TY - JOUR
T1 - The differential cellular uptake of curcuminoids in vitro depends dominantly on albumin interaction
AU - Itaya, Mayuko
AU - Miyazawa, Taiki
AU - Zingg, Jean Marc
AU - Eitsuka, Takahiro
AU - Azzi, Angelo
AU - Meydani, Mohsen
AU - Miyazawa, Teruo
AU - Nakagawa, Kiyotaka
N1 - Funding Information:
This work was supported in part by the Grants-in-Aid for Scientific Research (KAKENHI (15K14725)), the Asahi Group Foundation, LTD (2018) and Urakami Shokuhin Foundation (2014). Taiki Miyazawa was supported by Japan Society for the Promotion of Science (JSPS) Postdoctoral Fellowships for Research Abroad (995900).
Publisher Copyright:
© 2019
PY - 2019/6
Y1 - 2019/6
N2 - 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-co-glycolic) 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.
AB - 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-co-glycolic) 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.
KW - Albumin
KW - Cellular uptakes
KW - Curcuminoids
KW - High-performance liquid chromatography (HPLC)
KW - Protein drug interaction
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U2 - 10.1016/j.phymed.2019.152902
DO - 10.1016/j.phymed.2019.152902
M3 - Article
C2 - 30981184
AN - SCOPUS:85064079368
SN - 0944-7113
VL - 59
JO - Phytomedicine
JF - Phytomedicine
M1 - 152902
ER -