Niemeyer H B, Honig D, Lange-Böhmer A, Jacobs E, Kulling S E, Metzler M
Institute of Food Chemistry, Department of Chemistry, University of Karlsruhe, P.O. Box 6980, GY-76128 Karlsruhe, Germany.
J Agric Food Chem. 2000 Jul;48(7):2910-9. doi: 10.1021/jf0000530.
Recent studies have shown that the mammalian lignans enterodiol (END) and enterolactone (ENL) are biotransformed in vitro by hepatic microsomes from rats and humans to various metabolites carrying one additional hydroxy group either at the aromatic or at the aliphatic moiety. To clarify whether these metabolites are also formed in vivo, each lignan was administered intraduodenally at a dose of 10 mg/kg of bw to bile duct-catheterized female Wistar rats and the 6 h bile analyzed by HPLC and GC-MS. With END-dosed rats, three products of aromatic and two of aliphatic monohydroxylation were found, whereas six aromatic and five aliphatic monohydroxylated biliary metabolites were detected after administration of ENL. The metabolites hydroxylated at the aromatic rings were unequivocally identified by comparison with synthetic reference compounds. The structures of the in vivo metabolites arising from aliphatic hydroxylation could not be completely elucidated; they were identical with some of the formerly reported microsomal products according to GC retention times and mass spectra. Significant amounts of most of the metabolites of the mammalian lignans identified in bile were also found in the urine of female rats after oral administration of 10 mg/kg of bw END or ENL and in the urine of female and male Wistar rats after they had been fed a diet containing 5% flaxseed. Thus, the mammalian lignans END and ENL give rise to several hydroxylated metabolites in vivo, which may contribute to the biological effects of these important food constituents.
最近的研究表明，哺乳动物木脂素肠二醇（END）和肠内酯（ENL）在体外可被大鼠和人类的肝微粒体生物转化为各种代谢产物，这些代谢产物在芳香族或脂肪族部分带有一个额外的羟基。为了阐明这些代谢产物在体内是否也会形成，将每种木脂素以10mg/kg体重的剂量经十二指肠给予胆管插管的雌性Wistar大鼠，并通过高效液相色谱（HPLC）和气相色谱-质谱联用（GC-MS）分析6小时的胆汁。给予END的大鼠中，发现了三种芳香族单羟基化产物和两种脂肪族单羟基化产物，而给予ENL后检测到六种芳香族和五种脂肪族单羟基化胆汁代谢产物。通过与合成参考化合物比较，明确鉴定了芳香环羟基化的代谢产物。脂肪族羟基化产生的体内代谢产物的结构无法完全阐明；根据气相色谱保留时间和质谱，它们与一些先前报道的微粒体产物相同。在口服10mg/kg体重的END或ENL后的雌性大鼠尿液中，以及在喂食含5%亚麻籽饮食后的雌性和雄性Wistar大鼠尿液中，也发现了胆汁中鉴定出的大多数哺乳动物木脂素代谢产物的大量存在。因此，哺乳动物木脂素END和ENL在体内会产生几种羟基化代谢产物，这可能有助于这些重要食物成分的生物学效应。
