Pharmacokinetics of curcumin conjugate metabolites in healthy human subjects.
ABSTRACT Curcumin is a polyphenol, found in the spice turmeric, that has promising anticancer properties, but previous studies suggest that absorption of curcumin may be limited.
This study examined the pharmacokinetics of a curcumin preparation in healthy human volunteers 0.25 to 72 h after a single oral dose. Curcumin was administered at doses of 10 g (n = 6) and 12 g (n = 6). Subjects were randomly allocated to dose level for a total of six subjects at each dose level. Serum samples were assayed for free curcumin, for its glucuronide, and for its sulfate conjugate. The data were fit to a one-compartment absorption and elimination model.
Using a high-performance liquid chromatography assay with a limit of detection of 50 ng/mL, only one subject had detectable free curcumin at any of the 14 time points assayed, but curcumin glucuronides and sulfates were detected in all subjects. Based on the pharmacokinetic model, the area under the curve for the 10 and 12 g doses was estimated (mean +/- SE) to be 35.33 +/- 3.78 and 26.57 +/- 2.97 mug/mL x h, respectively, whereas C(max) was 2.30 +/- 0.26 and 1.73 +/- 0.19 mug/mL. The T(max) and t(1/2) were estimated to be 3.29 +/- 0.43 and 6.77 +/- 0.83 h. The ratio of glucuronide to sulfate was 1.92:1. The curcumin conjugates were present as either glucuronide or sulfate, not mixed conjugates.
Curcumin is absorbed after oral dosing in humans and can be detected as glucuronide and sulfate conjugates in plasma.
- SourceAvailable from: Amanda Martins Baviera[Show abstract] [Hide abstract]
ABSTRACT: Knowing that curcumin has low bioavailability when administered orally, and that piperine has bioenhancer activity by inhibition of hepatic and intestinal biotransformation processes, the aim of this study was to investigate the antidiabetic and antioxidant activities of curcumin (90 mg/kg) and piperine (20 or 40 mg/kg), alone or co-administered, incorporated in yoghurt, in streptozotocin (STZ)-diabetic rats. The treatment for 45 days of STZ-diabetic rats with curcumin-enriched yoghurt improved all parameters altered in this experimental model of diabetes: the body weight was increased in association with the weight of skeletal muscles and white adipose tissues; the progressive increase in the glycemia levels was avoided, as well as in the glycosuria, urinary urea, dyslipidemia, and markers of liver (alanine and aspartate aminotransferases and alkaline phosphatase) and kidney (urinary protein) dysfunction; the hepatic oxidative stress was decreased, since the activities of the antioxidant enzymes superoxide dismutase, catalase and gluthatione peroxidase were increased, and the levels of malondialdehyde and protein carbonyl groups were reduced. The dose of 20 mg/kg piperine also showed antidiabetic and antioxidant activities. The treatment of STZ-diabetic rats with both curcumin and 20 mg/kg piperine in yoghurt did not change the antidiabetic and antioxidant activities of curcumin; notably, the treatment with both curcumin and 40 mg/kg piperine abrogated the beneficial effects of curcumin. In addition, the alanine aminotransferase levels were further increased in diabetic rats treated with curcumin and 40 mg/kg piperine in comparison with untreated diabetic rats. These findings support that the co-administration of curcumin with a bioenhancer did not bring any advantage to the curcumin effects, at least about the antidiabetic and antioxidant activities, which could be related to changes on its biotransformation.PLoS ONE 12/2014; 9(12):e113993. · 3.53 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Curcuminoids (curcumin, demethoxycurcumin and bis-demethoxycurcumin) are poorly absorbed and rapidly metabolised and excreted. We investigated in healthy young and aged women and men if co-administration of adjuvants (sesamin, ferulic acid, naringenin, and xanthohumol) alone or in combination with micellar solubilisation improves the bioavailability of curcuminoids. A single oral dose of 98 mg curcuminoids was administered as native curcuminoids (NC), native curcuminoids plus phytochemicals (NCP), curcuminoid micelles (MC) or curcuminoid plus phytochemical micelles (MCP). Total curcuminoids were quantified in blood samples collected over 24 h. Based on the area under the curve, NCP, MC, and MCP increased the bioavailability of the major curcuminoid curcumin 8-, 88-, and 73-fold, respectively, compared to NC. No sex or age differences were observed. Thus, simultaneous ingestion of phytochemicals does modestly increase curcuminoid bioavailability, but does not enhance the large increase in bioavailability observed with micellar curcuminoids.Journal of Functional Foods. 04/2015; 14.
- [Show abstract] [Hide abstract]
ABSTRACT: Curcumin (CUR) is a phytochemical that inhibits the xenobiotic ABC efflux transporters implicated in cancer multidrug resistance (MDR), such as P-glycoprotein (P-gp), Breast cancer resistance protein (BCRP) and Multidrug resistance-associated proteins 1 and 5 (MRP1 & MRP5). The use of CUR in the clinic however, is complicated by its instability and poor pharmacokinetic profile. Monocarbonyl analogues of CUR (MACs) are compounds without CUR's unstable β-diketone moiety and were reported to have improved stability and in vivo disposition. Whether the MACs can be used as MDR reversal agents is less clear, as the absence of a β-diketone may negatively impact transporter inhibition. In this study, we investigated 23 heterocyclic cyclohexanone MACs for inhibitory effects against P-gp, BCRP, MRP1 and MRP5. Using flow cytometry and resistance reversal assays, we found that many of these compounds inhibited the transport activity of the ABC transporters investigated, often with much greater potency than CUR. Overall the analogues were most effective at inhibiting BCRP and we identified three compounds, A12 (2,6-bis((E)-2,5-dimethoxy-benzylidene)cyclohexanone), A13 (2,6-bis((E)-4-hydroxyl-3-methoxybenzylidene)-cyclohexanone) and B11 (3,5-bis((E)-2-fluoro-4,5-dimethoxybenzylidene)-1-methylpiperidin-4-one), as the most promising BCRP inhibitors. These compounds inhibited BCRP activity in a non-cell line, non-substrate-specific manner. Their inhibition occurred by direct transporter interaction rather than modulating protein or cell surface expression. From these results, we concluded that MACs, such as the heterocyclic cyclohexanone analogues in this study, also have potential as MDR reversal agents and may be superior alternatives to the unstable parent compound, CUR. Copyright © 2014. Published by Elsevier Inc.Biochemical Pharmacology 12/2014; · 4.65 Impact Factor