Differential cellular uptake and metabolism of curcuminoids in monocytes/macrophages: regulatory effects on lipid accumulation

Abstract

We have previously shown that curcumin (CUR) may increase lipid accumulation in cultured human acute monocytic leukaemia cell line THP-1 monocytes/macrophages, but that tetrahydrocurcumin (THC), an in vivo metabolite of CUR, has no such effect. In the present study, we hypothesised that the 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 monocytes/macrophages. Chromatography with tandem MS revealed that CUR was readily taken up by THP-1 monocytes/macrophages and slowly metabolised to hexahydrocurcumin sulphate. By contrast, the uptake of THC was low. In parallel with CUR uptake, increased lipid uptake was observed in THP-1 macrophages but not with the uptake of THC or another CUR metabolite and structurally related compounds. From these results, it is possible to deduce that CUR and THC are taken up and metabolised 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 into cells may occur via a transporter.

Application of ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry to identify curcumin metabolites produced by human intestinal bacteria

“…In cells and in vivo, curcumin and its reductive metabolites appear to be easily conjugated [11][12][13][14][15][16][17][18][19]. Glucuronidation is the predominating pathway of conjugation, and the glucuronide of hexahydro-curcumin is usually found as the major metabolite of curcumin in body fluids, organs and cells [24][25][26]. Interestingly, no trace of its glucuronidate and sulfate conjugates could be found after incubation with human microflora.…”

Curcumin Differs from Tetrahydrocurcumin for Molecular Targets, Signaling Pathways and Cellular Responses

“…•Curcumin, but not THC, was taken up and increased lipid accumulation in monocytic cell line THP-1 [44].…”

“…Thus, the up-regulation of FOXO3a activity by curcumin, but not by THC, could be a mechanism to protect against oxidant-and lipid-induced damage in the inflammatory cells of the vascular system. Nakagawa et al [44] suggested that differential cellular uptake of curcumin and THC may be linked to the previously observed differences in their effects on lipid accumulation in macrophages. Indeed, the authors found that curcumin was readily taken up by the cells and slowly metabolized to hexahydrocurcumin sulfate but that uptake of THC was low; this finding correlated with increased lipid uptake of cells with curcumin but decreased lipid uptake of cells with THC.…”

Curcumin Inhibits Transforming Growth Factor β Induced Differentiation of Mouse Lung Fibroblasts to Myofibroblasts

“…Curcumin has shown a variety of potentially beneficial effects, including lower blood pressure, anti-tumor, anti-inflammatory, choleretic, antioxidant, and anti-inflammatory activities (Nakagawa et al, 2014; Seo et al, 2014; Zhang Y. et al, 2014). Notably, curcumin effectively reduces profibrotic effects in fibroblasts in vitro via the inhibition of key steps in the TGF-β signaling pathway (Smith et al, 2010).…”