Metabolism of ginger component [6]-shogaol in liver microsomes from mouse, rat, dog, monkey, and human.
Metabolism of ginger component [6]-shogaol in liver microsomes from mouse, rat, dog, monkey, and human.
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DOI：
10.1002/mnfr.201200708
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发表时间：
2013-05
影响因子：
5.2
通讯作者：
Sang, Shengmin
中科院分区：
文献类型：
--
作者：
Chen, Huadong;Soroka, Dominique;Zhu, Yingdong;Sang, Shengmin
生姜的主要生物活性成分[6]-shogaol的代谢数据有限。本研究证实了[6]-shogaol在小鼠、大鼠、狗、猴和人肝微粒体中的代谢。利用小鼠、大鼠、狗、猴和人的肝微粒体，比较了[6]-shogaol在5种动物体内的体外代谢。在[6]-shogaol的作用下，发现了3种主要的还原代谢产物1-（4'-羟基-3'-甲氧基苯基）-4-癸-3-醇（M6）、1-（4'-羟基-3'-甲氧基苯基）-癸-3-醇（M9）和1-（4'-羟基-3'-甲氧基苯基）-癸-3-酮（M11），以及2种新的氧化代谢产物(1E, 4E)-（4'-羟基-3'-甲氧基苯基）-癸-1,4-二烯-3-酮（M14）和（E)-（4'-羟基-3'-甲氧基苯基）-癸-1-烯-3-酮（M15））。采用Michaelis-Menten理论定量分析了各物种肝微粒体中M6的动力学参数。一种广泛的cyp450抑制剂，1-氨基苯并三唑，阻止氧化代谢物M14和M15的形成，18β-甘草次酸，一种醛酮还原酶抑制剂，在所有物种中根除还原性代谢物M6， M9和M11的形成。代谢产物M14和M15均具有抑制癌细胞生长和诱导细胞凋亡的活性，其中M14的活性高于[6]-shogaol。我们得出的结论是，[6]-shogaol在哺乳动物物种小鼠、大鼠、狗、猴和人类中广泛代谢，并且在规划[6]-shogaol化学预防的临床前试验时需要考虑显著的物种间差异。
There are limited data on the metabolism of [6]-shogaol, a major bioactive component of ginger. This study demonstrates metabolism of [6]-shogaol in liver microsomes from mouse, rat, dog, monkey, and human. The in vitro metabolism of [6]-shogaol was compared among five species using liver microsomes from mouse, rat, dog, monkey, and human. Following incubations with [6]-shogaol, three major reductive metabolites 1-(4'-hydroxy-3'-methoxyphenyl)-4-decen-3-ol (M6), 1-(4′-hydroxy-3′-methoxyphenyl)-decan-3-ol (M9), and 1-(4'-hydroxy-3'-methoxyphenyl)-decan-3-one (M11), as well as two new oxidative metabolites (1E, 4E)-1-(4'-hydroxy-3'-methoxyphenyl)-deca-1,4-dien-3-one (M14) and (E)-1-(4'-hydroxy-3'-methoxyphenyl)-dec-1-en-3-one (M15) were found in all species. The kinetic parameters of M6 in liver microsomes from each respective species were quantified using Michaelis-Menten theory. A broad CYP-450 inhibitor, 1-aminobenzotriazole, precluded the formation of oxidative metabolites M14 and M15, and 18β-glycyrrhetinic acid, an aldo-keto reductase inhibitor, eradicated the formation of the reductive metabolites M6, M9, and M11 in all species. Metabolites M14 and M15 were tested for cancer cell growth inhibition and induction of apoptosis and both showed substantial activity, with M14 displaying greater potency than [6]-shogaol. We conclude that [6]-shogaol is metabolized extensively in mammalian species mouse, rat, dog, monkey, and human, and that there are significant interspecies differences to consider when planning pre-clinical trials towards [6]-shogaol chemoprevention.
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姜的6个shogaol提取物上调细胞和小鼠的抗氧化剂防御系统。
DOI：
10.3390/molecules17078037
发表时间：
2012-07-04
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
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通讯作者：
Jeong WS
影响因子：
3.9
作者：
Chen, Huadong;Lv, Lishuang;Sang, Shengmin
通讯作者：
Sang, Shengmin
影响因子：
2
作者：
Jiang, HL;S贸lyom, AM;Gang, DR
通讯作者：
Gang, DR
影响因子：
3.9
作者：
Iwabu, Jun;Watanabe, Junko;Hanazaki, Kazuhiro
通讯作者：
Hanazaki, Kazuhiro
影响因子：
9.8
作者：
Chen, FC;Li, WH
通讯作者：
Li, WH