首页 / 院系成果 / 成果详情页

Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway 期刊论文

编号：

d3a56d75-b673-45a6-a89f-603fb7d76ef0
作者：

Dou, Wei(窦薇)#^[1,2]Zhang, Jingjing(张晶晶)^[1,2]Li, Hao^[3,4];Kortagere, Sandhya^[5];Sun, Katherine^[6];Ding, Lili(丁丽丽)^[1,2]Ren, Gaiyan(任改艳)^[1,2]Wang, Zhengtao(王峥涛)*^[1,2]Mani, Sridhar*^[3,4]
语种：

英文
期刊：

JOURNAL OF NUTRITIONAL BIOCHEMISTRY ISSN：0955-2863 2014 年 25 卷 9 期 (923 - 933) ; SEP
收录：
关键词：

Inflammatory bowel disease Pregnane X receptor Xenobiotic metabolism NF-kappa B Isorhamnetin
摘要：

Isorhamnetin is an O-methylated flavonol present in fruit and vegetables. We recently reported the identification of isorhamnetin as an activator of the human pregnane X receptor (PXR), a known target for abrogating inflammation in inflammatory bowel disease (IBD). The current study investigated the role of isorhamnetin as a putative mouse PXR activator in ameliorating chemically induced IBD. Using two different models (ulcerative colitis like and Crohn's disease like) of experimental IBD in mice, we demonstrated that isorhamnetin abrogated inflammation through inhibiting the activity of myeloperoxidase, the levels of TNF-alpha and IL-6, the mRNA expression of proinflammatory mediators (iNOS, ICAM-1, COX2, TNF-alpha, IL-2 and IL-6) and the phosphorylation of I kappa B alpha and NF-kappa B p65. PXR gene overexpression inhibited NF-kappa B luciferase activity, and the inhibition was potentiated by isorhamnetin treatment. PXR knockdown by siRNA demonstrated the necessity for PXR in isorhamnetin-mediated up-regulation of xenobiotic metabolism genes. Ligand pocket-filling mutants (S247W/C284W and S247W/C284W/S208W) of human PXR weakened the effect of isorhamnetin on PXR activation. Molecular docking studies and time-resolved fluorescence resonance energy transfer competitive binding assays confirmed the ligand (isorhamnetin)-binding affinity. These results clearly demonstrated the ameliorating effect of isorhamnetin on experimental IBD via PXR-mediated up-regulation of xenobiotic metabolism and down-regulation of NF-kappa B signaling. The novel findings may contribute to the effective utilization of isorhamnetin or its derivatives as a PXR ligand in the treatment of human IBD. (C) 2014 Elsevier Inc. All rights reserved.
推荐引用方式
GB/T 7714：

Dou Wei,Zhang Jingjing,Li Hao, et al. Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway [J].JOURNAL OF NUTRITIONAL BIOCHEMISTRY,2014,25(9):923-933.
APA：

Dou Wei,Zhang Jingjing,Li Hao,Kortagere Sandhya,&Mani Sridhar.(2014).Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway .JOURNAL OF NUTRITIONAL BIOCHEMISTRY,25(9):923-933.
MLA：

Dou Wei, et al. "Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway" .JOURNAL OF NUTRITIONAL BIOCHEMISTRY 25,9(2014):923-933.
条目包含文件：

文件类型：PDF,文件大小：

正在加载全文

未找到全文

浏览次数：59  下载次数：0

分享到：

浏览次数：59

下载次数：0

打印次数：0