Analyze the Metabolites in Rats Small Bowel by UPLC-Q-TOF/MS after Oral Administration of Icaritin

Jun Jiang^{1, 2}, Li Cui² and Xiaobin Jia^2,

¹College of Pharmacy, Nanjing University of Chinese Medicine, 138 Xianlin Avenue, Nanjing, Jiangsu Province, China

²Key Laboratory of New Drug Delivery System of Chinese Material Medica, Jiangsu Provincial Academy of Chinese Medicine, 100# Shizi Road, Nanjing, Jiangsu Province, China

Cite this paper:
Jun Jiang, Li Cui and Xiaobin Jia. Analyze the Metabolites in Rats Small Bowel by UPLC-Q-TOF/MS after Oral Administration of Icaritin. Journal of Food and Nutrition Research. 2014; 2(11):819-823. doi: 10.12691/jfnr-2-11-10

Abstract

Icaritin (IT) was the main product of intestinal metabolism of main flavonoid compounds in Epimedium. Our previous study of the intestinal metabolites of IT was mainly focused on detecting the metabolites in rat faeces, which did not directly reacted and premeditate the complex environment of small bowel. Therefore, in this paper, the contents of small bowel were collected and analyzed by ultra performance liquid chromatography/quadrupole time of flight mass spectrometry (UPLC-Q-TOF/ MS), and then the main metabolites and metabolic pathways of IT in rats small bowel were explained clearly. Finally, six major metabolites were found in rats small bowel after oral administration of IT, which were m/z 367.1187, 383.1125, 545.1678, 559.1448, 561.1610, and 721.1979, respectively. These six metabolites and their chemical structures were firstly discovered and identified by us. The metabolites m/z 559.1448 and 545.1678 were the combinations of m/z 383.1125 and 369.1308 (IT) linked with one glucuronic acid, respectively. In the intestinal contents, the IT prototype had the highest peak areas, which indicated that IT mainly existed in the form of prototype. Meanwhile, our results further confirmed that the bioavailability of IT might be low, and subsequent research would likely focus on improving the biopharmaceutical properties and enhancing the bioavailability of IT. This study was useful and complementary to our previous findings.

Keywords:
metabolites small bowel icaritin glucuronidation UPLC-Q-TOF/MS

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References:

