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Rapid screening and identification of metabolites of quercitrin produced by the human intestinal bacteria using ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry

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Abstract

Ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry (UPLC/Q-TOF MS) technique combined with Metabolynx™ software was used for analysis of the metabolites of quercitrin by the isolated human intestinal bacteria from the human feces. Four metabolites of quercitrin were detected and tentatively identified based on the characteristics of their protonated ions. The metabolites were metabolized by four main metabolic pathways including hydroxylation, demethylation, deglycosylation and ring-cleavage. Quercitrin was metabolized to the hydroxyquercitrin and desmethylquercitrin by the majority of the isolated intestinal bacteria such as Bacteroides sp. 54, and was degraded to the deglycosylated product quercetin by rhamnosidase and further ring-cleavage metabolite 3,4-dihydroxybenzoic acid by the minority of the isolated bacteria such as Bacteroides sp. 45. The metabolic pathways and most of the metabolites of quercitrin were reported for the first time.

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References

  • Babujanarthanam, R., P. Kavitha, U.S. Mahadeva Rao, and M.R. Pandian. 2011. Quercitrin: A bioflavonoid improves the antioxidant status in streptozotocin: Induced diabetic rat tissues. Molecular and Cellular Biochemistry 358: 121–129.

    Article  CAS  PubMed  Google Scholar 

  • Boots, A.W., L.C. Wilms, E.L. Swennen, J.C. Kleinjans, A. Bast, and G.R. Haenen. 2008. In vitro and ex vivo anti-inflammatory activity of quercetin in healthy volunteers. Nutrition 24: 703–710.

    Article  CAS  PubMed  Google Scholar 

  • Cai, Y.Z., S. Mei, X. Jie, Q. Luo, and H. Corke. 2006. Structure-radical scavenging activity relationships of phenolic compouds from traditional Chinese medicinal plants. Life Sciences 78: 2872–2888.

    Article  CAS  PubMed  Google Scholar 

  • Camuesco, D., M. Comalada, M.E. Rodriguez-Cabezas, A. Nieto, M.D. Lorente, A. Concha, A. Zarzuelo, and J. Galvez. 2004. The intestinal anti-inflammatory effect of quercitrin is associated with an inhibition in iNOS expression. British Journal of Pharmacology 143: 908–918.

    Article  CAS  PubMed  Google Scholar 

  • Chen, P., Y. Luo, L. Hai, S. Qian, and Y. Wu. 2010. Design, synthesis, and pharmacological evaluation of the aqueous prodrugs of desmenthyl anethole trithione with hepatoprotective activity. European Journal of Medicinal Chemistry 45: 3005–3010.

    Article  CAS  PubMed  Google Scholar 

  • Chen, Z.Y., P.T. Chan, K.Y. Ho, K.P. Fung, and J. Wang. 1996. Antioxidant activity of natural flavonoids is governed by number and location of their aromatic hydroxyl groups. Chemistry and Physics of Lipids 79: 157–163.

    Article  CAS  PubMed  Google Scholar 

  • Comalada, M., D. Camuesco, S. Sierra, I. Ballester, J. Xaus, J. Galvez, and A. Zarzuelo. 2005. In vivo quercitrin anti-inflammatory effect involves release of quercetin, which inhibits inflammation through down-regulation of the NF-kappaB pathway. European Journal of Immunology 35: 584–592.

    Article  CAS  PubMed  Google Scholar 

  • Da Silva, E.R., C. Maquiaveli Cdo, and P.P. Magalhaes. 2012. The leishmanicidal flavonols quercetin and quercitrin target Leishmania amazonensis arginase. Experimental Parasitology 130: 183–188.

    Article  PubMed  Google Scholar 

  • Dajas, F. 2012. Life or death: neuroprotective and anticancer effects of quercetin. Journal of Ethnopharmacology 143: 383–396.

    Article  CAS  PubMed  Google Scholar 

  • Gadotti, V.M., L.O. Schmeling, C. Machado, F.H. Liz, V.C. Filho, C. Meyre-Silva, and A.R. Santos. 2005. Antinociceptive action of the extract and the flavonoid quercitrin isolated from Bauhinia microstachya leaves. Journal of Pharmacy and Pharmacology 57: 1345–1351.

    Article  CAS  PubMed  Google Scholar 

  • Galvez, J., F. Sanchez de Medina, J. Jimenez, M.I. Torres, M.I. Fernandez, M.C. Nunez, A. Rios, A. Gil, and A. Zarzuelo. 1995. Effect of quercitrin on lactose-induced chronic diarrhoea in rats. Planta Medica 61: 302–306.

    Article  CAS  PubMed  Google Scholar 

  • Han, H., L. Yang, Y. Xu, Y. Ding, S.W. Annie Bligh, T. Zhang, and Z.T. Wang. 2011. Identification of metabolites of geniposide in rat urine using ultra-performance liquid chromatography time-of-flight tandem mass spectrometry. Rapid Communications in Mass Spectrometry 25: 3339–3350.

