Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway
文献类型：期刊论文
| 作者 | Dou, Wei2; Zhang, Jingjing2; Li, Hao1; Kortagere, Sandhya3; Sun, Katherine4; Ding, Lili2; Ren, Gaiyan2; Wang, Zhengtao2; Mani, Sridhar1 |
| 刊名 | The Journal of nutritional biochemistry
 |
| 出版日期 | 2014-09 |
| 卷号 | 25期号:9页码:923-33 |
| ISSN号 | 1873-4847 |
| DOI | 10.1016/j.jnutbio.2014.04.006 |
| 文献子类 | Article |
| 英文摘要 | 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-α and IL-6, the mRNA expression of proinflammatory mediators (iNOS, ICAM-1, COX2, TNF-α, IL-2 and IL-6) and the phosphorylation of IκBα and NF-κB p65. PXR gene overexpression inhibited NF-κB 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-κB 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. |
| 语种 | 英语 |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/266582]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Wang, Zhengtao; Mani, Sridhar |
| 作者单位 | 1.Departments of Medicine and Genetics, Albert Einstein College of Medicine, NY 10461, USA; 2.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, 201203, China; 3.Department of Microbiology and Immunology, Drexel University College of Medicine, PA 19129, USA; 4.Department of Pathology, Montefiore Medical Center, NY 10467, USA |
| 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]. The Journal of nutritional biochemistry,2014,25(9):923-33. |
| APA | Dou, Wei.,Zhang, Jingjing.,Li, Hao.,Kortagere, Sandhya.,Sun, Katherine.,...&Mani, Sridhar.(2014).Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway.The Journal of nutritional biochemistry,25(9),923-33. |
| MLA | Dou, Wei,et al."Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway".The Journal of nutritional biochemistry 25.9(2014):923-33. |
入库方式： OAI收割
来源：上海药物研究所
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