The DOI matches its Crossref record; 70 of the 70 references it cites were found in a registry or an index.
After cellular internalization, quercetin causes Nrf2 nuclear translocation, increases glutathione levels, and prevents neuronal death against an oxidative insult
Abstract
In this work we describe the protective effects of quercetin against H(2)O(2) in 24-h-pretreated neuronal cultures. We explored quercetin availability and subcellular fate through the use of HPLC-Diode Array Detection (DAD), epifluorescence, and confocal microscopy. We focused on quercetin modulation of thiol-redox systems by evaluating changes in mitochondrial thioredoxin Trx2, the levels of total glutathione (GSH), and the expression of the gamma-glutamate-cysteine ligase catalytic subunit (GCLC), the rate-limiting enzyme of GSH synthesis, by the use of Western blot, HPLC, and real-time PCR techniques, respectively. We further explored the activation of the protective NF-E2-related factor 2 (Nrf2)-dependent signaling pathway by quercetin using immunocytochemistry techniques. Our results showed rapid quercetin internalization into neurons, reaching the nucleus after its addition to the culture. Quercetin pretreatment increased total GSH levels, but did not increase Trx2. Interestingly it caused Nrf2 nuclear translocation and significantly increased GCLC gene expression. At the moment of H(2)O(2) addition, intracellular quercetin or related metabolites were undetectable in the cultures although quercetin pretreatment prevented neuronal death from the oxidant exposure. Our findings suggest alternative mechanisms of quercetin neuroprotection beyond its long-established ROS scavenging properties, involving Nrf2-dependent modulation of the GSH redox system.
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“to positively modulate Nrf2 signaling (Arredondo et al., 2010; Molaei et al., 2020; Yu et al., 2020)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Arredondo et al., 2010
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Neuropharmacological Effects of Quercetin: A Literature-Based Review
Islam, M. S., Quispe, C., Hossain, R., Islam, M. T., Al-Harrasi, A., Al-Rawahi, A., Martorell, M., Mamurova, A., Seilkhan, A., Altybaeva, N., et al. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.665031 · Cited by 165
Hesperidin-Mediated Expression of Nrf2 and Upregulation of Antioxidant Status in Senescent Rat Heart
Elavarasan, J., Velusamy, P., Ganesan, T., Ramakrishnan, S. K., Rajasekaran, D., & Periandavan, K. (2012) · Journal of Pharmacy and Pharmacology · doi:10.1111/j.2042-7158.2012.01512.x · Cited by 121
Henríquez, G., Gomez, A., Guerrero, E., & Narayan, M. (2020) · ACS Chemical Neuroscience · doi:10.1021/acschemneuro.0c00381 · Cited by 83
Piccialli, I., Tedeschi, V., Caputo, L., D’Errico, S., Ciccone, R., De Feo, V., Secondo, A., & Pannaccione, A. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.876614 · Cited by 73
Metadata
- Authors
- Arredondo, F., Echeverry, C., Abin-Carriquiry, J. A., Blasina, F., Antúnez, K., Jones, D. P., Go, Y.-M., Liang, Y.-L., & Dajas, F.
- Affiliations
- Instituto de Investigaciones Biológicas Clemente Estable (UY)
- Emory University (US)
- Corresponding author
- Arredondo, Florencia
- ORCID
- Venue
- Free Radical Biology and Medicine
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 49
- Issue
- 5
- Pages
- 738-747
- ISSN
- 0891-5849 (ISSN-L)
- OpenAlex
- W2040266289
- Cited by
- 220
- References
- 70
- Citations by year
- 2026: 9 · 2025: 8 · 2024: 16 · 2023: 14 · 2022: 15 · 2021: 18 · 2020: 20 · 2019: 12 · 2018: 16 · 2017: 13 · 2016: 13 · 2015: 12 · 2014: 13 · 2013: 17 · 2012: 15
- FWCI
- 5.34
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Free Radical Biology and Medicine (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Biochemistry (medical) › Phytochemicals and Antioxidant Activities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- quercetin, Nrf2 nuclear translocation, glutathione, GCLC, hydrogen peroxide, oxidative stress, neuronal cell death, neuroprotection, flavonoid metabolites
- MeSH terms
- Animals, Antioxidants, Cell Nucleus, Drug Evaluation, Preclinical, Glutathione, Hydrogen Peroxide, Neurons, Quercetin, Up-Regulation, Cell Death, Rats, Sprague-Dawley, Oxidative Stress, Neuroprotective Agents, Cytoprotection, Protein Transport, Active Transport, Cell Nucleus, NF-E2-Related Factor 2, Rats
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