    Article  CAS  PubMed  Google Scholar 

  • Hur, H.G., J.O. Lay, R.D. Beger, J.P. Freeman, and F. Rafii. 2000. Isolation of human intestinal bacteria metabolizing the natural isoflavone glycosides daidzin and genistin. Archives of Microbiology 174: 422–428.

    Article  CAS  PubMed  Google Scholar 

  • Justesen, U., and E. Arrigoni. 2001. Electrospray ionisation mass spectrometric study of degradation products of quercetin, quercetin-3-glucoside and quercetin-3-rhamnoside, produced by in vitro fermentation with human faecal flora. Rapid Communications in Mass Spectrometry 15: 477–483.

    Article  CAS  PubMed  Google Scholar 

  • Kaewamatawong, R., M. Kitajima, N. Kogure, and H. Takayama. 2008. Flavonols from Bauhinia malabarica. Journal of Natural Medicines 62: 364–365.

    Article  CAS  PubMed  Google Scholar 

  • Kim, D.H., S.Y. Kim, S.Y. Park, and M.J. Han. 1999. Metabolism of quercitrin by human intestinal bacteria and its relation to some biological activities. Biological and Pharmaceutical Bulletin 22: 749–751.

    Article  CAS  PubMed  Google Scholar 

  • Kleemann, R., L. Verschuren, M. Morrison, S. Zadelaar, M.J. van Erk, P.Y. Wielinga, and T. Kooistra. 2011. Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models. Atherosclerosis 218: 44–52.

    Article  CAS  PubMed  Google Scholar 

  • Knaup, B., K. Kahle, T. Erk, A. Valotis, W. Scheppach, P. Schreier, and E. Richling. 2007. Human intestinal hydrolysis of phenol glycosides-a study with quercetin and p-nitrophenol glycosides using ileostomy fluid. Molecular Nutrition and Food Research 51: 1423–1429.

    Article  CAS  PubMed  Google Scholar 

  • Lende, A.B., A.D. Kshirsagar, A.D. Deshpande, M.M. Muley, R.R. Patil, P.A. Bafna, and S.R. Naik. 2011. Anti-inflammatory and analgesic activity of protocatechui acid in rats and mice. Inflammopharmacology 19: 255–263.

    Article  CAS  PubMed  Google Scholar 

  • Lin, C.Y., C.S. Huang, C.Y. Huang, and M.C. Yin. 2009. Anticoagulatory, antiinflammatory, and antioxidative effects of protocatechuic acid in diabetic mice. Journal of Agriculture and Food Chemistry 57: 6661–6667.

    Article  CAS  Google Scholar 

  • Liu, H., Y. Mou, J. Zhao, J. Wang, L. Zhou, M. Wang, D. Wang, J. Han, Z. Yu, and F. Yang. 2010. Flavonoids from Halostachys caspica and their antimicrobial and antioxidant activities. Molecules 15: 7933–7945.

    Article  CAS  PubMed  Google Scholar 

  • Liu, J.B., T.S. Tang, and H.L. Yang. 2006. Antioxidation of quercetin against spinal cord injury in rats. Chinese Journal of Traumatology 9: 303–307.

    CAS  PubMed  Google Scholar 

  • Liu, K.S., S.M. Tsao, and M.C. Yin. 2005. In vitro antibacterial activity of roselle calyx and protocatechuic acid. Phytotherapy Research 19: 942–945.

    Article  CAS  PubMed  Google Scholar 

  • Minamida, K., M. Tanaka, A. Abe, T. Sone, F. Tomita, H. Hara, and K. Asano. 2006. Production of equol from daidzein by gram-positive rod-shaped bacterium isolated from rat intestine. Journal of Bioscience and Bioengineering 102: 247–250.

    Article  CAS  PubMed  Google Scholar 

  • Morand, C., C. Manach, V. Crespy, and C. Remesy. 2000. Respective bioavailability of quercetin aglycone and its glycosides in a rat model. BioFactors 12: 169–174.

    Article  CAS  PubMed  Google Scholar 

  • Muzitano, M.F., E.A. Cruz, A.P. de-Almeida, S.A. Da-Silva, C.R. Kaiser, C. Guette, B. Rossi-Bergmann, and S.S. Costa. 2006. Quercitrin: an antileishmanial flavonoid glycoside from Kalanchoe pinnata. Planta Medica 72: 81–83.

    Article  CAS  PubMed  Google Scholar 

  • Sanchez de Medina, F., J. Galvez, J.A. Romero, and A. Zarzuelo. 1996. Effect of quercitrin on acute and chronic experimental colitis in the rat. Journal of Pharmacology and Experimental Therapeutics 278: 771–779.

    CAS  PubMed  Google Scholar 

  • Sanchez de Medina, F., B. Vera, J. Galvez, and A. Zarzuelo. 2002. Effect of quercitrin on the early stages of hapten induced colonic inflammation in the rat. Life Sciences 70: 3097–3108.

