PMID- 24076371
OWN - NLM
STAT- MEDLINE
DCOM- 20140924
LR  - 20161125
IS  - 1878-1705 (Electronic)
IS  - 1567-5769 (Linking)
VI  - 17
IP  - 3
DP  - 2013 Nov
TI  - Quercetin inhibits lipopolysaccharide-induced nitric oxide production in BV2 
      microglial cells by suppressing the NF-kappaB pathway and activating the 
      Nrf2-dependent HO-1 pathway.
PG  - 808-13
LID - S1567-5769(13)00354-8 [pii]
LID - 10.1016/j.intimp.2013.09.009 [doi]
AB  - 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-kappaB (NF-kappaB) activation by inhibiting degradation of the 
      inhibitor of kappa Balpha (IkappaBalpha) in LPS-stimulated BV2 microglial cells corresponding 
      to the inhibitory effect of specific NF-kappaB 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-kappaB activation and inducing Nrf2-mediated HO-1 expression.
CI  - (c) 2013.
FAU - Kang, Chang-Hee
AU  - Kang CH
AD  - Laboratory of Immunobiology, Department of Marine Life Sciences, Jeju National 
      University, Jeju 690-756, Republic of Korea.
FAU - Choi, Yung Hyun
AU  - Choi YH
FAU - Moon, Sung-Kwon
AU  - Moon SK
FAU - Kim, Wun-Jae
AU  - Kim WJ
FAU - Kim, Gi-Young
AU  - Kim GY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130925
PL  - Netherlands
TA  - Int Immunopharmacol
JT  - International immunopharmacology
JID - 100965259
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Membrane Proteins)
RN  - 0 (NF-E2-Related Factor 2)
RN  - 0 (NF-kappa B)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nfe2l2 protein, mouse)
RN  - 31C4KY9ESH (Nitric Oxide)
RN  - 9IKM0I5T1E (Quercetin)
RN  - EC 1.14.13.39 (Nitric Oxide Synthase Type II)
RN  - EC 1.14.13.39 (Nos2 protein, mouse)
RN  - EC 1.14.14.18 (Heme Oxygenase-1)
RN  - EC 1.14.14.18 (Hmox1 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Heme Oxygenase-1/*metabolism
MH  - Lipopolysaccharides
MH  - Membrane Proteins/*metabolism
MH  - Mice
MH  - Microglia/drug effects/metabolism
MH  - NF-E2-Related Factor 2/*metabolism
MH  - NF-kappa B/*antagonists & inhibitors
MH  - Neuroprotective Agents/*pharmacology
MH  - Nitric Oxide/*antagonists & inhibitors
MH  - Nitric Oxide Synthase Type II/antagonists & inhibitors
MH  - Quercetin/*pharmacology
OTO - NOTNLM
OT  - Heme oxgenase-1
OT  - Nitric oxide
OT  - Nitric oxide synthase
OT  - Nuclear factor-2-erythroid 2-related factor 2
OT  - Nuclear factor-kappaB
OT  - Quercetin
EDAT- 2013/10/01 06:00
MHDA- 2014/09/25 06:00
CRDT- 2013/10/01 06:00
PHST- 2013/09/06 00:00 [received]
PHST- 2013/09/13 00:00 [revised]
PHST- 2013/09/13 00:00 [accepted]
PHST- 2013/10/01 06:00 [entrez]
PHST- 2013/10/01 06:00 [pubmed]
PHST- 2014/09/25 06:00 [medline]
AID - S1567-5769(13)00354-8 [pii]
AID - 10.1016/j.intimp.2013.09.009 [doi]
PST - ppublish
SO  - Int Immunopharmacol. 2013 Nov;17(3):808-13. doi: 10.1016/j.intimp.2013.09.009. 
      Epub 2013 Sep 25.