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Anti-inflammatory effects of beta-hydroxyisovalerylshikonin in BV2 microglia are mediated through suppression of the PI3K/Akt/NF-kB pathway and activation of the Nrf2/HO-1 pathway

Title
Anti-inflammatory effects of beta-hydroxyisovalerylshikonin in BV2 microglia are mediated through suppression of the PI3K/Akt/NF-kB pathway and activation of the Nrf2/HO-1 pathway
Authors
Jayasooriya, RGPT[Jayasooriya, Rajapaksha Gedara Prasad Tharanga]Lee, KT[Lee, Kyoung-Tae]Lee, HJ[Lee, Hak-Ju]Choi, YH[Choi, Yung Hyun]Jeong, JW[Jeong, Jin-Woo]Kim, GY[Kim, Gi-Young]
DGIST Authors
Jeong, JW[Jeong, Jin-Woo]
Issue Date
2014-03
Citation
Food and Chemical Toxicology, 65, 82-89
Type
Article
Article Type
Article
Keywords
(3 Hydroxyisovaleryl)ShikoninAnimalsAnti-Inflammatory ActivityAnti-Inflammatory AgentBeta-HydroxyisovalerylshikoninBeta HydroxyisovalerylshikoninCell LineConcentration ResponseControlled StudyCOX 2 GeneCyclooxygenase 2DinoprostoneDNADNA-BindingDown-RegulationDrug MechanismDrug ResearchDrug StructureEnzyme InductionGene Expression RegulationHeme Oxygenase-1I Kappa B AlphaImmunoglobulin Enhancer Binding ProteinInducible Nitric Oxide SynthaseInos GeneLipopolysaccharideLipopolysaccharidesMagnetic Resonance SpectroscopyMiceMicrogliaMolecular StructureNaphthoquinonesNerve Cell CultureNF-E2-Related Factor 2NF-Kappa BNitric OxideNuclear Factor-Erythroid 2-Related Factor 2nuclear factor-Kappa BPhosphatidylinositol 3-KinasesPhosphatidylinositol 3 KinasePhosphorylationProstaglandin E2Prostaglandin Synthesis InhibitionProtein DegradationProtein DNA BindingProtein ExpressionProtein Kinase BProtein PhosphorylationProtein SecretionProto-Oncogene Proteins C-AKTPyrrolidinesShikonin DerivativeThiocarbamatesTranscription Factor Nrf2Unclassified DrugUpregulation
ISSN
0278-6915
Abstract
In the present study, we investigated whether β-hydroxyisovalerylshikonin (β-HIVS) affects the production of proinflammatory mediators such as nitric oxide (NO) and prostaglandin E2 (PGE2) in BV2 microglial cells. Our data showed that β-HIVS inhibited secretion of NO and PGE2 and downregulated expression of their main regulatory genes, inducible NO synthesis (iNOS) and cyclooxygenase-2 (COX-2). β-HIVS also reduced the LPS-induced DNA-binding activity of nuclear factor-κB (NF-κB) by suppressing nuclear translocation of the NF-κB subunits and inhibiting the degradation and phosphorylation of IκBα. Furthermore, an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), attenuated LPS-stimulated iNOS and COX-2 expression, suggesting that NF-κB inhibition is a main effector in the expression of iNOS and COX-2. We also found that LPS-induced NF-κB activation is regulated through inhibition of PI3K/Akt phosphorylation in response to β-HIVS. Additionally, β-HIVS caused the induction of heme oxygenase-1 (HO-1) via upregulation of nuclear factor-erythroid 2-related factor 2 (Nrf2), both of which are involved in the secretion of proinflammatory mediators such as NO and PGE2. Taken together, our data indicate that β-HIVS diminishes the proinflammatory mediators NO and PGE2 and the expression of their regulatory genes, iNOS and COX-2, in LPS-stimulated BV2 microglial cells by inhibiting PI3K/Akt-dependent NF-κB activation and inducing Nrf2-mediated HO-1 expression. © 2013 Elsevier Ltd.
URI
http://hdl.handle.net/20.500.11750/2666
DOI
10.1016/j.fct.2013.12.011
Publisher
PERGAMON-ELSEVIER SCIENCE LTD
Files:
There are no files associated with this item.
Collection:
Center for Core Research Facilities1. Journal Articles


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