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Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-κB pathway and activating the Nrf2-dependent HO-1 pathway
Abstract
Abnormal nitrosative stress-induced neuroinflammation is implicated in the pathogenesis of neurodegenerative diseases. Therefore, it has been thought that nitric oxide (NO) production is a good therapeutic target. In this sense, quercetin is a good chemopreventive component, because it has free radical-scavenging and anti-inflammatory activities. However, explicit mechanisms are not clear in the lipopolysaccharide (LPS)-stimulated BV2 microglial cell line. Here, we found that quercetin significantly suppressed LPS-induced NO production and inducible NO synthase (iNOS) expression. Notably, quercetin inhibited nuclear factor-κB (NF-κB) activation by inhibiting degradation of the inhibitor of kappa Bα (IκBα) in LPS-stimulated BV2 microglial cells corresponding to the inhibitory effect of specific NF-κB inhibitors, namely proteasome inhibitor I (PSI) and MG132. Quercetin caused significant increases in the levels of heme oxgenase-1 (HO-1) mRNA and protein. Notably, treatment with an HO-1 inducer, cobalt protoporphyrin (CoPP), significantly diminished LPS-stimulated NO production. Additionally, quercetin induced the specific DNA-binding activity of nuclear factor-2-erythroid 2-related factor 2 (Nrf2), and siRNA-mediated knockdown of Nrf2 expression reduced the inhibitory effect of quercetin on LPS-stimulated NO production by inhibiting HO-1 expression, indicating that quercetin regulated NO production by inducing Nrf2-mediated HO-1 expression. Therefore, quercetin has the potential to decrease nitrosative stress by suppressing NF-κB activation and inducing Nrf2-mediated HO-1 expression.
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“Quercetin is also able to reduce iNOS-mediated NO production in lipopolysaccharide (LPS)-treated BV2 microglial cells by suppressing NF-κB activation (Kang et al., 2013)”
From Exploring the Therapeutic Potential of Phytochemicals in Alzheimer’s Disease: Focus on Polyphenols and Monoterpenes (2022) · cites this paper as Kang et al., 2013
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Metadata
- Authors
- Kang, C.-H., Choi, Y. H., Moon, S.-K., Kim, W.-J., & Kim, G.-Y.
- Affiliations
- Jeju National University (KR)
- Dong-Eui University (KR)
- Chung-Ang University (KR)
- Chungbuk National University (KR)
- Corresponding author
- Kim, Gi-Young
- Venue
- International Immunopharmacology
- Publisher
- Elsevier BV
- Published
- 2013-11
- Volume
- 17
- Issue
- 3
- Pages
- 808-813
- ISSN
- 1567-5769 (ISSN-L)
- OpenAlex
- W4247659709
- Cited by
- 138
- References
- 40
- Citations by year
- 2026: 6 · 2025: 12 · 2024: 10 · 2023: 6 · 2022: 8 · 2021: 11 · 2020: 11 · 2019: 8 · 2018: 11 · 2017: 14 · 2016: 18 · 2015: 15 · 2014: 7
- FWCI
- 7.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- International Immunopharmacology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Ministry of Education, Science and Technology (2008-0062611)
- National Research Foundation of Korea
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Pharmacology (medical) › Flavonoids in Medical Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Keywords
- quercetin, nitric oxide production, lipopolysaccharide, BV2 microglial cells, NF-κB signaling, Nrf2, heme oxygenase-1, inducible nitric oxide synthase, IκBα degradation, neuroinflammation, nitrosative stress, cobalt protoporphyrin, neurodegenerative diseases
- MeSH terms
- Animals, Cell Line, Lipopolysaccharides, Membrane Proteins, Nitric Oxide, Quercetin, NF-kappa B, Microglia, Neuroprotective Agents, NF-E2-Related Factor 2, Mice, Heme Oxygenase-1, Nitric Oxide Synthase Type II
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