title: The protective effect of piperine on dextran sulfate sodium induced inflammatory bowel disease and its relation with pregnane X receptor activation.
abstract: BACKGROUND
  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.
  
  
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei 230032, China; Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China; Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7000, Australia.
authors.forename: Donghua
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Yuguang
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Pharmacology, Anhui Medical University, Hefei 230032, China.
authors.forename: Zhiwu
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Zengchun
authors.initials: Z
authors.lastname: Ma
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: You
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Xianxie
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Qiande
authors.initials: Q
authors.lastname: Liang
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Hongling
authors.initials: H
authors.lastname: Tan
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Chengrong
authors.initials: C
authors.lastname: Xiao
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
authors.forename: Xianglin
authors.initials: X
authors.lastname: Tang
authors.affiliation: Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China. Electronic address: gaoyue@nic.bmi.ac.cn.
authors.forename: Yue
authors.initials: Y
authors.lastname: Gao
mesh_terms: D000470:Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D052117:Benzodioxoles / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D016264:Dextran Sulfate / Q000633:toxicity*; D056945:Hep G2 Cells; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000139:chemically induced* / Q000378:metabolism / Q000517:prevention & control*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D029222:Piper nigrum; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology / Q000627:therapeutic use*; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid / Q000819:agonists* / Q000378:metabolism
chemical_list: D000470:Alkaloids; D052117:Benzodioxoles; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D000077297:Pregnane X Receptor; D011987:Receptors, Steroid; D016264:Dextran Sulfate; C008922:piperine
keywords: Cytochrome 3A4; Inflammatory bowel disease; Nuclear factor B; Piperine; Pregnane X receptor