Espín Juan Carlos, González-Barrio Rocío, Cerdá Begoña, López-Bote Clemente, Rey Ana I, Tomás-Barberán Francisco A
Research Group on Quality, Safety and Bioactivity of Plant Foods, Department of Food Science and Technology, CEBAS-CSIC, P.O. Box 164, 30100 Campus de Espinardo, Murcia, Spain.
J Agric Food Chem. 2007 Dec 12;55(25):10476-85. doi: 10.1021/jf0723864. Epub 2007 Nov 9.
Ellagitannin-containing foods (strawberries, walnuts, pomegranate, raspberries, oak-aged wine, etc.) have attracted attention due to their cancer chemopreventive, cardioprotective, and antioxidant effects. Ellagitannins (ETs) are not absorbed as such but are metabolized by the intestinal flora to yield urolithins (hydroxydibenzopyran-6-one derivatives). In this study, Iberian pig is used as a model to clarify human ET metabolism. Pigs were fed either cereal fodder or acorns, a rich source of ETs. Plasma, urine, bile, lumen and intestinal tissues (jejunum and colon), feces, liver, kidney, heart, brain, lung, muscle, and subcutaneous fat tissue were analyzed. The results demonstrate that acorn ETs release ellagic acid (EA) in the jejunum, then the intestinal flora metabolizes EA sequentially to yield tetrahydroxy- (urolithin D), trihydroxy- (urolithin C), dihydroxy- (urolithin A), and monohydroxy- (urolithin B) dibenzopyran-6-one metabolites, which were absorbed preferentially when their lipophilicity increased. Thirty-one ET-derived metabolites were detected, including 25 urolithin and 6 EA derivatives. Twenty-six extensively conjugated metabolites were detected in bile, glucuronides and methyl glucuronides of EA and particularly urolithin A, C, and D derivatives, confirming a very active enterohepatic circulation. Urolithins A and B as well as dimethyl-EA-glucuronide were detected in peripheral plasma. The presence of EA metabolites in bile and in urine and its absence in intestinal tissues suggested its absorption in the stomach. Urolithin A was the only metabolite detected in feces and together with its glucuronide was the most abundant metabolite in urine. No metabolites accumulated in any organ analyzed. The whole metabolism of ETs is shown for the first time, confirming previous studies in humans and explaining the long persistency of urolithin metabolites in the body mediated by an active enterohepatic circulation.
富含鞣花单宁的食物（草莓、核桃、石榴、树莓、橡木桶陈酿葡萄酒等）因其癌症化学预防、心脏保护和抗氧化作用而受到关注。鞣花单宁（ETs）本身不会被吸收，而是被肠道菌群代谢产生尿石素（羟基二苯并吡喃 - 6 - 酮衍生物）。在本研究中，以伊比利亚猪作为模型来阐明人类ET代谢。给猪喂食谷物饲料或富含ETs的橡子。分析了血浆、尿液、胆汁、肠腔和肠道组织（空肠和结肠）、粪便、肝脏、肾脏、心脏、大脑、肺、肌肉和皮下脂肪组织。结果表明，橡子ETs在空肠中释放鞣花酸（EA），然后肠道菌群依次代谢EA产生四羟基 - （尿石素D）、三羟基 - （尿石素C）、二羟基 - （尿石素A）和单羟基 - （尿石素B）二苯并吡喃 - 6 - 酮代谢产物，随着它们亲脂性的增加，这些代谢产物被优先吸收。检测到31种ET衍生代谢产物，包括25种尿石素和6种EA衍生物。在胆汁中检测到26种广泛共轭的代谢产物，EA以及特别是尿石素A、C和D衍生物的葡萄糖醛酸苷和甲基葡萄糖醛酸苷，证实了非常活跃的肠肝循环。在外周血浆中检测到尿石素A和B以及二甲基 - EA - 葡萄糖醛酸苷。胆汁和尿液中存在EA代谢产物而肠道组织中不存在，表明其在胃中被吸收。尿石素A是粪便中检测到的唯一代谢产物，并且与其葡萄糖醛酸苷一起是尿液中最丰富的代谢产物。在所分析的任何器官中均未检测到代谢产物积累。首次展示了ETs的完整代谢过程，证实了先前在人体中的研究，并解释了由活跃的肠肝循环介导的尿石素代谢产物在体内的长期持久性。
