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The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation
Hu, D and Wang, Y and Chen, Z and Ma, Z and You, Q and Zhang, X and Liang, Q and Tan, H and Xiao, C and Tang, X and Gao, Y, The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation, Journal of Ethnopharmacology, 169 pp. 109-123. ISSN 0378-8741 (2015) [Refereed Article]
Copyright 2015 Elsevier Ireland ltd.
Ethnopharmacological relevance: Inflammatory bowel disease (IBD) is associated with chronic inflammation of the intestinal tract. Piperine (1-peperoylpiperidine), the primary lipophilic component in black pepper (Piper nigrum) and long pepper (Piper longum), has been reported to be effective for anti-inflammatory. Rencently, several ethnopharmacological purity compounds, such as baicalin and artemisinin, are reported to have potentially therapeutic role in treating IBD. In the present study, the effects of piperine on pregnane X receptor (PXR)-mediated CYP3A expression and its therapeutic role in IBD were investigated.
Materials and methods: LS174T cells and C57BL/6J mice were treated by the piperine. Gene expressions were analyzed by real-time PCR, Western blot analysis, transient transfections assay and histological analysis.
Results: Data indicated that treatment of LS174T cells with piperine markedly increased both CYP3A4 and PXR mRNA and protein. Transient transfection experiments indicated that transcriptional activation of the CYP3A4 gene via piperine was PXR-dependent. Data show that pre-administration of piperine decreased clinical hallmarks of colitis in DSS-treated PXR mice as measured by body weight loss and assessment of diarrhea, rectal bleeding, colon length, and histology. Inflammatory mediators (CCR2, ICAM-1, IL-1β, IL-6, IL-10, iNOS, MCP-1, and TNFα) after DSS treatment were significantly decreased in mice pretreated with piperine but corresponding conditions did not occur in mice with down-regulation of PXR by small interfering RNA (siRNA).
Conclusion: Piperine is a potential agonist of PXR and an inducer of PXR, which may induce CYP3A4 gene expression at the mRNA and protein levels. These results establish that piperine may contribute to prevention or reduction of colonic inflammation.
|Item Type:||Refereed Article|
|Keywords:||cytochrome 3A4, inflammatory bowel disease, nuclear factor B, piperine, pregnane X receptor|
|Research Division:||Biomedical and Clinical Sciences|
|Research Field:||Immunology not elsewhere classified|
|Objective Group:||Clinical health|
|Objective Field:||Clinical health not elsewhere classified|
|UTAS Author:||Hu, D (Mr Donghua Hu)|
|Web of Science® Times Cited:||39|
|Deposited By:||Menzies Institute for Medical Research|
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