Institute of Applied Biosciences, Chair of Food Chemistry, Karlsruhe Institute of Technology (KIT), Karlsruhe, Germany.
Mol Nutr Food Res. 2013 Sep;57(9):1543-9. doi: 10.1002/mnfr.201200113. Epub 2012 Aug 29.
Curcumin (CUR) and its major metabolite hexahydro-CUR were studied in Caco-2 cells and in the Caco-2 Millicell® system in vitro to simulate their in vivo intestinal metabolism and absorption in humans.
Analysis of the incubation medium and cell lysate showed that Caco-2 cells reduce CUR to hexahydro-CUR and octahydro-CUR, and conjugate CUR and its reductive metabolites with glucuronic acid and sulfate. Using the Caco-2 Millicell® system, an efficient transfer of the conjugates into the basolateral, but not the apical, compartment was observed after apical administration. Likewise, hexahydro-CUR was reduced to octahydro-CUR, and glucuronide and sulfate conjugates almost exclusively permeated to the basolateral side. The apparent permeability coefficients (Papp values) of CUR, hexahydro-CUR and their metabolites were determined and found to be extremely low for unchanged CUR, but somewhat higher for hexahydro-CUR and the conjugated metabolites.
The results of this study clearly show that the systemic bioavailability of CUR from the intestine after oral intake must be expected to be virtually zero. Reductive and conjugated metabolites, formed from CUR in the intestine, exhibit moderate absorption. Thus, any biological effects elicited by CUR in tissues other than the gastrointestinal tract are likely due to CUR metabolites.
姜黄素 (CUR) 及其主要代谢物六氢-CUR 在 Caco-2 细胞和 Caco-2 Millicell®系统中进行了研究，以模拟其在人体中的肠道代谢和吸收。
对孵育介质和细胞裂解物的分析表明，Caco-2 细胞将 CUR 还原为六氢-CUR 和八氢-CUR，并与葡萄糖醛酸和硫酸盐结合 CUR 和其还原代谢物。使用 Caco-2 Millicell®系统，在给予顶端后，观察到缀合物有效地转移到基底外侧，但不在顶端侧。同样，六氢-CUR 被还原为八氢-CUR，而葡萄糖醛酸和硫酸盐缀合物几乎完全渗透到基底外侧。测定了 CUR、六氢-CUR 及其代谢物的表观渗透系数 (Papp 值)，发现未改变的 CUR 的 Papp 值极低，但六氢-CUR 和缀合代谢物的 Papp 值略高。
本研究的结果清楚地表明，口服摄入后从肠道进入全身的 CUR 的生物利用度几乎可以预计为零。在肠道中形成的 CUR 的还原和缀合代谢物表现出中等的吸收。因此，除胃肠道以外的组织中 CUR 引起的任何生物学效应可能归因于 CUR 代谢物。
