کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8337154 | 1540657 | 2014 | 43 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway
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کلمات کلیدی
DSSGSTsICAM-1IBDiNOScox2Cytochromes P450CYPs - CYPinducible NO synthase - NO سنتاز القاء شدهenzyme linked immunosorbent assay - آنزیم تست ایمونوسیورسانس مرتبط استCrohn's disease - بیماری کرونInflammatory bowel disease - بیماریهای التهابی رودهELISA - تست الیزاdextran sodium sulfate - سولفات سدیم سدیمcyclooxygenase 2 - سیکلوکوکسیژناز 2intercellular adhesion molecule-1 - مولکول چسبندگی بین سلولی -1glutathione S-transferases - گلوتاتیون S-transferases
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway Plant flavonol isorhamnetin attenuates chemically induced inflammatory bowel disease via a PXR-dependent pathway](/preview/png/8337154.png)
چکیده انگلیسی
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.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Nutritional Biochemistry - Volume 25, Issue 9, September 2014, Pages 923-933
Journal: The Journal of Nutritional Biochemistry - Volume 25, Issue 9, September 2014, Pages 923-933
نویسندگان
Wei Dou, Jingjing Zhang, Hao Li, Sandhya Kortagere, Katherine Sun, Lili Ding, Gaiyan Ren, Zhengtao Wang, Sridhar Mani,