatments for NDs.

show abstract

Pinocembrin-7-Methylether Protects SH-SY5Y Cells Against 6-Hydroxydopamine-Induced Neurotoxicity via Modulating Nrf2 Induction Through AKT and ERK Pathways

Cited by 18 publications

References 43 publications

Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease

Pharmacological Modulation of Nrf2/HO-1 Signaling Pathway as a Therapeutic Target of Parkinson’s Disease

Neuroprotective Capability of Narcissoside in 6-OHDA-Exposed Parkinson’s Disease Models through Enhancing the MiR200a/Nrf-2/GSH Axis and Mediating MAPK/Akt Associated Signaling Pathway

Natural Products as Modulators of Nrf2 Signaling Pathway in Neuroprotection

Contact Info

Product

Resources

About