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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
Author(s)
Jayasooriya, Rajapaksha Gedara Prasad TharangaLee, Kyoung-TaeLee, Hak-JuChoi, Yung HyunJeong, Jin-WooKim, Gi-Young
Issued Date
2014-03
Citation
Food and Chemical Toxicology, v.65, pp.82 - 89
Type
Article
Author Keywords
beta-HydroxyisovalerylshikoninNitric oxideProstaglandin E2Nuclear factor-kappa BHome oxygenase-1Nuclear factor-erythroid 2-related factor 2
Keywords
NF-KAPPA-BNITRIC-OXIDEHEME OXYGENASE-1INFLAMMATIONCELLSMACROPHAGESINHIBITIONEXPRESSIONSYNTHASECANCER
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
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Appears in Collections:
ETC 1. Journal Articles
Center for Core Research Facilities 1. Journal Articles

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