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BMC Complementary Medicine and Therapies

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Open Access 01-12-2020 | Research article

Cyanidin-3-glucoside activates Nrf2-antioxidant response element and protects against glutamate-induced oxidative and endoplasmic reticulum stress in HT22 hippocampal neuronal cells

Authors: Monruedee Sukprasansap, Pithi Chanvorachote, Tewin Tencomnao

Published in: BMC Complementary Medicine and Therapies | Issue 1/2020

Abstract

Background

Cyanidin-3-glucoside (C3G), a major anthocyanin present in berries, exhibits a strong antioxidant and has been shown to possess a neuroprotection. Prolonged exposure to glutamate will lead to oxidative damage and endoplasmic reticulum stress which could play a key detrimental role in the development of neurodegenerative disorders (NDs). In the present study, we investigated the neuroprotective effect and underlying mechanisms of C3G on the reduction of oxidative/ER stress-induced apoptosis by glutamate in HT22 mouse hippocampal neuronal cells.

Method

Cells were pre-treated with C3G in various concentrations, followed by glutamate. Cell viability and toxicity were examined using MTT and LDH assays. The apoptotic and necrotic cell death were carried out by Annexin V-FITC/propidium iodide co-staining assays. Generation of intracellular reactive oxygen species (ROS) in cells was measured by flow cytometry using DCFH-DA probe. Expression of antioxidant genes was evaluated by Real-time polymerase chain reaction analysis. The possible signaling pathways and proteins involved were subsequently demonstrated by Western blot analysis.

Result

The pretreatment of the HT22 cells with C3G protected cell death from oxidative toxicity induced by glutamate. We demonstrated that treatment cells with glutamate caused several radical forms of ROS formation, and they were abolished by specific ROS inhibitors. Interestingly, C3G directly scavenged radical activity and inhibited intracellular ROS generation in our cell-based system. In addition, C3G pretreatment suppressed the up-regulation of specific ER proteins namely calpain, caspase-12 and C/EBP homologous proteins (CHOP) induced by glutamate-mediated oxidative and ER stress signal by up-regulating the expressions of survival proteins, including extracellular regulated protein kinase (ERK) and nuclear factor E2-related factor 2 (Nrf2). Furthermore, dramatically activated gene expression of endogenous antioxidant enzymes (i.e. superoxide dismutases (SODs), catalase (CAT) and glutathione peroxidase (GPx)), and phase II enzymes (glutathione-S-transferases (GSTs)) was found in C3G-treated with cells.

Conclusions

Our finding suggest that C3G could be a promising neuroprotectant via inhibition of glutamate-induced oxidative and ER stress signal and activation of ERK/Nrf2 antioxidant mechanism pathways.

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Title: Cyanidin-3-glucoside activates Nrf2-antioxidant response element and protects against glutamate-induced oxidative and endoplasmic reticulum stress in HT22 hippocampal neuronal cells
Authors: Monruedee Sukprasansap
Pithi Chanvorachote
Tewin Tencomnao
Publication date: 01-12-2020
Publisher: BioMed Central
Published in: BMC Complementary Medicine and Therapies / Issue 1/2020
Electronic ISSN: 2662-7671
DOI: https://doi.org/10.1186/s12906-020-2819-7

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cyanidin-3-glucoside activates Nrf2-antioxidant response element and protects against glutamate-induced oxidative and endoplasmic reticulum stress in HT22 hippocampal neuronal cells

Abstract

Background

Method

Result

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Method

Result

Conclusions

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