Allred Clinton D, Twaddle Nathan C, Allred Kimberly F, Goeppinger Tracy S, Churchwell Mona I, Ju Young H, Helferich William G, Doerge Daniel R
Department of Food Science and Human Nutrition, University of Illinois, Urbana-Champaign, IL 61801, USA.
J Agric Food Chem. 2005 Nov 2;53(22):8542-50. doi: 10.1021/jf051246w.
Soy foods and nutritional supplements are widely consumed for potential health benefits. It was previously shown that isoflavone-supplemented diets, which contained equal genistein equivalents, differentially stimulated mammary tumor growth in athymic mice based on the degree of processing. This paper reports plasma pharmacokinetic analysis and metabolite identification using the parental mouse strain fed the same diets, which contained genistin, mixed isoflavones, Novasoy, soy molasses, or soy flour plus mixed isoflavones. Whereas the degree of soy processing did affect several parameters reflecting isoflavone bioavailability and gut microflora metabolism of daidzein to equol, stimulation of tumor growth correlated significantly with only the plasma concentration of aglycon genistein produced by the diets. This conclusion is consistent with the known estrogen agonist activity of genistein aglycon on mammary tumor growth. Conversely, plasma equol concentration was inversely correlated with the degree of soy processing. Although antagonism of genistein-stimulated tumor growth by equol could explain this result, the very low concentration of aglycon equol in plasma (12-fold lower relative to genistein) is inconsistent with any effect. These findings underscore the importance of food processing, which can remove non-nutritive components from soy, on the pharmacokinetics and pharmacodynamics of isoflavones. Such changes in diet composition affect circulating, and presumably target tissue, concentrations of genistein aglycon, which initiates estrogen receptor-mediated processes required for the stimulation of tumor growth in a mouse model for postmenopausal breast cancer.
大豆食品和营养补充剂因其潜在的健康益处而被广泛食用。先前的研究表明，在无胸腺小鼠中，含有等量染料木黄酮当量的异黄酮补充饮食，根据加工程度的不同，对乳腺肿瘤生长的刺激作用也不同。本文报告了对使用相同饮食喂养的亲本小鼠品系进行血浆药代动力学分析和代谢物鉴定，这些饮食包含染料木苷、混合异黄酮、诺瓦大豆、大豆糖蜜或大豆粉加混合异黄酮。虽然大豆的加工程度确实影响了反映异黄酮生物利用度和大豆苷元向雌马酚肠道微生物代谢的几个参数，但肿瘤生长的刺激作用仅与饮食产生的苷元染料木黄酮的血浆浓度显著相关。这一结论与染料木黄酮苷元对乳腺肿瘤生长已知的雌激素激动剂活性一致。相反，血浆雌马酚浓度与大豆加工程度呈负相关。虽然雌马酚对染料木黄酮刺激的肿瘤生长的拮抗作用可以解释这一结果，但血浆中苷元雌马酚的浓度非常低（相对于染料木黄酮低12倍），与任何效应都不一致。这些发现强调了食品加工的重要性，食品加工可以去除大豆中的非营养成分，对异黄酮的药代动力学和药效学产生影响。饮食组成的这种变化会影响循环中以及可能的靶组织中染料木黄酮苷元的浓度，而染料木黄酮苷元会启动雌激素受体介导的过程，这些过程是绝经后乳腺癌小鼠模型中刺激肿瘤生长所必需的。
