Department of Food Science, University of Massachusetts, Amherst, MA, USA.
Mol Nutr Food Res. 2013 Nov;57(11):1999-2007. doi: 10.1002/mnfr.201300211. Epub 2013 Jul 26.
Biotransformation of dietary components is important for their in vivo biological activities after oral ingestion. Herein, we investigated biotransformation of 5-demethylnobiletin (a polymethoxyflavone found in citrus fruits) in mice, and its implication in the inhibition of human colon cancer cells.
Urine samples were collected from mice fed with 5-demethylnobiletin (1) and analyzed by LC-ESI-MS and HPLC coupled with an electrochemical detector. Three major metabolites were identified as 5,3'-didemethylnobiletin (2), 5,4'-didemethylnobiletin (3), and 5,3',4'-tridemethylnobiletin (4) by comparing their ESI-MS and HPLC profiles with those of authentic standards synthesized by a multistep route. Cell viability assay in human colon cancer cells demonstrated that all three metabolites of 5-demethylnobiletin, especially 5,3'-didemethylnobiletin (2), showed much stronger inhibitory effects on cancer cell growth than 5-demethylnobiletin. For example, metabolites (2-4) showed IC50 of 0.12, 5.5, and 4.2 μM in SW620 cells, respectively, while 5-demethylnobiletin at 10 μM only caused 37% inhibition after 72 h of treatment.
Three novel metabolites were identified in mice after oral administration of 5-demethylniobiletin. These metabolites exhibited strong inhibitory effects against human colon cancer cells. Our results provide a first report on these bioactive metabolites and warrant further investigation on their molecular mechanism of actions.
膳食成分的生物转化对于其口服摄入后的体内生物学活性非常重要。在此，我们研究了 5-去甲川陈皮素（一种在柑橘类水果中发现的多甲氧基黄酮）在小鼠体内的生物转化及其对人结肠癌细胞的抑制作用。
给喂食 5-去甲川陈皮素（1）的小鼠收集尿液样品，并通过 LC-ESI-MS 和 HPLC 与电化学检测器联用进行分析。通过将其 ESI-MS 和 HPLC 图谱与通过多步途径合成的标准品的图谱进行比较，鉴定出三种主要代谢产物为 5,3'-二甲氧基川陈皮素（2）、5,4'-二甲氧基川陈皮素（3）和 5,3',4'-三甲氧基川陈皮素（4）。在人结肠癌细胞中的细胞活力测定表明，5-去甲川陈皮素的三种代谢产物，特别是 5,3'-二甲氧基川陈皮素（2），对癌细胞生长的抑制作用明显强于 5-去甲川陈皮素。例如，代谢产物（2-4）在 SW620 细胞中的 IC50 分别为 0.12、5.5 和 4.2 μM，而 5-去甲川陈皮素在 10 μM 时仅在 72 h 处理后引起 37%的抑制。
在给小鼠口服 5-去甲川陈皮素后，在体内鉴定出三种新的代谢产物。这些代谢产物对人结肠癌细胞表现出强烈的抑制作用。我们的研究结果首次报道了这些具有生物活性的代谢产物，并需要进一步研究其作用机制。
