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Polish Journal of Food and Nutrition Sciences

The Journal of Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn

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1H NMR-Based Metabolic Profiling of Urine from Mice Fed Lentinula edodes-Derived Polysaccharides

Xiaofei Xu
  • College of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China
  • Other articles by this author:
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/ Jiguo Yang
  • College of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China
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/ Zhengxiang Ning
  • College of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China
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/ Xuewu Zhang
  • Corresponding author
  • College of Food Science and Engineering, South China University of Technology, 381 Wushan Road, Guangzhou 510640, China
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Published Online: 2018-02-14 | DOI: https://doi.org/10.1515/pjfns-2017-0029


A heteropolysaccharide, named L2, from Lentinula edodes has been proved to possess immunostimulating and anti-ageing activities in previous studies, but its acting mechanism was not completely understood. In this study, 1H NMR spectroscopy approach was employed to investigate the metabolic profiles of the urine from adult mice after L2 intervention. Using principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA), 22 potential biomarkers were found to be mainly involved in some metabolic pathways: amino acid metabolism, energy metabolism, lipid metabolism, tricarboxylic acid (TCA) cycle, urea cycle and gut microbiota metabolism. Among them, the significantly altered metabolites include: elevated glutamate (75%) and creatine (64%); decreased proline (65%), betaine (58%), fucose (63%) and dimethylamine (59%). In conclusion, the present data is helpful to understand the mechanisms related to previously confirmed immunomodulation and anti-aging effects of L2, and provide valuable information for mining new functions of L2.

Keywords: Lentinula edodes; polysaccharide; metabolomics; NMR spectroscopy; metabolic pathways


  • 1. Alvers A.L., Fishwick L.K., Wood M.S., Hu D., Chung H.S., Dunn W.A. Jr., Aris J.P., Autophagy and amino acid homeostasis are required for chronological longevity in Saccharomyces cerevisiae. Aging Cell, 2009, 8(4), 353–369.Google Scholar

  • 2. Al-Waiz M., Mikov M., Mitchell S.C., Smith R.L., The exogenous origin of trimethylamine in the mouse. Metabolism, 1992, 41(2), 135–136.CrossrefGoogle Scholar

  • 3. Ascha M., Wang Z., Ascha M.S., Dweik R., Zein N.N., Grove D., Brown J.M., Marshall S., Lopez R., Hanouneh I.A., Metabolomics studies identify novel diagnostic and prognostic indicators in patients with alcoholic hepatitis. World J. Hepatol., 2016, 8(10), 499–508.Google Scholar

  • 4. Barrios C., Beaumont M., Pallister T., Villar J., Goodrich J.K., Clark A., Pascual J., Ley R.E., Spector T.D., Bell J.T., Menni C., Gut-microbiota-metabolite axis in early renal function decline. PLoS One, 2015, 10(8), art. no. e0134311.Google Scholar

  • 5. Bordbar A., Mo M.L., Nakayasu E.S., Schrimpe-Rutledge A.C., Kim Y.M., Metz T.O., Jones M.B., Frank B.C., Smith R.D., Peterson S.N., Hyduke D.R., Adkins J.N., Palsson B.O., Model-driven multi-omic data analysis elucidates metabolic immunomodulators of macrophage activation. Mol. Syst. Biol., 2012, 8, art. no. 558.Google Scholar

  • 6. Chaleckis R., Murakami I., Takada J., Kondoh H., Yanagida M., Individual variability in human blood metabolites identifies age-related differences. Proc. Natl. Acad. Sci. USA, 2016, 113(16), 4252–4259.Google Scholar

  • 7. Collino S., Montoliu I., Martin F.P., Scherer M., Mari D., Salvioli S., Bucci L., Ostan R., Monti D., Biagi E., Brigidi P., Franceschi C., Rezzi S., Metabolic signatures of extreme longevity in northern Italian centenarians reveal a complex remodeling of lipids, amino acids, and gut microbiota metabolism. PLoS One, 2013, 8(3), art. no. e56564.Google Scholar

  • 8. da Silva V.R., Ralat M.A., Quinlivan E.P., DeRatt B.N., Garrett T.J., Chi Y.Y., Frederik Nijhout H., Reed M.C., Gregory J.F., Targeted metabolomics and mathematical modeling demonstrate that vitamin B-6 restriction alters one-carbon metabolism in cultured HepG2 cells. Am. J. Physiol. Endocrinol. Metab., 2014, 307(1), E93–101.Web of ScienceGoogle Scholar