[1]	Ma, H., He, X., Yang, Y., Li, M., Hao, D., Jia, Z., “The genus Epimedium: an ethnopharmacological and phytochemical review,” Journal of Ethnopharmacology, 34 519-541. 2011.
[2]	Lee, S.H., Jung, B.H., Kim, S.Y., Chung, B.C., “Determination of phytoestrogens in traditional medicinal herbs using gas chromatography-mass spectrometry,” Journal of Nutritional Biochemistry, 15 452-460. 2004.
[3]	Cui, L., Sun, E., Zhang, Z.H., Tan, X.B., Wei, Y.J., Jin, X., Xiao, B.J., “Enhancement of epimedium fried with suet oil based on in vivo formation of self-assembled flavonoid compound nanomicelles,” Molecules, 17 12984-12996. 2012.
[4]	Zhang, J.F., Li, G., Meng, C.L., Dong, Q., Chan, C.Y., He, M.L., “Total flavonoids of Herba Epimedii improves osteogenesis and inhibits osteoclastogenesis of human mesenchymal stem cells,” Phytomedicine, 16 521-529. 2009.
[5]	Zhang, D., Zhang, J., Fong, C., Yao, X., Yang, M., “Herba epimedii flavonoids suppress osteoclastic differentiation and bone resorption by inducing G2/M arrest and apoptosis,” Biochimie, 94 2514-2522. 2012.
[6]	Zhang, G., Qin, L., Hung, W.Y., Shi, Y.Y., Leung, P.C., Yeung, H.Y., “Flavonoids derived from herbal Epimedium Brevicornum Maxim prevent OVX-induced osteoporosis in rats independent of its enhancement in intestinal calcium absorption,” Bone, 38 818-825. 2006.
[7]	Tong, J.S., Zhang, Q.H., Huang, X., Fu, X.Q., Qi, S.T., Wang, Y.P., Hou, Y., Sheng, J., Sun, Q.Y., “Icaritin causes sustained ERK1/2 activation and induces apoptosis in human endometrial cancer cells,” PLoS One, 6 e16781. 2011.
[8]	Zhou, J., Chen, Y., Wang, Y., Gao, X., Qu, D., Liu, C., “A comparative study on the metabolism of Epimedium koreanum Nakai-prenylated flavonoids in rats by an intestinal enzyme (lactase phlorizin hydrolase) and intestinal flora,” Molecules, 19 177-203. 2013.
[9]	Van, E.J., Robben, J., De, P.G., Merckx, R., Eyssen, H., “Isolation and identification of intestinal steroid-desulfating bacteria from rats and humans,” Applied and Environmental Microbiology, 54 2112-2117. 1988.
[10]	Chen, Y., Wang, J.Y.,,Jia, X.B., Tan, X.B., Hu, M., “Rloe of intestinal hydrolase in the absorption of prenylated flavonoids present in Yinyanghuo,” Molecules, 16 1336-1348. 2011.
[11]	Bowey, E., Adlercreutz, H., Rowland, I., “Metabolism of isoflavones and lignans by the gut microflora: a study in germ-free and human flora associated rats,” Food and Chemical Toxicology, 41 631-636. 2003.
[12]	Jiang, J., Feng, L., Sun, E., Li, H., Cui, L., Jia, X., “Metabolic profiling of isomeric aglycones central-icaritin (c-IT) and icaritin (IT) in osteoporotic rats by UPLC-QTOF-MS,” Drug Testing and Analysis. [Epub ahead of print]. 2014.
[13]	Chang, Q., Wang, G.N., Li, Y., Zhang, L., You, C., Zheng, Y., “Oral absorption and excretion of icaritin, an aglycone and also active metabolite of prenylflavonoids from the Chinese medicine Herba Epimedii in rats,” Phytomedicine, 19 1024-1028. 2012.
[14]	Qian, Q., Li, S.L., Sun, E., Zhang, K.R., Tan, X.B., Wei, Y.J., Fan, H.W., Cui, L., Jia, X.B., “Metabolite profiles of icariin in rat plasma by ultra-fast liquid chromatography coupled to triple-quadrupole/time-of-flight mass spectrometry,” Journal of Pharmaceutical and Biomedical Analysis, 66 392-398. 2012.
[15]	Zhao, H., Fan, M., Fan, L., Sun, J., Guo, D., “Liquid chromatography-tandem mass spectrometry analysis of metabolites in rats after administration of prenylflavonoids from Epimediums,” Journal of Chromatography B, 878 1113-1124. 2010.
[16]	Liang, Z., Zhang, J., Wong, L., Yi, T., Chen, H., Zhao, Z., Characterization of secondary metabolites from the raphides of calcium oxalate contained in three araceae family plants using laser microdissection and ultra-high performance liquid chromatography quadrupole time of flight-mass spectrometry. European Journal of Mass Spectrometry, 19 195-210. 2013.
[17]	Li, S.L. Shen, H., Zhu, L.Y., Xu, J., Jia, X.B., Zhang, H.M., “Ultra-high- performance liquid chromatography quadrupole/time of flight mass spectrometry based chemical profiling approach to rapidly reveal chemical transformation of sulfur-fumigated medicinal herbs, a case study on white ginseng,” Journal of Chromatography A, 1231 31-45. 2012.
[18]	Gika, H.G., Theodoridis, G.A., Wilson, I.D., “Hydrophilic interaction and reversed-phase ultra-performance liquid chromatography TOFMS for metabono- mic analysis of Zucker rat urine”. Journal of Separation Science, 31 1598-1608. 2008.
[19]	He, C., Zhou, D., Li, J., Han, H., Ji, G., Yang, L., “Identification of 20(S)-protopanaxatriol metabolites in rats by ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight tandem mass spectrometry and nuclear magnetic resonance spectroscopy,” Journal of Pharmaceutical and Biomedical Analysis, 88 497-508. 2014.
[20]	Lenz, E.M., Williams, R.E., Sidaway, J., Smith, B.W., Plumb, R.S., Johnson, K.A., “The application of microbore UPLC/oa TOF-MS and 1H NMR spectroscopy to the metabonomic analysis of rat urine following the intravenous administration of pravastatin,” Journal of Pharmaceutical and Biomedical Analysis, 44 845-852. 2007.
[21]	Cui, L., Sun, E., Zhang, Z., Qian, Q., Tan, X., Xu, F., Jia, X.B., “Metabolite profiles of epimedin B in rats by ultraperformance liquid chromatography quadrupole time of flight mass spectrometry,” Journal of Agricultural and Food Chemistry, 61 3589-3599. 2013.