Chrysin ameliorates chemically induced colitis in the mouse through modulation of a PXR/NF-κB signaling pathway

doi:10.1124/jpet.112.201863

	Chrysin ameliorates chemically induced colitis in the mouse through modulation of a PXR/NF-κB signaling pathway
	Dou, Wei; Zhang, Jingjing; Zhang, Eryun; Sun, Aning; Ding, Lili; Chou, Guixin; Wang, Zhengtao; Mani, Sridhar
刊名	The Journal of pharmacology and experimental therapeutics
	2013-06
卷号	345 期号:3 页码:473-82
ISSN号	1521-0103
DOI	10.1124/jpet.112.201863
文献子类	Article
英文摘要	Targeted activation of pregnane X receptor (PXR) in recent years has become a therapeutic strategy for inflammatory bowel disease. Chrysin is a naturally occurring flavonoid with anti-inflammation activity. The current study investigated the role of chrysin as a putative mouse PXR agonist in preventing experimental colitis. Pre-administration of chrysin ameliorated inflammatory symptoms in mouse models of colitis (dextran sodium sulfate- and 2,4,6-trinitrobenzene sulfonic acid-induced) and resulted in down-regulation of nuclear transcription factor κB (NF-κB) target genes (inducible NO synthase, intercellular adhesion molecule-1, monocyte chemotactic protein-1, cyclooxygenase 2, tumor necrosis factor-α, and interleukin 6) in the colon mucosa. Chrysin inhibited the phosphorylation/degradation of inhibitor κBα (IκBα), which correlated with the decrease in the activity of myeloperoxidase and the levels of tumor necrosis factor-α and interleukin 6 in the colon. Consistent with the in vivo results, chrysin blocked lipopolysaccharide -stimulated nuclear translocation of NF-κB p65 in mouse macrophage RAW264.7. Furthermore, chrysin dose-dependently activated human/mouse PXR in reporter gene assays and up-regulated xenobiotic detoxification genes in the colon mucosa, but not in the liver. Silencing of PXR by RNA interference demonstrated necessity of PXR in mediating chrysin's ability to induce xenobiotic detoxification genes and NF-κB inactivation. The repression of NF-κB transcription activity by chrysin was confirmed by in vitro PXR transduction. These findings suggest that the effect of chrysin in preventing chemically induced colitis is mediated in large part by a PXR/NF-κB pathway. The data also suggest that chrysin or chrysin-like flavonoids could be further developed as intestine-specific PXR activators.
语种	英语
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/266470]
专题	中国科学院上海药物研究所
作者单位	Shanghai Key Laboratory of Complex Prescription and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
推荐引用方式 GB/T 7714	Dou, Wei,Zhang, Jingjing,Zhang, Eryun,et al. Chrysin ameliorates chemically induced colitis in the mouse through modulation of a PXR/NF-κB signaling pathway[J]. The Journal of pharmacology and experimental therapeutics,2013,345(3):473-82.
APA	Dou, Wei.,Zhang, Jingjing.,Zhang, Eryun.,Sun, Aning.,Ding, Lili.,...&Mani, Sridhar.(2013).Chrysin ameliorates chemically induced colitis in the mouse through modulation of a PXR/NF-κB signaling pathway.The Journal of pharmacology and experimental therapeutics,345(3),473-82.
MLA	Dou, Wei,et al."Chrysin ameliorates chemically induced colitis in the mouse through modulation of a PXR/NF-κB signaling pathway".The Journal of pharmacology and experimental therapeutics 345.3(2013):473-82.