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Title 

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

Authors 

J S ShinY S NohY S LeeY W ChoN I BaekM S ChoiTae Sook JeongE KangH G ChungK T Lee

Publisher 

Wiley-Blackwell

Issue Date 

2011

Citation 

British Journal of Pharmacology, vol. 164, no. 1, pp. 145-158

Keywords 

arvelexinBrassica rapacyclooxygenase-2IKKinducible nitric oxideinflammationNF-κBpaw oedema

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 E2 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.

ISSN 

0007-1188

Link 

http://dx.doi.org/10.1111/j.1476-5381.2011.01351.x

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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