Microsomal hydroxylation and glucuronidation of [6]-gingerol
Microsomal hydroxylation and glucuronidation of [6]-gingerol
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DOI：
10.1021/jf062235l
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发表时间：
2006-11-15
影响因子：
6.1
通讯作者：
Metzler, Manfred
中科院分区：
文献类型：
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作者：
Pfeiffer, Erika;Heuschmid, Franziska F.;Metzler, Manfred
[6]-姜酚是生姜的主要辛辣成分，经常与各种调味品和营养补充剂一起摄入。我们在此报道，[6]-姜酚与 NADPH 强化的大鼠肝微粒体一起孵育产生了 8 种代谢物，通过 GC-MS 分析初步鉴定为两种芳香族羟基化产物以及两种脂肪族羟基化产物的非对映体和 [6]-姜二醇的非对映体。通过 LC-MS/MS 分析，还鉴定了大鼠和人类的肝微粒体，该肝微粒体主要在酚羟基处用 UDPGA 葡萄糖醛酸化 [6]-姜酚强化，但也鉴定出了少量涉及脂肪族羟基的第二种单葡萄糖苷酸。人肠道微粒体仅形成酚类葡萄糖醛酸苷。含有人 UGT1A1 和 1A3 的超体专门生成酚类葡萄糖醛酸苷，尽管活性非常低，而 UGT1A9 催化醇类葡萄糖醛酸苷的特异性形成，UGT2B7 催化酚类葡萄糖醛酸苷的主要形成，具有高活性。我们的研究表明[6]-姜酚的代谢相当复杂，该化合物的多种生物活性应考虑到这一点。
[6]-Gingerol is the major pungent principle of ginger and frequently is ingested with various condiments and nutritional supplements. We report here that incubation of [6]-gingerol with NADPH-fortified rat hepatic microsomes gave rise to eight metabolites, which were tentatively identified by GC-MS analysis as two products of aromatic hydroxylation as well as the diastereomers of two aliphatic hydroxylation products and the diastereomers of [6]-gingerdiol. Hepatic microsomes from rats and humans fortified with UDPGA glucuronidated [6]-gingerol predominantly at the phenolic hydroxyl group, but small amounts of a second monoglucuronide involving the aliphatic hydroxyl group were also identified by LC-MS/MS analysis. Human intestinal microsomes formed the phenolic glucuronide only. Supersomes containing human UGT1A1 and 1A3 exclusively generated the phenolic glucuronide, albeit with very low activities, whereas UGT1A9 catalyzed the specific formation of the alcoholic glucuronide and UGT2B7 the predominant formation of the phenolic glucuronide with high activities. Our study indicates a rather complex metabolism of [6]-gingerol, which should be taken into consideration for the multiple biological activities of this compound.