  • 9. D’Antona G., Ragni M., Cardile A., Tedesco L., Dossena M., Bruttini F., Caliaro F., Corsetti G., Bottinelli R., Carruba M.O., Valerio A., Nisoli E., Branched-chain amino acid supplementation promotes survival and supports cardiac and skeletal muscle mitochondrial biogenesis in middle-aged mice. Cell Metab., 2010, 12(4), 362–372.CrossrefWeb of ScienceGoogle Scholar

  • 10. de Souza L.F., Jardim F.R., Sauter I.P., de Souza M.M., Bernard E.A., High glucose increases RAW 264.7 macrophages activation by lipoteichoic acid from Staphylococcus aureus. Clin. Chim. Acta., 2008, 398(1–2), 130–133.Google Scholar

  • 11. Ferrante R.J., Andreassen O.A., Jenkins B.G., Dedeoglu A., Kuemmerle S., Kubilus J.K., Kaddurah-Daouk R., Hersch S.M., Beal M.F., Neuroprotective effects of creatine in a transgenic mouse model of Huntington’s disease. J. Neurosci., 2000, 20(12), 4389– –4397.Google Scholar

  • 12. Gheni G., Ogura M., Iwasaki M., Yokoi N., Minami K., Nakayama Y., Harada K., Hastoy B., Wu X., Takahashi H., Kimura K., Matsubara T., Hoshikawa R., Hatano N., Sugawara K., Shibasaki T., Inagaki N., Bamba T., Mizoguchi A., Fukusaki E., Rorsman P., Seino S., Glutamate acts as a key signal linking glucose metabolism to incretin/cAMP action to amplify insulin secretion. Cell Rep., 2014, 9(2), 661–673.Web of ScienceGoogle Scholar

  • 13. Gibbons H., Brennan L., Metabolomics as a tool in the identification of dietary biomarkers. Proc. Nutr. Soc., 2017, 76(1), 42–53.Google Scholar

  • 14. Gleeson M., Bishop N.C., Modification of immune responses to exercise by carbohydrate, glutamine and anti-oxidant supplements. Immunol. Cell Biol., 2000, 78, 554–561.Google Scholar

  • 15. Hou W., Zhong D., Zhang P., Li Y., Lin M., Liu G., Yao M., Liao Q., Xie Z., A strategy for the targeted metabolomics analysis of 11 gut microbiota-host co-metabolites in rat serum, urine and feces by ultra-high performance liquid chromatography-tandem mass spectrometry. J. Chromatogr. A., 2016, 1429, 207–217.CrossrefWeb of ScienceGoogle Scholar

  • 16. Ji P., Wei Y., Sun H., Xue W., Hua Y., Li P., Zhang W., Zhang L., Zhao H., Li J., Metabolomics research on the hepatoprotective effect of Angelica sinensis polysaccharides through gas chromatography-mass spectrometry. J Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2014, 973, 45–54.Google Scholar

  • 17. Jung J., Kim S.H., Lee H.S., Choi G.S., Jung Y.S., Ryu D.H., Park H.S., Hwang G.S., Serum metabolomics reveals pathways and biomarkers associated with asthma pathogenesis. Clin. Exp. Allergy, 2013, 43(4), 425–433.CrossrefWeb of ScienceGoogle Scholar

  • 18. Klysz D., Tai X., Robert P.A., Craveiro M., Cretenet G., Oburoglu L., Mongellaz C., Floess S., Fritz V., Matias M.I., Yong C., Surh N., Marie J.C., Huehn J., Zimmermann V., Kinet S., Dardalhon V., Taylor N., Glutamine-dependent α-ketoglutarate production regulates the balance between T helper 1 cell and regulatory T cell generation. Sci. Signal., 2015, 8(396), ra97.Google Scholar

  • 19. Lezcano Meza D., Terán Ortiz L., Carvajal Sandoval G., Gutiérrez de la Cadena M., Terán Escandón D., Estrada Parra S., Effect of glycine on the immune response of the experimentally diabetic rats. Rev. Alerg. Mex., 2006, 53(6), 212–216.Google Scholar

  • 20. Li Z.Y., Ding L.L., Li J.M., Xu B.L., Yang L., Bi K.S, Wang Z.T., H-1-NMR and MS based metabolomics study of the intervention effect of curcumin on hyperlipidemia mice induced by highfat diet. PLoS One, 2015, 10, art. no. e0120950.Google Scholar

  • 21. Lieber C.S., Alcoholic liver disease: new insights in pathogenesis lead to new treatments. J. Hepatol., 2000, 32(1 Suppl), 113–128.CrossrefGoogle Scholar

