Comparison of systemic availability of curcumin with that of curcumin formulated with phosphatidylcholine
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Curcumin, a major constituent of the spice turmeric, suppresses expression of the enzyme cyclooxygenase 2 (Cox-2) and has cancer chemopreventive properties in rodents. It possesses poor systemic availability. We explored whether formulation with phosphatidylcholine increases the oral bioavailability or affects the metabolite profile of curcumin.
Male Wistar rats received 340 mg/kg of either unformulated curcumin or curcumin formulated with phosphatidylcholine (Meriva) by oral gavage. Rats were killed at 15, 30, 60 and 120 min post administration. Plasma, intestinal mucosa and liver were analysed for the presence of curcumin and metabolites using HPLC with UV detection. Identity of curcumin and metabolites was verified by negative ion electrospray liquid chromatography/tandem mass spectrometry.
Curcumin, the accompanying curcuminoids desmethoxycurcumin and bisdesmethoxycurcumin, and the metabolites tetrahydrocurcumin, hexahydrocurcumin, curcumin glucuronide and curcumin sulfate were identified in plasma, intestinal mucosa and liver of rats which had received Meriva. Peak plasma levels and area under the plasma concentration time curve (AUC) values for parent curcumin after administration of Meriva were fivefold higher than the equivalent values seen after unformulated curcumin. Similarly, liver levels of curcumin were higher after administration of Meriva as compared to unformulated curcumin. In contrast, curcumin concentrations in the gastrointestinal mucosa after ingestion of Meriva were somewhat lower than those observed after administration of unformulated curcumin. Similar observations were made for curcumin metabolites as for parent compound.
The results suggest that curcumin formulated with phosphatidylcholine furnishes higher systemic levels of parent agent than unformulated curcumin.
KeywordsCurcumin Phosphatidylcholine Bioavailability Rat Cancer Chemoprevention Metabolism
This study was supported by programme grant G0100874 from the UK Medical Research Council. The authors thank staff of the Biomedical Services Unit, University of Leicester, for animal husbandry and Indena SpA, Milan, Italy, for the provision of formulated curcumin.
- 3.Cheng AL, Hsu CH, Lin JK, Hsu MM, Ho YF, Shen TS, Ko JY, Lin JT, Lin BR, Wu MS, Yu HS, Jee SH, Chen GS, Chen TM, Chen CA, Lai MK, Pu YS, Pan MH, Wang YJ, Tsai CC, Hsieh CY (2001) Phase 1 clinical trial of curcumin, a chemopreventive agent, in patients with high-risk or pre-malignant lesions. Anticancer Res 21:2895–2900PubMedGoogle Scholar
- 5.Fagerholm U, Sjostrom B, Sroka-Markovic J, Wijk A, Svensson M, Lennernas H (1998) The effect of a drug-delivery system consisting of soybean phosphatidyl choline and medium chain monoacylglycerol on the intestinal permeability of hexarelin in the rat. J Pharm Pharmacol 50:467–473PubMedGoogle Scholar
- 7.Garcea G, Berry DP, Jones DJL, Singh R, Dennison AR, Farmer PB, Sharma RA, Steward WP, Gescher AJ (2005) Consumption of the putative chemopreventive agent curcumin by cancer patients: assessment of curcumin levels in the colorectum and their pharmacodynamic consequences. Cancer Epidemiol Biomarkers Prev 14:120–125PubMedGoogle Scholar
- 9.Ireson C, Orr S, Jones DJL, Verschoyle R, Lim CK, Luo JL, Howells L, Plummer S, Jukes R, Williams M, Steward WP, Gescher A (2001) Characterization of metabolites of the chemopreventive agent curcumin in human and rat hepatocytes and in the rat in vivo, and evaluation of their ability to inhibit phorbol ester-induced prostaglandin E-2 production. Cancer Res 61:1058–1064PubMedGoogle Scholar
- 12.Kelloff GJ, Crowell JA, Hawk ET, Steele VE, Lubet RA, Boone CW, Covey JM, Doody LA, Omenn GS, Greenwald P, Hong WK, Parkinson DR, Bagheri D, Baxter GT, Blunden M, Doeltz MK, Eisenhauer KM, Johnson K, Knapp GG, Longfellow DG, Malone WF, Nayfield SG, Seifried HE, Swall LM, Sigman CC (1996) Strategy and planning for chemopreventive drug development: clinical development plans II. J Cell Biochem 63(suppl 26):54–71CrossRefGoogle Scholar
- 18.Plummer SM., Holloway KA, Manson MM, Munks RJL, Kaptein A, Farrow S, Howells L (1999) Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF- kappa B activation via the NIK/IKK signalling complex. Oncogene 18:6013–6020PubMedCrossRefGoogle Scholar
- 21.Sharma RA, Euden SA, Platton SL, Cooke DN, Shafayat A, Hewitt HR, Marczylo TH, Morgan B, Hemingway D, Plummer SM, Pirmohamed M, Gescher AJ, Steward WP (2004) Phase I clinical trial of oral curcumin: biomarkers of systemic activity and compliance. Clin Cancer Res 10:6847–6854PubMedCrossRefGoogle Scholar
- 24.Uehara SI, Yasuda I, Akiyama K, Morita H, Takeya K, Itokawa H (1987) Diarylheptanoids from the rhizomes of curcuma xanthorrhiza and alponia officinarum. Chem Pharm Bull 35:3298–3304Google Scholar
- 25.Workman P, Twentyman P, Balkwill F, Balmain A, Chaplin D, Double J, Embleton J, Newell D, Raymond R, Stables J, Stephens T, Wallace J (1998) United Kingdom Co-ordinating Committee on Cancer Research (UKCCCR) guidelines for the welfare of animals in experimental neoplasia (second edition). Br J Cancer 77:1–10Google Scholar