Arvelexin from Brassica rapa suppresses NF-kappa B-regulated pro-inflammatory gene expression by inhibiting activation of I kappa B kinase

作者：Shin Ji Sun; Noh Young Su; Lee Yong Sup; Cho Young Wuk; Baek Nam In; Choi Myung Sook; Jeong Tae Sook; Kang Eunkyung; Chung Hae Gon; Lee Kyung Tae^*

来源：British Journal of Pharmacology, 2011, 164(1): 145-158.

DOI：10.1111/j.1476-5381.2011.01351.x

• arvelexin
• Brassica rapa
• cyclooxygenase-2
• inducible nitric oxide
• inflammation
• NF-kappa B
• IKK
• paw oedema

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-alpha, IL-6 and IL-1 beta were determined by Western blot and/or RT-PCR respectively. To elucidate the underlying mechanism(s), activation of NF-kappa B 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-kappa B-dependent inflammatory responses by modulating a series of intracellular events of I kappa B kinase (IKK)-inhibitor kappa B alpha (I kappa B alpha)-NF-kappa B signalling. Moreover, arvelexin inhibited IKK beta-elicited NF-kappa B 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-alpha, IL-6 and IL-1 beta gene expression in macrophages interfering with the activation of IKK beta and p38 mitogen-activated protein kinase, and thus, preventing NF-kappa B activation.

• 出版日期2011-9