  • 22. Lin H.M., Barnett M.P., Roy N.C., Joyce N.I., Zhu S., Armstrong K., Helsby N.A., Ferguson L.R., Rowan D.D., Metabolomic analysis identifies inflammatory and noninflammatory metabolic effects of genetic modification in a mouse model of Crohn’s disease. J. Proteome Res., 2010, 9(4), 1965–1975.CrossrefWeb of ScienceGoogle Scholar

  • 23. Liu G., Xiao L., Cao W., Fang T., Jia G., Chen X., Zhao H., Wu C., Wang J., Changes in the metabolome of rats after exposure to arginine and N-carbamylglutamate in combination with diquat, a compound that causes oxidative stress, assessed by 1H NMR spectroscopy. Food Funct., 2016, 7(2), 964–974.Web of ScienceCrossrefGoogle Scholar

  • 24. Long L.H., Halliwell B., Artefacts in cell culture: α-Ketoglutarate can scavenge hydrogen peroxide generated by ascorbate and epigallocatechin gallate in cell culture media. Biochem. Biophys. Res. Commun., 2011, 406(1), 20–24.Google Scholar

  • 25. Manna S.K., Tanaka N., Krausz K.W., Haznadar M., Xue X., Matsubara T., Bowman E.D., Fearon E.R., Harris C.C., Shah Y.M., Gonzalez F.J., Biomarkers of coordinate metabolic reprogramming in colorectal tumors in mice and humans. Gastroenterology, 2014, 146(5), 1313–1324.Google Scholar

  • 26. McMorris T., Mielcarz G., Harris R.C., Swain J.P., Howard A., Creatine supplementation and cognitive performance in elderly individuals. Neuropsychol. Dev. Cogn. B Aging Neuropsychol. Cogn., 2007, 14(5), 517–528.Google Scholar

  • 27. Monteiro M.S., Carvalho M., Bastos M.L., Guedes de Pinho P., Metabolomics analysis for biomarker discovery: advances and challenges. Curr. Med. Chem., 2013, 20(2), 257–271.CrossrefGoogle Scholar

  • 28. NINDS NET-PD Investigators., A randomized, double-blind, futility clinical trial of creatine and minocycline in early Parkinson disease. Neurology, 2006, 66(5), 664–671.Google Scholar

  • 29. Obi A.T., Stringer K.A., Diaz J.A., Finkel M.A., Farris D.M., Yeomans L., Wakefield T., Myers D.D. Jr., 1D-(1)H-nuclear magnetic resonance metabolomics reveals age-related changes in metabolites associated with experimental venous thrombosis. J. Vasc. Surg. Venous Lymphat. Disord., 2016, 4(2), 221–230.Web of ScienceGoogle Scholar

  • 30. Pan Z., Raftery D., Comparing and combining NMR spectroscopy and mass spectrometry in metabolomics. Anal. Bioanal. Chem., 2007, 387, 525–527.Google Scholar

  • 31. Pedersen H.K., Gudmundsdottir V., Nielsen H.B., Hyotylainen T., Nielsen T., Jensen B.A.H., Forslund K., Hildebrand F., Prifti E., Falony G., Le Chatelier E., Levenez F., Doré J., Mattila I., Plichta D.R., Pöhö P., Hellgren L.I., Arumugam M., Sunagawa S., Vieira-Silva S., Jørgensen T., Holm J.B., Trošt K., Consortium M., Kristiansen K., Brix S., Raes J., Wang J., Hansen T., Bork P., Brunak S., Oresic M., Ehrlich S.D., Pedersen O., Human gut microbes impact host serum metabolome and insulin sensitivity. Nature, 2016, 535(7612), 376–381.Web of ScienceGoogle Scholar

  • 32. Perasso L., Spallarossa P., Gandolfo C., Ruggeri P., Balestrino M., Therapeutic use of creatine in brain or heart ischemia: available data and future perspectives. Med. Res. Rev., 2013, 33(2), 336–363.CrossrefWeb of ScienceGoogle Scholar

  • 33. Ren M., Zhang S.H., Zeng X.F., Liu H., Qiao S.Y., Branched-chain amino acids are beneficial to maintain growth performance and intestinal immune-related function in weaned piglets fed protein restricted diet. Asian-Australas. J. Anim. Sci., 2015, 28(12), 1742–1750.Google Scholar

  • 34. Richards S.E., Wang Y., Claus S.P., Lawler D., Kochhar S., Holmes E., Nicholson J.K., Metabolic phenotype modulation by caloric restriction in a lifelong dog study. J. Proteome Res., 2013, 12(7), 3117–3127.CrossrefWeb of ScienceGoogle Scholar

