Metabolites Identification of Curcumin,Demethoxycurcumin and Bisdemethoxycurcuminin Rats After Oral Administration of NanoparticleFormulations by Liquid Chromatography Coupledwith Mass Spectrometry

Rui Li<sup>ab</sup>; Qi Wang<sup>a</sup>; Jing-Ran Fan<sup>ac</sup>; Jun-Bin He<sup>a</sup>; Xue Qiao<sup>a</sup>; Cheng Xiang<sup>a</sup>; De-An Guo<sup>a</sup>; Min Ye<sup>a*</sup>

Metabolites Identification of Curcumin,Demethoxycurcumin and Bisdemethoxycurcuminin Rats After Oral Administration of NanoparticleFormulations by Liquid Chromatography Coupledwith Mass Spectrometry

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DOI：10.15806/j.issn.2311-8571.2016.0035

KeyWord:Curcumin, Demethoxycurcumin, Bisdemethoxycurcumin, Solid lipid nanoparticles, Metabolic pathway

Author	Institution
Rui Li^ab	a.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University,38 Xueyuan Road,Beijing , China b.Key Laboratory of Food Biotechnology of Sichuan Province,School of Bioengineering, Xihua University, Chengdu ,China
Qi Wang^a	a.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road,Beijing , China
Jing-Ran Fan^ac	a.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, 38 Xueyuan Road,Beijing , China;c.School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing , China
Jun-Bin He^a	a.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University,38 Xueyuan Road,Beijing ,China
Xue Qiao^a	a.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University,38 Xueyuan Road,Beijing ,China
Cheng Xiang^a	a.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University,38 Xueyuan Road,Beijing ,China
De-An Guo^a	a.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University,38 Xueyuan Road,Beijing ,China
Min Ye^a*	a.State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University,38 Xueyuan Road,Beijing ,China

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Abstract:

Background: Curcuminoids are promising cancer chemopreventive agents. Curcumin, demethoxycurcumin (DMC) and bisdemethoxycurcumin (BDMC) are the major bioactive curcuminoids in turmeric. However, comprehensive metabolic studies of these three curcuminoids are still limited. Objective: To identify the metabolites of curcumin, DMC and BDMC in rats after oral administration of solid lipid nanoparticles (SLNs). Methods: Male Sprague-Dawley rats (250 ± 20 g, body weight) were randomly divided into 4 groups (n=3), and were orally administered with curcumin-SLN, DMC-SLN, BDMC-SLN, or blank-SLN, respectively. Plasma samples (500 μL) via the angular vein were collected at 1, 2 and 4 h post dosing, and the urine and feces samples were collected at 0–12 h and 12–24 h post-intake. An HPLC-DAD-ESI-MSn method was developed to identify the metabolites. The structures of phase II metabolites were further confirmed by enzyme hydrolysis. Results: A total of 34 metabolites were identified in rats plasma, urine, and feces. Most of them were phase II metabolites, including glucuronide conjugates and sulfate conjugates. Among them, the glucuronide conjugates were the major metabolites in rats plasma. In the meanwhile, the three parent curcuminoids were detected in high amounts in the urine and feces samples. Conclusion: The possible metabolic pathways of curcuminoids in rats were proposed.