Tissue distribution in mice and metabolism in murine and human liver of apigenin and tricin, flavones with putative cancer chemopreventive properties
Tissue distribution in mice and metabolism in murine and human liver of apigenin and tricin, flavones with putative cancer chemopreventive properties
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DOI：
10.1007/s00280-006-0368-5
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发表时间：
2007-07-01
影响因子：
3
通讯作者：
Gescher, Andreas J.
中科院分区：
文献类型：
--
作者：
Cai, Hong;Boocock, David J.;Gescher, Andreas J.
目的芹菜素和麦黄酮分别存在于叶菜和米糠中，在临床前啮齿动物模型中具有癌症化学预防特性。其药理学仅知之甚少。方法采用HPLC-UV法测定芹菜素或麦黄酮（0.2%）对小鼠血浆、肝脏和胃肠道黏膜中黄酮含量的影响。在体外与尿苷5 '-二磷酸葡萄糖醛酸或3'-磷酸腺苷-5 '磷酸硫酸盐共孵育的小鼠和人肝微粒体或胞质溶胶中研究黄酮代谢。黄酮代谢产物的特点是通过在线HPLC-MS spectrometer.Results饮食管理黄酮7天后，麦黄酮在血浆，肝脏和粘膜中的水平超过芹菜素的350，33和100%，分别。芹菜素在肝微粒体中比麦黄酮葡萄糖醛酸化更快，而麦黄酮在肝细胞溶质中比芹菜素更容易发生磺化。无论是黄酮的葡萄糖醛酸化的速度比磺化快得多。黄酮monoglucuronides和单硫酸盐被确定为代谢产物在微粒体和胞质incubations.Conclusions的代谢产物时，在小鼠的饮食麦黄酮似乎是更可用的血液和组织中的芹菜素。其葡萄糖醛酸化的差异可能是其不同可用性的原因。因此，麦黄酮可能比芹菜素具有药代动力学优势。这种类型的信息可能有助于决定选择哪种黄酮类化合物用于临床开发。
Purpose The flavones apigenin and tricin, which occur in leafy vegetables and rice bran, respectively, possess cancer chemopreventive properties in preclinical rodent models. Their pharmacology is only poorly understood. We compared their tissue levels in mice in vivo and their metabolism in liver fractions in vitro.Methods Mice received apigenin or tricin (0.2%) with their diet for 5-7 days, and flavone levels were compared in the plasma, liver and gastrointestinal mucosa using HPLC-UV. Flavone metabolism was investigated in murine and human liver microsomes or cytosol in vitro co-incubated with uridine 5'-diphosphoglucuronic acid or 3'-phosphoadenosine-5' phosphosulfate. Flavone metabolites were characterized by on-line HPLC-mass spectrometry.Results After dietary administration of flavones for 7 days, levels of tricin in plasma, liver and mucosa exceeded those of apigenin by 350, 33 and 100%, respectively. Apigenin was more rapidly glucuronidated than tricin in liver microsomes, whilst tricin underwent swifter sulfonation than apigenin in liver cytosol. For either flavone the rate of glucuronidation was much faster than that of sulfonation. Flavone monoglucuronides and monosulfates were identified as metabolites in microsomal and cytosolic incubations, respectively.Conclusions When consumed with the diet in mice tricin seems to be more available than apigenin in blood and tissues. Differences in their glucuronidation may account for their differential availability. Thus tricin may have a pharmacokinetic advantage over apigenin. This type of information may help decide which flavonoids to select for clinical development.