Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients
Targeted metabolic profiling of pomegranate polyphenols and urolithins in plasma, urine and colon tissues from colorectal cancer patients
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DOI：
10.1002/mnfr.201300931
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发表时间：
2014-06-01
影响因子：
5.2
通讯作者：
Espin, Juan C.
中科院分区：
文献类型：
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作者：
Nunez-Sanchez, Maria A.;Garcia-Villalba, Rocio;Espin, Juan C.
范围：尿素素是肠道微生物区系产生的生物活性代谢物，由鞣皮单宁(ETS)和鞣花酸(EA)产生。目的：探讨石榴提取物(PE)对结直肠癌(CRC)患者结肠组织尿结石的影响。方法与结果：52例结直肠癌患者分为对照组和PES组，均于手术前给予石榴提取物900 mg/d，连续15d。分别给予低(PE-1)和高(PE-2)Pe：EA比值的PEs。用UPLC-ESI-QTOF-MS/MS(UPLC，超高效液相色谱；QTOF，四极TOF)在尿液、血浆、正常(NT)和恶性(MT)结肠组织中检测到23种代谢物，但未检测到鞣质。在结肠组织中发现了游离EA、5个EA结合物、没食子酸和12个尿素衍生物。NT组的个体代谢物和总代谢物水平高于MT组，与PE消耗无关。摄入PE-1后，NT的平均浓度最高(1671+/-367 ng/g)，使用PE-2的MT的平均浓度最低(42.4+/-10.2 ng/g)。尿素A或异尿酸A是产生尿石素的主要成分(尿素A或异尿酸A表型分别占54%和46%)。结论：结直肠癌患者进食石榴后，结肠组织中存在显著水平的EA衍生物和尿石脂。为了阐明它们的生物活性，还需要进一步的研究。
Scope: Urolithins are bioactive metabolites produced by the gut microbiota from ellagitannins (ETs) and ellagic acid (EA). We investigated whether urolithins could be detected in colon tissues from colorectal cancer (CRC) patients after pomegranate extract (PE) intake.Methods and results: CRC patients (n = 52) were divided into controls and PEs consumers (900 mg/day for 15 days) before surgical resection. PEs with low (PE-1) and high (PE-2) punicalagin: EA ratio were administered. Twenty-three metabolites, but no ellagitannins, were detected in urine, plasma, normal (NT) or malignant (MT) colon tissues using UPLC-ESI-QTOF-MS/MS (UPLC, ultra performance liquid chromatography; QTOF, quadrupole TOF). Free EA, five EA conjugates, gallic acid and 12 urolithin derivatives were found in colon tissues. Individual and total metabolites levels were higher in NT than in MT, independently of the PE consumed. The maximal mean concentration (1671 +/- 367 ng/g) was found in NT after consumption of PE-1 and the lowest concentration (42.4 +/- 10.2 ng/g) inMT with PE-2. Urolithin A or isourolithin A were the main urolithins produced (54 and 46% patients with urolithin A or isourolithin A phenotype, respectively). High punicalagin content (PE-2) hampered urolithins formation.Conclusion: Significant levels of EA derivatives and urolithins are found in human colon tissues from CRC patients after consumption of pomegranate. Further studies are warranted to elucidate their biological activity.