    Article  CAS  PubMed  Google Scholar 

  • Shen, J.Z., C.Y. Yang, C.M. Wu, P.S. Feng, Z.H. Wang, Y. Li, Y.S. Li, and S.X. Zhang. 2010. Identification of the major metabolites of quinocetone in swine urine using ultra-performance liquid chromatography/electrospray ionization quadrupole time-of-flight tandem mass spectrometry. Rapid Communications in Mass Spectrometry 24: 375–383.

    Article  CAS  PubMed  Google Scholar 

  • Tatsis, E.C., S. Boeren, V. Exarchous, A.N. Troganis, J. Vervoort, and I.P. Gerothanassis. 2007. Identification of the major constituents of Hypericum perforatum by LC/SPE/NMR and/or LC/MS. Phytochemistry 68: 383–393.

    Article  CAS  PubMed  Google Scholar 

  • Tsuchihashi, R., M. Kodera, S. Sakamoto, Y. Nakajima, T. Yamazaki, Y. Niiho, T. Nohara, and J. Kinjo. 2009. Microbial transformation and bioactivation of isoflavones from Pueraria flowers by human intestinal bacterial strains. Journal of Natural Medicines 63:254–260.

    Google Scholar 

  • Velvadapu, V., I. Glassford, M. Lee, T. Paul, C. Debrosse, D. Klepacki, M.C. Small, A.D. Mackerell Jr, and R.B. Andrade. 2012. Desmethyl macrolides: Synthesis and evaluation of 4,10-didesmethyl telithromycin. ACS Medicinal Chemistry Letters 3: 211–215.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Venkatakrishnan, K., K.E. Culm, B.L. Ehrenberg, J.S. Harmatz, K.E. Corbett, J.C. Fleishaker, and D.J. Greenblatt. 2005. Kinetics and dynamic of intravenous adinazolam, N-desmethyl adinazolam, and alprazolam in healthy volunteers. Journal of Clinical Pharmacology 45: 529–537.

    Article  CAS  PubMed  Google Scholar 

  • Wagner, C., R. Fachinetto, C.L. Dalla Corte, V.B. Brito, D. Severo, G. de Oliveira CostaDias, A.F. Morel, C.W. Nogueira, and J.B. Rocha. 2006. Quercitrin, a glycoside form of quercetin, prevents lipid peroxidation in vitro. Brain Research 1107: 192–198.

    Article  CAS  PubMed  Google Scholar 

  • Wang, J., J. Lou, C. Luo, L. Zhou, M. Wang, and L. Wang. 2012. Phenolic compounds from halimodendron halodendron (pall.) voss and their antimicrobial and antioxidant activities. International Journal of Molecular Sciences 13: 11349–11364.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wiczkowski, W., J. Romaszko, A. Bucinski, D. Szawara-Nowak, J. Honke, H. Zielinski, and M.K. Piskula. 2008. Quercetin from shallots (Alliumcepa L. var. aggregatum) is more bioavailable than its glucosides. Journal of Nutrition 138: 885–888.

    CAS  PubMed  Google Scholar 

  • Xue, C.F., J.M. Guo, D.W. Qian, J.A. Duan, and Y. Shu. 2011a. Absorption of flavonoids from Abelmoschus manihot extract by in situ intestinal perfusion. Acta Pharmaceutica Sinica 46: 454–459.

    CAS  PubMed  Google Scholar 

  • Xue, X.Y., L.F. Lin, F. Xiao, T. Pi, Y.C. Lai, and H.M. Luo. 2011b. Neurotrophic effects of newborn rat. Chinese Traditional and Herbal Drugs 34: 567–572.

    CAS  Google Scholar 

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Acknowledgments

This work was financially supported by Jiangsu province colleges and universities natural science major basic research projects (No.10KJA360039), Construction Project for Jiangsu Key Laboratory for High Technology Research of TCM Formulae (BM2010576), National Basic Research Program of China (973 Program) (2011CB505300, 2011CB505303), the Nature Science Foundation of China (No.81072996). We are also pleased to thank Waters China Ltd. for technical support.

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  1. Jiangsu Key Laboratory for High Technology Research of TCM Formulae, Nanjing University of Chinese Medicine, 138 Xianlin Road, Nanjing, 210046, People’s Republic of China

    Shu Jiang, Jing Yang, Dawei Qian, Jianming Guo, Er-xin Shang, Jin-ao Duan & Jun Xu

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  1. Shu Jiang
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Correspondence to Shu Jiang or Jin-ao Duan.

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Jiang, S., Yang, J., Qian, D. et al. Rapid screening and identification of metabolites of quercitrin produced by the human intestinal bacteria using ultra performance liquid chromatography/quadrupole-time-of-flight mass spectrometry. Arch. Pharm. Res. 37, 204–213 (2014). https://doi.org/10.1007/s12272-013-0172-9

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