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Title: Cellular uptake and metabolism of curcuminoids in monocytes/macrophages: regulatory effects on lipid accumulation

Author
item Nakagawa, Kiyotaka - Tohoku University
item Zingg, Jean-marc - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Kim, Sharon - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Thomas, Michael - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Dolnikowski, Gregory - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Azzi, Angelo - Jean Mayer Human Nutrition Research Center On Aging At Tufts University
item Miyazawa, Teruo - Tohoku University
item Meydani, Mohsen - Jean Mayer Human Nutrition Research Center On Aging At Tufts University

Submitted to: British Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/5/2014
Publication Date: 4/1/2014
Citation: Nakagawa, K., Zingg, J., Kim, S.H., Thomas, M.J., Dolnikowski, G.D., Azzi, A., Miyazawa, T., Meydani, M. 2014. Cellular uptake and metabolism of curcuminoids in monocytes/macrophages: regulatory effects on lipid accumulation. British Journal of Nutrition. 11:1-7.

Interpretive Summary: Curcumin is the principal component of the popular Indian spice turmeric, which is a member of the ginger family. Some studies suggest that curcumin may be useful for the prevention and treatment of several diseases such as atherosclerosis, a disease in which fat plaques can block blood flow and lead to stroke or heart attack. We have previously showed that curcumin may help remove fat from the bloodstream in mice. Therefore, in the present study, we wanted to learn more about the way in which curcumin is able to clear up fats from the bloodstream by using immune cells (known as monocytes and macrophages). We found that curcumin was readily taken up by monocytes/macrophages. In parallel with this action, fats or lipids were also taken up by these cells. The efficient uptake of curcumin into the cells implies that this uptake may occur via some mechanism that also allows the fats to be taken up and cleared from the bloodstream. Present results would be useful for applying the use of curcumin and similar natural substances for nutritional and medicinal purposes, especially in the area of vascular health and disease.

Technical Abstract: We previously showed that curcumin (CUR) may increase lipid accumulation in cultured THP-1 monocytes/macrophages, but tetrahydrocurcumin (THC), an in vivo metabolite of CUR, had no such effect. In the present study, we have hypothesized that different cellular uptake and/or metabolism of CUR and THC might be a possible explanation for the previously observed differences in their effects on lipid accumulation in THP-1. Chromatography with tandem mass spectrometry revealed that CUR was readily taken up by THP-1 monocytes/macrophages and slowly metabolized to hexahydrocurcumin sulfate. In contrast, uptake of THC was low. In parallel with CUR uptake, lipid uptake was observed in THP-1 macrophages but not with THC or with another CUR metabolite and structurally related compounds. From these results, it is possible to deduce that CUR and THC are taken up and metabolized differently in THP-1 cells, which determine their biological activity. The remarkable differential cellular uptake of CUR, relative to THC and other similar molecules, may imply that the CUR uptake in the cells may occur via a transporter.