Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent
Palmitoylethanolamide, a naturally occurring lipid, is an orally effective intestinal anti-inflammatory agent
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DOI：
10.1111/bph.12907
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发表时间：
2015-01-01
影响因子：
7.3
通讯作者：
Izzo, Angelo A.
中科院分区：
文献类型：
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作者：
Borrelli, Francesca;Romano, Barbara;Izzo, Angelo A.
背景和目的棕榈酰乙醇酰胺 (PEA) 通过多个靶点发挥作用，包括大麻素 CB1 和 CB2 受体、瞬时受体电位香草酸 1 型 (TRPV1) 离子通道、过氧化物酶体增殖物激活受体 α (PPAR) 和孤儿 G 蛋白偶联受体 55 (GRR55)，所有这些都参与肠道炎症的控制。在此，我们研究了 PEA 在小鼠结肠炎模型中的作用。实验方法通过结肠内给予二硝基苯磺酸 (DNBS) 诱导小鼠结肠炎。通过评估炎症标志物/参数和组织学来评估炎症；荧光法测定肠通透性；通过免疫组织化学检测结肠细胞增殖；通过液相色谱质谱法测定 PEA 和内源性大麻素水平；通过定量 RT-PCR 检测受体和酶 mRNA 表达。关键结果 DNBS 给药引起炎症损伤，增加结肠中 PEA 和内源性大麻素的水平，下调 TRPV1 和 GPR55 的 mRNA，但 CB1、CB2 和 PPAR 的 mRNA 没有变化。外源性PEA（腹腔注射和/或口服，1mgkg(-1)）可减轻炎症和肠道通透性，刺激结肠细胞增殖，并增加结肠TRPV1和CB1受体表达。 PEA 的抗炎作用被 CB2 受体、GPR55 或 PPAR 拮抗剂减弱或消除，并被 TRPV1 拮抗剂辣椒西平进一步增强。 结论和意义 PEA 改善小鼠实验性结肠炎，该作用由 CB2 受体、GPR55 和 PPAR 介导，并受 TRPV1 通道调节。
Background and PurposePalmitoylethanolamide (PEA) acts via several targets, including cannabinoid CB1 and CB2 receptors, transient receptor potential vanilloid type-1 (TRPV1) ion channels, peroxisome proliferator-activated receptor alpha (PPAR ) and orphan G protein-coupled receptor 55 (GRR55), all involved in the control of intestinal inflammation. Here, we investigated the effect of PEA in a murine model of colitis.Experimental ApproachColitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Inflammation was assessed by evaluating inflammatory markers/parameters and by histology; intestinal permeability by a fluorescent method; colonic cell proliferation by immunohistochemistry; PEA and endocannabinoid levels by liquid chromatography mass spectrometry; receptor and enzyme mRNA expression by quantitative RT-PCR.Key ResultsDNBS administration caused inflammatory damage, increased colonic levels of PEA and endocannabinoids, down-regulation of mRNA for TRPV1 and GPR55 but no changes in mRNA for CB1, CB2 and PPAR. Exogenous PEA (i.p. and/or p.o., 1mgkg(-1)) attenuated inflammation and intestinal permeability, stimulated colonic cell proliferation, and increased colonic TRPV1 and CB1 receptor expression. The anti-inflammatory effect of PEA was attenuated or abolished by CB2 receptor, GPR55 or PPAR antagonists and further increased by the TRPV1 antagonist capsazepine.Conclusions and ImplicationsPEA improves murine experimental colitis, the effect being mediated by CB2 receptors, GPR55 and PPAR, and modulated by TRPV1 channels.