Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism
Anti-inflammatory properties of a pomegranate extract and its metabolite urolithin-A in a colitis rat model and the effect of colon inflammation on phenolic metabolism
复制标题
DOI：
10.1016/j.jnutbio.2009.04.012
复制
发表时间：
2010-08-01
影响因子：
5.6
通讯作者：
Carlos Espin, Juan
中科院分区：
文献类型：
--
作者：
Larrosa, Mar;Gonzalez-Sarrias, Antonio;Carlos Espin, Juan
石榴的有益效果是由于鞣花单宁还是由于其微生物来源的尿石素尚不清楚。我们的目的是评估石榴摄入量及其主要微生物群衍生的代谢产物尿石素A（UROA）对结肠炎症的影响，并评估UROA是否是主要的抗炎化合物。此外，还探讨了炎症对酚类物质代谢的影响。雄性Fisher大鼠连续25天喂食250 mg kg（-1）/天（-1）石榴提取物（PE）或15 mg kg（-1）/天（-1）UROA。在最后5天给予右旋糖酐硫酸钠（5%）（DSS），然后对大鼠实施安乐死。DSS是一种众所周知的炎症性肠病模型。评价结肠组织损伤、微生物群变化、抗氧化状态、前列腺素E-2（PGE（2））、一氧化氮产生、诱导型一氧化氮合酶（iNOS）、前列腺素E合酶（PTGES）、基因表达（微阵列和RT-PCR）和多酚代谢（LC-MS-MS）。PE和UROA均降低炎症标志物（结肠粘膜中的iNOS、环氧合酶-2、PTGES和PGE（2）），并有利地调节肠道微生物群。两组G1 → S细胞周期均上调。UROA组表现出多种下调途径，包括炎症反应。PE，而不是UROA，降低血浆和结肠粘膜的氧化应激。只有UROA保留了结肠结构。在炎症过程中，PE喂养的大鼠中尿石素的正常形成被阻止。我们的研究结果表明，UROA可能是最活跃的抗炎化合物石榴摄入健康受试者，而在结肠炎症，影响可能是由于非代谢鞣花单宁相关的馏分。(C)2010年爱思唯尔公司All rights reserved.
Whether the beneficial effects of pomegranate are due to the ellagitannins or to their microbiota-derived urolithins is not known. Our objectives were to evaluate the effects of pomegranate intake and its main microbiota-derived metabolite urolithin-A (UROA) on colon inflammation and to assess whether UROA is the main anti-inflammatory compound. In addition, the effect of the inflammation on the phenolic metabolism was also explored. Male Fisher rats were fed with 250 mg kg(-1) day(-1) pomegranate extract (PE) or 15 mg kg(-1) day(-1) UROA for 25 days. Dextran sodium sulfate (5%) (DSS) was administered for the five last days and then rats were euthanized. DSS is a well-known model of inflammatory bowel disease. Colon tissue damage, microbiota changes, antioxidant status, prostaglandin E-2 (PGE(2)), nitric oxide production, inducible nitric oxide synthase (iNOS), prostaglandin E synthase (PTGES), gene expression (microarrays and RT-PCR) and polyphenol metabolism (LC-MS-MS) were evaluated. Both PE and UROA decreased inflammation markers (iNOS, cycloxygenase-2, PTGES and PGE(2) in colonic mucosa) and modulated favorably the gut microbiota. The G(1) to S cell cycle pathway was up-regulated in both groups. UROA group showed various down-regulated pathways, including that of the inflammatory response. PE, but not UROA, decreased oxidative stress in plasma and colon mucosa. Only UROA preserved colonic architecture. The normal formation of urolithins in PE-fed rats was prevented during inflammation. Our results suggest that UROA could be the most active anti-inflammatory compound derived from pomegranate ingestion in healthy subjects, whereas in colon inflammation, the effects could be due to the nonmetabolized ellagitannin-related fraction. (C) 2010 Elsevier Inc. All rights reserved.