Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver
Glucuronidation of resveratrol, a natural product present in grape and wine, in the human liver
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DOI：
10.1080/00498250010002487
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发表时间：
2000-11-01
期刊：
影响因子：
1.8
通讯作者：
Pacifici, GM
中科院分区：
文献类型：
--
作者：
De Santi, C;Pietrabissa, A;Pacifici, GM
1. 白藜芦醇是一种存在于葡萄和矿山中的多酚化合物，具有抗癌作用和对心血管系统的保护作用。研究表明，该化合物在人肝脏中被硫酸化，本研究的目的是研究人肝微粒体中的白藜芦醇葡萄糖醛酸化，并确定黄酮类化合物是否抑制白藜芦醇葡萄糖醛酸化。2．开发了一种简单且可重复的白藜芦醇葡萄糖醛酸化放射测定法。该测定采用尿苷-5'-二磷酸葡萄糖醛酸-[C-14]和未标记的白藜芦醇。通过薄层色谱法分离白藜芦醇-葡萄糖苷酸。测定内和测定间变异分别为1%和1.5%。3．在 10 个肝脏样本中检测到了罕见的白藜芦醇葡萄糖醛酸化。白藜芦醇葡萄糖醛酸化率的平均值+/-SD和中位数分别为0.69+/-0.34和0.80nmol/min/mg。白藜芦醇葡萄糖醛酸基转移酶遵循 Michaelis-Menten 动力学，K-m 和 V-max（平均值 +/- SD；n = 5）分别为 0.15 +/- 0.09) mM 和 1.3 +/- 0.3 nmol/min/mg。内在清除率为11+/-4×10(-3)ml/min.mg.4。类黄酮槲皮素抑制白藜芦醇葡萄糖醛酸化，其 IC50（平均值+/-SD；n = 3）为 10+/-1 muM。杨梅素、儿茶素、山奈酚、非瑟酮和芹菜素（均为 20 muM）抑制白藜芦醇葡萄糖醛酸化，控制百分比范围在 46%（儿茶素）至 72%（芹菜素）之间。5．目前的结果表明，白藜芦醇在人肝脏中被葡萄糖醛酸化。葡萄糖醛酸化可能会降低该化合物的生物利用度，然而，类黄酮抑制白藜芦醇葡萄糖醛酸化，并且这种抑制可能会提高白藜芦醇的生物利用度。
1. Resveratrol, a polyphenolic compound present in grape and mine, has beneficial effects against cancer and protective effects on the cardiovascular system. It has been shown that the compound is sulphated in human liver and the aims of the present investigation were to study resveratrol glucuronidation in human liver microsomes and to determine whether flavonoids inhibit resveratrol glucuronidation.2. A simple and reproducible radiometric assay for resveratrol glucuronidation was developed. The assay employed uridine-5'-diphosphoglucuronic acid-[C-14] and unlabelled resveratrol. Resveratrol-glucuronide was isolated by TLC. The intra- and interassays variabilities were 1 and 1.5%, respectively.3. The rare of resveratrol glucuronidation was measured in 10 liver samples. The mean +/- SD and median of resveratrol glucuronidation rate were 0.69 +/- 0.34 and 0.80 nmol/ min/mg, respectively. Resveratrol glucuronosyl transferase followed Michaelis-Menten kinetics and the K-m and V-max (mean +/- SD; n = 5) were 0.15 +/- 0.09) mM and 1.3 +/- 0.3 nmol/ min/mg respectively. The intrinsic clearance was 11 +/- 4 x 10(-3) ml/min.mg.4. The flavonoid quercetin inhibited resveratrol glucuronidation and its IC50 (mean+/-SD; n = 3) was 10+/-1 muM. Myricetin, catechin, kaempferol, fisetin and apigenin (all at 20 muM) inhibited resveratrol glucuronidation and the percent of control ranged between 46% (catechin) to 72% (apigenin).5. The present results show that resveratrol is glucuronated in the human liver. Glucuronidation may reduce the bioavailability of this compound however, flavonoids inhibit resveratrol glucuronidation and such an inhibition might improve the bioavailability of resveratrol.