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Br J Pharmacol. 2011 Sep;164(1):145-58. doi: 10.1111/j.1476-5381.2011.01351.x.

Arvelexin from Brassica rapa suppresses NF-κB-regulated pro-inflammatory gene expression by inhibiting activation of IκB kinase.

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1
Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Korea.

Abstract

BACKGROUND AND PURPOSE:

Brassica rapa species constitute one of the major sources of food. In the present study, we investigated the anti-inflammatory effects and the underlying molecular mechanism of arvelexin, isolated from B. rapa, on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and on a model of septic shock induced by LPS.

EXPERIMENTAL APPROACH:

The expression of Inducible nitric oxide synthase (iNOS) and COX-2, TNF-α, IL-6 and IL-1β were determined by Western blot and/or RT-PCR respectively. To elucidate the underlying mechanism(s), activation of NF-κB activation and its pathways were investigated by electrophoretic mobility shift assay, reporter gene and Western blot assays. In addition, the in vivo anti-inflammatory effects of arvelexin were evaluated in endotoxaemia induced with LPS.

KEY RESULTS:

Promoter assays for iNOS and COX-2 revealed that arvelexin inhibited LPS-induced NO and prostaglandin E(2) production through the suppression of iNOS and COX-2 at the level of gene transcription. In addition, arvelexin inhibited NF-κB-dependent inflammatory responses by modulating a series of intracellular events of IκB kinase (IKK)-inhibitor κBα (IκBα)-NF-κB signalling. Moreover, arvelexin inhibited IKKβ-elicited NF-κB activation as well as iNOS and COX-2 expression. Serum levels of NO and inflammatory cytokines and mortality in mice challenged injected with LPS were significantly reduced by arvelexin.

CONCLUSION AND IMPLICATIONS:

Arvelexin down-regulated inflammatory iNOS, COX-2, TNF-α, IL-6 and IL-1β gene expression in macrophages interfering with the activation of IKKβ and p38 mitogen-activated protein kinase, and thus, preventing NF-κB activation.

PMID:
21434881
PMCID:
PMC3171867
DOI:
10.1111/j.1476-5381.2011.01351.x
[Indexed for MEDLINE]
Free PMC Article

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