The differential cellular uptake of curcuminoids in vitro depends dominantly on albumin interaction
The differential cellular uptake of curcuminoids in vitro depends dominantly on albumin interaction
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DOI：
10.1016/j.phymed.2019.152902
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发表时间：
2019-06-01
期刊：
影响因子：
7.9
通讯作者：
Nakagawa, Kiyotaka
中科院分区：
文献类型：
--
作者：
Itaya, Mayuko;Miyazawa, Taiki;Nakagawa, Kiyotaka
背景：姜黄素类化合物主要存在于姜黄属植物根茎中，主要由姜黄素(Cur)、双去甲氧基姜黄素(BDMC)和去甲氧基姜黄素(DMC)三种形式组成。据报道，不同形式的姜黄素具有不同的生物活性。然而，与这些差异相关的机制还没有被很好地理解。最近，我们的实验室发现细胞对这些姜黄素类化合物的摄取存在差异。目的：本研究探讨了细胞对姜黄素的不同摄取机制。方法：在以往研究的基础上，我们假设细胞摄取的差异是由(I)极性、(II)转运体、(III)姜黄素的代谢率和(IV)介质成分引起的。通过(I)将姜黄素类化合物包裹到聚乳酸-乙醇酸纳米粒(PLGA-NPs)中中和极性，(Ii)抑制多酚相关的吸收转运体，(Iii)用液相色谱-串联质谱仪(LC-MS/MS)分析细胞中的姜黄素及其代谢物，(Iv)在细胞研究中使用不同的介质。结果：(I-III)对细胞摄取的差异没有影响。然而，在研究(IV)时，当使用无血清培养液时，不仅Cur而且BDMC和DMC都被掺入细胞中。此外，在含牛血清白蛋白(BSA)的无血清培养液中，只摄取Cur，而不摄取BDMC和DMC。因此，我们确定了细胞对姜黄素类化合物的不同摄取是由介质成分引起的，尤其是BSA。此外，荧光猝灭研究还表明，细胞对姜黄素的不同摄取是由于BSA与各种姜黄素之间的相互作用不同所致。结论：姜黄素与BSA之间的不同相互作用导致了细胞对姜黄素的不同摄取。这项研究的结果可能为姜黄素类化合物显示不同生理活性的机制提供线索。
Background: Curcuminoids, mainly present in the plant rhizomes of turmeric (Curcuma longa), consist of mainly three forms (curcumin (CUR), bisdemethoxycurcumin (BDMC) and demethoxycurcumin (DMC)). It has been reported that different forms of curcuminoids possess different biological activities. However, the mechanisms associated with these differences are not well-understood. Recently, our laboratory found differences in the cellular uptake of these curcuminoids. Therefore, it has been inferred that these differences contribute to the different biological activities.Purpose: In this study, we investigated the mechanisms of differential cellular uptake of these curcuminoids.Method: Based on our previous study, we hypothesized the differential cellular uptake is caused by (I) polarity, (II) transporters, (III) metabolism rate of curcuminoids and (IV) medium components. These four hypotheses were each investigated by (I) neutralizing the polarities of curcuminoids by encapsulation into poly(lactic-coglycolic) acid nanoparticles (PLGA-NPs), (II) inhibition of polyphenol-related absorption transporters, (III) analysis of the cellular curcuminoids and their metabolites by liquid chromatography-tandem mass spectrometry (LC-MS/MS) and (IV) use of different mediums in cell study.Results: The differential cellular uptake was not affected by (I-III). However, when investigating (IV), not only CUR but also BDMC and DMC were incorporated into cells when serum free media was used. Furthermore, when we used the serum free medium containing bovine serum albumin (BSA), only CUR was taken up but BDMC and DMC were not. Therefore, we identified that the differential cellular uptake of curcuminoids is caused by the medium components, especially BSA. Also, the fluorescence quenching study suggested that differential cellular uptake is due to the different interaction between BSA and each curcuminoid.Conclusion: The differential cellular uptake of curcuminoids was caused by the different interaction between curcuminoids and BSA. The results from this study might give clues on the mechanisms by which curcuminoids exhibit different physiological activities.