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Arvelexin from Brassica rapa suppresses NF-κB-regulated pro-inflammatory gene expression by inhibiting activation of IκB kinase.
Br J Pharmacol. 2011 Sep; 164(1):145-58.BJ

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.

Authors+Show Affiliations

Department of Pharmaceutical Biochemistry, College of Pharmacy, Kyung Hee University, Seoul, Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21434881

Citation

Shin, Ji-Sun, et al. "Arvelexin From Brassica Rapa Suppresses NF-κB-regulated Pro-inflammatory Gene Expression By Inhibiting Activation of IκB Kinase." British Journal of Pharmacology, vol. 164, no. 1, 2011, pp. 145-58.
Shin JS, Noh YS, Lee YS, et al. Arvelexin from Brassica rapa suppresses NF-κB-regulated pro-inflammatory gene expression by inhibiting activation of IκB kinase. Br J Pharmacol. 2011;164(1):145-58.
Shin, J. S., Noh, Y. S., Lee, Y. S., Cho, Y. W., Baek, N. I., Choi, M. S., Jeong, T. S., Kang, E., Chung, H. G., & Lee, K. T. (2011). Arvelexin from Brassica rapa suppresses NF-κB-regulated pro-inflammatory gene expression by inhibiting activation of IκB kinase. British Journal of Pharmacology, 164(1), 145-58. https://doi.org/10.1111/j.1476-5381.2011.01351.x
Shin JS, et al. Arvelexin From Brassica Rapa Suppresses NF-κB-regulated Pro-inflammatory Gene Expression By Inhibiting Activation of IκB Kinase. Br J Pharmacol. 2011;164(1):145-58. PubMed PMID: 21434881.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Arvelexin from Brassica rapa suppresses NF-κB-regulated pro-inflammatory gene expression by inhibiting activation of IκB kinase. AU - Shin,Ji-Sun, AU - Noh,Young-Su, AU - Lee,Yong Sup, AU - Cho,Young-Wuk, AU - Baek,Nam-In, AU - Choi,Myung-Sook, AU - Jeong,Tae-Sook, AU - Kang,Eunkyung, AU - Chung,Hae-Gon, AU - Lee,Kyung-Tae, PY - 2011/3/26/entrez PY - 2011/3/26/pubmed PY - 2012/2/3/medline SP - 145 EP - 58 JF - British journal of pharmacology JO - Br J Pharmacol VL - 164 IS - 1 N2 - 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. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/21434881/Arvelexin_from_Brassica_rapa_suppresses_NF_κB_regulated_pro_inflammatory_gene_expression_by_inhibiting_activation_of_IκB_kinase_ DB - PRIME DP - Unbound Medicine ER -