Hu Donghua, Wang Yuguang, Chen Zhiwu, Ma Zengchun, You Qing, Zhang Xianxie, Liang Qiande, Tan Hongling, Xiao Chengrong, Tang Xianglin, Gao Yue
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.
Department of Pharmacology and Toxicology, Beijing Institute of Radiation Medicine, Beijing 100850, China.
J Ethnopharmacol. 2015 Jul 1;169:109-23. doi: 10.1016/j.jep.2015.04.006. Epub 2015 Apr 21.
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.
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.
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).
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.
炎症性肠病（IBD）与肠道慢性炎症相关。胡椒碱（1-胡椒酰哌啶）是黑胡椒（Piper nigrum）和荜茇（Piper longum）中的主要亲脂性成分，据报道具有抗炎作用。最近，有报道称几种民族药理学纯化合物，如黄芩苷和青蒿素，在治疗IBD方面具有潜在的治疗作用。在本研究中，研究了胡椒碱对孕烷X受体（PXR）介导的CYP3A表达的影响及其在IBD中的治疗作用。
用胡椒碱处理LS174T细胞和C57BL/6J小鼠。通过实时PCR、蛋白质印迹分析、瞬时转染试验和组织学分析来分析基因表达。
数据表明，用胡椒碱处理LS174T细胞显著增加了CYP3A4和PXR的mRNA及蛋白质水平。瞬时转染实验表明，胡椒碱对CYP3A4基因的转录激活是PXR依赖性的。数据显示，预先给予胡椒碱可降低DSS处理的PXR小鼠的结肠炎临床特征，通过体重减轻以及腹泻、直肠出血、结肠长度和组织学评估来衡量。在用胡椒碱预处理的小鼠中，DSS处理后的炎症介质（CCR2、ICAM-1、IL-1β、IL-6、IL-10、iNOS、MCP-1和TNFα）显著减少，但在通过小干扰RNA（siRNA）下调PXR的小鼠中未出现相应情况。
胡椒碱是PXR的潜在激动剂和诱导剂，可能在mRNA和蛋白质水平上诱导CYP3A4基因表达。这些结果表明胡椒碱可能有助于预防或减轻结肠炎症。
