An epoxide-furanoid rearrangement of spinach neoxanthin occurs in the gastrointestinal tract of mice and in vitro: Formation and cytostatic activity of neochrome stereoisomers
An epoxide-furanoid rearrangement of spinach neoxanthin occurs in the gastrointestinal tract of mice and in vitro: Formation and cytostatic activity of neochrome stereoisomers
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DOI：
10.1093/jn/134.9.2237
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发表时间：
2004-09-01
影响因子：
4.2
通讯作者：
Nagao, A
中科院分区：
文献类型：
--
作者：
Asai, A;Terasaki, M;Nagao, A
新黄质是绿叶蔬菜中的一种主要类胡萝卜素，据报道，它通过诱导人前列腺癌细胞凋亡而表现出强大的抗增殖作用。然而，哺乳动物饮食中新黄质的代谢命运仍然未知。本研究通过研究新黄质在小鼠体内的胃肠代谢和菠菜的体外消化，估计了新黄质代谢物对PC-3人前列腺癌细胞的抗增殖作用。给小鼠口服纯化的新黄质2小时后，在血浆、肝脏和小肠内容物中检测到不变的新黄质和新黄质立体异构体（8′-R/S）。为了评估胃酸对饲料中新黄质转化为新色素（环氧-类呋喃重排）的影响，将菠菜与pH为2.0或3.0的胃蛋白酶- hci溶液（胃相）和胰胆盐溶液（肠相）一起体外消化。当胃相pH为2.0时，菠菜新黄质在消化过程中大部分转化为(R/S)-新色素，而在pH为3.0时，这种重排程度较低。（R/S）-新色素在低于或等于20 μ mol/L的浓度下对PC-3细胞和新黄质增殖有剂量依赖性的抑制作用。虽然新黄质诱导凋亡细胞明显死亡，但(R/S)-新黄质抑制细胞增殖，无明显凋亡诱导作用。上述结果表明，饲料中的新黄质在肠道吸收前通过胃酸转化为(R/S)-新色素，(R/S)-新色素通过诱导细胞抑制作用对PC-3细胞具有抗增殖作用。
Neoxanthin, a major carotenoid in green leafy vegetables, was reported to exhibit potent antiproliferative effect via apoptosis induction on human prostate cancer cells. However, the metabolic fate of dietary neoxanthin in mammals remains unknown. In the present study, we investigated the gastrointestinal metabolism of neoxanthin in mice and the in vitro digestion of spinach, and estimated the anti proliferative effect of neoxanthin metabolites on PC-3 human prostate cancer cells. Two hours after the oral administration to mice of purified neoxanthin, unchanged neoxanthin and stereoisomers of neochrome (8'-R/S) were detected in the plasma, liver, and small intestinal contents. To estimate the effect of intragastric acidity on the conversion of dietary neoxanthin into neochrome (epoxide-furanoid rearrangement), spinach was digested in vitro by incubating it with a pepsin-HCI solution at pH 2.0 or 3.0 (gastric phase) followed by a pancreatin-bile salt solution (intestinal phase). Spinach neoxanthin was largely converted into (R/S)-neochrome during the digestion when the gastric phase was set at pH 2.0, whereas the rearrangement was observed to a lesser extent at pH 3.0. (R/S)-neochrome dose-dependently inhibited the proliferation of PC-3 cells as well as neoxanthin at concentrations less than or equal to 20 mumol/L. Although neoxanthin induced evident apoptotic cell death, (R/S)-neochrome inhibited the cell proliferation without obvious apoptosis induction. These results indicate that dietary neoxanthin is partially converted into (R/S)-neochrome by intragastric acidity before intestinal absorption and that (R/S)-neochrome exhibits an anti proliferative effect on PC-3 cells by the induction of cytostasis.