  • 35. Schoeman J.C., Hou J., Harms A.C., Vreeken R.J., Berger R., Hankemeier T., Boonstra A., Metabolic characterization of the natural progression of chronic hepatitis B. Genome Med., 2016, 8, art. no. 64.Google Scholar

  • 36. Song X., Wang J., Wang P., Tian N., Yang M., Kong L., 1H NMR-based metabolomics approach to evaluate the effect of Xue-Fu-Zhu-Yu decoction on hyperlipidemia rats induced by high-fat diet. J. Pharm. Biomed. Anal., 2013, 78–79, 202–210.Web of ScienceGoogle Scholar

  • 37. Wang X.Y., Luo J.P., Chen R., Zha X.Q., Pan L.H., Dendrobium huoshanense polysaccharide prevents ethanol-induced liver injury in mice by metabolomic analysis. Int. J. Biol. Macromol., 2015, 78, 354–362.Google Scholar

  • 38. Wissmann P., Geisler S., Leblhuber F., Fuchs D., Immune activation in patients with Alzheimer’s disease is associated with high serum phenylalanine concentrations. J. Neurol. Sci., 2013, 329(1–2), 29–33.Web of ScienceGoogle Scholar

  • 39. Worley B., Halouska S., Powers R., Utilities for quantifying separation in PCA/PLS-DA scores plots. Anal. Biochem., 2013, 433(2), 102–104.Web of ScienceGoogle Scholar

  • 40. Wu B., Yan S., Lin Z., Wang Q., Yang Y., Yang G., Shen Z., Zhang W., Metabolomic study on ageing: NMR-based investigation into rat urinary metabolites and the effect of the total flavone of Epimedium. Mol. Biosyst., 2008, 4(8), 855–861.Google Scholar

  • 41. Xia J., Sinelnikov I.V., Han B., Wishart D.S., MetaboAnalyst 3.0—making metabolomics more meaningful, Nucleic Acids Res., 2015, 43, W251-W257.Google Scholar

  • 42. Xu J., Jiang H., Li J., Cheng K.K., Dong J., Chen Z., 1H NMR-based metabolomics investigation of copper-laden rat: a model of Wilson’s disease. PLoS One, 2015, 10, art. no. e0119654.Google Scholar

  • 43. Xu X., Yan H., Zhang X., Structure and immuno-stimulating activities of a new heteropolysaccharide from Lentinula edodes. J. Agric. Food Chem., 2012, 60(46), 11560–1156.CrossrefGoogle Scholar

  • 44. Xu X., Yang J., Luo Z., Zhang X., Lentinula edodes-derived polysaccharide enhances systemic and mucosal immunity by spatial modulation of intestinal gene expression in mice. Food Funct., 2015a, 6(6), 2068–2080.Web of ScienceGoogle Scholar

  • 45. Xu X., Yang J., Ning Z., Zhang X., Lentinula edodes-derived polysaccharide rejuvenates mice in terms of immune responses and gut microbiota. Food Funct., 2015b, 6(8), 2653–2663.Web of ScienceGoogle Scholar

  • 46. Xu X., Yang J., Ning Z., Zhang X., Proteomic analysis of intestinal tissues from mice fed with Lentinula edodes-derived polysaccharides. Food Funct., 2016, 7(1), 250–261.CrossrefGoogle Scholar

  • 47. Xu X., Zhang X., Lentinula edodes-derived polysaccharide alters the spatial structure of gut microbiota in mice. PLoS One, 2015, 10(1), art. no. e0115037.Google Scholar

  • 48. Yap I.K., Li J.V., Saric J., Martin F.P., Davies H., Wang Y., Wilson I.D., Nicholson J.K., Utzinger J., Marchesi J.R., Holmes E., Metabonomic and microbiological analysis of the dynamic effect of vancomycin-induced gut microbiota modification in the mouse. J. Proteome Res., 2008, 7(9), 3718–3728.Web of ScienceGoogle Scholar

  • 49. Zhu K.X., Nie S.P., Gong D.M., Xie M.Y., Effect of polysaccharide from Ganoderma atrum on the serum metabolites of type 2 diabetic rats. Food Hydrocoll., 2016, 53, 31–36.Google Scholar

About the article

Received: 2017-03-03

Revised: 2017-08-07

Revised: 2017-09-11

Accepted: 2017-09-19

Published Online: 2018-02-14

Citation Information: Polish Journal of Food and Nutrition Sciences, ISSN (Online) 2083-6007, DOI: https://doi.org/10.1515/pjfns-2017-0029.

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© 2017 Xiaofei Xu et al., published by De Gruyter Open. This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License. BY-NC-ND 3.0

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