Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2 microglial cells by suppressing the NF-kappa B pathway and activating the Nrf2-dependent HO-1 pathway
- Authors
- Kang, Chang-Hee; Choi, Yung Hyun; Moon, Sung-Kwon; Kim, Wun-Jae; Kim, Gi-Young
- Issue Date
- Nov-2013
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Quercetin; Nitric oxide; Nitric oxide synthase; Nuclear factor-kappa B; Heme oxgenase-1; Nuclear factor-2-erythroid 2-related factor 2
- Citation
- INTERNATIONAL IMMUNOPHARMACOLOGY, v.17, no.3, pp 808 - 813
- Pages
- 6
- Journal Title
- INTERNATIONAL IMMUNOPHARMACOLOGY
- Volume
- 17
- Number
- 3
- Start Page
- 808
- End Page
- 813
- URI
- https://scholarworks.bwise.kr/cau/handle/2019.sw.cau/14181
- DOI
- 10.1016/j.intimp.2013.09.009
- ISSN
- 1567-5769
1878-1705
- 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-kappa B (NF-kappa B) activation by inhibiting degradation of the inhibitor of kappa B alpha (I kappa B alpha) in LPS-stimulated BV2 microglial cells corresponding to the inhibitory effect of specific NF-kappa B 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-kappa B activation and inducing Nrf2-mediated HO-1 expression. (C) 2013 Elsevier B.V. All rights reserved.
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